Experimental Data to Support Patentability of a Biological Pharmaceutical in the U.S.

1. Experimental Data to Support Patentability of a Biological Pharmaceutical in the U.S. October 14, 2011Presented by M. Paul Barker

2. Utility Requirement Under 35 U.S.C. § 101 Enablement Requirement Under 35 U.S.C. § 112 Non-obviousness Under 35 U.S.C. § 103 Agenda

3. Utility • § 101 has a utility requirement, mandating that a patentable invention be useful. • “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.”

4. USPTO Utility Guidelines • Utility Examination Guidelines published on January 5, 2001. 66 Fed. Reg. 1092 (January 5, 2001). See also, MPEP §2107. • The Guidelines and the legal analysis govern the internal operations of the PTO. They do not have the force and effect of law and cannot, therefore, constitute substantive rules creating or altering the rights or obligations of any party. • the utility asserted must be well-established or specific, substantial and credible, as judged by one of ordinary skill in the art.

5. USPTO Utility Guidelines In vitro or in vivo data reasonably correlated to the specific therapeutic or pharmacological utility generally "will be sufficient to establish therapeutic or pharmacological utility for a compound, composition or process." M.P.E.P. § 2107.02. Can be any animal model in support of an asserted utility, so long as those skilled in the art would have seen it as reasonably predictive of the asserted utility. M.P.E.P. § 2107.02. Need not be an art-recognized animal model for the particular disease or disease condition.

6. USPTO Utility Guidelines PTO cannot require human clinical data and or evidence of safety of the claimed invention. In fact, that an invention is in human clinical trials will presumptively satisfy the utility requirement. See M.P.E.P. § 2107.02(iv).

7. Utility – In re Fisher • Federal Circuit review of the utility guidelines -- In re Fisher, 421 F.3d 1365, 76 U.S.P.Q.2d 1225 (Fed. Cir. 2005). The claim at issue read: • A substantially purified nucleic acid molecule that encodes a maize protein or fragment thereof comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1 through SEQ ID NO: 5. •  Claimed 5 EST sequences. When Fisher filed the application, he did not know the precise structure or function of either the genes or the proteins encoded by those genes, but he disclosed a number of ways that the five claimed ESTs may be used.

8. Examiner and Board No known use for the proteins produced – no substantial utility. Using the claimed ESTs to isolate nucleic acid molecules of other plants and organisms, which themselves had no known utility, is not a substantial utility. Using the claimed ESTs in gene expression screens does not provide a benefit because the application fails to provide any teaching regarding how to use the data relating to gene expression. Uses were not specific to the claimed ESTs, but instead were generally applicable to any EST.

9. Federal Circuit -- No Substantial Utility While Fisher’s claimed ESTs may add a noteworthy contribution to biotechnology research, the application does not meet the utility requirement of § 101 because Fisher does not identify the function for the underlying protein-encoding genes. Absent such identification, we hold that the claimed ESTs have not been researched and understood to the point of providing an immediate, well-defined, real world benefit to the public meriting the grant of a patent.

10. Federal Circuit -- No Specific Utility Fisher’s uses were not “specific.” Any EST transcribed from any gene in the maize genome has the potential to perform any of the alleged uses. Nothing about Fisher’s alleged uses set the five claimed ESTs apart from the more than 32,000 ESTs disclosed in the application or any EST derived from any organism.

11. M.P.E.P. § 2107.02. A disclosure that identifies a particular biological activity of a compound and explains how that activity can be utilized in a particular therapeutic application of the compound does contain an assertion of specific and substantial utility for the invention.

12. Enablement 35 U.S.C. § 112 amended by patent law reform, effective Sept. 16, 2012. (a) IN GENERAL.—The specification shall contain a written description of the invention and of the manner and process of making and using it, in such full, clear, concise and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.

