BENITEC LTD ANNUAL REPORT · 2020. 7. 30. · Incitive Ltd, Peptech Ltd, Arana Therapeutics Ltd, Genera Biosystems Ltd. Dr John chiplin PH.D. Non-Executive Director ... Benitec Ltd

Benitec Ltd ABN 64 068 943 662

F6A / 1-15 Barr Street Balmain NSW 2041 Australia

Tel: +61 (0) 2 9555 6986 Email: [email protected]

www.benitec.com

BENITEC LTD ANNUAL REPORT 2011


ChAiRmAN ANd ThE CEO’s LETTER 1

diRECTORs’ REPORT 2

AUdiTOR’s iNdEPENdENCE dECLARATiON 11

CORPORATE GOVERNANCE sTATEmENT 12

FiNANCiAL sTATEmENTs 15

diRECTORs’ dECLARATiON 40

iNdEPENdENT AUdiT REPORT 41

shAREhOLdER iNFORmATiON 44

LisT OF PATENTs 48

CORPORATE diRECTORY iNsidE BACK COVER

BENiTEC LimiTEd

ABN 64 068 943 662

directors

Mr Peter Francis (Non-Executive Chairman)Mr Mel Bridges (Non-Executive Director)Dr John Chiplin (Non-Executive Director)Mr Iain Ross (Non-Executive Director)

Company secretary

Mr Greg West

Registered Office

Level 16356 Collins StreetMelbourne Vic 3000Australia

Principal Place of Business

F6A/1-15 Barr StreetBalmain NSW 2041Australia

Auditors

Grant Thornton Audit Pty LtdLevel 2215 Spring StreetMelbourne Vic 3000

Bankers

Westpac Banking CorporationBusiness Banking759 Burke RoadCamberwell Vic 3124

share Registry

Computershare Investor Services Pty LimitedYarra Falls452 Johnston StreetMelbourne Vic 3067

stock Exchange Listing

The Company is listed on the Australian Securities Exchange LimitedASX Code: BLT

Contents Corporate Directory

Dear Shareholder,

The past 12 months has been another year of significant achievements for Benitec. Highlights have included:

• Thesuccessfulraising,viaarenounceablerightsissue,of$8MtoenableBenitectopursuetheR&DprogramandtoterminatetheLaJollaCove Inc convertible note.

• TheOctober2010USPTOBoardofAppealsdecisiontoreverseallrejectionsoftheclaimsinthe‘099Grahampatent,clearedthewayforthepatenttobere-issuedintheUSinMarch2011,

• ThreekeyDivisionalsoftheGrahampatent(853,841and726)wereallowedintheUS• NotificationofallowanceoftheGrahampatentintheEUwasreceivedinJune2011,• Thecommencementofourneuropathicpainprogram,anditsdemonstrationbyagroupofChineseresearchers• GoodprogressinourhepatitisBandlungcancerprogramshasbeenmade• TheformationandfirstmeetingoftheBenitecChiefInvestigators’Group

ThecapitalraisinginMaywasahighlysignificantevent,demonstratingthesupportinthemarketforBenitecanditstechnology.Therenounceablerightsissuewasfullyunderwrittenandoversubscribed,andasignificantmajorityofshareholdersparticipated.

Ourresearchanddevelopmentprogram,supportedbyourrobustpatentposition,hasadvancedoverthepast12months.InhepatitisB,BenitecisworkingwithChina-basedBiomicsBiotechnologiesCo.Ltd.(Biomics)onaprojecttodevelopaddRNAi-basedtherapyforhepatitisBinfection.ThefirststageofthecollaborationaimedtoidentifytargetsequencesonagenecriticalforreplicationofthehepatitisBvirus(HBV).ThesecondstageoftheprojectcommencedinMarch2011.AnumberofactivesiRNAsidentifiedinthefirststagearecurrentlybeingtestedasddRNAiconstructs.OurgoalistodevelopatripleshRNAexpressingconstructtargetingthreeregionsofHBVanddeliverthistolivercellsusingadeno-associatedvirus(AAV).ThestrategyissimilartothatbeingdevelopedbyanotherBenitecpartner,TacereTherapeutics(SanJose,USA),whoaretargetingHepatitisCvirus(HCV).Benitec’sfoundingscientist,DrMickGraham,isheavilyinvolvedinthedesignandtestingofddRNAiconstructstargetedatsomeofthesesequencesinmodelsofhepatitisB,inpreparationfortestinginapatientpopulation.TheuseofddRNAiforHBVwouldhaveseveraladvantagesovercurrenttherapy,particularlyinthatitprovidesapotentialcureforthedisease,astheddRNAigeneconstructscanexpressshRNApermanentlyafterintegratingintothelivercellsofpatients.

2010alsosawthecontinuationofBenitec’sfirstcancertherapeuticprogram,incollaborationwiththeChildren’sCancerInstituteAustralia,attheUniversityofNewSouthWales.ThecollaborationisusingddRNAitoknockdownagene(betaIIItubulin)associatedwithdrugresistanceinnon-smallcelllungcancer(NSCLC)withtheaimoftakingthistoaclinicaltrial.Thefirststageoftheprojectconfirmedthatthevector-expressedRNAi(intheformofamulti-promotermulticassettevector)provideveryhighsilencingoftheβIII-tubulingeneandconsequentlyrendersthecancercellssensitivetokillingbychemotherapydrugs.

OurprogramtodevelopanexpressedRNAiproductforchronicneuropathicpainassociatedwithcancerhasprogressed.Benitec’sgenesilencingtechnologyhasthepotentialtobecomethenextmajorclassoftherapeuticdrugsinthisarea,becauseofitspotencyandselectivitytoknockdownmoleculartargetsknowntobeinvolvedinchronicpain.Weareconductingadualstrategyinthisarea–undertakingaprogramofmovingtheprojectthroughtotheclinic,andatthesametimeseekingpartnersfromwithinthepharmaceuticalindustrytoassistusinthedevelopmentofthese products.

TheInauguralChiefInvestigators’MeetingbroughttogetherkeyscientistswhoareworkingwithBenitecaroundtheworld-ProfJohnRossi(CityofHope,USA);ProfYorkZhu(BiomicsBiotechnologies,China);ProfMariaKavallaris(UNSW);DrMickGraham,andDrKenReed,twoofthefoundersofBenitec.ThemeetingwasattendedbytheBoardandseniormanagementofBenitecandwasastimulatingandengagingexpositionoftheuseandpotentialofddRNAiforhumantherapeutics.TheCIGwillbeinattendanceaftertheNovemberAGM,andwillpresenttheresultsoftheirresearchtoshareholdersandotherinterestedpartiesinbothSydneyandMelbourneonNovember17and18respectively.

Finally,2011sawsomesignificantoperationalchangesatBenitec.WehavemovedtheoperationstoSydney,intheinnercitysuburbofBalmain.WewelcomedtheappointmentofMrGregWestasCompanySecretaryandChiefFinancialOfficer(toreplaceMrJohnRawling),andMsChingChungastheAdministrativeOfficer.Botharecurrentlyparttimeemployees.WehaveadoptedanewlogowithacontemporarylooktoencapsulatethenewenergywithintheCompanyaswedrivetowardsproducinganewclassoftherapeuticsbasedonthetransformationalddRNAigenesilencingtechnology.

OnbehalfoftheBoardwewouldliketothanktheshareholdersfortheirsupportoverthelasttwelvemonths.AsChairman,PeterFranciswouldliketoacknowledgeandthanktheBoardandExecutivesfortheirdedicationandhardworkthroughouttheyear.

Welookforwardtoaveryexcitingandproductivenextyear,asBenitecprogressesitsR&Dpipelineprogramsininfectiousdisease,cancerandpain,andseekstomoveoneormoreoftheseprogramsintotheclinic.

WehopetoseeyouatBenitec’sAnnualGeneralMeetinginSydneyonNovember17.

Peter Francis Peter French Chairman Chief Executive Officer

BenitecLtdAnnualReport2011 Page1

Chairman’sandCEO’sletter

Page2BenitecLtdAnnualReport2011

YourDirectorssubmittheirreportonBenitecLimited(“theCompany”)forthefinancialyearended30June2011.

DirectorsThenamesanddetailsoftheCompany’sDirectorsinofficeduringthefinancialyearanduntilthedateofthisreportareasfollows.Directorswereinofficeforthisentireperiodunlessotherwisestated.

Names, qualifications, experience and special responsibilities

Mr Peter Francis LLB,GRADDIP(INTELLECTUALPROPERTY) Non-ExecutiveChairman Appointed23February2006

Mr.PeterFrancisisapartneratFrancisAbourizkLightowlers(FAL),afirmofcommercialandtechnologylawyerswithofficesinMelbourne,Australia.Heisalegalspecialistintheareasofintellectualpropertyand licensing and provides legal advice to a large number of corporations and research bodies.

Other Current Directorships of Listed Companies

None.

Former Directorships of Listed Companies in last three years

XceedCapitalLimited.

Mr Mel Bridges BAPPSC,FAICD Non-ExecutiveDirector Appointed12October2007

MrMelBridgeshasmorethan30yearsexperienceintheglobalbiotechnology and healthcare industry. During this period, he founded and managed successful diagnostics, biotechnology and medical devicebusinesses.MeliscurrentlyChairmanofanumberoflisted andunlistedcompanies.HeisChairmanofAlchemiaLtdandImpedimedLimited.Healsoco-foundedthelistedcompanyPanbioLtd.MelhasextensiveexperienceasapubliccompanydirectorandisaNon-ExecutiveDirectorofCampbellBrothersLimitedandTissueTherapiesLimited.

ThebusinessesthatMelhasfoundedhavewonnumerousawardsincludingtheQueenslandExportAward,AustralianSmallBusinessoftheYear,QueenslandTop400,BRW’sTop100FastestGrowingCompaniesforsevenconsecutiveyearsandTheAustralianQualityAward.MelhaswonnumerousawardsforhisachievementsincludingtheErnstandYoung2002EntrepreneuroftheYear.In2004hewasanointedtheQueenslandEntrepreneuroftheYear,andin2005industrygroupAusBiotechawardedhimtheChairman’sIndustryGoldMedalforcontributionstotheAustralianbiotechindustry.


AlchemiaLtd,CampbellBrothersLtd,ImpedimedLtd, TissueTherapiesLtd.


IncitiveLtd,PeptechLtd,AranaTherapeuticsLtd, GeneraBiosystemsLtd.

Dr John chiplin PH.D. Non-ExecutiveDirector Appointed1February2010

DrJohnChiplinhasbroad-basedexperienceinthelifescienceandtechnology industries, both from an operational and investment perspective.HismostrecentaccomplishmentwasthecorporatereengineeringofAranaTherapeutics,aworldleadingAntibodydeveloper,whichresultedintheacquisitionofthecompanybyCephalonforasignificantpremiumtomarket(July2009).ImmediatelypriortorunningArana,Dr.Chiplinwasheadofthe$300MITILifeSciencesinvestmentfundintheUK.

Hisowninvestmentvehicle,NewstarVenturesLtd,hasfundedmorethanadozenearlystagecompaniesinthepasttenyears.Dr.Chiplin’sPharmacyandDoctoraldegreesarefromtheUniversityofNottingham,UK.InadditiontoBenitec,hecurrentlyservesontheBoardsofCalzadaLtd,HealthlinxLtdandScienceMedia,Inc.


CalzadaLtd,HealthlinxLtd.


AranaTherapeuticsLtd,ProgenPharmaceuticalsLtd.

Mr iain ross BSC, CH.D. Non-ExecutiveDirector Appointed1June2010

MrIainRossisanexperiencedbusinessentrepreneurwith30yearsexperienceintheinternationallifesciencessector.FollowingacareerwithSandoz,Fisons,HoffmanLaRoche,andCelltechhehasundertakenandinputtoanumberofcompanyturnaroundsandstartβupsasaboardmemberonbehalfofbanksandprivateequitygroups.Hehasledandparticipatedin4IPOs,hasdirectexperienceoflifesciencemergersandacquisitionsbothintheUKandUSAandhasraisedmorethan£200minthebiotechsector.

HeisaQualifiedCharteredDirectorwithawealthofexperienceinthelifesciencessectorandspecificallyinthefieldofRNAiandwasChairmanofSilenceTherapeuticsplcfrom2004-2010.HeiscurrentlyChairmanofPharminoxLtdandBiomerTechnologyLtdandExecutiveChairmanofArkTherapeuticsGroupplc.


ArkTherapeuticsGroupplc,PharminoxLtd,BiomerTechnologyLtd.


Silence Therapeutics plc.

Directors’Report


coMPaNy secretary

Mr Greg West CA Appointed26May2011

MrWestisaCharteredAccountantandoverrecentyearshasworkedonASXlistingstart-ups.HeisaDirectorandauditcommitteeChairmanofITCLimited(abusinessarmofWollongongUniversity),IDPEducationPtyLtd,EducationAustraliaLimited,andSydneyInternationalFilmSchoolPtyLimited.HecompletedhisstudieswithPriceWaterhouseandworkedinseniorfinanceexecutiverolesininvestmentbankingwithBankersTrust,Bain&Company(nowDeutscheBank),NZI,andwasCFOatthelargestAustraliancreditunion.

MrWestwasformallyappointedtothepositionofcompanysecretaryon26May2011.

Departing company secretary

Mr John rawling

MrRawlingwasappointedcompanysecretaryon2January2007 andresignedon24August2011.

interests in the shares and options of the company and related bodies corporate

Atthedateofthisreport,theinterestoftheDirectorsinthesharesandoptionsofBenitecLimitedwere:

Director Number of Number of options over ordinary shares ordinary shares

MrPeterFrancis 2,237,175 4,474,350

MrMelBridges 860,000 2,998,333

DrJohnChiplin 1,190,846 264,063

MrIainRoss 750,000 187,500

corPorate iNForMatioN

corporate structure

BenitecLimitedisacompanylimitedbysharesthatisincorporatedanddomiciledinAustralia.BenitecLimitedhaspreparedaconsolidated financial report incorporating the entities that it controlledduringthefinancialyear,whichareoutlinedinnote11 of the financial statements.

Principal activities

BenitecisanRNAi-basedtherapeuticscompanyusingitsproprietaryDNA-directedRNAinterference(ddRNAi)orvectorexpressedtechnology to develop therapies for the treatment of life threatening diseaseswithsignificantunmetneedandcommercialattractiveness.Benitec’sprimarytherapeuticprogramfocusesonhumanimmunodeficiencyvirus(HIV)andHepatitisB.Thecompaniesotherprojectsareintheareaofotherinfectiousdiseases,deliveryoptionsand cancer. Benitec also licenses its technology outside of its core in-house programs in order to generate revenue to support its corporate and operational activities.

TheprincipalactivityoftheGroupduringtheyearwasthemanagement,fundingandcommercialisationoftheseprojects.ThisalsoincludedpatentprosecutionandmaintenanceofthefullyownedBenitecpatentportfolioandkeylicensedtechnology.

employees

TheGroupemployed4employeesasat30June2011 (2010:3employees).

DiViDeNDsNodividendsinrespectofthecurrentorpreviousfinancialyearhavebeen paid, declared or recommended for payment.

oPeratiNG aND FiNaNciaL reVieW

overview of operations

ThelasttwelvemonthswillundoubtedlybeseenastheCompany’swatershedyear.Thisperiodhasseenanumberofmajor“game-changing”eventsforBenitec,including:

• there-issuingofthepivotalGrahamgenesilencingpatentintheUSAinMarch,

• theraisingof$8Minafullyunderwrittenandover-subscribedrightsissueinMay,

• commencementofinnovativepre-clinicalprogramsincancerandinfectiousdiseaseinChinaandAustralia,

• thepublicationoftheworld’sfirstclinicaltrialutilisingourtechnology,

• publicationsbyscientistsinQueensland,theUSandChinaofresearchwhichdemonstratesthepotentialofBenitec’stechnologytoprovidetherapiesforcervixcancer,prostatecancerandpain

• anewandenergisedBoardand,• arebrandingoftheCompanytoreflectthewaythattheeventsof

the last 12 months has turned around the company.

TherenounceablerightsissueinMay2011sawsupportfrommostofourexistingshareholdersandseveralnewshareholdershavealsojoinedBenitec.ThefollowingisareviewoftheCompany’sextraordinarytechnology,itspotentialtopreventandevencuredisease,andtomakeadifferencetothelivesofpeoplearoundtheworld.Thisisthe(new)Benitecstory.

about Benitec

BenitecisanAustralian-basedbiotechnologycompanydevelopingbreakthroughtreatmentsforchronicandlife-threateningconditionsbasedonatransformationalgenesilencingtechnology,DNA-directedRNAinterference(ddRNAi).Thetechnology’spotentialtoaddressunmet medical needs and, potentially, to cure disease results from its demonstrated ability to permanently silence genes that cause the condition. Benitec holds the predominant patent position in the use of ddrNaiforhumantherapeuticapplications.Ournewtagline“silencinggenesforlife”encapsulatesthetwostrengthsofourtechnology–longtermsilencingofgenesforhumanhealth.

Directors’Report


the transformational technology

ThediscoveryofRNAiwasawardedtheNobelPrizein2006.Benitec’sRNAimodalitydifferssignificantlyfromthatofstandardsiRNA.Benitec’stechnologydeliversDNa coding for specific sequences of double stranded rNaintothecell,which,afterprocessingbycellularenzymes,interfereswithmRNAandsilencesthetargetgene.Theeffectofthisistoensurethataspecificproteinisnotmade,withthe result that the course of the target disease can be profoundly altered.Thisinnovativeapproachmimicsthebody’sownmachineryforfighting disease.

the Market Potential for rNai

By2017,theworldRNAInterferencemarketwillbeworth$4billion,accordingtoanewreportfromcompaniesandmarkets.com.TheUSandEuroperepresentthelargestmarketsforRNAi,withEuropeexpectedtogrowrapidly,ataCAGRof13.6%to2017.

ThereportpredictsthatthelongertermRNAimarketwillbedrivenbytheR&DofRNAitherapeuticdrugsforvariousdiseases;thefirstofwhichwillemergeduring2013.ThereportpointsoutthatdevelopmentofRNAi-basedtherapeuticsisstillinitsinfancy,howevermanyblockbusterdrugsareexpectedtolosetheirpatentsinthenextfewyearsanditislikelythatpharmaceuticalcompanieswillinvestinRNAitherapies,tomaximisechancesoflaunchingnovelnewdrugs.

Thecompaniesandmarkets.comreportincludesprofilesof136keyindustry participants, including Benitec.

First clinical trial Using Benitec’s ddrNai technology

Untillate2010,BenitecwasinvolvedindevelopingaddRNAi-basedHIV/AIDStherapeutic.ThisprogramwasundertakenincollaborationwiththeCityofHoperesearchhospitalinCalifornia.Thisstudy,whichisnowcomplete,wasafirst-in-manpilotstudyonfourAIDS-relatedlymphomapatients.Theaimofthestudywastodeterminethesafetyand feasibility of lentivirus-transduced stem cell immunotherapy inpatientsundergoingautologoustransplantation.ThedatawaspublishedinScienceTranslationalMedicineinJune20101.

ThetrialdemonstratedthattherewasnooverttoxicityassociatedwiththeprocessandpersistentlevelsofshRNAexpressionwereobservedintwopatientsupto24monthsaftertheclinicalprocedure.Pleasingly,therewasalsoevidencethatdifferentiatedcellsfromtransfectedprogenitorcellscarriedtheddRNAiconstruct.TheseresultssupportthedevelopmentofanRNAi-basedcelltherapyplatformforHIV,andsupportthesafetyofBenitec’sddRNAitechnology in humans. Furthermore, they provide evidence for the potential for stem cell-based therapies to provide long-lasting or even permanentHIVviralcontrol.

BenitecisexploringoptionstopartnerthisprogramsothatthepotentialofddRNAi-modifiedhematopoieticstemcellstotreatandultimatelycureHIV/AIDScanberealized.

Directors’Report

1DL.DiGiusto,etal.RNA-BasedGeneTherapyforHIVWithLentiviralVector–ModifiedCD34+CellsinPatientsUndergoingTransplantationforAIDS-RelatedLymphoma.Sci Trans Med 2(36):36ra43,2010.

robust intellectual Property

Benitechasseenseveralsignificantpatentsgrantedorallowedoverthepast12monthsintheUS,Europeandotherjurisdictions.ThishasgreatlyturnedaroundBenitec’spositiontoapointwhereweonceagaindominatethegenesilencinglandscapeusingddRNAi.Benitecholdsanon-revocable,exclusiveworldwidelicensefromCSIROforthedevelopmentandcommercializationofallhumantherapeuticapplicationsunderthe‘099Grahampatent,recentlysuccessfullyre-examinedandreissuedintheUsandallowedintheeU, and granted broadlyinotherkeyjurisdictionsincludingaustralia, Japan, south africa, india, china, canada and the UK. This patent estate containskeyclaimscoveringmethodsforsilencinggenesbygeneratingdsRNAinsideacellfromageneticconstruct.IthasbeenrecentlyextendedbytwofurtherUSpatentsbeingallowed–the‘726and‘853Grahampatents,givingaverybroadscopeofddRNAicoverage

InadditiontotheCSIRO-licensedpatentestate,BenitechasseveralothergrantedpatentswhichweowninourownrighttospecificapplicationsandimprovementsoftheddRNAitechnology.Benitechasover100filedpatentsandhasin-licensedseveraladditionalpatentsthatextendthescopeofitspatentestateandenhancetheutilityandvalueofitsRNAiplatform.

