Clinical Trials and Research Tools in Practical ......1 30/03/04 1 Los lunes del Centro de Patentes Patentes de Investigacion Clinical Trials and Research Tools in Practical Pharmaceutical

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Los lunes del Centro de PatentesPatentes de Investigacion

Clinical Trials and Research Toolsin Practical Pharmaceutical R&D

with an Emphesis on US Law and Pactice

(Dr. Hajo Peters – Laboratorios Dr. Esteve S.A.)

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Fears associated with Biotech-PatentsNo Patents on Life!

(How can a part of the body be patented?)

Rights to clone food, animals and ultimately : INDIVIDUALS!

Less Progress in Life Science

Worse Medical treatment

Monopoly for and ultimately Control of Companies on Treatment

Undeservedly Large Rewards for the Inventors

Patents are the Death of Small Companies

Clinical Trials and Research Tools

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Rights to clone food, animals and ultimately : INDIVIDUALS!







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No Patents on Life(How can a part of the body be patented?)

Not a new issue: see Patented Plant Extracts

Patenting of isolated natural products is well established in Patent law asan selection invention.

Legal:

R.23c EPC (established since 09/1999)

(“biological material which is isolated from its natural environment”)


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Rights to clone food, animals and ultimately: INDIVIDUALS!







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Patents are primarily a negative right!

They allow the patentee to forbid the use of his invention

but:

Patents do not give an allowance to use the patented matter

This is regulated by national law!


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Less progress/less companies

USAThe most Biotech patents issued

(at least in part thanks to a more liberal attitude of the US-Patent Office).

The most and most successful Biotech firms.

The quantitatively broadest and most successful life science research.


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Less progress/less companies

USAThe most Biotech patents issued

(at least in part thanks to a more liberal attitude of the US-Patent Office).

The most and most successful Biotech firms.

The quantitatively broadest and most successful life science research.

Patents are the only true tool of small companies for protecting theirinventions and ultimately produce income!


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Fears associated with Biotech-PatentsJuly 06, 1998 Directive 98/44 EG of the European Parliament/Council

concerning the Protection of Biotechnological Inventions comes into force.

Effective September 01, 1999 it becomes part of the EPC

The Netherlands objected but were rejected before the Court of Justiceof the EC.

The German “Via Dolorosa”

(compulsary licence; limitation of substance claims; no utility patents)


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Expectations associated with Biotech-Patents

Expert Opinion of the Boston Consulting Group

December 1999:

“Gene/Biotech Patents are filed much earlier in the Research chain”Patents on targets

Patents on Assays

Patents based on therapeutic concepts


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Problems associated with Biotech-PatentsMonopoly for and Blocking of a Target for the Cure of a certain Disease

(Breast Cancer Mutation Gene / Myriad Genetics (US) vs. Curie Institute (FR))

Key Patents on certain well established Technology(Reporter Gene Assay (SIBIA))

Necessity to licence a load of different Patents to conduct Research(bgh-Polydadenylation Signal (RCT))

Blocking the Progress or best Technology in Medicinal Testing/Diagnosis(Merz et al., Diagnostic testing fails the test, Nature 415, 577-579 (2000))

Reach Through Claims/Extended Use Claims(EP0552 202 B1 (SIBIA))

Antibodies (production)(Cabilly patent (Genentech); Morrison Patent (Stanford))


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ααααs

luciferase-geneSV406 x CREPol IICREB

AC

ATP cAMP

forskolin

P

luciferinATP + O2

luciferinox.AMP + light

luciferasecytosol

ββββγγγγ

Host -cell

FGGFTGARKSARKLA

NQ

Messenger

Receptor Co-expressedstructure

Hypothetical model of a test system: Reporter gene assay

bgh

nucleus


Molecule

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General problems with test systems

• receptor (EST)• necessarily coexprimed proteins• test method, test principle• modified cells or animals•gene constructs (vectors, plasmids, hybrids and so on)• antibodies (use and production)• measuring procedures, the (optical, electrical) signal• materials: devices, colour markers, plasmids, cells• „reach-through claims“


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General AspectsReach through claims

Example:Invention: Gene encoding an enzymeClaim: enzyme, DNA encoding the enzyme, homologues, screeningassay with enzyme, any inhibitor of the enzyme, medicamentcontaining an inhibitor of the enzyme, use of the inhibitor of the enzymein the preparation of a medicament for treatment of disease X,...