13. Enablement Overlaps with §101 Utility • Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318 (Fed. Cir. 2005) • “the how to use prong of section 112 incorporates as a matter of law the requirement of 35 U.S.C. § 101 that the specification disclose as a matter of fact a practical utility for the invention.” [citations omitted] In explaining what constitutes a sufficient showing of utility in the context of the enablement requirement, this court has stated that an applicant's failure to disclose how to use an invention may support a rejection under either section 112, paragraph 1 for lack of enablement, or “section 101 for lack of utility ‘when there is a complete absence of data supporting the statements which set forth the desired results of the claimed invention.’ ” [citations omitted]

14. Enablement – Undue Experimentation • Disclosure can still comply with the requirements of § 112 even if it leaves some technological problems unresolved so long as one of ordinary skill in the art could resolve them in reasonable time. • Only objective enablement required. • Routine experimentation acceptable but undue experimentation is not.

15. Undue Experimentation Factors Quantity of experimentation necessary; Amount of direction or guidance provided; Presence or absence of examples; Nature of the invention; State of the prior art; Relative skill of those in the art; Predictability or unpredictability of the art; and Breadth of the claims.

16. Enablement -- Predictability “The predictability or unpredictability of the science is relevant to deciding how much experimental support is required to adequately describe the scope of an invention.” Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)

17. Enabled Throughout Scope Of Claims • Martek Biosciences Corp. v. Nutrinova, Inc., 579 F.3d 1363 (Fed. Cir. 2009) • Claim 1: A process for producing lipids comprising use of a genus of about 10,000 organisms. • Claim 5: A process according to claim 1 where the “euryhaline microorganisms are selected from the group consisting of [T], [S], and mixtures thereof [22 possible organisms].” • One working example • FC: Enablement • NO to 10,000 – Undue Experimentation • YES to 22 -- Not Undue Experimentation

18. Enabled Throughout Scope Of Claims • Pharmaceutical Resources, Inc. v. Roxane Laboratories, Inc., 2007 WL 3151692 (Fed. Cir. 2007), reh’g denied (Nov. 27, 2007)(not for publication) • Claim: 19. An oral pharmaceutical composition in the form of a stable flocculated suspension in water comprising: (a) megestrol acetate; (b) at least two compounds selected from the group consisting of polyethylene glycol, propylene glycol, glycerol, and sorbitol; and (c) a surfactant. • Par argued that one of ordinary skill in the art would choose a surfactant from twenty-two surfactants approved by the United States Pharmacopoeia and National Formulary (USP-NF) for use in oral pharmaceuticals. • DC: Not Enabled • “Par is not entitled to the broad claims it asserts in this action.”

19. Enabled Throughout Scope Of Claims • Pharmaceutical Resources (con’t) • FC: Affirmed. • Par “sought extremely broad claims in a field of art that it acknowledged was highly unpredictable[.]” • “the language of the claims and the specification both suggest that the claims encompass hundreds of possible surfactants.” • Only three working examples, utilizing only one new surfactant. Given the highly unpredictable nature of the invention and the extremely broad scope of the claims, these three working examples do not provide an enabling disclosure commensurate with the entire scope of the claims.

20. Enablement Judged as of Filing Date • Applicant may submit additional evidence in support of enablement after the filing date, as long as the evidence uses teachings known in the art at the time of filing (Knoll Pharmaceutical Company, Inc. v. Teva Pharmaceuticals USA, Inc., 367 F.3d 1381, 1385 (Fed. Cir. 2004) (per curiam)). • Claims may encompass later-developed subject matter not contemplated at the time of filing.

21. Enablement Requirement Is Dynamic Applicants sought to claim methods for treating cancer using a broad genus of compounds on the basis of data obtained for only a small subset. Earlier case, cancer considered incurable, so showing insufficient (In re Buting, 418 F.2d 540, 163 U.S.P.Q. 689 (C.C.P.A. 1969)). Later case, cancer treatment not incredible. Compounds at issue “have a close structural relationship” to prior art compounds “known to be useful in cancer chemotherapy,” so showing enabled entire genus (In re Jolles, 628 F.2d 1322, 206 U.S.P.Q. 885 (C.C.P.A. 1980)).

