Clinical Trials and Research Tools in Practical Pharmaceutical R&D

Transcription

1 in Practical Pharmaceutical R&D with an Emphesis on US Law and Pactice (Dr. Hajo Peters Laboratorios Dr. Esteve S.A.) 30/03/04 1 Page 1

2 No Patents on Life! Fears associated with Biotech-Patents (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 30/03/04 2 Page 2

3 No Patents on Life! Fears associated with Biotech-Patents (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 30/03/04 3 Page 3

4 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 as an selection invention. Legal: R.23c EPC (established since 09/1999) ( biological material which is isolated from its natural environment ) 30/03/04 4 Page 4

5 No Patents on Life! Fears associated with Biotech-Patents (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 30/03/04 5 Page 5

6 Rights to clone food, animals and ultimately: INDIVIDUALS! 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! 30/03/04 6 Page 6

7 No Patents on Life! Fears associated with Biotech-Patents (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 30/03/04 7 Page 7

8 Less progress/less companies USA The 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. 30/03/04 8 Page 8

9 Less progress/less companies USA The 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 their inventions and ultimately produce income! 30/03/04 9 Page 9

10 Fears associated with Biotech-Patents July 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 Justice of the EC. The German Via Dolorosa (compulsary licence; limitation of substance claims; no utility patents) 30/03/04 10 Page 10

11 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 30/03/04 11 Page 11

12 Problems associated with Biotech-Patents Monopoly 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, (2000)) Reach Through Claims/Extended Use Claims (EP B1 (SIBIA)) Antibodies (production) (Cabilly patent (Genentech); Morrison Patent (Stanford)) 30/03/04 12 Page 12

13 Hypothetical model of a test system: Reporter gene assay forskolin cytosol ATP bgh Molecule Receptor AC P CREB 6 x CRE camp Messenger F G G F T G A RK S N Q AR K LA α s SV40 nucleus Pol II luciferase-gene luciferin luciferin ox. ATP + O 2 AMP + light luciferase 30/03/04 13 β γ Co-expressed structure Host -cell Page 13

14 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 30/03/04 14 Page 14

15 General Aspects Reach through claims Example: Invention: Gene encoding an enzyme Claim: enzyme, DNA encoding the enzyme, homologues, screening assay with enzyme, any inhibitor of the enzyme, medicament containing an inhibitor of the enzyme, use of the inhibitor of the enzyme in 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 invention of broad applicability. 30/03/04 15 Page 15

16 THE BLOWPIPE 30/03/04 16 Page 16

17 THE BLOWPIPE 30/03/04 17 Page 17

18 General Aspects Reach through claims (USA) Limited by Bayer vs. Housey (by District Court of Dellaware, 2001) but still not completely dismissed (pending parallel cases). Still Bayer vs. Housey mostly deals with the misuse of patents in regards to the licencing deal rendering the patents unenforceable). Additionally: claims for data importation infringing patents were made but largely dismissed (Bayer vs. Housey US Court of Apeals, 2003). 30/03/04 18 Page 18

19 General Aspects Extended Use Example: Claim: USE of a cgmp PDE inhibitor in the preparation of a medicament for the oral treatment of erectile dysfunction in man (EP B1; Pfizer) 30/03/04 19 Page 19

20 General Aspects Receptors and EST s Scope of Receptor claims: An isolated nucleotide comprising a nucleic acid sequence which encodes the amino acid sequence of Figure 1 or a kainate-binding fragment thereof or an amino acid sequence that is at least 97% homologues to the amino acid sequence of Figure 1 or a kainate binding fragment thereof. (Claim 1; issued patent EP B1; Allelix) 30/03/04 20 Page 20

21 General Aspects EST s EST s (Expressed Sequence Tags): Thousands of EST s were applied for following the Human Genome Project. Many were issued. But now: The industrial application of a sequence of a gene must be disclosed in the patent application. (Rule 23e) 3) EPC) Guidelines for Utility of the USPTO. 30/03/04 21 Page 21

22 General Aspects Research Privilege EU The 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 experimental activities. This will apply also to Universities!! But beware also:. Not in the same way in: e.g. Switzerland, Sweden, USA etc. 30/03/04 22 Page 22

23 General Aspects Research 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 through patents they are willing to enforce them on University groups (Duke University). Exceptions are all drawn to research on fully philosophical background. 30/03/04 23 Page 23

24 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!! 30/03/04 24 Page 24

25 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 (not only EMEA!) But: HATCH-WAXMAN gives this privilege to ANDA filing. What about a later NDA filing using a biotech invention in production without an NDA to it (Integra vs. Merck)? 30/03/04 25 Page 25

26 Clinical Trials EU Careful with literature/articles! According to Art. 10.1(a) Directive 2001/83 only 3 ways to copy a product without own data in an abridged application exists: consent of data owner, use of published literature with well established medicinal use. (This is being obviously discouraged by authorities at the moment, cross-referral without consent after 10 (6) years from first EU approval for essentially similar product. 30/03/04 26 Page 26

27 Clinical Trials General Aspect Ethical pressure to market product in countries with Clinical Trial Patent applications? 30/03/04 27 Page 27

28 THE END 30/03/04 28 Page 28