1. Nov. 26, 2006 Kuzuwa & Partners1 Care required to draft pharma patents and prosecution of pharma patents Ahmedabad, November 26, 2006 Kiyoshi Kuzuwa Patent Attorney KUZUWA & PARTNERS Tokyo, Japan

2. Nov. 26, 2006 Kuzuwa & Partners2 Care required to draft pharma patents and prosecution of pharma patents I. Patentability on pharmaceutical/medical inventions II. Historical background of pharmaceutical/ medical patent practice in JPO, EPO and USPTO III. How to draft pharmaceutical/medical patent specification IV.Special attention to experimental data for pharmaceutical patent applications

3. Nov. 26, 2006 Kuzuwa & Partners3 I.Patentability on pharmaceutical/ medical inventions 1. Categories of medical inventions (1) Novel chemical compounds (2) “ Pharmaceutical ” agent comprising chemical compounds (3) “ Anti-cancer ” agent comprising chemical compounds (4) Use of chemical compounds for manufacturing anti- cancer agent (Swiss-type) (5) Therapeutic or diagnostic method (6) Medical devices

4. Nov. 26, 2006 Kuzuwa & Partners4 I.Patentability on pharmaceutical/medical inventions 2. Criterion on patentability of pharmaceutical/medical inventions (1) Novelty (2) Inventiveness (3) Industrial applicability (4) Reproducibility/Enablement

5. Nov. 26, 2006 Kuzuwa & Partners5 I.Patentability on pharmaceutical/medical inventions 2. Criterion on patentability of pharmaceutical/ medical inventions (1) Novelty Novelty of chemical compounds, novelty of use, novelty of medical devices

6. Nov. 26, 2006 Kuzuwa & Partners6 I.Patentability on pharmaceutical/medical inventions 2. Criterion on patentability of pharmaceutical/medical inventions (2) Inventiveness Unexpectedly remarkable effects : most critical proven by experimental data -in the original disclosure -later submission

7. Nov. 26, 2006 Kuzuwa & Partners7 I.Patentability on pharmaceutical/medical inventions 2. Criterion on patentability of pharmaceutical/medical inventions (3) Industrial applicability depends on political, ethical, humanitarian reasons in each country.

8. Nov. 26, 2006 Kuzuwa & Partners8 I.Patentability on pharmaceutical/medical inventions 2. Criterion on patentability of pharmaceutical/medical inventions (4) Reproducibility/Enablement Experimental data on ● chemical entity per se, i.e. identification data (m.p. IR etc.) ● medical use, i.e. pharmacological data (in vivo, in vitro) -in the original disclosure -later submission

9. Nov. 26, 2006 Kuzuwa & Partners9 II. Historical background of pharmaceutical/ medical patent practice in JPO, EPO and USPTO 1. JPO (1) General principle on pharmaceutical/medical inventions -Medical devices, pharmaceutical products per se: patentable since 1975, where substance patent was introduced -Method for surgery, therapy or diagnosis: unpatentable due to lack of industrial applicability

10. Nov. 26, 2006 Kuzuwa & Partners10 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) 1960s Inventions having features involving human bodies e.g. method for permanent wave to hairs: unpatentable 1970s Only method for surgery, therapy or diagnosis out of inventions having features involving human bodies: unpatentable

11. Nov. 26, 2006 Kuzuwa & Partners11 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) 1993 Method for surgery, therapy or diagnosis: unpatentable irrespective of whether inventions have features involving human bodies Note inventions involving a process to return extracts to the same human body (e.g. artificial dialysis): unpatentable

12. Nov. 26, 2006 Kuzuwa & Partners12 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) 2003 A part of regenerative medicine and/or gene therapy related technology: patentable -inventions involving a process to return extracts to the same human body for therapeutic purpose (e.g. dialytic treatment): unpatentable, but -method for producing medical products by using extracts, even if inventions involve a process to return said extracts to the same human body for therapeutic purpose (e.g. dialytic treatment): patentable Method for operating medical devices not involving the process applying to the human body: patentable

13. Nov. 26, 2006 Kuzuwa & Partners13 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) 2003 A part of regenerative medicine and gene therapy related technology: patentable Example (patentable) “Process for producing a therapeutic cell for treating cancer characterized by introducing the gene by vector Z comprising DNA encoding protein X into tissue W extracted from a human body”

14. Nov. 26, 2006 Kuzuwa & Partners14 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) 2003 A part of regenerative medicine and gene therapy related technology: patentable Extract Tissue W Therapeutic cell Gene: DNA encoding protein X Vector Z Example (patentable)

15. Nov. 26, 2006 Kuzuwa & Partners15 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) 2005 -Broader protection on method for operating medical devices, e.g. driving and moving incision means, transmitting and detecting radiation etc.: patentable unless the claim sets forth a work of medical doctor directly applied to human bodies.

