Post-Grant for Practitioners: Significant PTAB Decisions ... · PDF filePost-Grant for Practitioners: Significant PTAB Decisions in BioPharma 1 ... Bausch & Lomb, Inc., and Bausch

Post-Grant for Practitioners: Significant PTAB Decisions in BioPharma

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November 9, 2016

Dorothy Whelan

Principal and Post-Grant

Practice Co-Chair

Tasha Francis

Associate

Overview

• How often? … bi-monthly

• When? … 2nd Wednesday

• Topics? …

• Important decisions

• Developments

• Practice tips

• Housekeeping

• CLE

• Questions

• Materials

• http://fishpostgrant.com/webinars/

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Agenda

• Overview of Webinar Series

• USPTO Statistics on Adversarial Post-Grant

Proceedings

• Kyle Bass Update

• Noteworthy PTAB Decisions in Bio-Pharma

• Upcoming Post-Grant Webinar

• Post-Grant Resources

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USPTO Statistics on Adversarial Post-Grant Proceedings

PTAB – Most Active Forum

In 2014, the PTAB was the most active forum for US patent validity

challenges, and in 2015 the PTAB had a record year for filings.

*11/8/2016. Source: DocketNavigator Analytics

Most active

courts by

number of

cases

2011 2012 2013 2014 2015 2016

PTAB - 112 792 1,677 1,800 1,474

TXED 580 1,252 1,498 1,428 2,548 1,385

DED 486 1,001 1,335 942 544 382

CACD 329 506 411 320 277 268

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AIA Petitions Have Exceeded Expectations . .

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91%

8%

1%

IPR CBM PGR

5,744 AIA

Petitions Filed

Since 2013

Source: LexMachina, data current as of 11/7/2016

. . . But They May Be Leveling Off Slightly

Source: LexMachina, data current as of 10/31/2016

0

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2013 2014 2015 2016 (Projected)

IPR CBM PGR

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BioPharma IPR Filings Steadily Increase

8

44

125

186

161

0

20

40

60

80

100

120

140

160

180

200

2013 2014 2015 2016 YTD

IPRs Filed in TC1600

Source: LexMachina, data current as of 11/7/2016; projecting

187 IPRs in TC1600 at year end

Technology Breakdown by USPTO Tech Center (2013-Present)

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Source: LexMachina, data current as of 11/7/2016; Design

Patents make up <1% of remaining petitions

Electrical/Computer59%

Mechanical/Business Method

25%

Bio/Pharma9%

Chemical7%

BioPharma by the Numbers

• 2016 YTD, the institution win rate for biopharma is 57.7%*

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89.3%

60.8%

40.0%

53.6%

92.0%

63.2%

55.0%57.7%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

2013 2014 2015 2016 YTD

Institution Win Rate "Pure" Institution Win Rate

Source: LegalMetric, data current as of 11/4/2016;

*“Institution win rate” includes pre-institution settlements, “pure institution win rate” does not

BioPharma by the Numbers

• 2016 YTD, the percentage of claims for which trial is instituted is

44.7%

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Source: LegalMetric, data current as of 11/4/2016

0

500

1,000

1,500

2,000

2,500

3,000

2013 2014 2015 2016

Number of Claims Challenged Number of Claims Instituted

FWD Win Rates – BioPharma IPRs (2014-2016)

• 73 biopharma petitions have reached a Final Written Decision

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Source: LegalMetric, data current as of 11/4/2016; “Petitioner Win on At Least 1

Claim includes all cases where petition resulted in at least one instituted claim

being cancelled and also includes those cases where all claims were invalidated.

63.2%

57.7% 46.4%

73.7%

61.5%53.6%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2014 2015 2016

Complete Petitioner Win Petitioner Win on At Least 1 Claim

Kyle Bass Update

Kyle Bass IPRs

• 37 IPR Petitions Filed between February 2015 and March 2016

• 21 trials instituted (56.8%)

• 9 FWD

• 8 victories for Bass

• Shire/NPS patent covering Gattex® was invalidated

• 2 Celgene patents covering Pomalyst® and Revlimid® were invalidated

• Alpex Pharma declined to file a Response to Bass’s petition and a FWD

was entered against it, canceling claims covering Suprenza®

• Nissan Chemical abandoned contest and FWD was entered against patent

covering Bravecto®

• Shire’s challenged patent covering Lialda® was upheld

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Other IPR Activity Related to Biologics