Benitec thus holds a dominant international patent position for the useofddRNAiingenesilencingforhumantherapeuticapplications.Benitec leverages its strong intellectual property position to out-license and partner its technology along the entire drug development process.

UK revocation application Progress

Latelastyear,StirlingIPonbehalfofanunknownparty,madeanApplicationforRevocationontheUKGrahamPatentGB2,353,282.UKPatentOfficedictatestheprocessanditisrollingon.Benitechasbriefed patent attorneys and they are providing required documents. Atthetimeofwriting,atimetableforevidenceisexpectedsoon,togetherwithahearingdate,whichisexpectedtobetowardstheendofthisyear.Afinaloutcomefromthehearingisnotexpecteduntil2012.Benitecarguments,whichweresuccessfullyusedtore-instatetheGrahampatentintheUS,andotherjurisdictions,arebeingusedintheUK,inadditiontootherpoints,andtheCompanyremainsconfident,asitwaswiththeUSPTO,thatBenitecwillbesuccessfulindefending the patent. The Company has an increasingly strong patent positioninmostmajorjurisdictions,asevidencedbythemostrecentUSPTOallowanceofthe‘726Grahampatent,andtheallowanceoftheEuropeanGrahampatent,andtheUKactionisproofthatitisastrongpositionotherwiseitwouldn’tbechallenged.

Broad collaborative Pipeline of Human therapy Projects

Beniteccollaborateswithorganisationsgloballytoutiliseitspatentestate to develop novel gene silencing therapeutics for chronic life threatening diseases and disorders, particularly in cancer and infectious disease.Benitecishappytoexplorecollaborationswithresearch groups and biotechnology companies to further develop therapeuticproductsbasedonthepowerofddRNAi.

ThefollowingisabriefdescriptionofeachprogramthatisbeingworkedonbyourcollaboratorstoprovetheefficacyandsafetyofourddRNAigenesilencingtechnology.

collaborator / Licensee r & D Pre-clin Ph i Ph ii Ph iii

Partneredprogram

Benitec funded programs

Licensedprogram

Cancer- associated pain UQ(Aust)

Drug resistant lung cancer UNSW(Aust)

Hepatitis B Biomics(China)

Hepatitis C Tacere (Pfizer)(US)

a revolutionary therapeutic for cancer-associated Pain

the Market: Theglobalmarketforcancer-associatedpainproductsisvaluedat$2billionandisexpectedtoincreaseto$2.9billionbytheyear2016.InresearchcommissionedbyBenitec,aEuropeanpalliativecareexpertstatesthatopioidefficacyisnotsufficient,particularlyforcomplexneuropathicpainwhichisverydifficulttotreatincancer-associated pain patients.

Benitec’s approach: TheconceptistouseaddRNAiconstructtosilenceageneexpressingakeymoleculeinthespinalcordthatisresponsibleformediatingpaintothecentralnervoussystem.Usingalentiviralvector,theconstructwillbedeliveredtothetargetcells,integrateandcontinuouslyexpressanshRNAthatwillspecificallysilencethetargetgene,thusreducingtheexpressionofthepainmediatortosuchlowlevelsthateffectiveandlong-lastingpainreliefisachieved.Ideally,asinglespinalcordinjectionisallthatwillberequiredtoprovidethislonglastingpainrelief.Twotargetmoleculeshave been identified for this approach. In the case of one of them, PKCg,theproofofconceptofthisapproachhasbeendemonstratedpre-clinically.

BenitecisnowworkingwithresearchersattheUniversityofQueensland to gather sufficient and appropriate data to be able toconductaclinicaltrialonterminallyillcancerpatientswhoaresuffering from severe neuropathic pain that is difficult to manage.

TheCompanyisalsoindiscussionswithaClinicalResearchOrganisation,amanufacturerofGMPgradematerial,andalicensinggroup, to facilitate the development, trialling and commercialisation of this program.

BenitecBiopharmaLtdAnnualReport2011 Page5

Directors’Report


programs.ThefoundingmembershipoftheCIGincludesinternationalexpertsinthefieldofRNAitherapeutics.

Thesixstronggroupcomprises:DrMichaelGraham(thediscovererofBenitec’sRNAitechnology);DrKenReed(Benitecfounder);ProfessorJohnRossi(CityofHopeCancerCentre,CA,USA);DrYorkZhu(BiomicsBiotechnologies,Nantong,China);andProfessorMariaKavallaris(Children’sCancerInstituteAustralia(CCIA)attheUniversityofNewSouthWales(UNSW),Australia).ThegroupischairedbyBenitec’sCEODr.PeterFrench.CIGmembershipisnotaremuneratedrole.

TheinauguralCIGmeetingwasheldinMelbourneinMarch2011,andwasafullandveryexcitingbriefingtotheBoard,whowereinspiredbythequalityofthescienceandofthepeoplewhoarecollaboratingwithBeniteconourimportantclinicalandpre-clinicalpipeline.

Financial overview

Benitec’snetlossfortheyearended30June2011was$3,534,874comparedtoanetlossof$4,640,671forthepreviousfinancialyear.

Operatingrevenueforthe12monthsto30June2011was$342,545,upfrom$181,417inthepreviousfinancialyearduetoanunexpecteddividendreceivedfromTacereTherapeutics,Inc.,aUScorporationinwhichtheCompanyhasasmallinterest.Otherincomeduringtheyearwas$3,000,comparedto$616inthepreviousfinancialyear.

Operatingexpensesforthefinancialyear,excludingtheLJCIsettlementchargeof$660,957inthecurrentyearandtheCSIROsettlementof$2,004,951inthepreviousyear,were$3,219,461upfrom$2,817,853inthepreviousyear.TravelrelatedcostsincreasedduetoattendanceattheUSPTOre-examinationhearingintheUSinAugust2010aswellatripthroughtheUS,UKandEuropetovisitcurrentshareholdersandpotentialinvestorsaswellaspresentattheBioEquityEurope2011conference.ConsultantscostsincreasedfollowingthefavourabledecisionattheUSPTOinordertoensurethewidestreachoftheCompany’splansforthefuture.Employmentrelatedcostsroseduetotheadditionofstaffforbusinessdevelopment and administration.

Benitec’scurrentassetsbalanceat30June2011was$6,838,897(2010:$1,029,541),withcurrentliabilitiesof$1,197,474(2010:$967,355).Nettangibleassetswere0.56centspershare(2010:(0.17)cents).ThissignificantlyimprovedpositionreflectsthecompletionoftherenounceablerightsissueinMay2011

cash Flows

ThecashflowsoftheCompanyconsistof:licensingoftheCompany’stechnology, payments to employees and suppliers in order to conductproductdevelopmentandco-investmentand/orlicensingcollaborationstoexploittheGeneSilencingintellectualpropertyportfolio;andthemaintenanceofthesmallcorporatestructure,whichmanagesexistingactivitiesaswellasseekingoutandinvestigatingnewopportunities.

caPitaL raisiNGs / caPitaL strUctUreDuringtheyearunderreview,theCompanyraised$9,334,368,netofcosts, to provide funding for the ongoing research and development projectsandtosupporttheevaluationofadditionalprojectandpartnering opportunities.

Knocking Down Lung cancer

the Market: Lungcanceristhemostcommoncauseofcancerdeathinthewesternworld.Thedominanttypeoflungcancerisnon-smallcelllungcancer(NSCLC).

the Need:TheprognosisforapatientdiagnosedwithNSCLCremainspoor,withonly~15%ofpatientssurvivingmorethan5yearsfromtime of diagnosis. In addition, the benefit of the chemotherapeutic agentsusedtotreatNSCLCislimitedbythehighincidenceofdoselimitingtoxicityandemergenceoftreatmentresistantcelllines.Thus there remains an unmet clinical need for treatments that can be usedatlowerdosesorwhichcanavoidthecancercells’resistancemechanisms.

Benitec’s approach:IncollaborationwiththeChildren’sCancerInstituteAustraliaattheUniversityofNewSouthWales,BenitecisworkingtodevelopaddRNAi-basedtherapytoovercomechemotherapyresistanceinhumanNSCLCcells.ThetargetgeneforsilencingisbetaIIItubulin,andBenitecandCCIAscientistshavedesignedandtestedapowerfulddRNAimoleculethatsignificantlyknocksdownbetaIIItubulininhumanlungcancercells.

TheCompanyisnowworkingontestingtheddRNAimoleculeinapreclinical model of human lung cancer, as part of the process required forhumanclinicaltrials.Benitecbelievesthatthisapproachwillhave the potential to substantially increase the efficacy of current chemotherapyforlungcancerpatientsresultinginextensionoflifeand/ordecreaseintoxicity-relatedadversesideeffectsofcurrentchemotherapy.TheCompanywillcontinuetodevelopthiswiththeUNSWresearchers,inparticularProfessorMariaKavallaris.

a cure for Hepatitis B?

the Market: HBVisaseriousandcommoninfectiousdiseaseoftheliver,affectingmillionsofpeoplethroughouttheworld.Morethan2,000millionpeoplealivetodayhavebeeninfectedwithHBVatsometimeintheirlivesandoftheseabout350millionremainchronicallyinfectedandbecomecarriersofthevirus.Everyyearabout25%oftheover4millionacuteclinicalcases(i.e.1millionpeopleworldwide)diefromchronicactivehepatitis,cirrhosisorHBV-inducedlivercancer.AsaconsequenceHBVrankssecondonlytotobaccoasaknownhumancarcinogen.

Benitec’s approach:BenitecisundertakingaprogramtodevelopanoveltreatmentforhepatitisBwithBiomicsBiotechnologies,aChinabasedbiotechnologycompanywithconsiderableRNAiexpertise.Thetwocompanieshaveidentifiedover100effectiveRNAicandidatesthat can silence the hepatitis B virus and has selected the five most promising of them for further evaluation and development using ddRNAiconstructs.Theseconstructswillbetestedinpre-clinicalmodels of hepatitis B, and ultimately in a China-based clinical trial of hepatitis B virus-infected patients.

chief investigators’ Group

Ascanbeseenfromtheabove,Benitec’sR&Dpipelineofhumantherapeuticsareallconductedincollaborationwithleadingorganisationsinternationally.Inrecognitionofthis,inFebruary2011,BenitecformedaChiefInvestigators’Group(CIG),bringingtogethertheCompany’sscientificfounderswithitscollaborativepartners.TheCIG,whichreplacedBenitec’sScientificAdvisoryBoard,reflectsboththecollaborativeapproachtoitsR&Dandtheclinicalfocusofits

Directors’Report


ThefollowingESOPoptionslapsedduringthefinancialyear:

expiry Date exercise Price No. Lapsed

4September2011 $0.0224 2,580,000

21February2013 $0.0781 3,000,000

total 5,580,000

NED OptionsAtotalof7,666,666NEDOptionsarecurrentlyonissue,with4,666,666grantedbyshareholderstoNon-ExecutiveDirectorsattheCompany’s2007AnnualGeneralMeetingandafurther3,000,000grantedon13July2010followingapprovalbyshareholdersintheGeneralMeetingheldon30June2010.

Other OptionsAtotalof34,244,444unlistedOptionshavebeenissuedtoDrChrisBremneraspartofshareplacementsinNovember2008,February2009andFebruary2010.

ThebalanceofDirectors’OptionsandOtherOptionswereissuedduringtheperiodwhenBenitecconducteditsoperationsintheUS.

Summary of Shares, Options and Warrants on Issue – 30 June 2011Asaresultoftheissueofsharesandoptions,theCompanyhad926,337,910listedordinarysharesand247,976,445listedoptionsonissueatreportingdate.Therearealso56,681,795unlistedoptionsand6,126,962warrantsonissue,fulldetailsofwhichareincludedinnote15tothefinancialstatements.

Unissued SharesAsatthedateofthisreport,therewere310,785,202unissuedordinaryshares(310,785,202atthereportingdate).Refertonote16ofthefinancial statements for further details of the options outstanding.

Optionholdersdonothavetheright,byvirtueoftheoption,toparticipate in any share issue of the Company or any related body corporate or in the interest issue of any other registered scheme.

Shares issued as a result of the exercise of OptionsDuringtheyearnoshareswereissuedontheexerciseofoptionsissuedbytheCompany(2010:nil).

siGNiFicaNt cHaNGes iN tHe state oF aFFairsDuringtheyear,therewerenosignificantchangesintheCompany’sstate of affairs.

siGNiFicaNt eVeNts aFter tHe rePortiNG Date Nomattersorcircumstanceshavearisensince30June2011whichhave significantly affected or may significantly affect the operations of theGroup,theresultsofthoseoperationsorthestateofaffairsoftheGroup,insubsequentfinancialyears.

ordinary shares

Therewereanumberofshareissuesduringthefinancialyear.Thedetails are:

• 404,588,257ordinarysharesissuedinMayandJune2011atapriceof$0.02pershareaspartoftherenounceablerightsissue;

• 98,306,033ordinarysharesissuedduringtheyearatpricesrangingfrom$0.017to$0.0231pershareaspartialconversionsoftheConvertibleNoteheldbyLaJollaCoveInvestors,Inc.;

• 8,019,405ordinarysharesissuedtoCSIROastop-upsharesinJuly2010andJanuary2011pursuanttothesettlementinJanuary2010;and

• 420,000ordinarysharesissuedupontheexerciseofESOPoptionsatanexercisepriceof$0.0224.

options

AtthedateofthisDirectors’Report,theCompanyhasatotalof310,785,202optionstoacquireordinarysharesintheCompany.Unlessotherwisenoted,alloptionsareunlisted,restrictedandarecategorisedasfollows:

type Number

ListedOptions(BLTO) 46,673,907

ListedOptions(BLTOB) 201,302,538

EmployeeShareOptionPlan 12,800,000

NEDOptions 7,666,666

Directors’Options 1,953,125

StrategicAdvisorWarrants 6,126,962

UnlistedOptions 34,244,444

Other 17,560

total 310,785,202

Listed Options201,302,538ListedOptionswereissuedaspartoftherenounceablerightsissueinMay2011.Theseoptionshavetherighttoacquireoneordinaryshareat$0.04withanexpirydateof31December2013.

56,081,915ListedOptionswithanexercisepriceof$0.15expiredon 3April2011.

Employees Share Option Plan (ESOP)EmployeeOptionsareregulatedbythePlanwhichhasbeenpreviouslyannounced.Insummary,alloptionsfallingundertheESOPexpireonthedatessetoutbelow.OptionsheldbyanyemployeewhoresignedearlierwillexpireonatimedeterminedbytheBoardorotherwiseinsixmonths.TheBoardhasthepowertoadjust,amendandcanceltheESOP.Non-ExecutiveDirectorsarecurrentlyexcludedfromtheESOP.

Grant Date expiry Date exercise Price Number

14December2006 14December2011 $0.0407 1,000,000

21February2008 21February2013 $0.0781 300,000

13July2010 19August2014 $0.0204 6,500,000

13July2010 10June2013 $0.0289 5,000,000

total 12,800,000

Directors’Report


The Board is responsible for determining the appropriate remuneration packagefortheCEO,andtheCEOisinturnresponsiblefordeterminingtheappropriateremunerationpackagesforseniormanagement.

Allexecutivesareeligibletoreceiveabasesalary(whichisbasedonfactorssuchasexperienceandcomparableindustryinformation),fringe benefits, options, and performance incentives. The Board reviewstheCEO’sremunerationpackage,andtheCEOreviewstheotherseniorexecutives’remunerationpackages,annuallybyreferencetotheconsolidatedentity’sperformance,executiveperformance,andcomparableinformationwithintheindustry.

Theperformanceofexecutivesismeasuredagainstcriteriaagreedannuallywitheachexecutiveandisbasedpredominantlyontheoverallsuccess of the Company in achieving its broader corporate goals. Bonusesandincentivesarelinkedtopredeterminedperformancecriteria.TheBoardmay,however,exerciseitsdiscretioninrelationto approving incentives, bonuses, and options, and can recommend changestotheCEO’srecommendations.Thepolicyisdesignedtoattractthehighestcalibreofexecutivesandrewardthemforperformancethatresultsinlong-termgrowthinshareholderwealth.

ExecutivesareentitledtoparticipateintheEmployeeShare OptionPlan.

AnyAustralianexecutivesordirectorsreceiveasuperannuationguaranteecontributionrequiredbythegovernment,whichiscurrently9%,anddonotreceiveanyotherretirementbenefits.

AllremunerationpaidtodirectorsandexecutivesisvaluedatthecosttotheCompanyandexpensed.OptionsarevaluedusingtheBlack-Scholes methodology.

TheBoardpolicyistoremuneratenon-executivedirectorsatmarketratesforcomparablecompaniesfortime,commitment,andresponsibilities.TheBoardasawholedeterminespaymentstothenon-executivedirectorsandreviewstheirremunerationannually,basedonmarketpractice,duties,andaccountability.Themaximumaggregateamountoffeesthatcanbepaidtonon-executivedirectorsissubjecttoapprovalbyshareholdersattheAnnualGeneralMeeting.Feesfornon-executivedirectorsarenotlinkedtotheperformanceoftheconsolidatedentity.However,toaligndirectors’interestswithshareholderinterests,the directors are encouraged to hold shares in the Company.

Performance Based remuneration

Aspartofeachexecutive’sremunerationpackagethereisaperformance-based component. The intention of this program is tofacilitategoalcongruencebetweenexecutiveswiththatofthebusinessandshareholders.Generally,theexecutive’sperformancebasedremunerationistiedtotheCompany’ssuccessfulachievementofcertainkeymilestonesasrelatestoitsoperatingactivities,aswellastheCompany’soverallfinancialposition.

company Performance, shareholder Wealth, and Directors’ and executives’ remuneration

The remuneration policy has been tailored to increase goal congruence betweenshareholders,directors,andexecutives.Therehavebeentwomethods applied in achieving this aim, the first being a performance basedbonusbasedonachievementofkeycorporatemilestones,andthesecondbeingtheissueofoptionstothemajorityofdirectors andexecutivestoencouragethealignmentofpersonalandshareholder interests.

LiKeLy DeVeLoPMeNts aND eXPecteD resULtsFurtherinformationonlikelydevelopmentsintheoperationsoftheGrouphasnotbeenincludedinthisreportbecauseatthisstagethedirectorsbelieveitwouldbelikelytoresultinunreasonableprejudicetotheGroup.AsBenitecLimitedislistedontheAustralianStockExchange,itissubjecttothecontinuousdisclosurerequirementsoftheASXListingRuleswhichrequireimmediatedisclosuretothemarketofinformationthatislikelytohaveamaterialeffectonthepriceorvalueofBenitecLimited’ssecurities.

eNViroNMeNtaL reGULatioNTheGroup’soperationsarenotsubjecttoanysignificantenvironmentalregulationsundereitherCommonwealthorStatelegislation.

MeetiNGs oF DirectorsThe number of meetings of the Directors held during the year and the numberofmeetingsattendedbyeachdirectorwasasfollows:

Board of Directors risk & audit committee attended Held attended Held

Current Directors

PeterFrancis 6 6 2 2

MelBridges 6 6 2 2

JohnChiplin 6 6 - -

IainRoss 6 6 - -

committee membership

DuetothesmallnumberofDirectors,itwasdeterminedthattheBoardwouldundertakeallofthedutiesofaproperlyconstitutedRemunerationandNominationCommittee.

TheRiskandAuditCommitteeischairedbyMrBridgesandmettwiceduring the financial year.

reMUNeratioN rePortThis report details the nature and amount of remuneration for each directoroftheCompany,andfortheexecutivesreceivingthehighestremuneration.

TheinformationprovidedintheRemunerationReporthasbeenauditedasrequiredbys308(3c)oftheCorporationsAct2001.

remuneration Philosophy

The remuneration policy of the Company has been designed to align directorandexecutiveobjectiveswithshareholderandbusinessobjectivesbyprovidingafixedremunerationcomponentandofferinglong-termincentivesbasedonkeyperformanceareas.TheBoardbelieves the remuneration policy to be appropriate and effective in its abilitytoattractandretainthebestexecutivesanddirectorstorunandmanagetheconsolidatedentity,aswellascreategoalcongruencebetweendirectors,executives,andshareholders.

Directors’Report


Details of remuneration for year ended 30 June 2011

table 1. Non-ExecutiveDirectorRemunerationfortheyearended30June2011

short term Post employment equity total

% of remuneration consisting of

options

salary & Fees cash Bonus

Non Monetary

Benefits

super-annuation

termination Benefits

options

$ $ $ $ $ $ $

PeterFrancis 2011 64,166 - - - - 26,211 90,377 29.0%2010 60,000 - - - - 22,967 82,967 27.7%

MelBridges 2011 55,000 - - - - 20,673 75,673 27.3%2010 55,000 - - - - 15,311 70,311 21.8%

JohnChiplin 2011 50,000 - - - - - 50,000 -2010 20,833 - - - - - 20,833 -

IainRoss 2011 50,000 - - - - - 50,000 -2010 4,167 - - - - - 4,167 -

Therewasnoperformancerelatedremunerationpayabletonon-executivedirectorsduringtheyear.

table 2.RemunerationoftheExecutiveDirectorandotherkeymanagementpersonnelwhoreceivethehighestremuneration fortheyearended30June2011


% of remuneration consisting of

options

salary & Fees

cash Bonus

Non Monetary

Benefits

super-annuation

termination Benefits

options

$ $ $ $ $ $ $

SueMacLeman(1) 2011 - - - - - - - -2010 260,684 94,500 - 14,461 - 18,400 388,045 4.7%

JohnRawling(2) 2011 210,813 - - 15,199 - 10,486 236,498 4.4%2010 122,916 5,000 - 11,512 - 1,840 141,268 1.3%

PeterFrench(3) 2011 249,801 35,000 - 15,199 - 54,125 354,125 15.3%2010 86,009 - - 27,822 - - 113,831 -

(1) MsMacLemanwasappointedChiefExecutiveOfficeron4September2006,becameaDirectoron1July2007, resignedasChiefExecutiveOfficerandDirectoron31March2010.