“Scope of protection should be commensurate or be justified by the invention”(Guidelines EPC; Art 83 & 84)

Reach through claims may be allowable in case of a pioneer inventionof broad applicability.


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THE BLOWPIPE


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THE BLOWPIPE


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General AspectsReach through claims (USA)


•Limited by Bayer vs. Housey (by District Court of Dellaware, 2001)but still not completely dismissed (pending parallel cases). StillBayer vs. Housey mostly deals with the misuse of patents in regardsto the licencing deal rendering the patents unenforceable) .

•Additionally: claims for data importation infringing patents weremade but largely dismissed (Bayer vs. Housey US Court of Apeals,2003).

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General AspectsExtended Use

Example:Claim: USE of a cGMP PDE inhibitor in the preparation of amedicament for the oral treatment of erectile dysfunction in man(EP 702 555 B1; Pfizer)


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General AspectsReceptors and EST’s

Scope of Receptor claims:An isolated nucleotide comprising a nucleic acid sequencewhich encodes the amino acid sequence of Figure 1 or akainate-binding fragment thereof or an amino acid sequencethat is at least 97% homologues to the amino acid sequenceof Figure 1 or a kainate binding fragment thereof.

(Claim 1; issued patent EP 0 617 123 B1; Allelix)


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General AspectsEST’s

EST’s (Expressed Sequence Tags):Thousands of EST’s were applied for following the Human GenomeProject.Many were issued.

But now:The industrial application of a sequence of a gene must be disclosed inthe patent application.

(Rule 23e) 3) EPC)Guidelines for Utility of the USPTO.


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General AspectsResearch Privilege

EUThe most important help for Researchers:

The patent does not prevent activities for experimental purposes, if:- the invention is the object of the experimental activities- but not if the invention is the means or the tool of the experimentalactivities.

This will apply also to Universities!!

But beware also:. Not in the same way in:e.g. Switzerland, Sweden, USA etc.


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General AspectsResearch Privilege

USA

VERY LIMITED:

Integra vs. Merck: any use of a patent tool/ “safe harbour (HATCH-WAXMAN)not for general biomedical research” (US Court of Appeals, 2003).

As in the eyes of US Judges University make part of their living throughpatents they are willing to enforce them on University groups (Duke University).

Exceptions are all drawn to research on fully “philosophical” background.


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Clinical Trials (with patented substance/super generic)EU

Research Privilege?

Complete different view of courts in the European Union.

(depending on different wording in enforcing the guideline ion national law)

Germany (very liberal)Netherlands (very strict)Spain (no case law but tendency: infringements)

Please check locally!!


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Clinical Trials (with patented substance/super generic)USA

Research Privilege through Hatch-Waxman Act

No problem (safe harbour) as long as the trials are for the FDA (notonly EMEA!)

But: HATCH-WAXMAN gives this privilege to ANDA filing.

What about a later NDA filing using a biotech invention in productionwithout an NDA to it (Integra vs. Merck)?


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Clinical TrialsEU

Careful with literature/articles!

According to Art. 10.1(a) Directive 2001/83 only 3 ways to copy aproduct without own data in an abridged application exists:

consent of data owner,use of published literature with well established medicinal use. (This isbeing obviously discouraged by authorities at the moment,cross-referral without consent after 10 (6) years from first EU approval for“essentially similar” product.


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Clinical TrialsGeneral Aspect

Ethical pressure to market product in countries with Clinical Trial

Patent applications?


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THE END


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Clinical Trials and Research Tools in Practical ......1 30/03/04 1 Los lunes del Centro de Patentes Patentes de Investigacion Clinical Trials and Research Tools in Practical Pharmaceutical