• Avastin (bevacizumab)

• Patent Owner Response pending

• Herceptin (trastuzumab)


• Neulasta (pegfilgrastim)


• Rituxan (rituximab)


• Humira (adalimumab)

• Trial instituted, no FWD

• Orencia (abatacept)

• FWD due by 1/15/2017

• Tysabri (natalizumab)

• Denied institution

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Noteworthy PTAB Decisions in Bio-Pharma

PTAB Decisions—Objective Evidence

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Innopharma Licensing, Inc., et al., Mylan Pharmaceuticals, Inc. and Mylan, Inc. v. Senju Pharm. Co.,

Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma Holdings, IPR2015-00902, Paper No. 90

(PTAB July 28, 2016)

• Claims covered an aqueous liquid preparation for ophthalmic use comprising two components: (1) bromfenac (type of NSAID) and (2) tyloxapol in an amount “sufficient to stabilize” bromfenac

• Petitioner challenged claims as obvious over the combination of two references (Ogawa and Sallman)

• Ogawa disclosed ophthalmic compositions containing bromfenac and polysorbate 80. Both tyloxapol and polysorbate 80 were non-ionic surfactants.

• Sallman disclosed the use of tyloxapol as a solubilizer for a different NSAID in an ophthalmic composition.

• Final written decision: Petitioner failed to prove that any of the claims were unpatentable

• Objective evidence of nonobviousness key to decision!


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• Issue was the interchangeability of tyloxapol and polysorbate 80

• Patent Owner put in objective evidence of non-obviousness and the

PTAB analyzed it:

“We put Patent Owner on notice that, ‘absent evidence to the contrary,

it would have been well within the level of ordinary skill in the art to

replace one non-ionic surfactant (polysorbate 80) with another non-

ionic surfactant (tyloxapol) in Ogawa’s Example 5=6, because both

were known to be useful as surfactants in ophthalmic preparations ….’

In that regard, we take account of objective considerations of non-

obviousness raised by Patent Owner in the Response ….” Paper 90,

p. 13


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• PTAB cited recent Federal Circuit decision rejecting proposition that

objective evidence of nonobviousness could never overcome strong

prima facie case of obviousness. WBIP, LL, v. Kohler Co.., Nos.

2015-1038, 2015-1044, 2016 WL 3902668 at *5 (Fed. Cir. July 19,

2016).

• Patent owner presented evidence of unexpected results, commercial

success, and industry acclaim.


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• Unexpected results evidence: experimental results showing

tyloxapol increased bromfenac stability significantly better than

polysorbate 80. Expert witness explained test results and

significance.

• Commercial success evidence: showed that success of commercial

product (Prolensa) falling within claims was due to stabilizing effect

of tyloxapol and ability to eliminate burning and stinging associated

with other eye drops. PTAB: “The fact that Prolensa replaced such

prescriptions suggests commercial success.” Paper 90, p. 20.

• Industry acclaim evidence: Expert testimony “supported by objective

evidence” describing benefits of Prolensa, praise by leading doctors,

and praise in peer-reviewed medical journals.


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• PTAB credited objective evidence of nonobviousness in concluding that claims would not have been obvious:

“Taking account of the objective indicia of non-obviousness, including Patent Owner’s significant evidence of unexpected results, we are not persuaded that Petitioner demonstrates sufficiently that the combined disclosures of Ogawa and Sallmann, when considered in light of the asserted background prior art references, establish the obviousness of the claimed invention. Petitioner’s proposed substitution of tyloxapol for polysorbate 80 produced a surprising and unexpected stabilizing effect on bromfenac. The other objective indicia of non-obviousness flow from that surprising results.” Paper 90, p. 72 (emphasis added).


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• Note that PTAB placed most emphasis on evidence of unexpected

results based upon experimental data

• Unexpected results evidence is still the most persuade objective

evidence of non-obviousness.


23

Coalition for Affordable Drugs II LLC v. NPS Pharmaceuticals, Inc., IPR2015-01093, Paper No. 67 (PTAB October 21, 2016)

• Kyle Bass hedge fund filing.

• Claims covered L-histidine stabilized drug formulations of glucagon-

like peptide-2 (“GLP-2”) and GLP-2 analogs (sold by Shire as

GATTEX®).