(2) MrRawlingwasappointedCompanySecretaryon2January2007andChiefFinancialOfficeron13April2007.

(3) DrFrenchwasappointedChiefScientificOfficeron4August2009andChiefExecutiveOfficeron4June2010.

Directors’Report


Directors’Report

iNDeMNiFicatioN aND iNsUraNce oF Directors aND oFFicersTheCompanyhasenteredintoDeedsofIndemnitywiththeDirectors,theChiefExecutiveOfficerandtheCompanySecretaries,indemnifyingthemagainstcertainliabilitiesandcoststotheextentpermittedbylaw.

The Company has also agreed to pay a premium in respect of a contractinsuringtheDirectorsandOfficersoftheCompany.Fulldetails of the cover and premium are not disclosed as the insurance policy prohibits the disclosure.

corPorate GoVerNaNceIn recognising the need for the highest standards of corporate behaviourandaccountability,theDirectorsofBenitecLimitedadheretostrictprinciplesofcorporategovernance.TheCompany’scorporategovernance statement is included on page 12 of this annual report.

aUDitor iNDePeNDeNceThe Directors received the declaration included on page 11 of this annualreportfromtheauditorofBenitecLimited.

ProceeDiNGs oN BeHaLF oF coMPaNyNopersonhasappliedforleaveofCourttobringproceedingsonbehalfoftheCompanyorinterveneinanyproceedingstowhichtheCompanyisapartyforthepurposeoftakingresponsibilityonbehalfofthe Company for all or any part of those proceedings.

NoN-aUDit serVicesNon-auditservicesprovidedbyexternalauditorsduringtheyearended30June2011relatetotaxationadviceinrespectoftheEmployeeShareOptionPlanforwhichfeesof$7,975werepaid.

ThisreporthasbeenmadeinaccordancewitharesolutionoftheDirectors.

Peter Francis Chairman

Melbourne,Victoria 24August2011

options issued as Part of remuneration for the year ended 30 June 2011

Optionscanbeissuedtoexecutivesaspartoftheirremuneration.The options are not issued based on performance criteria, but are issuedtotheexecutivesoftheCompanytoincreasegoalcongruencebetweenexecutives,directors,andshareholders.Duringtheyearended30June2011,11,500,000options(2010:nil)weregrantedtoDrPeterFrenchandMrJohnRawlingunderthetermsoftheiremploymentagreements.Optionswereissuedtodirectorsaspartoftheirremunerationfollowingapprovalatameetingofshareholderson30June2010.

Payments to related Parties of Directors

Legalservicesatnormalcommercialratestotalling$133,068(2010:$88,214)wereprovidedbyFrancisAbourizkLightowlers,alawfirminwhichMrPeterFrancisisapartnerandhasabeneficialinterest.

Consultancyfeesforexecutivedutiestotalling$15,000(2010:$30,000)wereprovidedbyParmaCorporationPtyLtd,acompanyinwhichMrMelBridgesisadirectorandhasabeneficialinterest.

Consultancyfeesforexecutivedutiestotalling$62,250(2010:$21,375)wereprovidedbyNewStarVenturesLtd,acorporationinwhichDrJohnChiplinisadirectorandhasabeneficialinterest.

Consultancyfeesforexecutivedutiestotalling$40,000(2010:$nil)wereprovidedbyGladstoneConsultancyPartnership,anentityinwhichMrIainRossisapartnerandhasabeneficialinterest.

employment contracts

TheemploymentconditionsofDrPeterFrench,theChiefExecutiveOfficer,areformalisedinacontractofemployment.Thecurrentemploymentcontractcommencedon4June2010uponhisappointmentasChiefExecutiveOfficer.DrFrench’sappointmentwiththeCompanymaybeterminatedwiththeCompanygiving6months notice or by Dr French giving 2 months notice. The Company may elect to pay Dr French an equal amount to that proportion of his salaryequivalentto6monthspayinlieuofnotice,togetherwithanyoutstanding entitlements due to him. The Company may, at any time, bynoticeinwritingterminateDrFrench’scontractimmediatelyintheevent of serious misconduct.

TheemploymentconditionsofMrGregWest,theparttimeBusinessDevelopmentOfficerandCompanySecretary,areformalisedinacontractofemployment.ThecurrentemploymentcontractwithMrWestcommencedon1March2011.MrWest’sappointmentwiththeCompanymaybeterminatedwiththeCompanygiving2month’snoticeorbyMrWestgiving2month’snotice.TheCompanymayelecttopayMrWestanequalamounttothatproportionofhissalaryequivalentto2month’spayinlieuofnotice,togetherwithanyoutstandingentitlements due to him. The Company may, at any time, by notice inwritingterminateMrWest’scontractimmediatelyintheeventofserious misconduct.


Auditor’sIndependenceDeclaration


CorporateGovernanceStatement

• MrBridges,DrChiplinandMrRossdonothaveanypreviousassociationwiththeCompanyoranyotherrelationshipsthatisrelevant to their independence.

TheBoardcontinuallyassessesitsmembershipandmakesappointmentstocomplementandenhancetheexistingskillbaseoftheBoard.TheBoardhasestablishedaRemunerationandNominationsCommitteecomprisingofallnon-executivedirectors.FormallettersofappointmentareusedforallnewNEDs.

TheCompany’sConstitutionprovidesthat:

• themaximumnumberofDirectorsshallbetenunlessamendedbyaresolutionataGeneralMeetingofShareholders;

• onethirdoftheDirectors(excludingtheManagingDirectorandroundeddown)mustretirefromofficeattheAnnualGeneralMeeting(AGM)eachyear;suchretiringDirectorsareeligibleforre-election;

• Directorsappointedtofillcasualvacanciesmustsubmittoelectionatthenextgeneralmeeting;and

• thenumberofDirectorsnecessarytoconstituteaquorumisnotlessthantwoDirectorscurrentlyinoffice.

The duties of a nomination committee have been assumed by the BoardduetothesizeandscaleoftheCompany.

The Board carries out a Board performance assessment on an annual basis.Inthelastreview,theBoardundertookadetailedreviewofitsperformance and that of its committees and individual Directors. This involvedaselfassessmentprocesswhichrequiredthecompletionandevaluation of detailed questionnaires on business and management matters.TheresultsofthisreviewwereindependentlycollatedandanalysedbytheBoard.FollowingrecentchangestotheBoard,thenextreviewisexpectedtotakeplaceduringtheyearended30June2012.

PriNciPLe 3 Promote ethical and responsible decision-making

The Board and management ensure that the business processes of BenitecLimitedareconductedaccordingtosoundethicalprinciples.The Board has established a formal Code of Conduct in this regard. ThiscodeispostedontheCompany’swebsite.

AllDirectorsandemployeesoftheCompanyareexpectedtoactwiththeutmostintegrityandobjectivity,strivingatalltimestoenhancethereputation and performance of the Company.

AllDirectorsandemployeesoftheCompanyaremadeawareoftheirobligationsundertheCorporationsAct2001withregardtotradinginthe securities of the Company. In addition, the Company has adopted a ShareTradingPolicy,whichisreviewedandupdatedonaregularbasisasrequired.ThispolicyispostedontheCompany’swebsite.

BoardmemberswhohaveormayhaveaconflictofinterestinanyactivityoftheCompanyorwithregardtoanydecisionbeforetheBoard,notifytheBoardofsuchandadecisionismadeastowhethertheBoardmemberconcernedistobeexcludedfrommakingdecisionsthatrelatestotheparticularmatter.TheCompany’sconstitutionallowsaDirectortoenterintoanycontractwiththeCompanyotherthanthatofauditorfortheCompany,subjecttothelaw.

TheBoardhasdeterminedthatDirectorsareabletoseekindependentprofessionaladviceforCompanyrelatedmattersattheCompany’sexpense,subjecttotheinstructionandestimatedcostbeingapprovedby the Chairman in advance as being respectively necessary and reasonable.

The Board of Directors is responsible for establishing the corporate governanceframeworkoftheGroup.TheBoardguidesandmonitorsthebusinessandaffairsofBenitecLimitedonbehalfofitsshareholdersbywhomtheyareelectedandtowhomtheyareaccountable.

TheCompany’scorporategovernancereflectstheASXCorporateGovernanceCouncil’sprinciplesandrecommendations.ThefollowingcommentarysummarisestheCompany’scompliancewiththeASXCorporateGovernanceCouncil’srecommendations.

PriNciPLe 1 Lay solid foundations for management and oversight

The Board has adopted a formal charter that sets out their responsibilities.ThischarterispostedontheCompany’swebsitewww.benitec.com.TheBoardsetsobjectives,goalsandstrategicdirectionalongwithapolicyframeworkwhichmanagementthenworkswithintomanageday-to-daybusiness.TheBoardmonitorsthisonaregularbasis.ThereisclearsegregationbetweentheBoardandmanagement.AnyfunctionsnotreservedfortheBoardandnotexpresslyreservedformembersbytheCorporationsActandASXListingRulesarereservedforseniorexecutives.

Seniorexecutivesaresubjecttoaformalperformancereviewprocessonanannualbasis.Thefocusoftheperformancereviewistosetspecificobjectives,andmonitorperformanceagainstthemforeachexecutive,thatarealignedwiththeCompany’sbusinessobjectives.Anannualreviewoftheperformanceofeachsenorexecutivewasconductedinaccordancewiththisprocessduringtheyear.

PriNciPLe 2 structure the Board to add value

Details on the Board members and their qualifications are included in theDirectors’Report.TheBoardhasapolicyofmaintainingamajorityof independent directors. The current Board composition is four independentNon-ExecutiveDirectors(NEDs).TheBoardhasresolvedthatamajorityofthemembersofeachBoardcommitteeshouldbeNEDs.TheBoardhasapprovedthat,wherenecessary,NEDsshouldmeet during the year in absence of management at such times as they determine necessary.

Directorsareconsideredtobeindependentwhentheyareindependent of management and free from any business or other relationshipthatcouldmateriallyinterferewiththeexerciseoftheirindependentjudgement.TheBoardassessesdirectorindependenceonanannualbasis,ormoreoftenifitfeelsitiswarranted,dependingondisclosuresmadebyindividualDirectors.Inthecontextofdirectorindependence,tobeconsideredindependentaNEDmaynothaveadirectorindirectmaterialrelationshipwiththeCompany.TheBoardhasdeterminedthatamaterialrelationshipisonewhichhas,orhasthepotentialto,impairorinhibitaDirector’sexerciseofjudgementonbehalf of the Company and its shareholders.

TheBoardhasconcludedthatallNEDsareindependent.Inreachingthis conclusion, the Board considered that:

• MrFrancis,theNon-ExecutiveChairman,isaprincipalofFrancisAbourizkLightowlers,amaterialprofessionaladvisertotheCompany.Notwithstandingthisassociation,theBoardissatisfiedthatitwillnotinterferewiththeindependentexerciseofhisjudgment.


PriNciPLe 5 Make timely and balanced disclosure

TheBoardiscommittedtoinformitsshareholdersandthemarketofanymajoreventsthatinfluencetheCompanyinatimelyandconscientious manner. The Board is responsible for ensuring that theCompanycomplieswiththecontinuousdisclosurerequirementsassetoutinASXListingRule3.1andtheCorporationsAct2001.TheCompany’sCommunicationProtocolshavebeenpostedontheCompany’swebsite.

AnymarketsensitiveinformationisdiscussedbytheBoardbeforeitisapprovedtobereleasedtothemarket.

TheCompany’sprocedureistolodgetheinformationwiththeASXandmakeitavailableontheCompany’swebsiteshortlythereafter.

AllexecutivesoftheCompanyhavebeenmadeawareoftheCompany’sobligationswithregardtothecontinuousdisclosureregime.

PriNciPLe 6 respect the rights of shareholders

The Board ensures that its shareholders are fully informed of matters likelytobeofinteresttothem.TheCompanyprovidesallobligatoryinformationsuchasannualreports,halfyearlyreportsandotherASXrequiredreportsinaccordancewiththelawandregulations.

Noticesofshareholdersmeetings,annualandextraordinary,aredistributed in a timely manner and are accompanied by all information that the Company has obtained.

TheCompanyisalwaysavailabletobecontactedbyshareholdersfor any query that the shareholders may have. The queries can be submittedbytelephone,emailorfaxtotheCompany’soffice.

ThechairmanencouragesquestionsandcommentsattheAGMensuring that shareholders have a chance to obtain direct response fromtheCEOandotherappropriateBoardmembers.TheCompanyrequeststhattheauditorsattendtheAGMandareavailabletoansweranyquestionswithregardtotheconductoftheauditandtheirreport.

PriNciPLe 4 safeguard integrity in financial reporting

TheBoardhasestablishedaRiskandAuditCommitteewhichmeetsatleasttwicethroughtheyear.TheBoardhasassumedalloftheresponsibilitiesoftheCommitteeatthistimeduetothesizeandscaleoftheCompanyatthistime.MrMelBridgeshasbeenappointedtochair the Committee.

The members of the Committee have significant financial, business andlegalbackgrounds,expertiseandqualifications,fullparticularsofwhicharecontainedinthisannualreport,asaredetailsofmeetingsofthis Committee.

TheCommitteeisresponsiblefortheappointmentoftheCompany’sauditorsandhasaformalcharter,whichispostedontheCompany’swebsite.Thecharterisreviewedannuallytoensurethatitinlinewithemergingmarketpracticeswhichareinthebestinterestsofshareholders.

ThemainobjectiveoftheCommitteeistoassisttheBoardinreviewinganymattersofsignificanceaffectingfinancialreportingandcompliance of the consolidated entity including:

• exercisingoversightoftheaccuracyandcompletenessofthefinancialstatements;

• makinginformeddecisionsregardingaccountingandcompliancepolicies,practices,anddisclosures;

• reviewingthescopeandresultsofoperationalriskreviews,compliancereviews,andexternalaudits;and

• assessingtheadequacyoftheconsolidatedentity’sinternalcontrolframeworkincludingaccounting,compliance,andoperationalriskmanagementcontrolsbasedoninformationprovided or obtained.

“Compliance”referstocompliancewithlawsandregulations,internalcompliance guidelines, policies and procedures, and other prescribed internal standards of behaviour.

AllotherdirectorsandtheChiefFinancialOfficerareinvitedtoattendCommitteemeetings.Whentheauditorsarepresentatmeetings,theCommitteeasksallexecutivestoleavethemeetingsothattherecanbeopenandfrankcommunicationbetweentheCommitteeandtheauditor.

TheCommitteehasthepowertoconductorauthoriseinvestigationsinto,orconsultindependentexpertson,anymatterswithintheCommittee’sscopeofresponsibility.

The Committee also considers the independence of the auditor. The Company requires that the audit partner be rotated every five years and, on an annual basis, the auditor provides a certificate to the Committee confirming their independence.

TheChiefExecutiveOfficerandChiefFinancialOfficerhavecertifiedtothecommitteethattheGroup’sfinancialreportspresentatrueandfairview,inallmaterialrespects,oftheGroup’sfinancialconditionandoperationalresultsandareinaccordancewithrelevantaccountingstandards.



PriNciPLe 8 remunerate fairly and responsibly

TheRemunerationandNominationCommitteeassiststheBoardinensuringthattheCompany’sremunerationlevelsareappropriateinthemarketsinwhichitoperatesandareapplied,andseentobeapplied, fairly. The Board has assumed all of the responsibilities of the CommitteeatthistimeduetothesizeandscaleoftheCompanyatthis time.

TheCompany’sremunerationpolicyisdescribedintheRemunerationReportcontainedwithintheDirectors’Report.

BusinessoftheCommitteehasbeendealtwithaspartoftheregular Board meetings as needed. The Board has access to senior managementoftheCompanyandmayconsultindependentexpertswheretheBoardconsidersitnecessarytocarryoutthedutiesoftheCommittee.

CurrentlytheCompanypaysdirectors’feestotheNEDs.AsstatedintheDirectors’Report,businessesassociatedwithdirectorsmayreceive fees for professional services provided to the Company in additiontotheirdutiesasaNED.


PriNciPLe 7 recognise and manage risk

The Directors continually monitor areas of significant business risk,recognisingthatthereareinherentrisksassociatedwiththemanagement,fundingandcommercialisationofbiotechnologyprojects.

The Board has delegated the responsibility for the establishment and maintenanceofaframeworkforriskoversightandthemanagementofriskfortheGrouptotheRiskandAuditCommittee.

TheCommittee’sroleistoprovideadirectlinkbetweentheBoardandtheexternalfunctionoftheCompany.Thisincludes:

• Monitoringcorporateriskassessmentandtheinternalcontrolsinstituted;

• Monitoringtheestablishmentofanappropriateinternalcontrolframework,includinginformationsystems,andconsideringenhancements;

• Reviewingreportsonanydefalcations,fraudsandtheftsfromtheCompanyandactiontakenbymanagements;

• ReviewingpoliciestoavoidedconflictsofinterestbetweentheCompanyandmembersofmanagement;and

• Consideringthesecurityofcomputersystemsandapplications,and the contingency plans for processing financial information in theeventofasystemsbreakdown.

TheChiefExecutiveOfficerandChiefFinancialOfficerhavemaderepresentationstotheCommitteeonthesystemofriskmanagementandinternalcomplianceandcontrolwhichimplementsthepoliciesadoptedbytheBoard.TheChiefExecutiveOfficerandChiefFinancialOfficerhavealsorepresentedthat,tothebestoftheirknowledge,theCompany’sriskmanagementandinternalcomplianceandcontrolsystem is operating efficiently and effectively in all material respects.

stateMeNt oF coMPreHeNsiVe iNcoMe

For the year ended 30 June 2011

Note 2011 2010

$ $

continuing operations

Revenue 2 342,545 181,417

Otherincome 2 3,000 616

345,545 182,033

Royalties&licencefees (28,033) (50,511)

Researchanddevelopment 3 (1,280,313) (1,211,394)

Employmentrelated 3 (1,067,508) (919,275)

Travelrelatedcosts (187,107) (106,867)

Consultantscosts (226,875) (67,257)

Occupancycosts 3 (50,893) (35,813)

Corporateexpenses (438,433) (354,764)

Financecosts 3 (29,124) (56,381)

Foreignexchangetranslation 88,824 (15,591)

Settlements 3 (660,957) (2,004,851)

(3,880,419) (4,822,704)

Lossbeforeincometax (3,534,874) (4,640,671)

Incometaxexpense/(benefit) 4 - -

Loss for the year attributable to members of the parent entity (3,534,874) (4,640,671)

other comprehensive income

other comprehensive income for the year, net of tax - -

total comprehensive income for the year (3,534,874) (4,640,671)

total comprehensive income attributable to members of the parent entity (3,534,874) (4,640,671)

Earnings per share (cents per share)

Basic and diluted for loss for the year attributable toordinaryequityholdersoftheparententity 6 (0.68) (1.21)

The accompanying notes form part of these financial statements


FinancialStatementandNotestotheFinancialStatements



stateMeNt oF FiNaNciaL PositioN

as at 30 June 2011

Note 2011 2010 $ $

cUrreNt assets Cashandcashequivalents 8 6,654,097 651,007Tradeandotherreceivables 9 147,832 350,470Othercurrentassets 10 36,968 28,064

totaL cUrreNt assets 6,838,897 1,029,541

NoN-cUrreNt assets Property,plantandequipment 12 26,461 7,621 totaL NoN-cUrreNt assets 26,461 7,621

totaL assets 6,865,358 1,037,162

cUrreNt LiaBiLities Tradeandotherpayables 13 1,141,559 817,729Provisions 15 55,915 149,626

totaL cUrreNt LiaBiLities 1,197,474 967,355

NoN-cUrreNt LiaBiLities Tradeandotherpayables 13 171,048 231,826Borrowings 14 292,488 459,655Provisions 15 - 75,000

totaL NoN-cUrreNt LiaBiLities 463,536 766,481

totaL LiaBiLities 1,661,010 1,733,836

Net assets/(LiaBiLities) 5,204,348 (696,674)

eQUity Contributedequity 16 86,821,961 77,487,593Reserves 17 2,810,599 2,709,071Accumulatedlosses (84,428,212) (80,893,338)

totaL eQUity 5,204,348 (696,674)




stateMeNt oF casH FLoWs


Note 2011 2010 $ $

casH FLoWs FroM oPeratiNG actiVities Receiptsfromcustomers(inclusiveofGST) 159,702 170,581Paymentstosuppliersandemployees(inclusiveofGST) (3,498,800) (2,527,243)

Net cash used in operating activities 8 (3,339,098) (2,356,662)

casH FLoWs FroM iNVestiNG actiVities Interestreceived 48,171 30,249Dividendsreceived 137,671 -Purchaseofproperty,plantandequipment (27,893) (2,525)

Net cash provided by investing activities 157,949 27,724

casH FLoWs FroM FiNaNciNG actiVities Netproceedsfromissueofshares 7,431,881 562,476Proceedsfromborrowings 1,791,681 560,656Interestpaid (24,098) (5,438)

Net cash provided by/(used in) financing activities 9,199,464 1,117,694

Net increase/(decrease) in cash held 6,018,315 (1,211,244)Exchangedifferencesoncashandcashequivalents (15,225) (4,354)Cashandcashequivalents,beginningofyear 651,007 1,866,605

cash and cash equivalents, end of year 8 6,654,097 651,007




stateMeNt oF cHaNGes iN eQUity


convertible share-based contributed Note equity Payments accumulated equity reserve reserve Losses total $ $ $ $ Balance at 1 July 2009 74,836,046 - 2,565,405 (76,252,667) 1,148,784Lossfortheyear - - - (4,640,671) (4,640,671)Othercomprehensiveincomeforyear - - - - -Totalcomprehensiveincomeforyear - - - (4,640,671) (4,640,671)Equitycomponentofconvertiblenote - 77,156 - - 77,156TransfertoContributedEquityuponpartial conversionofconvertiblenote 7,319 (7,319) - - -Fairvalueofoptionsvestedduringperiod - - 73,829 - 73,829Shareissues,netoftransactioncosts 2,644,228 - - - 2,644,228Transactionswithowners 2,651,547 69,837 73,829 - 2,795,213 Balance 30 June 2010 77,487,593 69,837 2,639,234 (80,893,338) (696,674) Lossfortheyear - - - (3,534,874) (3,534,874)Othercomprehensiveincomeforyear - - - - -Totalcomprehensiveincomeforyear - - - (3,534,874) (3,534,874)Equitycomponentofconvertiblenote - 200,593 - - 200,593TransfertoContributedEquityuponpartialc onversionofconvertiblenote 221,633 (221,633) - - -Fairvalueofoptionsvestedduringperiod - - 122,568 - 122,568Shareissues,netoftransactioncosts 9,112,735 - - - 9,112,735Transactionswithowners 9,334,368 (21,040) 122,568 9,435,896 Balance 30 June 2011 86,821,961 48,797 2,761,802 (84,428,212) 5,204,348


The consolidated financial statements have been prepared using the measurementbasesspecifiedbyAustralianAccountingStandardsforeachtypeofasset,liability,incomeandexpense.Themeasurementbasesaremorefullydescribedintheaccountingpoliciesbelow.