16. Nov. 26, 2006 Kuzuwa & Partners16 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) 2005 -Protection on method for generating a new efficacy and/or new indication for producing and/or selling medicaments, e.g. “therapeutic agent for Hepatitis C for treating patient having α-type gene, characterized by administering compound A in a dosage of 5.0 - 10.0 mg at the first time and 0.3 – 0.5 mg every two days”

17. Nov. 26, 2006 Kuzuwa & Partners17 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) Compound A α-type gene administer 5.0-10.0 mg/ first time 0.3-0.5 mg/ every two days

18. Nov. 26, 2006 Kuzuwa & Partners18 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (1) General principle on pharmaceutical/medical inventions under current EPC Article 52 (patentable inventions) (1) European patents shall be granted for any inventions which are susceptible of industrial application, which are new and which involve an inventive step. …………. (4) Methods for treatment of human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body shall not be regarded as inventions which are susceptible of industrial application within the meaning of paragraph 1. This provision shall not apply to products, in particular substances or compositions, for use in any of these methods.

19. Nov. 26, 2006 Kuzuwa & Partners19 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (2) Current practice under EPC -Method for surgery, therapy or diagnosis: unpatentable due to lack of industrial applicability (Art. 52(4)) Exceptions, e.g. Out of 3 steps, i.e. data collecting step, comparison step and medical determination step, invention related to only 1 st and 2 nd steps: patentable -Medical devices, pharmaceutical products: patentable -2 nd medical use: patentable only in Swiss type claim

20. Nov. 26, 2006 Kuzuwa & Partners20 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (3) EPC2000 will come into effect on December 13, 2007. Article 53 (Exceptions to patentability) in place of Article 52 European patents shall not be granted in respect of: …………. (c) methods for treatment of human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body; this provision shall not apply to products, in particular substances or compositions, for use in any of these methods.

21. Nov. 26, 2006 Kuzuwa & Partners21 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (3) EPC2000 -Methods for treatment of human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body have been excluded from patentablity by the fiction of their lack of industrial applicability. -This fiction is not appropriate, because those methods are excluded in the interests of public health rather than lack of industrial applicability. ↓ Article 52 (industrial applicability) → Article 53 (Exceptions to patentability)

22. Nov. 26, 2006 Kuzuwa & Partners22 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (4) Possible practice under EPC2000 2 nd medical use: -Swiss type claim no longer necessary -Product claim patentable “Use of compound A and/or its physiologically acceptable salts for manufacturing a therapeutic agent treating diabetes” (Swiss type claim) ↓ “A therapeutic agent treating diabetes comprising compound A and/or its physiologically acceptable salts” (product claim)

23. Nov. 26, 2006 Kuzuwa & Partners23 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. USPTO (1) General principle on pharmaceutical/medical inventions -Any inventions are patentable -exceptions for infringements against practitioner ’ s performance of medical activity Art. 287, Art. 271

24. Nov. 26, 2006 Kuzuwa & Partners24 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. USPTO US patent law §287 ………… (c) (1) with respect to a medical practitioner ’ s performance of a medical activity that constitutes an infringement under section 271(a) or (b) of this title, the provisions of sections 281, 283, 284, and 285 of this title shall not apply against the medical practitioner or against a related health care entity with respect to such medical activity.

25. Nov. 26, 2006 Kuzuwa & Partners25 II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. USPTO (2) History of practice on pharmaceutical/medical inventions - 1950 medical methods: unpatentable 1950 - medical methods: patentable 1993 Pallin vs Singer (both practitioners) 1996 current US patent law §287(c)

26. Nov. 26, 2006 Kuzuwa & Partners26 III. How to draft pharmaceutical/ medical patent specification Novelty, Inventiveness, Industrial applicability, Reproducibility (enablement) must be met. How to draft - Claims - Specification How to amend specification How and when to submit - Working examples, comparative examples - Pharmacological data

27. Nov. 26, 2006 Kuzuwa & Partners27 1. Comparison on patentability of pharmaceutical/medical inventions among JPO, EPO and USPTO (1) Category of inventionJPOEPOEPC2000USPTO Chemical entityYes Pharmaceutical agent comprising novel compounds(1 st use) Yes Pharmaceutical agent comprising known compounds(1 st use) No(EN)YesNo(NV) Anticancer agent comprising known compounds(1 st use) Yes No(NV) Anticancer agent comprising known compounds(2 nd use) YesNo(IA)YesNo(NV) Swiss-typeNo needYesNo need EN:enablement NV:novelty IA:industrial applicability III. How to draft pharmaceutical/medical patent specification

