Care required to draft pharma patents and prosecution

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

I. Care required to draft pharma patents and prosecution of pharma patents 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 Nov. 26, 2006 Kuzuwa & Partners specification 2

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 anticancer agent (Swiss-type) (5) Therapeutic or diagnostic method (6) Medical devices Nov. 26, 2006 Kuzuwa & Partners 3

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

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

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 Nov. 26, 2006 Kuzuwa & Partners 6

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. Nov. 26, 2006 Kuzuwa & Partners 7

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 Nov. 26, 2006 Kuzuwa & Partners 8

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 Nov. 26, 2006 Kuzuwa & Partners 9

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

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 Nov. 26, 2006 Kuzuwa & Partners 11

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 Nov. 26, 2006 Kuzuwa & Partners 12

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” Nov. 26, 2006 Kuzuwa & Partners 13

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) Extract Tissue W Vector Z Therapeutic cell Gene: DNA encoding protein X Nov. 26, 2006 Kuzuwa & Partners 14

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. Nov. 26, 2006 Kuzuwa & Partners 15

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” Nov. 26, 2006 Kuzuwa & Partners 16

II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 1. JPO (2) History in patent practice (Examination Standard) administer α-type gene Compound A • 5. 0 -10. 0 mg/ first time • 0. 3 -0. 5 mg/ every two days Nov. 26, 2006 Kuzuwa & Partners 17

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. Nov. 26, 2006 Kuzuwa & Partners 18

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 Nov. 26, 2006 Kuzuwa & Partners 19

II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (3) EPC 2000 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. Nov. 26, 2006 Kuzuwa & Partners 20

II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (3) EPC 2000 -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) Nov. 26, 2006 Kuzuwa & Partners 21

II. Historical background of pharmaceutical/medical patent practice in JPO, EPO and USPTO 2. EPO (4) Possible practice under EPC 2000 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) Nov. 26, 2006 Kuzuwa & Partners 22

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 Nov. 26, 2006 Kuzuwa & Partners 23

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. Nov. 26, 2006 Kuzuwa & Partners 24

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) Nov. 26, 2006 Kuzuwa & Partners 25

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 Nov. 26, 2006 Kuzuwa & Partners 26

III. How to draft pharmaceutical/medical patent 1. specification Comparison on patentability of pharmaceutical/medical inventions among JPO, EPO and USPTO (1) Category of invention JPO EPC 2000 USPTO Chemical entity Yes Yes Pharmaceutical agent comprising novel compounds(1 st use) Yes Yes Pharmaceutical agent comprising known compounds(1 st use) No(EN) Yes No(NV) Anticancer agent comprising known compounds(1 st use) Yes No(NV) Anticancer agent comprising known compounds(2 nd use) Yes Swiss-type No need Yes No(IA) Yes No need No(NV) No need EN: enablement NV: novelty IA: industrial applicability Nov. 26, 2006 Kuzuwa & Partners 27

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) Nov. 26, 2006 Kuzuwa & Partners 28

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). Nov. 26, 2006 Kuzuwa & Partners 29

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. Nov. 26, 2006 Kuzuwa & Partners 30

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, EPC 2000) 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) Nov. 26, 2006 Kuzuwa & Partners 31

III. How to draft pharmaceutical/medical patent specif 6. Comparison on patentability of pharmaceutical/medical inventions among JPO, EPO and USPTO (2) JPO EPO Therapeutic, diagnostic method No(IA) No(EX) Yes Regenerative medicine related method Yes No(IA) No(EX) Yes No(IA) Yes No(NV) Dosage form characterized Yes by administering method EPC 2000 Medical devices Yes Operating method for medical devices Yes if not If not involving diagnostic human body determination USPTO Yes No(NV) EN: enablement NV: novelty IA: industrial applicability, EX: exception to patentability Nov. 26, 2006 Kuzuwa & Partners 32

III. How to draft pharmaceutical/medical patent specification 7. Therapeutic or diagnostic method using pharmaceutical products JP: unpatentable, due to lack of industrial applicability EPC 2000: unpatentable, due to unpatentable invention US: patentable Nov. 26, 2006 Kuzuwa & Partners 33

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 EPC 2000: patentable? US: patentable Nov. 26, 2006 Kuzuwa & Partners 34

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 EPC 2000: patentable? US: unpatentable due to lack of novelty, but patentable as administering method Nov. 26, 2006 Kuzuwa & Partners 35

III. How to draft pharmaceutical/medical patent specification 10. Operating method for medical devices JP: patentable, if not involving human body EP(EPC 2000): patentable, if not involving diagnostic determination → depends on how to draft the claim US: patentable Nov. 26, 2006 Kuzuwa & Partners 36

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 (§ 17 bis)> US (§ 132) Nov. 26, 2006 Kuzuwa & Partners 37

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 Nov. 26, 2006 Kuzuwa & Partners 38

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

IV. Special attention to experimental data pharmaceutical patent applications Recent Court decisions (JP) Case A Case B Case C Case D Oct. 2001 Oct. 2002 Dec. 2003 Aug. 2005 Ausimont SPA Pfizer Inc. Univ. of Virginia Astellas Pharma Process for preparing Medicine Dietary supplement Medicine How to use/make Yes Yes Effects Yes Yes Data No Yes ? No No Data late submission Yes Yes Decision Rejected Corresponding EP, US Granted Date of Decision Plaintiff Category of invention Nov. 26, 2006 Kuzuwa & Partners 40

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

IV. Special attention to experimental data pharmaceutical patent applications 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 A-R Identification data Pharmacological data A-H Late submission A- H Late submission AN A- Late submission Nov. 26, 2006 Kuzuwa & Partners 42

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

IV. Special attention to experimental data pharmaceutical patent applications 1. Hypothetical example 2 New chemical compounds represented by following formula I A-R (A: novel chemical structure) 2. Anticancer agent comprising chemical compounds represented by formula I A-R Identification data Pharmacological data A-H Originally disclosed Late submission A- H Late submission AN A- Late submission Nov. 26, 2006 Kuzuwa & Partners 44

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

IV. Special attention to experimental data pharmaceutical patent applications 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 A-R Identification data Pharmacological data A-H Originally disclosed A- Late submission A- H Late submission N A- Late submission Nov. 26, 2006 Kuzuwa & Partners 46

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

IV. Special attention to experimental data pharmaceutical patent applications Suggestion 1. General n n 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. Nov. 26, 2006 Kuzuwa & Partners 48

IV. Special attention to experimental data pharmaceutical patent applications Suggestion 2. Substance invention u 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. u The reasonably categorized group has more chance to be granted, whereas the other groups are likely rejected. u Pharmacological data are not necessarily needed for enablement requirements for substance invention, but would be useful for asserting inventiveness. Nov. 26, 2006 Kuzuwa & Partners 49

IV. Special attention to experimental data pharmaceutical patent applications 3. Suggestio n Pharmaceutical (use) invention u Pharmacological data on at least one chemical compound selected from a reasonably categorized group should be given in the specification. u The reasonably categorized group may well be patentable. u 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. Nov. 26, 2006 Kuzuwa & Partners 50

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