(b) Principles of consolidation

AcontrolledentityisanyentitycontrolledbyBenitecLimitedwherebyBenitecLimitedhasthepowertocontrolthefinancialandoperatingpolicies of an entity so as to obtain benefits from its activities.

Allinter-companybalancesandtransactionsbetweenentitiesintheconsolidated entity, including any unrealised profits or losses, have beeneliminatedonconsolidation.Accountingpoliciesofcontrolledentitieshavebeenchangedwherenecessarytoensureconsistencieswiththosepoliciesappliedbytheparententity.

Wherecontrolledentitieshaveenteredorlefttheconsolidatedentityduringtheyear,theiroperatingresultshavebeenincluded/excludedfromthedatecontrolwasobtainedoruntilthedatecontrolceased.

Alistofcontrolledentitiesiscontainedinnote11tothefinancialstatements.AllcontrolledentitieshaveaJunefinancialyear-endexceptforBenitecLtd(UK)whichhasaDecemberyear-end.

(c) New accounting standards and interpretations not yet adopted

Anumberofnewstandards,amendmentstostandardsandinterpretations are effective for annual periods beginning after 1July2010,andhavenotbeenappliedinpreparingtheseconsolidatedfinancialstatements.Noneoftheseisexpectedtohavea significant effect on the consolidated financial statements of the consolidated entity.

(d) revenue

Revenuefromthegrantingoflicensesisrecognisedinaccordancewiththetermsoftherelevantagreementsandisusuallyrecognisedon an accruals basis, unless the substance of the agreement provides evidence that it is more appropriate to recognise revenue on some other systematic rational basis. Interest revenue is recognised on a proportionalbasistakingintoaccounttheinterestratesapplicabletothefinancialassets.Revenuefromtherenderingofaserviceisrecogniseduponthedeliveryoftheservicetothecustomers.Allrevenueisstatednetoftheamountofgoodsandservicestax(GST).

(e) income tax

Thechargeforcurrentincometaxexpenseisbasedonthelossfortheyearadjustedforanynon-assessableordisalloweditems.Itiscalculatedusingtaxratesthathavebeenenactedoraresubstantiallyenacted by reporting date.

Deferredtaxisaccountedforusingtheliabilitymethodinrespectoftemporarydifferencesarisingbetweenthetaxbasesofassetsandliabilitiesandtheircarryingamountsinthefinancialstatements.Nodeferredincometaxwillberecognisedfromtheinitialrecognitionofanassetorliability,excludingabusinesscombination,wherethereisnoeffectonaccountingortaxableprofitorloss.

Deferredtaxiscalculatedatthetaxratesthatareexpectedtoapplytotheperiodwhentheassetisrealisedorliabilityissettled.Deferredtaxiscreditedinthestatementofcomprehensiveincomeexcept


NotestotheFinancialStatementsfortheYearEnded30June2011

1. SummaryofSignificantAccountingPolicies

2. RevenuefromContinuingOperations

3. LossfortheYear

4. IncomeTaxExpense/(Benefit)

5. Auditor’sRemuneration

6. EarningsperShare

7. KeyManagementPersonnelDisclosures

8. CashandCashEquivalents

9. TradeandOtherReceivables

10. OtherAssets

11. ControlledEntities

12. Property,PlantandEquipment

13. TradeandOtherPayables

14. Borrowings

15. Provisions

16. ContributedEquity

17. Reserves

18. SegmentReporting

19. FinancialRiskManagementObjectivesandPolicies

20. FinancialInstruments

21. ShareBasedPayments

22. EventsSubsequenttoReportingDate

23. ContingentLiabilities

24. RelatedPartyTransactions

25. BenitecLimitedParentCompanyInformation

Note 1: sUMMary oF siGNiFicaNt accoUNtiNG PoLicies

(a) Basis of Preparation

ThefinancialreportcoversBenitecLimitedanditscontrolledentitiesasaconsolidatedentity(“Group”).BenitecLimitedisalistedpubliccompany,incorporatedanddomiciledinAustralia.

The consolidated general purpose financial report statements of the GrouphavebeenpreparedinaccordancewiththerequirementsoftheCorporationsAct2001,AustralianAccountingStandardsandotherauthoritativepronouncementsoftheAustralianAccountingStandardsBoard.CompliancewithAustralianAccountingStandardsresultsinfullcompliancewiththeInternationalFinancialReportingStandards(IFRS)asissuedbytheInternationalAccountingStandardsBoard(IASB).

Theconsolidatedfinancialstatementsfortheyearended30June2011(includingcomparatives)wereapprovedandauthorisedforissuebytheboardofdirectorson24August2011.


whereitrelatestoitemsthatmaybecrediteddirectlytoequity,inwhichcasethedeferredtaxisadjusteddirectlyagainstequity.

Deferredincometaxassetsarerecognisedtotheextentthatitisprobablethatfuturetaxprofitswillbeavailableagainstwhichdeductible temporary differences can be utilised.

Theamountofbenefitsbroughttoaccountorwhichmayberealisedinthefutureisbasedontheassumptionthatnoadversechangewilloccurinincometaxationlegislationandtheanticipationthattheconsolidatedentitywillderivesufficientfutureassessableincometoenablethebenefittoberealisedandcomplywiththeconditionsofdeductibilityimposedbythelaw.

BenitecLimitedanditswholly-ownedAustraliansubsidiaryhasformedanincometaxconsolidatedgroupundertheTaxConsolidationRegime.BenitecLimitedisresponsibleforrecognisingthecurrentanddeferredtaxassetsandliabilitiesforthetaxconsolidatedgroup.TheGroupnotifiedtheATOon12February2004thatithadformedanincometaxconsolidatedgrouptoapplyfrom1July2002.Notaxsharingagreementhasbeenenteredbetweenentitiesinthetaxconsolidated group.

(f) critical accounting estimates and Judgments

TheDirectorsevaluateestimatesandjudgmentsincorporatedintothefinancialreportbasedonhistoricalknowledgeandbestavailablecurrentinformation.Estimatesassumeareasonableexpectationoffuture events and are based on current trends and economic data, obtainedbothexternallyandwithintheGroup.

Key estimates – share-based payments transactionsTheGroupmeasuresthecostofequity-settledtransactionswithemployees by reference to the fair value of the equity instruments at thedateatwhichtheyaregranted.ThefairvalueisdeterminedusingaBlack-Scholesmodel,usingtheassumptionsdetailedinnote21.

Key judgements – tax lossesGiventhecompany’sandeachindividualentities’historyofrecentlosses,theGrouphasnotrecognisedadeferredtaxassetwithregardtounusedtaxlossesandothertemporarydifferences,asithasnotbeendeterminedwhetherthecompanyoritssubsidiarieswillgeneratesufficienttaxableincomeagainstwhichtheunusedtaxlosses and other temporary differences can be utilised.

Key judgements – compound financial instrumentsTheGroupmeasuresthefairvalueoftheliabilitycomponentusingtheprevailingmarketinterestrateforsimilarconvertibleinstruments.

(g) impairment of Non-Financial assets

TheGroupassessesateachreportingdatewhetherthereisanindicationthatanassetmaybeimpaired.Ifanysuchindicationexists,orwhenannualimpairmenttestingforanassetisrequired,theGroupmakesanestimateoftheasset’srecoverableamount.Anasset’srecoverable amount is the higher of its fair value less costs to sell and its value in use and is determined for an individual asset, unless the assetdoesnotgeneratecashinflowsthatarelargelyindependentofthosefromotherassetsorgroupsofassetsandtheasset’svalueinuse cannot be estimated to be close to its fair value. In such cases the asset is tested for impairment as part of the cash generating unittowhichitbelongs.Whenthecarryingamountofanassetorcash-generatingunitexceedsitsrecoverableamount,theassetor

cash-generatingunitisconsideredimpairedandiswrittendowntoitsrecoverable amount.

Inassessingvalueinuse,theestimatedfuturecashflowsarediscountedtotheirpresentvalueusingapre-taxdiscountratethatreflectscurrentmarketassessmentsofthetimevalueofmoneyandtherisksspecifictotheasset.Impairmentlossesrelatingtocontinuingoperationsarerecognisedinthoseexpensecategoriesconsistentwiththefunctionoftheimpairedassetunlesstheassetiscarriedatrevaluedamount(inwhichcasetheimpairmentlossistreatedasarevaluationdecrease).

(h) cash and cash equivalents

Cash and cash equivalents includes cash on hand, deposits held atcallwithbanks,othershort-termhighlyliquidinvestmentswithoriginalmaturitiesofthreemonthsorless,andbankoverdrafts.Bankoverdraftsareshownwithinshorttermborrowingsincurrentliabilitieson the statement of financial position.

(i) trade and other receivables

Tradereceivables,whichgenerallyhave30dayterms,arerecognisedandcarriedatoriginalinvoiceamountlessanallowanceforanyuncollectible amounts.

Anestimatefordoubtfuldebtsismadewhencollectionofthefullamountisnolongerprobable.Baddebtsarewrittenoffwhenidentified.

(j) Property, Plant and equipment

Eachclassofproperty,plantandequipmentiscarriedatcostorfairvalueless,whereapplicable,anyaccumulateddepreciationandimpairment losses.

Plant and equipmentPlantandequipmentaremeasuredonthecostbasislessdepreciationand impairment losses. The carrying amount of plant and equipment isreviewedannuallybydirectorstoensureitisnotinexcessoftherecoverable amount from these assets. The recoverable amount is assessedonthebasisoftheexpectednetcashflowsthatwillbereceived from the assets employment and subsequent disposal. The expectednetcashflowshavebeendiscountedtotheirpresentvaluesin determining recoverable amounts.

Subsequentcostsareincludedintheasset’scarryingamountorrecognisedasaseparateasset,asappropriate,onlywhenitisprobablethatfutureeconomicbenefitsassociatedwiththeitemwillflowtothegroupandthecostoftheitemcanbemeasuredreliably.Allotherrepairsandmaintenancearechargedtothestatementofcomprehensiveincomeduringthefinancialperiodinwhichthey are incurred.

DepreciationThedepreciableamountofallfixedassetsincludingcapitalisedleaseassets is depreciated on a diminishing value basis over their useful lives to the consolidated entity commencing from the time the asset isheldreadyforuse.Leaseholdimprovementsaredepreciatedovertheshorterofeithertheunexpiredperiodoftheleaseortheestimateduseful lives of the improvements.


The depreciation rates used for each class of depreciable assets are:

Class of Fixed Asset Depreciation Rate Plantandequipment 20-40%

Theassets’residualvaluesandusefullivesarereviewed,andadjustedifappropriate,ateachreportingdate.

Anasset’scarryingamountiswrittendownimmediatelytoitsrecoverableamountiftheasset’scarryingamountisgreaterthanitsestimated recoverable amount.

Gainsandlossesondisposalsaredeterminedbycomparingproceedswiththecarryingamount.Thesegainsandlossesareincludedinthestatementofcomprehensiveincome.Whenrevaluedassetsaresold,amounts included in the revaluation reserve relating to that asset are transferred to retained earnings.

(k) Leases

Leasesoffixedassetswheresubstantiallyalltherisksandbenefitsincidentaltotheownershipoftheasset,butnotthelegalownershipthat are transferred to entities in the consolidated entity are classified as finance leases.

Finance leases are capitalised by recording an asset and a liability at theloweroftheamountsequaltothefairvalueoftheleasedpropertyor the present value of the minimum lease payments, including any guaranteedresidualvalues.Leasepaymentsareallocatedbetweenthereductionoftheleaseliabilityandtheleaseinterestexpensefortheperiod.Leasedassetsaredepreciatedonastraight-linebasisovertheirestimatedusefulliveswhereitislikelythattheconsolidatedentitywillobtainownershipoftheassetoroverthetermofthelease.Leasepaymentsforoperatingleases,wheresubstantiallyalltherisksandbenefitsremainwiththelessor,arechargedasexpensesintheperiodsinwhichtheyareincurred.

Leaseincentivesunderoperatingleasesarerecognisedasaliabilityand amortised on a straight-line basis over the life of the lease term.

(l) Financial instruments

RecognitionFinancial instruments are initially measured at cost on trade date, whichincludestransactioncosts,whentherelatedcontractualrightsorobligationsexist.Subsequenttoinitialrecognitiontheseinstrumentsaremeasuredassetoutbelow.

Loans and receivablesLoansandreceivablesarenon-derivativefinancialassetswithfixedordeterminablepaymentsthatarenotquotedinanactivemarketandare stated at amortised cost using the effective interest rate method.

Financial liabilitiesNon-derivativefinancialliabilitiesarerecognisedatamortisedcost,comprising original debt less principal payments and amortisation.

Compound instrumentsThecomponentpartsofcompoundinstruments(convertiblenotes)issuedbytheGroupareclassifiedseparatelyasfinancialliabilitiesandequityinaccordancewiththesubstanceofthecontractualarrangement. The liability component is recorded on an amortised costbasisusingtheeffectiveinterestmethoduntilextinguisheduponconversionorattheinstrument’smaturitydate.Theequitycomponent

is determined by deducting the amount of the liability component fromthefairvalueofthecompoundinstrumentasawhole.Thisisrecognisedandincludedinequity,netofincometaxeffects,andisnotsubsequently remeasured.

Fair valueFair value is determined based on current bid prices for all quoted investments.Valuationtechniquesareappliedtodeterminethefairvalueforallunlistedsecurities,includingrecentarm’slengthtransactions, reference to similar instruments and option pricing models.

ImpairmentAteachreportingdate,thegroupassesswhetherthereisobjectiveevidence that a financial instrument has been impaired. In the case of available-for-sale financial instruments, a prolonged or significant decline in the value of the instrument is considered to determine whetherimpairmenthasarisen.Impairmentlossesarerecognisedinthe statement of comprehensive income.

(m) intangibles

Research and developmentExpenditureduringtheresearchphaseofaprojectisrecognisedasanexpensewhenincurred.Developmentcostsarecapitalisedonlywhentechnicalfeasibilitystudiesidentifythattheprojectwilldeliverfutureeconomic benefits and these benefits can be measured reliably.

Development costs have a finite life and are amortised on a systematic basis matched to the future economic benefits over the useful life of theproject.

(n) trade and other Payables

Trade payables and other payables are carried at amortised costs and represent liabilities for goods and services provided to the group priortotheendofthefinancialyearthatareunpaidandarisewhenthegroupbecomesobligedtomakefuturepaymentsinrespectofthepurchase of these goods and services.

(o) employee Benefits

ProvisionismadefortheGroup’sliabilityforemployeebenefitsarisingfromservicesrenderedbyemployeestoreportingdate.Employeebenefitsthatareexpectedtobesettledwithinoneyearhavebeenmeasuredattheamountsexpectedtobepaidwhentheliabilityissettled,plusrelatedon-costs.Employeebenefitspayablelaterthanone year have been measured at the present value of the estimated futurecashoutflowstobemadeforthosebenefits.

(p) Provisions

ProvisionsarerecognisedwhentheGrouphasalegalorconstructiveobligation,asaresultofpastevents,forwhichitisprobablethatanoutflowofeconomicbenefitswillresultsandthatoutflowcanbereliably measured.

(q) contributed equity

Ordinarysharesareclassifiedasequity.Incrementalcostsdirectlyattributabletotheissueofnewsharesoroptionsareshowninequityasadeduction,netoftax,fromtheproceeds.




(r) share-based Payment transactions

BenefitsareprovidedtoemployeesoftheGroupintheformofshare-basedpaymenttransactions,wherebyemployeesrenderservicesinexchangeforsharesorrightsovershares(‘equity-settledtransactions’).TheplancurrentlyinplacetoprovidethesebenefitsistheEmployeeShareOptionPlan(ESOP),whichprovidesbenefitstoseniorexecutives.

Thecostoftheseequity-settledtransactionswithemployeesismeasuredbyreferencetothefairvalueatthedateatwhichtheyaregranted.ThefairvalueisdeterminedusingaBlack-Scholesmodel.Invaluingequity-settledtransactions,noaccountistakenofanyperformanceconditions,otherthanconditionslinkedtothepriceofthesharesofBenitecLimited(‘marketconditions’).

Thecostofequity-settledtransactionsisrecognised,togetherwithacorrespondingincreaseinequity,overtheperiodinwhichtheperformanceconditionsarefulfilled,endingonthedateonwhichtherelevantemployeesbecomefullyentitledtotheaward(‘vestingdate’).

Thecumulativeexpenserecognisedforequity-settledtransactionsateachreportingdateuntilvestingdatereflects(i)theextenttowhichthevestingperiodhasexpiredand(ii)thenumberofawardsthat,intheopinionofthedirectorsofthegroup,willultimatelyvest.Thisopinion is formed based on the best available information at reporting date.Noadjustmentismadeforthelikelihoodofmarketperformanceconditions being met as the effect of these conditions is included in the determination of fair value at grant date.

Noexpenseisrecognisedforawardsthatdonotultimatelyvest,exceptforawardswherevestingisconditionaluponamarketcondition.

Wherethetermsofanequity-settledawardaremodified,asaminimumanexpenseisrecognisedasifthetermshadnotbeenmodified.Inaddition,anexpenseisrecognisedforanyincreaseinthevalue of the transaction as a result of the modification, as measured at thedateofmodification.Whereanequity-settledawardiscancelled,it is treated as if it had vested on the date of cancellation, and any expensenotyetrecognisedfortheawardisrecognisedimmediately.However,ifanewawardissubstitutedforthecancelledaward,anddesignatedasareplacementawardonthedatethatitisgranted,thecancelledandnewawardaretreatedasiftheywereamodificationoftheoriginalaward,asdescribedinthepreviousparagraph.

Thedilutiveeffect,ifany,ofoutstandingoptionsisreflectedasadditional share dilution in the computation of earnings per share.

(s) earnings per share

Basic earnings per share is calculated as net profit attributable to membersoftheparent,adjustedtoexcludeanycostsofservicingequity(otherthandividends)andpreferencesharedividends,dividedbytheweightedaveragenumberofordinaryshares,adjustedforanybonus element.

Diluted earnings per share is calculated as net profit attributable to membersoftheparent,adjustedfor:

- costsofservicingequity(otherthandividends)andpreferencesharedividends;

- theaftertaxeffectofdividendsandinterestassociatedwithdilutive potential ordinary shares that have been recognised as expenses;and

- othernon-discretionarychangesinrevenuesorexpensesduringtheperiodthatwouldresultfromthedilutionofpotentialordinaryshares;

dividedbytheweightedaveragenumberofordinarysharesanddilutivepotentialordinaryshares,adjustedforanybonuselement.

(t) Foreign currency transactions and Balances

Functional and presentation currencyThefunctionalcurrencyofeachoftheGroup’sentitiesismeasuredusingthecurrencyoftheprimaryeconomicenvironmentinwhichthatentity operates. The consolidated financial statements are presented inAustraliandollarswhichistheparententity’sfunctionalandpresentation currency.