28. Nov. 26, 2006 Kuzuwa & Partners28 III. How to draft pharmaceutical/medical patent specification 2. Chemical compounds “Chemical compounds of chemical formula X” (JP,EP,US patentable) -Novelty and inventiveness are met, when compounds are new and inventive. -Industrial applicability are met, when disclosed how to make, how to use (medical use) in the original specification. -Reproducibility (enablement) is met, when data on identification of compounds, e.g., IR, m.p., etc. are disclosed in the original specification (at least for JP). (pharmacological data not necessarily needed)

29. Nov. 26, 2006 Kuzuwa & Partners29 III. How to draft pharmaceutical/medical patent specification 3. First medical use of novel (inventive) compounds “ Pharmaceutical agent comprising novel chemical compounds of chemical formula X” (JP,EP,US patentable) Industrial applicability is met, when identification data on at least one chemical compound. Reproducibility is met, when pharmacological data (in vivo or in vitro) on at least one disease, e.g., diabetes, are disclosed in the original specification (at least for JP).

30. Nov. 26, 2006 Kuzuwa & Partners30 III. How to draft pharmaceutical/medical patent specification 4. First medical use of known compounds “ Pharmaceutical agent comprising known chemical compounds of chemical formula X“ (only EP patentable) Industrial applicability are met in JP,EP,US. Novelty are met in JP,EP, but not in US due to known compounds. Reproducibility is met, when pharmacological data on at least one disease (e.g. diabetes) in EP, but not in JP due to insufficient disclosure.

31. Nov. 26, 2006 Kuzuwa & Partners31 III. How to draft pharmaceutical/medical patent specification 5. Second medical use of known compounds For novelty/inventiveness and industrial applicability Product: Anticancer agent comprising chemical compounds of chemical formula X (JP, EPC2000) Swiss type: Use of chemical compounds of chemical formula X for producing therapeutic agents for treating cancer (Swiss-type, current EPO) Method: Therapeutic method for treating cancer using chemical compounds of chemical formula X (US) For reproducibility/enablement At least one pharmacological data (in vivo or in vitro) on the second indication, e.g., anticancer in the original specification (at least for JP)

32. Nov. 26, 2006 Kuzuwa & Partners32 6. Comparison on patentability of pharmaceutical/medical inventions among JPO, EPO and USPTO (2) JPOEPOEPC2000USPTO Therapeutic, diagnostic method No(IA) No(EX)Yes Regenerative medicine related method YesNo(IA)No(EX)Yes Dosage form characterized by administering method YesNo(IA)YesNo(NV) Medical devicesYes Operating method for medical devices Yes if not involving human body Yes If not involving diagnostic determination No(NV) EN:enablement NV:novelty IA:industrial applicability, EX:exception to patentability III. How to draft pharmaceutical/medical patent specification

33. Nov. 26, 2006 Kuzuwa & Partners33 III. How to draft pharmaceutical/medical patent specification 7. Therapeutic or diagnostic method using pharmaceutical products JP: unpatentable, due to lack of industrial applicability EP: unpatentable, due to lack of industrial applicability EPC2000: unpatentable, due to unpatentable invention US: patentable

34. Nov. 26, 2006 Kuzuwa & Partners34 III. How to draft pharmaceutical/medical patent specification 8. Regenerative medical method JP: patentable if extracts used for producing medical products EP: unpatentable, due to lack of industrial applicability EPC2000: patentable? US: patentable

35. Nov. 26, 2006 Kuzuwa & Partners35 III. How to draft pharmaceutical/medical patent specification 9. Dosage form characterized by administering method JP: patentable EP: unpatentable, due to lack of industrial applicability EPC2000: patentable? US: unpatentable due to lack of novelty, but patentable as administering method

36. Nov. 26, 2006 Kuzuwa & Partners36 III. How to draft pharmaceutical/medical patent specification 10. Operating method for medical devices JP: patentable, if not involving human body EP(EPC2000): patentable, if not involving diagnostic determination → depends on how to draft the claim US: patentable

37. Nov. 26, 2006 Kuzuwa & Partners37 III. How to draft pharmaceutical/medical patent specification 11. How to draft original specification and how to amend claims in the prosecution -Practice on amendments, so strict … so called new matter practice: EP (§123)> JP (§ 17bis)> US (§ 132)

38. Nov. 26, 2006 Kuzuwa & Partners38 III. How to draft pharmaceutical/medical patent specification 11. How to draft original specification and how to amend claims in the prosecution In the original specification, - more working examples, - more specific compounds listing, - more stepwise numerical ranges, e.g. “5-50°C, preferably 10-30°C, more preferably 15-20°C”, - less negative expression, e.g. “if higher than 50°C, adverse effect appears” ↓ more possibilities for amending claims during prosecution