• Claims set forth several combinations of GLP-2 peptides and

peptide concentrations, pH levels, L-histidine concentrations, and

different bulking agents and concentrations.

• Claims challenged as obvious on 4 related grounds. Issue was

whether it would have been obvious to formulate GLP-2 analogs

with histidine and mannitol (bulking agent/excipient).

• PTAB found all claims unpatentable under § 103.


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• Patent owner presented objective evidence of nonobviousness:

unexpected results, commercial success, and satisfaction of long-felt

need.

• PTAB was not persuaded.


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• Unexpected results: Patent Owner presented bar graphs illustrating

heat stress stability studies. PTAB concluded that results were NOT

unexpected:

“[W]e determine that a preponderance of the evidence demonstrates

that an ordinary artisan would have expected the addition of histidine

to improve the stability of a protein formulation, at least to some

degree, based on the disclosures [of the prior art].” Paper 67, p. 29.

• PTAB further held that even if results were unexpected, they were

not probative of nonobviousness because any differences in stability

improvement were “a difference in degree, not kind.” Id., p. 30.


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• Commercial success: Patent Owner presented evidence of large

market share, high price, sales and sale growth, and large economic

returns for GATTEX®.

• PTAB held that Patent Owner failed to establish a nexus between

GATTEX® sales and patent claims:

“[I]t is unclear if the sales are due to the stability of the product, or to

the active agent, which is disclosed [by the prior art].” Paper 67, p. 32.


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• Long-felt need: Patent Owner presented evidence that GATTEX®

was the first approved GLP-2 product for short bowel syndrome.

• PTAB held that Patent Owner failed to establish a nexus between

the alleged long-felt need and the patent claims:

“Patent Owner does not provide evidence sufficient to permit a

determination as to whether the long-felt need was met by the

discovery of GLP-2 analogs having the necessary activity (disclosed in

the prior art), or the use of L-histidine and mannitol or sucrose in a

stabilized GLP-2 analog formulation.” Paper 67, p. 33.


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Take-Aways

• Experimental evidence to support unexpected results is the most

persuasive evidence but it will be scrutinized.

• Commercial success and long-felt need are given lesser weight. For

formulations and dosing, need to ask whether success/need is

attributable to the drug or to the subsequent formulation/dosing

regimen?

PTAB Decisions—Lead Compound Analysis

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Mylan Laboratories Ltd. v. Aventis Pharma S.A., IPR2016-00627, Paper No. 10 (PTAB Aug. 23, 2016)

• Claim directed towards a specific compound (cabataxel)

with methoxy group at C-7 position.

• Petitioner raised two grounds of unpatentability based on

§ 103: Kant and Kant + Klein. Arguments were based

on a “lead compound” analysis.

• PTAB declined to grant the petition.

• Patent owner did not file an expert declaration with its

preliminary response (option not available).


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• Petitioner proposed Kant’s compound 20 as the lead compound and

proposed modifying compound 20 (docetaxel) to include a C-7

methoxy group.

• PTAB: Kant taught modifying a precursor of docetaxel (“10-DAB”)

only at the C-10 position to prepare docetaxel. Kant did not suggest

additionally modifying docetaxel, let alone at the C-7 position.


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• Petitioner argued a POSITA would modify both the C-10 and C-7

positions to increase potency and lipophilicity. PTAB disagreed.

“Petitioner recognizes that alkylating the C-7 and C-10 functional

groups would optimize lipophilicity (Pet. 22) but does not address the

well-known problems with lipophilicity and limited aqueous solubility of

intravenously administered paclitaxel and docetaxel. Therefore, we

are not persuaded by Petitioner’s argument that a POSA would have

been motivated to optimize lipophilicity in a paclitaxel or docetaxel

analogue via simultaneous substitution of the C-7 and C-10 positions.”

Paper 10, p. 14


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• PTAB also rejected Petitioner’s proposed ground combining Kant

with Klein. Petitioner used Kant’s compound 20 as the lead

compound and argued a POSA would have substituted compound

20’s C-7 hydroxyl group with the methoxy groups shown in Klein’s

compounds. Unlike Kant’s compound 20 and the claimed

compound, Klein’s compounds had an acetyl group at C-10 and a

hydroxyl group at C-9.