Transaction and balancesForeign currency transactions are translated into functional currency usingtheexchangeratesprevailingatthedateofthetransaction.Foreign currency monetary items are translated at the year-end exchangerate.Non-monetaryitemsmeasuredathistoricalcostcontinuetobecarriedattheexchangerateatthedateofthetransaction.Non-monetaryitemsmeasuredatfairvaluearereportedattheexchangerateatthedatewhenfairvaluesweredetermined.

Exchangedifferencesarisingonthetranslationofmonetaryitemsarerecognisedinthestatementofcomprehensiveincome,exceptwheredeferredinequityasaqualifyingcashflowornetinvestmenthedge.Exchangedifferencesarisingonthetranslationofnon-monetaryitemsarerecogniseddirectlyinequitytotheextentthatthegainorlossisdirectlyrecognisedinequity,otherwisetheexchangedifferenceisrecognised in the statement of comprehensive income.

Group companiesThefinancialresultsandpositionofforeignoperationswhosefunctionalcurrencyisdifferentfromtheGroup’spresentationcurrencyaretranslatedasfollows:

• Assetsandliabilitiesaretranslatedatyear-endexchangeratesprevailing at that reporting date.

• Incomeandexpensesaretranslatedataverageexchangeratesforthe period.

• Retainedprofitsaretranslatedattheexchangeratesprevailingatthe date of the transaction.

(u) Goods and services tax (Gst)

Revenues,expensesandassetsarerecognisednetoftheamountofGST,exceptwheretheamountofGSTincurredisnotrecoverablefromtheAustralianTaxOffice.InthesecircumstancestheGSTisrecognised as part of the cost of acquisition of the asset or as part of anitemoftheexpense.ReceivablesandpayablesinthestatementoffinancialpositionareshowninclusiveofGST.

Cashflowsarepresentedinthestatementofcashflowsonagrossbasis,exceptfortheGSTcomponentofinvestingandfinancingactivities,whicharedisclosedasoperatingcashflows.

(v) comparative Figures

WhenrequiredbyAccountingStandards,comparativefigureshavebeenadjustedtoconformtochangesinpresentationforthecurrentfinancial year.


2011 2010 $ $

Note 2: reVeNUe FroM coNtiNUiNG oPeratioNs revenue -Licensingrevenueandroyalties 156,702 151,168-Financeincome-dividendsreceived 137,671 --Financeincome-interestreceived 48,172 30,249

342,545 181,417

other income -Governmentgrants 3,000 --Sundryincome - 616

3,000 616

totaL reVeNUe aND otHer iNcoMe 345,545 182,033

Note 3: Loss For tHe year (a) expenses incurred by continuing operations items included in statement of comprehensive income Finance costs Interestpayable–otherpersons 26,826 7,693Doubtfuldebts - 47,837Other 2,298 851

Financecosts 29,124 56,381

Depreciation Included in Occupancy expenses Depreciationofplantandequipment 9,053 3,686employee benefits expense Included in Employment related expenses Wagesandsalaries 573,823 569,109Superannuationcosts 43,977 54,008Share-basedpaymentsexpense 122,568 73,829

csiro iP settlement - 2,004,851

Duringthe2010year,theCompanyreachedasettlementwiththeCSIROtoreplacetheexisting LicenceAgreementandCommercialAgreementwithanewexclusiveLicenceAgreementforthe useofintellectualpropertyandtheCapitalGrowthAgreementwiththeissueofordinaryshares. TheLicenceAgreementcontainsanumberoffurthercontingentpaymentsasoutlinedinNote23.

LJci settlement 660,957 -

During the year, the Company negotiated the end of the convertible note facility provided by LaJollaCoveInvestorsInc.(“LJCI”).ThisfacilitycommencedinApril2010andby30June2011 anamountofUSD$2,250,000hadbeendrawndown.




2011 2010 $ $

Note 3: Loss For tHe year (coNtiNUeD) (b) expensesThefollowingexpenseitemsarerelevantinexplainingthefinancialperformance: Researchanddevelopmentcostsconsistof:Projectexpenses 386,896 471,995IPlitigationexpenses (15,703) 58,219OtherIPrelatedexpenses 909,120 681,180

1,280,313 1,211,394

Note 4: iNcoMe taX eXPeNse (a) Theprimafacietaxonlossfromordinaryactivitiesbeforeincometaxisreconciledtotheincometaxasfollows:

Primafacietaxpayableonlossfromordinaryactivitiesbeforeincometaxat30%(2010:30%) (1,060,462) (1,392,201)Add Tax effect of: Non-deductibleshare-basedpaymentexpense 36,770 22,149Non-deductiblelegalfees 15,674 18,839Non-deductibleCSIROIPsettlement - 601,455Non-deductibleLJCIsettlement 198,287 -Capitalitemsdeductible (159,136) (240,142)Othernondeductibleitems 39,283 82,755Deductibleitemsnotincludedinoperatingresult (81,790) (178,146)Deferredtaxassetnotbroughttoaccount 1,011,374 1,085,291

Incometaxbenefitreportedintheincomestatement - -

(b) Theparententity,actingastheHeadEntity,notifiedtheAustralianTaxationOfficeon12February2004thatithadformedaTaxConsolidatedGroupapplicableasfrom1July2002.Notaxsharingagreementhasbeenenteredbetweenentitiesinthetaxconsolidatedgroup.

(c) DeferredTaxAssetnotbroughttoaccount Asat30June2011,theTaxConsolidatedGrouphasanetdeferredtaxassetof$9,902,859(2010:$8,855,092)arisingfromsignificantavailableAustraliantaxlosses(calculatedat30%),whichhasnotbeenrecognisedinthefinancialstatements.

TheConsolidatedGroupalsohasAustraliancapitaltaxlossesforwhichnodeferredtaxassetisrecognisedonthestatementoffinancialpositionof$381,588(2010:$381,588)whichareavailableindefinitelyforagainstfuturecapitalgainssubjecttocontinuingtomeetrelevantstatutory tests.

Therecoupmentofavailabletaxlossesasat30June2011iscontingentuponthefollowing: (i) theConsolidatedGroupderivingfutureassessableincomeofanatureandofanamountsufficienttoenablethebenefitfromthelosses toberealised;

(ii) theconditionsfordeductibilityimposedbytaxlegislationcontinuingtobecompliedwith;and (iii) therebeingnochangesintaxlegislationwhichwouldadverselyaffecttheTaxConsolidatedGroupfromrealisingthebenefitfrom

the losses.


2011 2010 $ $

Note 5: aUDitor’s reMUNeratioN audit services RemunerationofGrantThorntonAuditPtyLtdfor: -auditingorreviewingthefinancialreport 46,000 -Remunerationofpriorauditorsfor: -auditingorreviewingthefinancialreport - 46,000other services RemunerationofGrantThorntonAustraliaPtyLtdfor: -taxationcompliance 7,975 -

Note 6: earNiNGs Per sHare Basic earnings per share amounts are calculated by dividing net loss for the year attributable to ordinary equity holders of the parent by the weightedaveragenumberofordinarysharesoutstandingduringtheyear.Dilutedearningspershareamountsarecalculatedbydividingthenetlossattributabletoordinaryshareholdersbytheweightedaveragenumberofordinarysharesoutstandingduringtheyear(adjustedfortheeffectsofdilutiveoptions)andtheweightedaveragenumberofordinarysharesthatwouldbeissuedonconversionofalldilutivepotentialordinarysharesintoordinaryshares.Thefollowingreflectstheincomeandsharedatausedinthetotaloperationsbasicanddilutedearningspersharecomputations:

consolidated 2011 2010 $ $

LossafterincometaxusedinthecalculationofbasicEPSanddilutiveEPS (3,534,873) (4,640,671) No. No.Weightedaveragenumberofordinarysharesforbasicanddilutedearningspershare 519,094,683 383,203,917Weightedaveragenumberofconverted,lapsedorcancelledpotentialordinaryshares included in diluted earnings per share - - Alloptionstoacquireordinarysharesarenotconsidereddilutivefortheyearended30June2011andthecomparativeperiod. Classification of securities NosecuritiesorconvertibledebtinstrumentscouldbeclassifiedaspotentialordinarysharesunderAASB133andthereforehavenotbeenincludedindeterminationofdilutiveEPS.




Note 7: Key MaNaGeMeNt PersoNNeL

(a) Details of Key Management Personnel

(i) Specified Directors

MrPeterFrancis Chairman-Non-Executive Appointedon23February2006

MrMelBridges Director-Non-Executive Appointedon12October2007

DrJohnChiplin Director-Non-Executive Appointedon1February2010

MrIainRoss Director-Non-Executive Appointedon1June2010

(ii) Specified Executives

DrPeterFrench ChiefScientificOfficer/ AppointedCSOon4August2009, ChiefExecutiveOfficer appointedCEOon4June2010

MsSueMacLeman ChiefExecutiveOfficer Appointedon4September2006 resignedon31March2010

MrJohnRawling CompanySecretary/CFO Appointedon2January2007

(b) specified Directors’ remuneration

short term Post equity other total employment

Salary,Fees& Cash Non-Cash Super- specified Directors Commission Bonus Benefits annuation Options

2011

PeterFrancis 64,166 - - - 26,211 - 90,377

MelBridges 55,000 - - - 20,673 - 75,673

JohnChiplin 50,000 - - - - - 50,000

IainRoss 50,000 - - - - - 50,000

219,166 - - - 46,884 - 266,050

2010

PeterFrancis 60,000 - - - 22,967 - 82,967

MelBridges 55,000 - - - 15,311 - 70,311

JohnChiplin 20,833 - - - - 20,833

IainRoss 4,167 - - - - - 4,167

140,000 - - - 38,278 - 178,278


(c) specified executives’ remuneration


Salary,Fees& Cash Non-Cash Super- Termination specified executives Commission Bonus Benefits annuation Benefits Options

2011

PeterFrench 249,801 35,000 - 15,199 - 54,125 354,125

SueMacLeman - - - - - -

JohnRawling 210,813 - - 15,199 - 10,486 236,508

460,614 35,000 - 30,398 - 64,611 590,623

2010

PeterFrench 86,009 - - 27,822 - - 113,831

SueMacLeman 260,684 94,500 - 14,461 - 18,400 388,045

JohnRawling 122,916 5,000 - 11,512 - 1,840 141,268

469,609 99,500 - 53,795 - 20,240 643,144

(d) options Granted as remuneration

Inrespectofthekeymanagementpersonnel,therewerenooptionsgrantedasremuneration.

(e) shares issued on exercise of remuneration options

Inrespectofthekeymanagementpersonnel,therewerenosharesissuedonexerciseofremunerationoptions.

(f) options and rights Holdings

NumberofOptionsheldbyKeyManagementPersonnel

options total Balance Granted as options exercised/ Balance total Vested exercisable 01-Jul-10 remuneration aquired Lapsed/other at 30-Jun-11 at 30-Jun-11 at 30-Jun-11

specified Directors

PeterFrancis 2,474,350 1,500,000 500,000 - 4,474,350 3,807,684 3,807,684

MelBridges 1,333,333 1,500,000 165,000 - 2,998,333 1,053,888 1,053,888

Sub-total 3,807,683 3,000,000 665,000 - 7,472,683 4,861,572 4,861,572

specified executives

PeterFrench - 10,000,000 - - 10,000,000 7,500,000 7,500,000

SueMacLeman 6,000,000 - - (6,000,000) - - -

JohnRawling 1,300,000 1,500,000 - 2,800,000 2,150,000 2,150,000

Sub-total 7,300,000 11,500,000 - (6,000,000) 12,800,000 9,650,000 9,650,000

total 11,107,683 14,500,000 665,000 (6,000,000) 20,272,683 14,511,572 14,511,572




(g) shareholdings

NumberofSharesheldbyKeyManagementPersonnel

Balance received as Upon 01-Jul-10 remuneration options exercised Net change other * Balance 30-Jun-11

specified Directors

PeterFrancis 237,175 - - 2,000,000 2,237,175

MelBridges 200,000 - - 660,000 860,000

JohnChiplin 134,596 - - 1,056,250 1,190,846

IainRoss - - - 750,000 750,000

Sub-total 571,771 - - 4,466,250 5,038,021

specified executives

PeterFrench - - - - -

SueMacLeman - - - - -

JohnRawling - - - - -

Sub-total - - - - -

total 571,771 - - 4,466,250 5,038,021

*NetChangeOtherreferstototalsharespurchasedorsoldduringthefinancialyear.AlloftheseshareswerepurchasedbyparticipationintherenounceablerightsissueinMay2011.


2011 2010 $ $

Note 8: casH aND casH eQUiVaLeNts Cashatbank 68,406 172,662Depositsatcall 6,585,691 478,345

6,654,097 651,007

reconciliation of cash Flow from operations with Loss after income tax LossafterIncomeTax (3,534,874) (4,640,671) Non-cashflowsincludedinoperatingloss: Interestreceived (48,171) (30,249)Dividendsreceived (137,671) -Depreciation 9,053 3,686Interestpaid 26,826 5,438Share-basedpayments 122,568 73,829CSIROsettlement - 2,004,851Foreigncurrencytranslationunrealised (88,824) 22,018Provisionsandnon-cashadjustments (168,710) 167,159

Changes in assets and liabilities: (Increase)/decreaseintradeandotherreceivables 202,638 (243,549)(Increase)/decreaseinothercurrentassets (8,904) (12,424)Increase/(decrease)intradeandotherpayables 286,971 293,250

Netcashflowsfromoperations (3,339,098) (2,356,662)

Note 9: traDe aND otHer receiVaBLes

cUrreNt SundryDebtors 147,832 350,470

Note 10: otHer assets

cUrreNt

Prepayments 30,515 13,064Othercurrentassets 6,453 15,000

36,968 28,064




Note 11: coNtroLLeD eNtities

(a) controlled entities:

country of incorporation Percentage owned 2011 2010Parent entity: BenitecLimited Australia controlled entities of Benitec Limited: BenitecAustraliaLimited Australia 100% 100%BenitecLimited UnitedKingdom 100% 100%Benitec,Inc. USA 100% 100%BenitecLLC USA 100% 100%RNAiTherapeutics,Inc. USA 100% 100%

(b) controlled entities acquired or disposed:

Nocontrolledentitieswereacquiredordisposedduringthefinancialyear.

2011 2010 $ $

Note 12: ProPerty, PLaNt aND eQUiPMeNt Plant and equipment Atcost 51,539 23,645Accumulateddepreciation (25,078) (16,024)

TotalProperty,PlantandEquipment 26,461 7,621

Movements in Carrying Amounts Movementinthecarryingamountsforeachclassofproperty,plantandequipment betweenthebeginningandtheendofthecurrentfinancialyear. Plant and equipment total $ $Balanceat30June2009 8,782 8,782Additions 2,525 2,525Depreciationexpense (3,686) (3,686)Balanceat30June2010 7,621 7,621Additions 27,893 27,893Depreciationexpense (9,053) (9,053)

Balanceat30June2011 26,461 26,461


2011 2010 $ $

Note 13: traDe aND otHer PayaBLes cUrreNt Unsecured liabilities Tradecreditors 470,243 695,845Sundrycreditorsandaccruedexpenses 671,316 121,884

1,141,559 817,729

NoN-cUrreNt Unsecured liabilities Sundrycreditorsandaccruedexpenses 171,048 231,826

Note 14: BorroWiNGs ConvertibleNote 292,488 459,655

On1April2010,theCompanyenteredintoaconvertiblenotefacilitywithLaJollaCoveInvestors,Inc.(LJCI),anonrelatedentity,toprovideuptoUS$6millioninfundingover2years.

Thekeytermsoftheconvertiblenotefacilityareasfollows:

• Thefacilitycomprisesuptofour(4)US$1.5millionconvertiblenotes,eachwithadurationof2yearsfromthefirstdrawdownoftherelevantconvertible note.

• FundsaretobedrawndownbyBeniteconthebasisofUS$250,000permonth.• Thenotesbearinterestpayabletotheholderataninterestrateof4.75%(calculatedontheoutstandingprincipalamount).• Thenotesmustberepaiduponmaturityunlessconvertedtoordinarysharesinaccordancewiththetermsofthenotes.Thenotescanbeconvertedattheelectionoftheholder(orupondefaulttriggers)atthelesserofAU$0.15pershareora20%discounttothevalueweightedaveragepricecalculatedatconversion,subjecttotheissuer’selectiontorepaytheamountborrowedwitha20%premium.

• Theleveloffundingpotentiallyavailableissubjecttoongoingcompliancewithapplicabletermsandconditions.

On6April2011,aSettlementAgreementwasexecutedbetweentheCompanyandLJCI.Thepurposeofthesettlementwastomodifythefinancialarrangementsoftheconvertiblenotefacilityfollowingcompletionofthesuccessfulrenounceablerightsissue.Underthisagreement,LJCIhavearighttoprovideafurtherUS$200,000infundingtotheCompany.

At30June2011,theCompanyhaddrawndownUS$2,250,000underthisfacilityandhadelectedtoconvertUS$1,907,254intofullypaidordinarysharesoftheCompanyinaccordancewiththeformuladetailedabove.Anamountof$8,428representinginterestwascapitalisedatthetimeoftherenounceablerightsissueresultinginabalanceofUS$351,174beingrepayableat30June2011.Underthetermsofthefacility,thisamountisrepayableinJanuary2013shouldLJCIelectnottoconvertanyfurtherdebt.

At30June2011,thepartialconversionsbyLJCIhadresultedintheissueof100,205,396fullypaidordinaryshares.

Note 15: ProVisioNs cUrreNt Provisionforemployeebenefits 55,915 74,626Provisionforpatentcosts - 75,000

55,915 149,626

NoN-cUrreNt Provisionforpatentcosts - 75,000

- 75,000




2011 2010 $ $

Note 16: coNtriBUteD eQUity 926,337,910(2010:415,004,245)fullypaidordinaryshares 86,821,961 77,487,593

(a) ordinary shares Atthebeginningofthereportingperiod 77,487,593 74,836,046Sharesissuedduringtheyear 8,101,173 2,667,418Transactioncostsrelatingtoshareissues (656,805) (23,190)ConvertibleNoteconversion 1,890,000 7,319

Atreportingdate 86,821,961 77,487,593

No. No.

Atthebeginningofreportingperiod 415,004,215 352,500,230Sharesissuedduringtheyear 511,333,695 62,503,985


(b) share options

Attheendofthefinancialyear,therewere310,785,202unissuedordinaryshares(2010:157,064,579)overwhichoptionswereoutstanding:

Details No. of options expiry Date exercise Price

ListedOptionsBLTO 46,673,907 08-Apr-14 $0.10ListedOptionsBLTOB 201,302,538 31-Dec-13 $0.04Employeeshareoptionsplanoptions 1,000,000 14-Dec-11 $0.0407Employeeshareoptionsplanoptions 300,000 31-Dec-12 $0.0781Employeeshareoptionsplanoptions 5,000,000 10-Jun-13 $0.0289Employeeshareoptionsplanoptions 6,500,000 19-Aug-14 $0.0204Non-executivedirectoroptions 4,666,666 31-Dec-12 $0.0889Non-executivedirectoroptions 3,000,000 19-Aug-14 $0.0228Directors’options 1,953,125 23-Oct-15 $0.17StrategicAdviserWarrants 6,126,962 04-Aug-14 $0.90Unlistedoptions 22,244,444 31-Dec-12 $0.10Unlistedoptions 12,000,000 10-Apr-15 $0.10Other 17,560 30-Sep-13 $0.03 310,785,202

Since30June2011,nooptionshavebeenissuedundertheESOP.


2011 2010 $ $

Note 17: reserVes convertible Note equity reserve Atthebeginningofthereportingperiod 69,837 -Equitycomponentofconvertiblenote 200,593 77,156TransfertoContributedEquityuponpartialconversionofconvertiblenote (221,633) (7,319)

Atreportingdate 48,797 69,837

share-based Payments reserve Atthebeginningofthereportingperiod 2,639,234 2,565,405Fairvalueofoptionsvestedduringyear 122,568 73,829


2,810,599 2,709,071

Nature and purpose of reserves

Convertible Note Equity Reserve

TheConvertibleNoteEquityReserverecordstheequitycomponentofconvertiblenotesupondrawdownoffunds.Whenaconversiontoordinarysharestakesplace,theequitycomponentoftheconvertiblenotebeingconvertedistransferredtoContributedEquity.

Share-based Payments Reserve

TheShare-basedPaymentsReserverecordsitemsrecognisedasexpensesonvaluationandvestingofemployeeshareoptionsgranted.

Note 18: oPeratiNG seGMeNts

Business segments

TheGrouphadonlyonebusinesssegmentduringthefinancialyear,beingtheglobalcommercialisation(bylicensingandpartnering)ofpatentsandlicencesdevelopedintheareaofbiotechnology,morespecificallyinfunctionalgenomics,withapplicationsinbiomedicalresearchandhumantherapeutics.