39. Nov. 26, 2006 Kuzuwa & Partners39 How important Identification data, Pharmacological data etc. are? Critical for fulfilling enablement requirements Must be present in the original specification.  Late submission of data is not acceptable when none of data was given in the original specification (at least for Japan). IV. Special attention to experimental data for pharmaceutical patent applications

40. Nov. 26, 2006 Kuzuwa & Partners40 Recent Court decisions (JP) Case ACase BCase CCase D Date of DecisionOct. 2001Oct. 2002Dec. 2003Aug. 2005 PlaintiffAusimont SPAPfizer Inc.Univ. of VirginiaAstellas Pharma Category of inventionProcess for preparingMedicineDietary supplementMedicine How to use/makeYes EffectsYes DataNoYes ?No Data late submissionYes DecisionRejected Corresponding EP, USGranted IV. Special attention to experimental data for pharmaceutical patent applications

41. Nov. 26, 2006 Kuzuwa & Partners41 How to cope with the strict practice (at least for Japan) on pharmaceutical/ medical patent application? IV. Special attention to experimental data for pharmaceutical patent applications

42. Nov. 26, 2006 Kuzuwa & Partners42 Hypothetical example 1 1. New chemical compounds represented by following formula I A-R (A: novel chemical structure) 2. Anticancer agent comprising chemical compounds represented by formula I H A-RIdentification dataPharmacological data A-HLate submission N A- IV. Special attention to experimental data for pharmaceutical patent applications

43. Nov. 26, 2006 Kuzuwa & Partners43 Hypothetical example 1 Substance invention  No chance Pharmaceutical invention  No chance IV. Special attention to experimental data for pharmaceutical patent applications

44. Nov. 26, 2006 Kuzuwa & Partners44 Hypothetical example 2 1. New chemical compounds represented by following formula I A-R (A: novel chemical structure) 2. Anticancer agent comprising chemical compounds represented by formula I H A-RIdentification dataPharmacological data A-HOriginally disclosedLate submission N A- IV. Special attention to experimental data for pharmaceutical patent applications

45. Nov. 26, 2006 Kuzuwa & Partners45 Hypothetical example 2 Substance invention  A-H: Likely patentable  A- Pharmaceutical invention  No chance Patentable if pharmacologically equivalent to A-H H N IV. Special attention to experimental data for pharmaceutical patent applications

46. Nov. 26, 2006 Kuzuwa & Partners46 Hypothetical example 3 1. New chemical compounds represented by following formula I A-R (A: novel chemical structure) 2. Anticancer agent comprising chemical compounds represented by formula I H A-RIdentification dataPharmacological data A-HOriginally disclosed Late submission N A- IV. Special attention to experimental data for pharmaceutical patent applications

47. Nov. 26, 2006 Kuzuwa & Partners47 Hypothetical example 3 Substance invention  A-H: Likely patentable  A- Pharmaceutical invention  A-H: Likely patentable  A- Patentable if pharmacologically equivalent to A-H H N H N IV. Special attention to experimental data for pharmaceutical patent applications

48. Nov. 26, 2006 Kuzuwa & Partners48 Suggestion 1. General The more experimental data, the more chance. Experimental data for at least one embodiment, which support the utility of said embodiment, are absolutely necessary for chemical/pharmaceutical inventions. IV. Special attention to experimental data for pharmaceutical patent applications

49. Nov. 26, 2006 Kuzuwa & Partners49 Suggestion 2. Substance invention  Identification data on at least one chemical compound selected from a reasonably categorized group should be given in the specification. Otherwise, almost no chance as a whole.  The reasonably categorized group has more chance to be granted, whereas the other groups are likely rejected.  Pharmacological data are not necessarily needed for enablement requirements for substance invention, but would be useful for asserting inventiveness. IV. Special attention to experimental data for pharmaceutical patent applications

50. Nov. 26, 2006 Kuzuwa & Partners50 Suggestion 3. Pharmaceutical (use) invention  Pharmacological data on at least one chemical compound selected from a reasonably categorized group should be given in the specification.  The reasonably categorized group may well be patentable.  The other groups falling within the claim are theoretically also patentable, only if -a reasonable explanation on why compounds falling within the other groups are pharmacologically equivalent to the above compound and -additional pharmacological data on the other group’s compounds are submitted. IV. Special attention to experimental data for pharmaceutical patent applications

51. Nov. 26, 2006 Kuzuwa & Partners51 Thank you !