22. Data for Enablement of a Pharmaceutical • In re Brana, 51 F.3d 1560, 34 U.S.P.Q.2d 1436 (Fed. Cir. 1995) • Compound for treatment of lymphocytic leukemia. • Animal Model -- Disease artificially introduced into mice from cell lines derived from diseased mice – results showed that compounds within scope of claims demonstrated significant antitumor activity. • Prior art showed structurally similar compounds shown to be effective against tumor models.

23. Data for Enablement of a Pharmaceutical • Brana (con’t) • PTO argued that tests should be discounted because not naturally occurring disease in animals. • PTO cited articles that questioned accuracy of in vivo murine tests in predicting results in humans. • PTO found claims were not enabled.

24. Data for Enablement of a Pharmaceutical • Brana (con’t) • FC found claims enabled • Cell lines were derived from diseased mice. • Making applicant wait for disease to develop in mice would make testing almost impossible. • Articles did not show that one skilled in the art would question antitumor activity. • Activity shown in the animal model and activity of structurally similar compounds was compelling. • Only need “statistically significant tests with standard experimental animals.”

25. Enablement of a Method of Treatment • Method of treatment claims often subject to higher standard than compound claims • Compound claims have no specific statement of use – so demonstration of in vitro pharmacological activity can suffice. • Treatment claims, or claims that recite a pharmacological result in a patient, require effective use in patient.

26. Enablement of a Method of Treatment • In re Gardner, 427 F.2d 786, 166 U.S.P.Q. 138 (C.C.P.A. 1970) • Claims -- pharmaceutical compositions having antidepressant activity and methods of producing antidepressant activity by administering the compositions • In animal models, showed compositions could affect activity of neurotransmitters shown to be associated with depression. But failed to show antidepressant activity by behavioral criteria. • CCPA held that the claims were not enabled because the claims were not directed to the compounds, but to compositions having antidepressant activity and methods of producing such activity.

27. Obviousness – Prima Facie Case Allocate burdens between the USPTO and applicant. USPTO bears the initial burden of establishing the prima facie case -- a reason why one of skill in the art would have modified prior art and had an expectation of success. Make determination from the point of view of the hypothetical person of ordinary skill in the art just prior to when the inventor discovered the invention. If no prima facie case established, no rebuttal necessary. If prima facie case established, burden shifts to applicant to come forward with evidence persuasive of nonobviousness. If applicant submits rebuttal evidence, the initial holding of prima facie obviousness dissipates, and “the examiner must consider all of the evidence anew.”

28. Thwarting the Presumption: Showing the Unexpected • Comparative testing: compound and all its properties are inseparable. • Claimed compounds posses properties the prior art compound doesn’t. • Claimed compounds exhibit unexpectedly enhanced activity in common property. • Surprising results. • An assumed similarity based on a comparison of structure must give way to evidence that the assumption is erroneous (In re Papesch (C.C.P.A. 1963)). • Be careful with testing though.

29. Rebuttal Evidence • Unexpected results • Must compare to closest prior art. • Must compare to closest example within closest prior art. • Showing must be commensurate in scope with the claims. • Objective indicia of unobviousness • commercial success • long-felt need • failure by others • copying • teaching away • initial disbelief and subsequent acclaim by experts

30. Showing Unexpected Results Must provide some scientific support – Many cases hold that lawyer’s arguments and conclusory statements in the specification are insufficient. Specification needs to discuss the property alleged to exhibit unexpected results. (Many cases) Data can be generated after the filing date. (Knoll Pharmaceutical Company, Inc. v. Teva Pharmaceuticals USA, Inc., 367 F.3d 1381, 1385 (Fed. Cir. 2004) (per curiam)).

31. Thank you. M. Paul Barker Finnegan, Henderson, Farabow, Garrett & Dunner, LLP Stanford Research Park3300 Hillview AvenuePalo Alto, CA 94304-1203 Tel 1 650 849 6620Fax 1 650 849 6666paul.barker@finnegan.com

32. Paul Barker practices patent prosecution, patent interferences, and strategic counseling, with a particular focus in the fields of biotechnology and pharmaceuticals. In his patent prosecution practice, he prepares patent applications and responses to office actions, represents clients in reexamination and reissue proceedings, and prepares briefs to the appeal board. Speaker Information

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