Geographical segments

BusinessoperationsareconductedinAustralia.HowevertherearecontrolledentitiesbasedintheUSAandUnitedKingdom.

segment revenues segment results carrying amount of from external customers segment assets

2011 2010 2011 2010 2011 2010

$ $ $ $ $ $

Geographical location

Australia 345,545 182,033 (3,524,449) (4,623,814) 6,848,328 1,007,012

UnitedStatesofAmerica - - (2,803) (14,698) 17,030 30,150

UnitedKingdom - - (7,621) (2,159) - -

345,545 182,033 (3,534,873) (4,640,671) 6,865,358 1,037,162




accounting Policies

Segmentrevenuesandexpensesaredirectlyattributabletotheidentifiedsegmentsandincludejointventurerevenueandexpenseswhereareasonableallocationbasisexists.Segmentassetsincludeallassetsusedbyasegmentandconsistmainlyofcash,receivables,inventories,intangiblesandproperty,plantandequipment,netofanyallowances,accumulateddepreciationandamortisation.Wherejointassetscorrespondtotwoormoresegments,allocationofthenetcarryingamounthasbeenmadeonareasonablebasistoaparticularsegment.Segmentliabilitiesincludemainlyaccountspayable,employeeentitlements,accruedexpenses,provisionsandborrowings.Deferredincometaxprovisionsarenotincluded in segment assets and liabilities.

Note 19: FiNaNciaL risK MaNaGeMeNt oBJectiVes aND PoLiciesTheGroup’sprincipalfinancialinstrumentscomprisereceivables,payables,cashandshort-termdepositswhicharisedirectlyfromitsoperations.

TheGroupmanagesitsexposuretokeyfinancialrisks,includinginterestrateandcurrencyriskinaccordancewiththefinancialriskmanagementpolicy.Theobjectiveofthepolicyistosupportthedeliveryofthefinancialtargetswhilstprotectingfuturefinancialsecurity.

Themainrisksarisingfromthefinancialinstrumentsareinterestraterisk,liquidityrisk,foreigncurrencyriskandcreditrisk.TheBoardreviewsandagreespoliciesformanagingeachoftheserisksandtheyaresummarisedbelow.

risk exposures and responses

Interest rate riskTheGroupgeneratesincomefrominterestonsurplusfunds.

Atreportingdate,theGrouphadthefollowingmixoffinancialassetsandliabilitiesexposedtoAustralianvariableinterestrateriskthatarenotdesignatedincashflowhedges:

2011 2010 $ $

Financial assets Cashandcashequivalents 6,654,097 651,007

FinancialLiabilities - -

NetExposure 6,654,097 651,007

Thepolicyistoanalyseitsinterestrateexposurewhenithasfinancialliabilities.Withinthisanalysisconsiderationisgiventoalternativefinancing,hedgingpositionsandthemixoffixedandvariableinterestrates.

TheGroupcurrentlyhasshorttermdepositsatvariableinterestrates.Theaverageinterestrateapplyingtocashintheyearwas 2.62%(2010:2.50%).

Thefollowingsensitivityanalysisisbasedontheinterestrateriskexposuresinexistenceatthereportingdate:

At30June2011,ifinterestrateshadmoved,asillustratedinthetablebelow,withallothervariablesheldconstant,posttaxprofitandequitywouldhavebeenaffectedasfollows:

Judgmentsofreasonablypossiblemovements:

Post tax result equity Higher/ (Lower) Higher/ (Lower)

2011 2010 2011 2010

$ $ $ $

+1%(100basispoints) 15,753 12,098 15,753 12,098

-0.5%(50basispoints) (7,876) (6,049) (7,876) (6,049)

Themovementsinoperatingresultareduetohigher/lowerinterestincomefromcashbalances.Thesensitivityismarginallyhigherin2011thanin2010duetohighercashbalancesinMayandJunefollowingtherightsissueandlittlechangeininterestratesduringtheyear.


Liquidity riskTheGroup’sobjectiveistomaintainabalancebetweencontinuityoffundingandflexibilitythroughtheuseofbankloans,financeleasesandissuesofequitysecuritieswherenecessary.Leasingobligations,tradepayablesandotherfinancialliabilitiesmainlyoriginatefromthefinancingofassetsusedinourongoingoperationssuchasproperty,plantandequipmentandinvestmentsinworkingcapitale.g.inventoriesandtradereceivables.

Thetablebelowreflectsallcontractuallyfixedpay-offsandreceivablesforsettlement,repaymentsandinterestresultingfromrecognisedfinancialassetsandliabilitiesasat30June2011.Cashflowsforfinancialassetsandliabilitieswithfixedamountortimingarepresentedwiththeirrespectivediscountedcashflowsfortherespectiveupcomingfiscalyears.

TheremainingcontractualmaturitiesoftheGroup’sfinancialliabilitiesare:

2011 2010 $ $

6monthsorless 113,087 57,9556-12months 57,955 57,9551-5years 171,048 231,826Over5years - -

342,090 347,736

Maturity analysis of financial assets and liabilities based on management’s expectation

Theriskimpliedfromthevaluesshowninthetablebelow,reflectsabalancedviewofcashinflowsandoutflows.Leasingobligations,tradepayables and other financial liabilities mainly originate from the financing of assets used in our ongoing operations such as property, plant and equipmentandinvestmentsinworkingcapitale.g.inventoriesandtradereceivables.TheseassetsareconsideredintheGroup’soverallliquidityrisk.Tomonitorexistingfinancialassetsandliabilitiesaswellastoenableandeffectivecontrollingoffuturerisks,Benitechasestablishedcomprehensiveriskreportingthatreflectsexpectationsofmanagementofexpectedsettlementoffinancialassetsandliabilities.

≤6 months 6-12 months 1-5 years >5 years total

$ $ $ $ $

Financial assets

Cashandcashequivalents 6,654,097 - - - 6,654,097

Tradeandotherreceivables 147,832 - - - 147,832

Financial Liabilities

Tradeandotherpayables (1,083,604) (57,955) (171,048) - (1,312,607)

Borrowings - - (292,488) - (292,488)

NetMaturity 5,718,325 (57,955) (463,536) - 5,196,834

TheGroupmonitorsrollingforecastsofliquidityreservesonthebasisofexpectedcashflow.




Forecastliquidityreservesasat30June2011isasfollows: 30 June 2012 2013-2016 $’000 $’000 Openingbalancefortheperiod 6,654 2,842Operatinginflows 604 3,197Operatingoutflows (4,396) (15,703)Capitalexpenditure (20) (13)Financingproceeds - 15,359

Closingbalancefortheperiod 2,842 5,682

Foreign currency riskTheGrouphastransactionalcurrencyexposures.SuchexposurearisesfromlicensingfeesandroyaltiesaswellasexpenditurebytheGroupincurrenciesotherthantheunit’smeasurementcurrencymainly.Foreigncurrencyexpenditureaccountsforlessthan10%ofcostsoftheGroupwhilstrevenueisreceivedonanirregularbasis.Infutureperiods,itisexpectedthattheGroupwillgeneraterevenuesfrommilestonepaymentsandroyaltiesunderitsagreementswithforeigncompanies.

Credit riskCreditriskarisesfromthefinancialassetsoftheGroup,whichcomprisecashandcashequivalents,andtradeandotherreceivables.TheGroup’sexposuretocreditriskarisesfrompotentialdefaultofthecounterparty,withamaximumexposureequaltothecarryingamountoftheseinstruments.Exposureateachreportingdateisaddressedineachapplicablenote.

TheGroupdoesnotholdanycreditderivativestooffsetitscreditexposure.TheGrouptradesonlywithrecognised,creditworthythirdpartiesandassuchcollateralisnotrequestednorisitintheGroup’spolicytosecuritiseitstradeandotherreceivables.

ItistheGroup’spolicythatallcustomerswhowishtotradeoncredittermsaresubjecttocreditverificationproceduresincludinganassessmentoftheirindependentcreditrating,financialposition,pastexperienceandindustryreputation.Inaddition,receivablebalancesaremonitoredonanongoingbasiswiththeresultthattheGroup’sexposuretobaddebtsisnotsignificant.

TherearenosignificantconcentrationsofcreditriskwithintheGroup.

Note 20: FiNaNciaL iNstrUMeNts

Fair values

Fair values of financial assets and liabilities are equivalent to carrying values due their short term to maturity.

Note 21: sHare BaseD PayMeNts

Benitec Limited employees share option Plan (esoP):

Description of plan

TheGroupmayfromtimetotimeissueemployeesoptionstoacquiresharesintheparentatafixedpriceonthemarket.EachoptionwhenexercisedwillthenentitletheoptionholdertooneshareinBenitecLimited(ASXCode:BLT).Alloptionsareexercisableonorbeforeanexpirydate,donotcarryanyvotingordividendrightsandarenottransferableexceptondeathoftheoptionholder.

transactions during the year

AnemployeewhohadpreviouslybeengrantedoptionslefttheCompanyon4August2010.TheBoarddeterminedthatnofurthervestingofoptionsheldbytheseemployeeswouldtakeplaceandthatvestedoptionsheldbythisemployeewouldexpirenolaterthan4February2011.


share options granted during the year

Thefollowingoptionsweregrantedtodirectorsandexecutivesduringtheyear.

original adjusted Name Grant Date No. exercise Price exercise Price expiry Date

PeterFrench 13July2010 5,000,000 $0.03 $0.0204 19August2014

PeterFrench 13July2010 5,000,000 $0.0425 $0.0289 9June2013

JohnRawling 13July2010 1,500,000 $0.03 $0.0204 19August2014

11,500,000

TheseoptionswereissuedbyBenitecLimitedunderitsESOPandareunlisted.

PeterFrancis 13July2010 1,500,000 $0.03364 $0.0228 19August2014

MelBridges 13July2010 1,500,000 $0.03364 $0.0228 19August2014

3,000,000

TheseoptionswereissuedtoMrFrancisandMrBridgessubsequenttoapprovalbyshareholdersintheGeneralMeetingofshareholdersheldon30June2010.TheywerenotissuedaspartoftheESOP.

TheexercisepriceoftheoptionswasadjustedinaccordancewiththeirtermsandconditionsfollowingtherenounceablerightsissuewhichwascompletedinMay2011.

TheclosingmarketpriceofanordinaryshareofBenitecLimited(ASXCode:BLT)ontheAustralianStockExchangeat30June2011was$0.028(30June2010:$0.032)

Note 21: sHare BaseD PayMeNts (coNtiNUeD)

Thefollowingtableillustratesthenumber(No.)andweightedaverageexerciseprice(WAEP)ofshareoptionsissuedundertheESOP:

2011 2011 2010 2010 No. WaeP No. WaeP

Outstandingatthebeginningoftheyear 7,300,000 $0.071 8,808,334 $0.145

Grantedduringtheyear 11,500,000 $0.0371 - -

Exercisedduringtheyear (420,000) $(0.0224) - -

Lapsedorforfeitedduringtheyear (5,580,000) $(0.0722) (1,508,334) $0.524

Outstandingattheendoftheyear 12,800,000 $0.0267 7,300,000 $0.071




Details of esoP share options outstanding as at end of year:

consolidated Group 2011 2010 expiry Date and exercise Price Grant Date No. No.

4September2011@$0.0224each 04-Sep-06 - 3,000,000

14December2011@$0.0407each 14-Dec-06 1,000,000 1,000,000

21February2013@$0.0781each 21-Feb-08 300,000 3,300,000

10June2013@$0.0289each 13-Jul-10 5,000,000 -

19August2014@$0.0204each 13-Jul-10 6,500,000 -

12,800,000 7,300,000

Note 22: eVeNts sUBseQUeNt to rePortiNG Date There have been no material events subsequent to reporting date.

Note 23: coNtiNGeNt LiaBiLities InJanuary2010,theCompanyreachedasettlementwiththeCSIROtoreplacetheexistingLicenceAgreementandCommercialAgreementwithanewexclusiveLicenceAgreementfortheuseofintellectualpropertyandtheCapitalGrowthAgreementwiththeissueofordinaryshares.Aspartofthesettlement,aTransitionAgreementwasputinplaceinordertofacilitatethechangefromtheoldagreementstothenewagreementandtodealwithanumberofothermatters.

UnderthetermsoftheTransitionAgreement,theCompanyagreedtopayCSIROanamountof$297,293forpastpatentcostsonlyintheeventofa trigger event, being either a corporate transaction or an insolvency event.

Note 24: reLateD Party traNsactioNs Transactionsbetweenrelatedpartiesareonnormalcommercialtermsandconditionsnomorefavourablethanthoseavailabletootherpartiesunlessotherwisestated:

consolidated Group 2011 2010 $ $

TransactionswithDirectorsandDirector-relatedEntities: Legalservicespaid/payabletoFrancisAbourizkLightowlers, alawfirminwhichMrPeterFrancisisapartnerandhasabeneficialinterest. 133,068 88,214Consultancyfeesforexecutivedutiespaid/payabletoParmaCorporationPtyLtd, acompanyinwhichMrMelBridgesisadirectorandhasabeneficialinterest. 15,000 30,000Consultancyfeesforexecutivedutiespaid/payabletoNewStarVenturesLtd, acorporationinwhichDrJohnChiplinisadirectorandhasabeneficialinterest. 62,250 21,375Consultancyfeesforexecutivedutiespaid/payabletoGladstonePartnership, anentityinwhichMrIainRossisaprincipalandhasabeneficialinterest 40,000 -


Note 25: BeNitec LiMiteD PareNt coMPaNy iNForMatioN

Parent entity 2011 2010 $ $

assets Currentassets 6,821,867 999,391Non-currentassets 26,474 7,634 totaL assets 6,848,341 1,007,025 LiaBiLities Currentliabilities 1,185,376 955,042Non-currentliabilities 463,536 766,481 totaL LiaBiLities 1,648,912 1,721,523 Net assets/(DeFicieNcy) 5,199,429 (714,498) eQUity Contributedequity 86,821,961 77,557,430Reserves 2,810,599 2,639,234Accumulatedlosses (84,433,131) (80,911,162) totaL eQUity 5,199,429 (714,498) FiNaNciaL PerForMaNce Lossfortheyear (3,521,969) (4,613,426)Othercomprehensiveincome - - totaL coMPreHeNsiVe iNcoMe (3,521,969) (4,613,426)

Contingent liabilitiesTheparententityhadnocontingentliabilitiesasat30June2011.

Capital commitmentsTheparententityhasnocapitalcommitmentsasat30June2011.

Significant accounting policiesTheaccountingpoliciesoftheparentareconsistentwiththoseoftheconsolidatedentity,asdisclosedinNote1.




InaccordancewitharesolutionoftheDirectorsofBenitecLimited,Istatethat:

1. In the opinion of the Directors:

(a) theattachedfinancialstatementsandnotestheretoareinaccordancewiththeCorporationsAct2001,including

(i)givingatrueandfairviewofthefinancialpositionandperformanceoftheCompanyandconsolidatedentity;and

(ii)complyingwithAustralianAccountingStandards,includingtheInterpretations,andtheCorporationsRegulations2001.

(b) thefinancialstatementsandnotestheretoalsocomplywithInternationalFinancialReportingStandards,asdisclosedinNote1;and

(c) asindicatedinnote1(a),therearereasonablegroundstobelievethattheCompanywillbeabletopayitsdebtsasandwhenthey become due and payable.

2. TheDirectorshavebeengiventhedeclarationsbytheChiefExecutiveOfficerandChiefFinancialOfficerrequiredbysection295AoftheCorporationsAct2001.

Signedinaccordancewitharesolutionofthedirectorsmadepursuanttos.295(5)oftheCorporationsAct2001.

OnbehalfoftheDirectors

Peter Francis Director

Melbourne 24August2011

Directors’Declaration


IndependentAuditReport






1. sHare aND oPtioN HoLDiNG iNForMatioN

a) Distribution of equity security Holders

Thenumberofholdersandamountofholdingsbyarangeofholdingsizesoftheordinarysharesandoptionsasat30September2011aredetailedbelow.

range Fully Paid ordinary options options shares (asX:BLt) (asX:BLtoa) (asX:BLto)

Number of Number of Number of Number of Number of Number of holders shares held holders options held holders options held

1-1,000 154 65,377 61 29,622 37 24,461

1,001-5,000 493 1,597,768 166 473,996 157 412,668

5,001-10,000 341 2,786,396 109 826,423 68 478,734

10,001-100,000 1,310 58,453,127 328 12,750,439 119 3,796,190

morethan100,001 802 863,435,242 197 187,222,058 30 41,961,854

3,100 926,337,910 861 201,302,538 411 46,673,907

b) Marketable parcels

Thenumberofholdingsofordinaryshareslessthanamarketableparcelof$500asat30September2011is1,444.

c) substantial shareholders

ThenamesofsubstantialshareholderslistedintheCompany’sregisterasat30September2011were:

Holder Number of ordinary % of issued shares Held capital

DrChristopherBremner 192,637,678 20.80

d) Voting rights

Thevotingrightsattachedtoeachclassofequitysecurityareasfollows:

Eachordinaryshareholderisentitledtoonevotewhenapolliscalled,otherwiseeachmemberpresentatameetingorbyproxyhasonevoteonashowofhands.

Optionholdersdonothaveanyvotingrightsuntiltheoptionisconvertedintoanordinaryshare.

Shareholder Information

e) 20 Largest ordinary shareholders as at 30 september 2011


DrChristopherBremner 192,637,678 20.80CSIRO 48,116,431 5.19UBSWealthManagementAustraliaNomineesPtyLtd 33,564,562 3.62JPMorganNomineesAustraliaLimited<CashIncomeA/C> 33,056,271 3.57CiticorpNomineesPtyLimited 26,856,505 2.90KlipPtyLtd<BeirneSuperFundA/C> 25,702,402 2.77Sigma-AldrichPtyLimited 19,531,250 2.11KlipPtyLtd<BeirneSuperFundA/C> 13,974,089 1.51PromegaCorporation 12,996,339 1.40HSBCCustodyNominees(Australia)Limited 10,471,361 1.13BeirneTradingPtyLtd 8,283,067 0.89MrPaulLeonardGrimshaw+MrDaynePaulGrimshaw<PaulGrimshawFamilySuperFun> 7,669,380 0.83FitelNomineesLimited 7,000,000 0.76MrTrevorHaroldAhern+Mrs.SuzanneMargaretAhern<AhernPastoralCoPlS/FA/C> 6,214,430 0.67MrAronMalcolm 5,672,420 0.61MrEricRossMacdonald+MrsAnnalisaMacdonald 4,600,000 0.50MrManfredAdolfReiter+MsElizabethChristineMeixner<SkymarSuperFundA/C> 4,500,000 0.49MrChrisRetzos 4,500,000 0.49LaJollaCoveInvestorsInc 4,457,000 0.48BlamncoTradingPtyLtd 4,000,000 0.43total 473,803,185 51.15total shares on issue 926,337,910




f) 20 Largest BLto option holders (asX: BLto) as at 30 september 2011


DrChristopherBremner 25,408,240 54.44MrJeffreyConnor 4,000,000 8.57CiticorpNomineesPtyLimited 2,049,121 4.39MrIanDomaille 1,666,000 3.57MrMatthewBurford 1,550,000 3.32GoffacanPtyLtd 1,400,000 3.00JBWere(Nz)NomineesLimited<NzResidentA/C> 670,268 1.44MrArthurBarrieWrigglesworth 544,894 1.17ResoluteSecuritiesPtyLtd<BlueFamilySuperFundA/C> 480,942 1.03DrWarnaKarunasena+MrsAlankarageSriyaniKarunasena 425,982 0.91GoffacanPtyLtd<KmmFamilyA/C> 400,000 0.86HSBCCustodyNominees(Australia)Limited 374,832 0.80MrWayneAndrewGibson 347,921 0.75MrAdamMatthewPhilippe 241,000 0.52UBSNomineesPtyLtd<Tp0001415A/C> 240,000 0.51JYZPairPtyLtd 190,000 0.41MrSimonJohnMoran+MrsChristineJoyceMoran<WirrildaSuperFundA/C> 186,708 0.40MrMarkRaymondO’Brien 180,000 0.39MrLarryRaymondCook 163,805 0.35MrDavidBurtonGibson 159,959 0.34total 40,679,672 87.16Listed options BLto on issue at 30 september 2011 46,673,907

g) 20 Largest BLtoa option holders (asX: BLtoa) as at 30 september 2011

Name Units % of Units

DrChristopherBremner 45,297,373 22.50RetzosInvestmentsPtyLtd<RetzosAltonaPropertyA/C> 12,000,000 5.96ABNAmroClearingSydneyNomineesPtyLtd<CustodianA/C> 5,290,000 2.63SamGoulopoulosPtyLtd<SGoulopoulosF/SuperA/C> 5,000,000 2.48YondroPtyLtd<PasiasFamilyA/C> 5,000,000 2.48JPMorganNomineesAustraliaLimited<CashIncomeA/C> 3,560,023 1.77DrWarnakulasooriyaKarunasena+MrsAlankarageKarunasena<DrW&MrsAKarunasenaA/C> 3,500,000 1.74MGLCorpPtyLtd 3,039,371 1.51CiticorpNomineesPtyLimited 2,689,312 1.34CohenFamilyPtyLtd<CohenFamilySuperFundA/C> 2,500,000 1.24MrAndrewJohnMcfadzean 2,500,000 1.24MrPaulJamesMadden 2,400,000 1.19RWDNomineesPtyLtd<RwdSuperFundA/C> 2,365,500 1.18AtlantisMgPtyLtd<MgFamilyA/C> 2,000,000 0.99AtlantisMgPtyLtd<MgFamilySuperFundA/C> 2,000,000 0.99MrsChooiLinCheung 1,900,000 0.94MrColmPatrickCunningham 1,806,674 0.90MrChrisRetzos 1,672,051 0.83MrSajithRenukaKarunasena 1,620,000 0.80MrErminioRinna 1,601,000 0.80total 107,741,304 53.52Listed options BLtoa on issue at 30 september 2011 201,302,538


h. restricted securities

Therearenosecuritiesonissuesubjecttorestrictionagreements.

i. Unquoted securities

Asatthedateofthisreport,theCompanyhasunquotedsecuritiesasfollows:

Details Number of options Grant Date expiry Date exercise Price

Employeeshareoptionsplanoptions 1,000,000 14-Dec-06 14-Dec-11 $0.0407

Employeeshareoptionsplanoptions 300,000 21-Feb-08 31-Dec-12 $0.0781

Employeeshareoptionsplanoptions 5,000,000 13-Jul-10 10-Jun-13 $0.0289

Employeeshareoptionsplanoptions 6,500,000 13-Jul-10 19-Aug-14 $0.0204

Non-executivedirectoroptions 4,666,666 28-Nov-08 31-Dec-12 $0.0889

Non-executivedirectoroptions 3,000,000 13-Jul-10 19-Aug-14 $0.0228

Directors’options 1,953,125 17-May-04 23-Oct-15 $0.17

StrategicAdviserWarrants 6,126,962 04-Aug-04 4-Aug-14 $0.90

Unlistedoptions 22,244,444 06-Nov-08and06-Feb-09 31-Dec-12 $0.10

Unlistedoptions 12,000,000 24-Feb-10 10-Apr-15 $0.10

Options-Other 17,560 30-Sep-03 30-Sep-13 $0.03

62,808,757

2. on-Market Buy Back

Thereiscurrentlynoon-marketbuyback.