“[W]e are not persuaded a POSA would have disregarded the

improved aqueous solubility and stability provided by a C-9 hydroxyl, a

key teaching in Klein, when considering possible modifications to Kant

Compound 20 …. We reach the same conclusion with respect to

Klein’s C-10 acetyl.” Paper 10, p. 16.


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Take-Aways• Patent owner does not necessarily need an expert declaration to

defeat a petition based on the lead compound analysis, even when

the analysis is highly factual

• In Mylan, Patent owner successfully convinced the PTAB that

Petitioner was using a hindsight-based analysis by drilling down into

the details and rationales behind the proposed modifications.

• Petitioners must present more than superficial reasoning to support

selection of a proposed lead compound and proposed modifications.

PTAB Decisions—Printed Publications

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Teva Pharm. USA, Inc. v. Indivior UK Ltd., IPR2016-00280, Paper No. 23 (PTAB June 10, 2016)

• Claims directed towards an orally dissolvable film that included

buprenorphine, naloxone, a buffer, and a polymer carrier matrix.

Film had a bioequivalent release profile and drug absorption as a

Suboxone® tablet.

• Petitioner raised four grounds of unpatentability based on § 103.

Each included the “Suboxone® 2002 label” and the “Suboxone®

Table Summary Basis of Approval” (“SBOA”) as secondary

references.

• PTAB declined to grant the petition.

• PTAB held that Petitioner failed to establish that either the

Suboxone® 2002 label or the SBOA was a printed publication.


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Teva Pharm. USA, Inc. v. Indivior UK Ltd., IPR2016-00280, Paper No. 23 (PTAB June 10, 2016)

• Petitioner argued that in co-pending litigation, Patent Owner stipulated

that both the Suboxone® 2002 label and the SBOA were prior art to the

patent at issue. Petitioner offered no further evidence that either was a

printed publication.

• PTAB held Petitioner failed to meet its threshold burden of

demonstrating that either was a printed publication:

(a) Petitioner filed no exhibits, such as a court document, from the district

court case relating to the stipulation;

(b) The stipulation alone is insufficient to meet the threshold requirement

because parties may have had others reason to stipulate to the issue;

(c) The petition lacked any information “directly related” to whether either

the label or the SBOA were actually publicly accessible in the relevant

timeframe. Paper 23, p. 10.


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Take-Aways

• Do not simply rely on stipulations or statements made in briefs from

related proceedings to prove that a document qualifies as a printed

publication!

• Need to produce independent evidence

Post-Grant Resources

Resources

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• Fish websites:

• Post-Grant for Practitioners: http://fishpostgrant.com/webinars/

• General: http://fishpostgrant.com/

• IPR: http://fishpostgrant.com/inter-partes-review/

• PGR: http://fishpostgrant.com/post-grant-review/

• Rules governing post-grant: http://fishpostgrant.com/

• Post-Grant App: http://fishpostgrant.com/app/

• Post-Grant Radio: http://fishpostgrant.com/podcasts/

• USPTO sites:

• AIA Main: http://www.uspto.gov/aia_implementation/index.jsp

• Inter Partes: http://www.uspto.gov/aia_implementation/bpai.jsp

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http://fishpostgrant.com/webinars/

http://fishpostgrant.com/

http://fishpostgrant.com/inter-partes-review/

http://fishpostgrant.com/post-grant-review/

http://fishpostgrant.com/

http://fishpostgrant.com/app/

http://fishpostgrant.com/podcasts/

http://www.uspto.gov/aia_implementation/index.jsp

http://www.uspto.gov/aia_implementation/bpai.jsp

Post-Grant Webinar Series

Mark Your Calendar!

Our next Post-Grant for Practitioners webinar will be on Wednesday, January 11, 2017 (1:00-2:00PM ET)

Post-Grant Year in Review with Dorothy Whelan and Karl Renner – Fish’s Post-Grant Practice Chairs

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Thank You!

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Tasha Francis

Associate

Twin Cities

[email protected]

612-766-2015

Dorothy Whelan

Principal

Twin Cities

[email protected]

612-337-2509

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to Lauren McGovern at [email protected]

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Documents

Post-Grant for Practitioners: Significant PTAB Decisions ... · PDF filePost-Grant for Practitioners: Significant PTAB Decisions in BioPharma 1 ... Bausch & Lomb, Inc., and Bausch