3. Listing on exchanges

TradingoftheCompany’ssecuritiesisavailableontheAustralianSecuritiesExchangeLimited(ASX).




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or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

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ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

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d/

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ster

ed

JP20

05-2

2395

3G

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eale

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ster

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JP20

07-3

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7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

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sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

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PA/a

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0/00

8631

Pend

ing

MX

PA/a

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5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

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SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

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pris

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at le

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ne ta

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cific

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leot

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ence

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olog

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e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

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d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

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562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

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CA25

5877

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ted

CN20

0580

0139

79.5

Exam

in p

rogr

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IL17

7862

Exam

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rogr

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JP20

07-5

0209

4D

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to G

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May

20

11

KR20

06-7

0209

86Ex

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April

20

10

US77

2797

0

(11/

0725

92)

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nted

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201

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US12

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466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

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Gra

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DO

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LE-S

TRA

ND

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NU

CLEI

C A

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(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

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’ to

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ion

at le

ast f

our s

eque

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bei

ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

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bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

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CA25

2790

7Ex

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pro

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s

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474-

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2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

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led

28/1

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10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

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isio

nal o

f 06

7343

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)Ex

am in

pro

gres

s

US

11/8

8364

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otic

e of

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wan

ce 4

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gust

201

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CA25

9671

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am re

ques

ted

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3, 2

011

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0621

0443

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nted

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5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed


ListofPatents

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

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ted

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TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

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led/

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0520

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Gra

nted

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led/

Re

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AU20

0824

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Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

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xam

inat

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BRPI

9917

642.

4Aw

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amin

atio

n

CA23

2372

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rant

ed/ S

eale

d/

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ster

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ing

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0910

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quen

ce li

stin

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ed A

ugus

t 201

0

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rant

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Inte

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n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

isin

g in

a 5

’ to

3’ d

irect

ion

at le

ast f

our s

eque

nces

bei

ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS (C

ontin

ued)

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

(Con

tinue

d)

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

isin

g in

a 5

’ to

3’ d

irect

ion

at le

ast f

our s

eque

nces

bei

ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

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5438

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rant

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7358

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Exam

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2790

7Ex

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pro

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06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

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0507

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5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

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10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

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isio

nal o

f 06

7343

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)Ex

am in

pro

gres

s

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11/8

8364

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otic

e of

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wan

ce 4

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gust

201

1

CA25

9671

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am re

ques

ted

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3, 2

011

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0621

0443

Gra

nted

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5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed


ListofPatentsLI

CEN

SED

PAT

ENTS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS (C

ontin

ued)

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

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quen

ce li

stin

g fil

ed A

ugus

t 201

0

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9510

8G

rant

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ster

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EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

(Con

tinue

d)

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

isin

g in

a 5

’ to

3’ d

irect

ion

at le

ast f

our s

eque

nces

bei

ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

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nted

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5438

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rant

ed

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7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

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s

ZA20

05/0

9813

Gra

nted

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0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

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893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

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10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

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562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

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nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y , Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

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Gra

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Gran

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DO

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LE-S

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NU

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)

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NG

HA

IR P

IN)

A rib

onuc

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d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

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chni

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to

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nce

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rget

gen

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eque

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eque

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17 to

21

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th; a

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ntia

lly c

ompl

emen

tary

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e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

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10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

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0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed


ListofPatentsLI

CEN

SED

PAT

ENTS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS (C

ontin

ued)

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

(Con

tinue

d)

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

isin

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a 5

’ to

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ion

at le

ast f

our s

eque

nces

bei

ng

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st a

nd s

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d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

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leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

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562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

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to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

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nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

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Gra

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DO

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LE-S

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NU

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C A

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)

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NG

HA

IR P

IN)

A rib

onuc

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NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

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chni

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to

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nce

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rget

gen

e co

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eque

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st a

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fect

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17 to

21

nucl

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th; a

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bsta

ntia

lly c

ompl

emen

tary

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e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed


LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS (C

ontin

ued)

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

(Con

tinue

d)

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

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a 5

’ to

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ion

at le

ast f

our s

eque

nces

bei

ng

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st a

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fect

or s

eque

nce

17 to

21

nucl

eotid

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leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

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inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

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quen

ce li

stin

g fil

ed A

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t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

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562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

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to G

rant

May

20

11

KR20

06-7

0209

86Ex

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ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

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nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

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BRPI

0109

269-

3Pe

ndin

g

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221

Gra

nted

SG91

678

Gra

nted

ZA20

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DO

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LE-S

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NU

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)

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NG

HA

IR P

IN)

A rib

onuc

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NA)

for u

se a

s in

terfe

ring

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in g

ene

sile

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chni

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to

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nce

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rget

gen

e co

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eque

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st a

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17 to

21

nucl

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th; a

seq

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bsta

ntia

lly c

ompl

emen

tary

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e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

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0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

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gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

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0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

ListofPatents


LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

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Gra

nted

3/5

Gran

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DO

UB

LE-S

TRA

ND

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NU

CLEI

C A

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(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

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’ to

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at le

ast f

our s

eque

nces

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ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

ListofPatents


ListofPatents

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

isin

g in

a 5

’ to

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irect

ion

at le

ast f

our s

eque

nces

bei

ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed


ListofPatents

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS (C

ontin

ued)

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

(Con

tinue

d)

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

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g in

a 5

’ to

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ion

at le

ast f

our s

eque

nces

bei

ng

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st a

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fect

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eque

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17 to

21

nucl

eotid

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leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

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g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

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eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

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quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

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sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

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0/00

8631

Pend

ing

MX

PA/a

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5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

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562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

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BRPI

0109

269-

3Pe

ndin

g

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2377

221

Gra

nted

SG91

678

Gra

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ZA20

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)

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HA

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IN)

A rib

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se a

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ring

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in g

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chni

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17 to

21

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th; a

seq

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bsta

ntia

lly c

ompl

emen

tary

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e se

cond

effe

ctor

seq

uenc

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nd a

seq

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e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

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espe

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d w

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f the

four

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es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed


LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS (C

ontin

ued)

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

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g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

(Con

tinue

d)

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

7428

Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

ED

NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

isin

g in

a 5

’ to

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irect

ion

at le

ast f

our s

eque

nces

bei

ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

ith th

eir r

espe

ctiv

e ef

fect

or

sequ

ence

s an

d w

here

in a

t lea

st o

ne o

f the

four

seq

uenc

es is

sub

stan

tially

iden

tical

to

the

pred

icte

d tra

nscr

ipt o

f a re

gion

of t

he ta

rget

gen

e; a

nd th

e RN

A fu

rther

com

pris

ing

a sp

acin

g se

quen

ce o

f one

or m

ore

nucl

eotid

es,

the

spac

ing

sequ

ence

bei

ng lo

cate

d be

twee

n an

d sp

acin

g th

e fir

st e

ffect

or s

eque

nce

and

the

seco

nd e

ffect

or s

eque

nce,

or

betw

een

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

seco

nd e

ffect

or s

eque

nce

and

the

sequ

ence

sub

stan

tially

com

plem

enta

ry to

the

first

effe

ctor

seq

uenc

e.

Grah

am, R

ice,

Ro

elvi

nk, S

uhy,

Kolk

ykha

lov,

Harri

son,

Ree

d.

AU20

0424

3347

Gra

nted

NZ

5438

15G

rant

ed

EP04

7358

56.9

Exam

in p

rogr

ess

CA25

2790

7Ex

am in

pro

gres

s

JP20

06-5

0808

4Ex

am in

pro

gres

s

ZA20

05/0

9813

Gra

nted

SG20

0507

474-

5G

rant

ed

IL17

2191

Exam

in p

rogr

ess

US12

/914

893

Cont

inua

tion

of

10/8

6119

1Fi

led

28/1

0/20

10

RNA

i EXP

RESS

ION

CO

NST

RUCT

S (s

ingl

e pr

omot

er) (

114)

Com

posi

tions

and

met

hods

sui

tabl

e fo

r exp

ress

ing

1-x

RNAi

age

nts

agai

nst a

gen

e or

ge

nes

in c

ells

, tis

sues

or o

rgan

s of

inte

rest

in v

itro

and

in v

ivo

so a

s to

trea

t dis

ease

s or

di

sord

ers.

Roel

vink

, Suh

y, Ko

lykh

alov

,

Cout

o

US7,

803,

611

Gra

nted

28/9

/201

0

CN20

0680

0108

11.3

Exam

in p

rogr

ess

HK08

1124

95.7

Appl

icat

ion

filed

EP09

0159

50.0

(Div

isio

nal o

f 06

7343

72.3

)Ex

am in

pro

gres

s

US

11/8

8364

5N

otic

e of

Allo

wan

ce 4

Au

gust

201

1

CA25

9671

1Ex

am re

ques

ted

Feb

3, 2

011

AU20

0621

0443

Gra

nted

IL18

5315

(pat

ent o

f add

ition

to

IL17

7862

)Ex

am in

pro

gres

s

NZ

5609

36G

rant

ed 1

2/8/

2010

Cl

aim

s di

rect

ed to

HCV

, with

fall

back

cl

aim

s de

finin

g th

e sp

ecifi

c se

quen

ces

of k

ey c

omm

erci

al im

porta

nce.

RNA

i EXP

RESS

ION

CO

NST

RUCT

S W

ITH

LI

VER-

SPEC

IFIC

EN

HA

NCE

R/PR

OM

OTE

R

(115

)

An e

xpre

ssio

n co

nstru

ct c

ompr

isin

g: o

ne o

r mor

e en

hanc

er e

lem

ents

sel

ecte

d fro

m th

e gr

oup

cons

istin

g of

Apo

E en

hanc

er e

lem

ents

and

Syn

Enh

enha

ncer

ele

men

ts; o

ne o

r m

ore

liver

-spe

cific

pro

mot

ers;

and

one

or m

ore

RNAi

con

stru

cts

that

pro

vide

one

or m

ore

RNAi

age

nts.

Roel

vink

, Suh

y, Ko

lykh

alov

, Kay

,

Gier

ing

US8,

008,

468

Gra

nted

30

Aug

ust

2011

Ass

igne

d to

Ben

itec

by S

tanf

ord.

MIN

IGEN

E EX

PRES

SIO

N

CASS

ETTE

(STA

NFO

RD)

Met

hods

and

com

posi

tions

for e

xpre

ssin

g a

gene

or n

ucle

otid

e se

quen

ce o

f int

eres

t. Th

e co

mpo

sitio

ns in

clud

e an

exp

ress

ion

cass

ette

that

incl

udes

a s

ynth

etic

enh

ance

r, a

trans

thyr

etin

pro

mot

er, a

nd a

nuc

leot

ide

sequ

ence

ope

rabl

y un

der t

he c

ontro

l of t

he

synt

hetic

enh

ance

r and

the

trans

thyr

etin

pro

mot

er. T

he e

xpre

ssio

n ca

sset

te m

ay b

e us

ed

in a

n AA

V ve

ctor

, suc

h as

a s

elf-c

ompl

emen

tary

AAV

vec

tor.

Kay,

Hebe

rt,

Roel

vink

,

Suhy

US11

/731

198

Exam

in p

rogr

ess

HEP

ATIT

IS B

SE

QU

ENCE

SZh

u, F

renc

h,

Yixi

ang,

Gra

ham

, Ti

ejun

, Yun

chen

g,

Xiao

jun,

Li

PCT/

CN20

11/0

7110

7Ap

plic

atio

n fil

ed

LICE

NSE

D P

ATEN

TS

A. G

RAH

AM

FA

MIL

Y D

DRN

AI P

ATEN

TS –

Ben

itec

has

an e

xclu

sive

, irre

voca

ble

wor

ldw

ide

licen

ce fr

om C

SIRO

for h

uman

ther

apeu

tics

Title

Des

crip

tion

Inve

ntor

sCo

untr

y N

umbe

rEa

rlie

st

Prio

rity

D

ate

Stat

usCl

aim

s

GEN

ETIC

CO

NST

RUCT

S FO

R D

ELAY

ING

OR

REPR

ESSI

NG

TH

E EX

PRES

SIO

N O

F A

TA

RGET

GEN

E (‘0

99)

Synt

hetic

gen

es fo

r mod

ifyin

g en

doge

nous

ge

ne e

xpre

ssio

n in

a c

ell,

tissu

e or

org

an o

f a

trans

geni

c or

gani

sm, i

n pa

rticu

lar a

tran

sgen

ic

anim

al o

r pla

nt. M

ore

parti

cula

rly, t

he in

vent

ion

prov

ides

nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

of r

epre

ssin

g,

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o.

Grah

am, R

ice,

W

ater

hous

eUS

6,

573,

099

Re-i

ssue

d 16

/2/2

011

A do

uble

-stra

nded

DN

A co

nstru

ct w

hich

redu

ces

the

expr

essi

on o

f a

targ

et g

ene

in a

n an

imal

cel

l. Th

e co

nstru

ct c

ompr

ises

at l

east

two

iden

tical

cop

ies

of a

stru

ctur

al g

ene

sequ

ence

, the

regi

on o

f the

targ

et

gene

is 2

0-30

nts

long

or m

ore,

whe

rein

at l

east

one

cop

y of

the

stru

ctur

al g

ene

sequ

ence

is p

lace

d in

the

sens

e or

ient

atio

n re

lativ

e to

th

e pr

omot

er a

nd a

t lea

st o

ne id

entic

al c

opy

is p

lace

d in

the

antis

ense

or

ient

atio

n re

lativ

e to

the

prom

oter

. The

two

sequ

ence

s ar

e sp

aced

fro

m e

ach

othe

r by

a nu

clei

c ac

id s

tuffe

r fra

gmen

t of 1

0-10

0 nt

s.

SYN

THET

IC G

ENES

A

ND

GEN

ETIC

CO

NST

RUCT

S CO

MPR

ISIN

G T

HE

SAM

E

(Gra

ham

Fam

ily)

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

pre

sent

in

vent

ion

utili

ses

reco

mbi

nant

DN

A te

chno

logy

to

pos

t-tra

nscr

iptio

nally

mod

ify o

r mod

ulat

e th

e ex

pres

sion

of a

targ

et g

ene

in a

cel

l, tis

sue,

org

an

or w

hole

org

anis

m, t

here

by p

rodu

cing

nov

el

phen

otyp

es. N

ovel

syn

thet

ic g

enes

and

gen

etic

co

nstru

cts

whi

ch a

re c

apab

le o

r rep

ress

ing

dela

ying

or o

ther

wis

e re

duci

ng th

e ex

pres

sion

of

an

endo

geno

us g

ene

or a

targ

et g

ene

in a

n or

gani

sm w

hen

intro

duce

d th

eret

o ar

e al

so

prov

ided

.

Wat

erho

use,

Gr

aham

, Wan

g,

Rice

US

10/3

46,8

5320

Mar

199

8C N

otic

e of

Allo

wan

ce

4th A

ugus

t 201

1

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g:

a fir

st s

truct

ural

gen

e se

quen

ce c

ompr

isin

g ab

out 2

0-30

con

secu

tive

nts

iden

tical

in s

eque

nce

to a

regi

on o

f tar

get g

ene

enco

ding

a v

iral

DNA

poly

mer

ase,

a v

iral R

NA

poly

mer

ase,

or a

vira

l coa

t pro

tein

in a

m

amm

alia

n ce

ll;

a se

cond

stru

ctur

al g

ene

sequ

ence

com

pris

ing

abou

t 20-

30

cons

ecut

ive

nucl

eotid

es id

entic

al in

seq

uenc

e to

, and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

, the

abo

ut 2

0-30

con

secu

tive

nucl

eotid

es o

f the

firs

t stru

ctur

al g

ene

sequ

ence

, suc

h th

at a

repe

atin

g se

quen

ce w

hich

is o

nly

abou

t 20-

30 c

onse

cutiv

e nu

cleo

tides

in

leng

th id

entic

al to

the

regi

on o

f the

targ

et g

ene

is p

rese

nt in

the

DNA

cons

truct

;

a st

uffe

r fra

gmen

t whi

ch c

onsi

sts

of n

ucle

otid

es a

nd w

hich

sep

arat

es

and

links

the

first

and

sec

ond

stru

ctur

al g

ene

sequ

ence

s;

a pr

omot

er o

pera

ble

in th

e m

amm

alia

n ce

ll; a

nd

a tra

nscr

iptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

mam

mal

ian

cell,

whe

rein

the

repe

atin

g se

quen

ce o

f abo

ut 2

0-30

con

secu

tive

nucl

eotid

es is

pre

sent

with

in th

e fir

st s

truct

ural

gen

e se

quen

ce a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce,

whe

rein

the

first

stru

ctur

al g

ene

sequ

ence

, the

stu

ffer f

ragm

ent a

nd

the

seco

nd s

truct

ural

gen

e se

quen

ce a

re a

ll op

erab

ly c

onne

cted

to th

e pr

omot

er a

nd th

e tra

nscr

iptio

n te

rmin

atio

n se

quen

ce

US11

/218

,999

20 M

ar 1

998

Div

Pend

ing

A do

uble

-stra

nded

DN

A co

nstru

ct c

ompr

isin

g tw

o co

pies

of a

st

ruct

ural

gen

e re

gion

who

se n

ucle

otid

e se

quen

ce is

iden

tical

to th

e nu

cleo

tide

sequ

ence

of a

regi

on o

f a ta

rget

gen

e in

an

anim

al c

ell,

whe

rein

one

of t

he tw

o co

pies

is in

the

sens

e or

ient

atio

n an

d th

e ot

her o

f the

two

copi

es is

in th

e an

tisen

se o

rient

atio

n op

erab

ly u

nder

th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e w

hich

is o

pera

ble

in th

e ce

ll, a

nd w

here

in th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

sens

e or

ient

atio

n an

d th

e co

py o

f the

stru

ctur

al g

ene

regi

on in

the

antis

ense

or

ient

atio

n ar

e ar

rang

ed a

s an

inte

rrupt

ed p

alin

drom

e se

quen

ce w

hich

is

ope

rabl

y un

der t

he c

ontro

l of t

he s

ingl

e pr

omot

er s

eque

nce.

Targ

et g

ene

can

be e

ndog

enou

s to

the

anim

al c

ell,

a fo

reig

n ge

ne to

th

e an

imal

cel

l, or

a v

iral g

ene.

Whe

rein

the

stru

ctur

al g

ene

regi

on is

gr

eate

r tha

n 20

nuc

leot

ides

long

and

has

a le

ngth

up

to th

e fu

ll le

ngth

of

the

targ

et g

ene.

USPa

t: 77

5469

7

(was

10/

646,

070)

20 M

ar 1

998

C G

rant

ed

14 J

uly

2010

Key

clai

ms:

A d

oubl

e-st

rand

ed s

ynth

etic

DN

A ge

ne, c

ompr

isin

g m

ultip

le c

opie

s of

a s

truct

ural

gen

e re

gion

, whe

rein

the

stru

ctur

al

gene

regi

on c

ompr

ises

a n

ucle

otid

e se

quen

ce g

reat

er th

an 2

0 co

nsec

utiv

e nu

cleo

tides

; sin

gle

prom

oter

; mul

tiple

cop

ies;

50-

100

or 1

00-5

00 n

ucle

otid

e st

uffe

r fra

gmen

t

US10

/759

,841

20 M

ar 1

998

Expi

ry: 2

0 M

ar 2

019

Not

ice

of A

llow

ance

25

Augu

st 2

011

A co

nstru

ct c

onsi

stin

g of

20

nts

targ

et re

gion

of a

vira

l pol

ymer

ase

gene

or c

oat p

rote

in g

ene,

two

sequ

ence

s in

inve

rted

orie

ntat

ion

to e

ach

othe

r sep

arat

ed b

y a

stuf

fer f

ragm

ent o

f 10-

50 o

r 50-

100

nucl

eotid

es (o

ther

than

the

nucl

eotid

es o

f the

repe

atin

g se

quen

ce).

In

a vi

rus

parti

cle,

or a

lipo

som

e

US10

/821

,726

20 M

ar 1

998

Not

ice

of A

llow

ance

25

th J

uly

Clai

m a

men

dmen

ts fi

led

June

201

1.

Doub

le s

trand

ed D

NA

cons

truct

for t

rans

fect

ing

mam

mal

ian

cells

co

mpr

isin

g:

A do

uble

stra

nded

DN

A co

nstru

ct c

onsi

stin

g of

a p

rom

oter

ope

rabl

e in

the

cell,

a tr

ansc

riptio

n te

rmin

atio

n se

quen

ce a

ctiv

e in

the

cell,

an

d op

erab

ly c

onne

cted

ther

eto

a fir

st s

truct

ural

gen

e se

quen

ce

com

pris

ing

20-3

0 co

nsec

utiv

e nu

cleo

tides

iden

tical

to a

regi

on

of a

targ

et g

ene

in th

e m

amm

alia

n ce

ll; a

sec

ond

stru

ctur

al g

ene

sequ

ence

iden

tical

in s

eque

nce

and

in a

n in

verte

d or

ient

atio

n re

lativ

e to

the

20-3

0 co

nsec

utiv

e nt

s of

the

first

gen

e se

quen

ce th

ereb

y pr

ovid

ing

a re

peat

ing

sequ

ence

whi

ch is

onl

y 20

-30n

t in

leng

th a

nd a

st

uffe

r fra

gmen

t lin

king

firs

t and

sec

ond

stru

ctur

al g

ene

sequ

ence

s,

such

that

the

dsDN

A co

nstru

ct is

tran

scrib

ed to

pro

duce

a R

NA

mol

ecul

e.

2/7

Gran

ted

CON

TRO

L O

F G

ENE

EXPR

ESSI

ON

W

O99

/490

29

A m

etho

d of

mod

ifyin

g ge

ne e

xpre

ssio

n an

d to

syn

thet

ic g

enes

for m

odify

ing

endo

geno

us

gene

exp

ress

ion

in a

cel

l, tis

sue

or o

rgan

of a

tra

nsge

nic

orga

nism

, in

parti

cula

r a tr

ansg

enic

an

imal

or p

lant

. Mor

e pa

rticu

larly

, the

inve

ntio

n ut

ilise

s re

com

bina

nt D

NA

tech

nolo

gy p

ost-

trans

crip

tiona

lly m

odify

or m

odul

ate

the

expr

essi

on o

f a ta

rget

gen

e in

a c

ell,

tissu

e, o

rgan

or

who

le o

rgan

ism

, the

reby

pro

duci

ng n

ovel

ph

enot

ypes

. Nov

el s

ynth

etic

gen

es a

nd g

enet

ic

cons

truct

s w

hich

are

cap

able

or r

epre

ssin

g de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on

of a

n en

doge

nous

gen

e or

a ta

rget

gen

e in

an

orga

nism

whe

n in

trodu

ced

ther

eto

are

also

pr

ovid

ed.

Grah

am, R

ice,

W

ater

hous

e,

Wan

g

AU20

0520

2658

Gra

nted

AU20

0521

1538

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0520

9648

Gra

nted

/ Sea

led/

Re

gist

ered

AU20

0824

9157

Gran

ted

Mul

tiple

cop

ies;

gre

ater

than

20

nucl

eotid

es; i

nter

rupt

ed p

alin

drom

e;

sing

le p

rom

oter

;

BRPI

9908

967.

0Un

der e

xam

inat

ion

BRPI

9917

642.

4Aw

aitin

g ex

amin

atio

n

CA23

2372

6G

rant

ed/ S

eale

d/

Regi

ster

ed

CN20

0510

0833

25.1

Pend

ing

CN20

0910

2061

75Pe

ndin

gSe

quen

ce li

stin

g fil

ed A

ugus

t 201

0

CZ 2

9510

8G

rant

ed/ S

eale

d/

Regi

ster

ed

EP04

0150

41.9

Inte

ntio

n to

Gra

nt

8 Ju

ly 2

011

A sy

nthe

tic g

ene

whi

ch is

cap

able

of r

epre

ssin

g, d

elay

ing

or

othe

rwis

e re

duci

ng th

e ex

pres

sion

of a

targ

et g

ene

In a

n an

imal

cel

l

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of g

reat

er th

an 2

0 nu

cleo

tides

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP05

0130

10.3

Inte

ntio

n to

Gra

ntA

synt

hetic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

del

ayin

g or

ot

herw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e

In a

euk

aryo

tic c

ell

Whe

rein

sai

d ge

ne c

ompr

ises

…m

ultip

le c

opie

s of

a n

ucle

otid

e se

quen

ce

Of 1

00 n

ucle

otid

es

Whi

ch is

sub

stan

tially

iden

tical

to a

nuc

leot

ide

sequ

ence

of a

ta

rget

gen

e

Whe

rein

the

mul

tiple

cop

ies

are

pres

ente

d as

an

inte

rrup

ted

palin

drom

e se

quen

ce

Oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

EP07

0082

04.5

Pend

ing

EP10

1832

58.2

Divi

sion

al

UKGB

235

3282

Gra

nted

/ Re

ques

t for

Re

voca

tion

requ

est

rece

ived

Dec

embe

r 201

0

The

clai

ms

are

dire

cted

to u

se o

f nuc

leic

aci

d m

olec

ules

whi

ch in

clud

e “n

ucle

otid

e se

quen

ces”

, whi

ch c

ould

be

eith

er D

NA

or R

NA.

Som

e of

the

clai

ms

do n

ot re

quire

the

pres

ence

of p

rom

oter

s. To

the

exte

nt

the

clai

ms

read

on

exog

enou

s de

liver

y of

DN

A m

olec

ules

with

out

prom

oter

s, th

ere

is a

que

stio

n of

whe

ther

thos

e w

ould

wor

k to

redu

ce

targ

et g

ene

expr

essi

on. T

his

ques

tion

has

not b

een

rais

ed in

the

Requ

est f

or re

voca

tion

othe

r tha

n a

gene

ral p

oint

abo

ut s

uffic

ienc

y ac

ross

the

brea

dth

of th

e cl

aim

s. 2

0/12

/201

0: R

espo

nse

filed

, aw

aitin

g ot

her p

arty

’s re

spon

se

HK10

3574

2G

rant

ed/ S

eale

d/

Regi

ster

ed

HGPO

5000

631

Pend

ing

HGPO

1012

25Pe

ndin

g

IN39

01/D

ELN

P/20

05G

rant

edCl

aim

1 n

ow re

ads:

A s

ynth

etic

gen

e w

hich

is c

apab

le o

f rep

ress

ing,

de

layi

ng o

r oth

erw

ise

redu

cing

the

expr

essi

on o

f a ta

rget

gen

e in

a

euka

ryot

ic c

ell,

whe

rein

sai

d sy

nthe

tic g

ene

com

pris

es a

fore

ign

nucl

eic

acid

mol

ecul

e co

mpr

isin

g an

inve

rted

repe

at o

f a s

ense

and

an

ant

isen

se n

ucle

otid

e se

quen

ce e

ach

of w

hich

are

gre

ater

than

20

nuc

leot

ides

and

whi

ch a

re s

ubst

antia

lly id

entic

al to

a n

ucle

otid

e se

quen

ce o

f sai

d ta

rget

gen

e, w

here

in th

e in

verte

d re

peat

is p

rese

nt

as a

n in

terru

pted

pal

indr

ome

sequ

ence

, and

the

fore

ign

nucl

eic

acid

is

oper

ably

und

er th

e co

ntro

l of a

sin

gle

prom

oter

seq

uenc

e.

IN20

00/0

0169

/DE

Gra

nted

JP20

00-5

3799

0G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

05-2

2395

3G

rant

ed/ S

eale

d/

Regi

ster

ed

JP20

07-3

0223

7 G

rant

ed

JP20

09-1

6184

7Pe

ndin

g

KR10

-201

0-70

0689

2

Divi

sion

al o

f 70

1041

9/00

Not

ice

of A

llow

ance

KR70

0534

1/20

06Pe

ndin

g

MX

PA/a

/200

0/00

8631

Pend

ing

MX

PA/a

/200

5/00

6838

Pe

ndin

g

NZ

5066

48G

rant

ed

NZ

5472

83G

rant

ed

PLP-

3770

17Pe

ndin

g

SG75

542

Gra

nted

SG20

0205

122.

5G

rant

ed

SG14

1233

Gra

nted

29

Janu

ary

2010

SL28

7538

Gra

nted

Feb

201

1

ZA20

00/4

507

Gra

nted

B. C

SIRO

: WAT

ERH

OU

SE F

AM

ILY

– Be

nite

c ha

s an

exc

lusi

ve w

orld

wid

e lic

ense

for h

uman

ther

apeu

tics)

Pate

nt N

ame

Des

crip

tion

Inve

ntor

sCo

untr

yA

pplic

atio

n/ G

rant

No

Stat

us

MET

HO

DS

AN

D

MEA

NS

FOR

OB

TAIN

ING

M

OD

IFIE

D

PHEN

OTY

PES

Met

hods

for r

educ

ing

the

phen

otyp

ic e

xpre

ssio

n of

a n

ucle

ic a

cid

of in

tere

st in

eu

kary

otre

cel

ls b

y pr

ovid

ing

aber

rant

RN

A m

olec

ules

, pre

fera

bly

unpo

lyad

enyl

ated

RN

A m

olec

ules

com

pris

ing

at le

ast o

ne ta

rget

spe

cific

nuc

leot

ide

sequ

ence

hom

olog

ous

to th

e nu

clei

c ac

id o

f int

eres

t, pr

efer

ably

a s

ense

stra

nd, i

nto

the

nucl

eus

of p

lant

cel

ls.

Wat

erho

use

Wan

g

Grah

am

(Sm

ith)

AU29

514/

99 (7

6004

1)Pa

tent

sea

led

25

Aug

2005

CA23

2534

4Un

der e

xam

inat

ion

CNZL

9980

5925

.0 (C

N12

0224

6-C)

Gra

nted

18

May

200

5

EP99

9105

92.7

(EP1

0683

11)

Acc

epte

d 27

Apr

il 20

11

JP20

00-5

4359

8Un

der e

xam

inat

ion

NZ

5070

93G

rant

ed/s

eale

d

US09

/287

632

Unde

r exa

min

atio

n

US11

/364

183

Cont

inua

tion.

Pen

ding

US11

/841

737

US20

0801

0473

2.Di

visi

onal

, und

er e

xam

inat

ion.

C. N

SI-U

NSW

LIC

ENSE

D P

ATEN

T

Title

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Effe

ctiv

e fil

ing

date

St

atus

MO

DU

LATI

ON

OF

BET

A-T

UB

ULI

N E

XPRE

SSIO

N IN

TU

MO

UR

CELL

SKa

valla

ris

Gan

Kava

llaris

Gan

Kava

llaris

Gan

AU20

0790

1131

5/3/

2007

Expi

red

prov

INT

PCT/

AU20

08/0

0029

85/

3/20

08

THER

APE

UTI

C M

ETH

OD

AN

D C

OM

POSI

TIO

NS

FOR

TREA

TIN

G T

UM

OU

RS (U

S tit

le)

US12

/555

522

3/3/

2009

Unde

r exa

m

Met

hods

for d

etec

ting

and

mod

ulat

ing

the

sens

itivi

ty o

f tum

our c

ells

to a

nti-

mito

tic a

gent

sCN

2008

8001

4915

.05/

3/20

08Un

der e

xam

EP08

7143

46.7

5/3/

2008

Unde

r exa

m

CA26

7939

35/

3/20

08Fi

led

SG20

0905

810-

85/

3/20

08Un

der e

xam

JP20

09-5

5202

95/

3/20

08Fi

led

IN06

313/

DELN

P/09

5/3/

2008

File

d

IL20

0767

5/3/

2008

Exam

requ

este

d

AU20

0822

2601

5/3/

2008

File

d

D. C

ARN

EGIE

INST

ITU

TE L

ICEN

SED

PAT

ENT

– Be

nite

c ha

s a

wor

ldw

ide,

non

-exc

lusi

ve ro

yalty

bea

ring

licen

ce w

ithou

t the

righ

t to

sub-

licen

ce –

Res

earc

h Us

e On

ly)

Title

Clai

ms

Inve

ntor

sCo

untr

ySe

rial

No.

/Pat

ent N

o.

Filin

g da

te

Stat

us

GEN

ETIC

INH

IBIT

ION

B

Y D

OU

BLE

-ST

RAN

DED

RN

A

A pr

oces

s is

pro

vide

d of

intro

duci

ng a

n RN

A in

to a

livi

ng c

ell t

o in

hibi

t gen

e ex

pres

sion

of

a ta

rget

gen

e in

that

cel

l. Th

e pr

oces

s m

ay b

e pr

actic

ed e

x vi

vo o

r in

vivo

. The

RN

A ha

s a

regi

on w

ith d

oubl

e-st

rand

ed s

truct

ure.

Inhi

bitio

n is

seq

uenc

e-sp

ecifi

c in

that

the

nucl

eotid

e se

quen

ces

of th

e du

plex

regi

on o

f the

RN

A an

d of

a p

ortio

n of

the

targ

et g

ene

are

iden

tical

. The

pre

sent

inve

ntio

n is

dis

tingu

ishe

d fro

m p

rior a

rt in

terfe

renc

e in

gen

e ex

pres

sion

by

antis

ense

or t

riple

-stra

nd m

etho

ds.

1. A

met

hod

to in

hibi

t exp

ress

ion

of a

targ

et g

ene

in a

cel

l com

pris

ing

intro

duct

ion

of a

rib

onuc

leic

aci

d (R

NA)

into

the

cell

in a

n am

ount

suf

ficie

nt to

inhi

bit e

xpre

ssio

n of

the

targ

et g

ene,

whe

rein

the

RNA

com

pris

es a

dou

ble-

stra

nded

stru

ctur

e w

ith a

n id

entic

al

nucl

eotid

e se

quen

ce c

ompa

red

to a

por

tion

of th

e ta

rget

gen

e.

Fire

,

Xu,

Mon

tgom

ery,

Kost

as,

Tim

mon

s,

Taba

ra,

Driv

er,

Mel

lo

US60

/068

562

12/2

3/19

97Pr

ovis

iona

l - e

xpire

d

US6,

506,

559

12/1

8/19

98Gr

ante

d

US7,

538,

095

10/3

0/20

02Gr

ante

d

US7,

560,

438

10/3

0/20

02Gr

ante

d

US7,

622,

633

10/3

0/20

02Gr

ante

d

AU19

380/

99; 7

4379

812

/21/

1998

Gran

ted

CA

2311

999

12/2

1/19

98Ex

amin

atio

n re

ques

ted

JP20

00/5

2553

812

/21/

1998

EP98

9642

02.0

12/2

1/19

98Ex

amin

atio

n in

pro

gres

s

PCT

PCT/

US98

/272

3312

/21/

1998

BEN

ITEC

OW

NED

PAT

ENTS

/APP

LICA

TIO

NS

Title

and

Ben

itec

Ref N

o.D

escr

iptio

nIn

vent

ors

Coun

try

Num

ber

Stat

usRe

mar

ks

MU

LTIP

LE

PRO

MO

TER

EXPR

ESSI

ON

CA

SSET

TES

FOR

SIM

ULT

AN

EOU

S D

ELIV

ERY

OF

RNA

i A

GEN

TS

(105

)

(Lic

ense

d to

Tace

re

Ther

apeu

tics

for H

CV)

A ge

netic

con

stru

ct c

ompr

isin

g a

mul

ti-pr

omot

er e

xpre

ssio

n ca

sset

te c

ompr

isin

g at

leas

t th

ree

prom

oter

/RN

Ai/t

erm

inat

or c

ompo

nent

s w

here

in e

ach

prom

oter

/RN

Ai/t

erm

inat

or

com

pone

nt c

ompr

ises

a p

rom

oter

ele

men

t, a

term

inat

or e

lem

ent a

nd a

n RN

Ai s

peci

es

oper

ably

link

ed to

the

prom

oter

ele

men

t and

the

term

inat

or e

lem

ent,

and

whe

rein

eac

h of

the

RNAi

spe

cies

is d

iffer

ent f

rom

one

ano

ther

.

Roel

vink

,

Suhy

,

Koly

khal

ov,

NZ

5502

84G

rant

ed 1

3/8/

2009

AU20

0522

084

Gra

nted

5/8

/201

0

EP17

2566

0G

rant

ed

11 J

uly

2011

Valid

ated

in F

R, D

E, G

B, C

H, IE

, LU,

M

C, D

K, E

S, G

R, IT

, SE

EP11

1612

16Fi

led

CA25

5877

1Ex

am re

ques

ted

CN20

0580

0139

79.5

Exam

in p

rogr

ess

IL17

7862

Exam

in p

rogr

ess

JP20

07-5

0209

4D

ecis

ion

to G

rant

May

20

11

KR20

06-7

0209

86Ex

am re

ques

ted

April

20

10

US77

2797

0

(11/

0725

92)

Gra

nted

Jun

e 1,

201

0To

met

hods

US12

/723

466

File

d 22

Mar

ch 2

010

To c

onst

ruct

s

GEN

ETIC

SIL

ENCI

NG

(1

06)

A m

etho

d of

indu

cing

, pro

mot

ing

or o

ther

wis

e fa

cilit

atin

g a

chan

ge in

the

phen

otyp

e of

an

anim

al c

ell o

r gro

up o

f ani

mal

cel

ls in

clud

ing

an a

nim

al. T

he m

odul

atio

n of

ph

enot

ypic

exp

ress

ion

is a

ccom

plis

hed

via

geno

typi

c m

anip

ulat

ion

by in

duci

ng,

prom

otin

g or

oth

erw

ise

faci

litat

ing

the

sile

ncin

g of

exp

ress

ible

gen

etic

seq

uenc

es

thus

redu

cing

tran

slat

ion

of tr

ansc

ript t

o pr

otei

n. E

xpre

ssib

le g

enet

ic s

eque

nces

co

ntem

plat

ed b

y th

e in

vent

ion

incl

ude

not o

nly

gene

s no

rmal

ly re

side

nt in

a p

artic

ular

ce

ll (i.

e. in

dige

nous

gen

es) b

ut a

lso

gene

s in

trodu

ced

thro

ugh

reco

mbi

nant

mea

ns o

r

Grah

am, R

ice,

M

urph

y, Re

edJP

2011

-179

375

Pend

ing

BRPI

0109

269-

3Pe

ndin

g

UKGB

2377

221

Gra

nted

SG91

678

Gra

nted

ZA20

02/0

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Gra

nted

3/5

Gran

ted

DO

UB

LE-S

TRA

ND

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NU

CLEI

C A

CID

(107

)

(LO

NG

HA

IR P

IN)

A rib

onuc

leic

aci

d (R

NA)

for u

se a

s in

terfe

ring

RNA

in g

ene

sile

ncin

g te

chni

ques

to

sile

nce

a ta

rget

gen

e co

mpr

isin

g in

a 5

’ to

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ion

at le

ast f

our s

eque

nces

bei

ng

a fir

st a

nd s

econ

d ef

fect

or s

eque

nce

17 to

21

nucl

eotid

es in

leng

th; a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e se

cond

effe

ctor

seq

uenc

e; a

nd a

seq

uenc

e su

bsta

ntia

lly c

ompl

emen

tary

to th

e fir

st e

ffect

or s

eque

nce;

whe

rein

the

com

plem

enta

ry

sequ

ence

s ar

e ca

pabl

e of

form

ing

doub

le s

trand

ed re

gion

s w

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ListofPatents


ChAiRmAN ANd ThE CEO’s LETTER 1

diRECTORs’ REPORT 2

AUdiTOR’s iNdEPENdENCE dECLARATiON 11

CORPORATE GOVERNANCE sTATEmENT 12

FiNANCiAL sTATEmENTs 15

diRECTORs’ dECLARATiON 40

iNdEPENdENT AUdiT REPORT 41

shAREhOLdER iNFORmATiON 44

LisT OF PATENTs 48

CORPORATE diRECTORY iNsidE BACK COVER

BENiTEC LimiTEd

ABN 64 068 943 662

directors

Mr Peter Francis (Non-Executive Chairman)Mr Mel Bridges (Non-Executive Director)Dr John Chiplin (Non-Executive Director)Mr Iain Ross (Non-Executive Director)

Company secretary

Mr Greg West

Registered Office

Level 16356 Collins StreetMelbourne Vic 3000Australia

Principal Place of Business

F6A/1-15 Barr StreetBalmain NSW 2041Australia

Auditors

Grant Thornton Audit Pty LtdLevel 2215 Spring StreetMelbourne Vic 3000

Bankers

Westpac Banking CorporationBusiness Banking759 Burke RoadCamberwell Vic 3124

share Registry

Computershare Investor Services Pty LimitedYarra Falls452 Johnston StreetMelbourne Vic 3067

stock Exchange Listing

The Company is listed on the Australian Securities Exchange LimitedASX Code: BLT

Contents Corporate Directory

Benitec Ltd ABN 64 068 943 662

F6A / 1-15 Barr Street Balmain NSW 2041 Australia

Tel: +61 (0) 2 9555 6986 Email: [email protected]

www.benitec.com


Documents

BENITEC LTD ANNUAL REPORT · 2020. 7. 30. · Incitive Ltd, Peptech Ltd, Arana Therapeutics Ltd, Genera Biosystems Ltd. Dr John chiplin PH.D. Non-Executive Director ... Benitec Ltd