Ex Parte Senga et al

Patent Trial and Appeal BoardDec 12, 2012

11818783 (P.T.A.B. Dec. 12, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/818,783 06/15/2007 Hirobumi Senga 9747/101728 9874 24628 7590 12/12/2012 Husch Blackwell LLP Husch Blackwell Sanders LLP Welsh & Katz 120 S RIVERSIDE PLAZA 22ND FLOOR CHICAGO, IL 60606 EXAMINER AEDER, SEAN E ART UNIT PAPER NUMBER 1642 MAIL DATE DELIVERY MODE 12/12/2012 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte HIROBUMI SENGA, CAIXIA LI, YONGLING WAN, and LISHUI CHANG __________ Appeal 2011-000919 Application 11/818,783 Technology Center 1600 __________ Before ERIC GRIMES, JEFFREY N. FREDMAN, and SHERIDAN K. SNEDDEN, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of treating cancer, which have been rejected for nonenablement. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. STATEMENT OF THE CASE The Specification discloses that “Des A fibrin acts to inhibit the spreading and migration of malignant tumor cells” (Spec. 5: 15-16). Des A fibrin is obtained from fibrinogen by release of fibrinopeptide A (FPA) Appeal 2011-000919 Application 11/818,783 2 through the action of batroxobin, a thrombin-like serine protease (id. at 3: 5-7, 17-20). Claims 9-11 are on appeal. Claim 9 is representative and reads as follows: 9. A method of inhibiting the growth, invasion and metastasis of a malignant tumor in a patient comprising the step of administering an effective amount of Des A fibrin to the patient wherein the malignant tumor is selected from the group consisting of melanoma, breast cancer, and fibrosarcoma. The Examiner has rejected claims 9-11 under 35 U.S.C. § 112, first paragraph, for nonenablement (Answer 4). The Examiner finds that, although the Specification shows that cancer cells in culture spread and migrate less when cultured with Des A fibrin as compared to other agents, the Specification lacks working examples showing inhibition of a malignant tumor (id. at 5). The Examiner finds that “clinical correlations are generally lacking” between in vitro assays and effective treatments (id. at 6). The Examiner cites evidence1 to show that “cultured cells, over a period of time, lose phenotypic characteristics associated with their normal counterpart cell type” (id.), that some researchers believe that “‘Petri dish cancer’ is a poor representation of malignancy” (id.), and that “therapeutic cancer treatments, in general, are unpredictable” (id. at 7). The Examiner concludes that 1 The Examiner cites the following references: R. Ian Freshney, Culture of Animal Cells, A Manual of Basic Technique, Alan R. Liss, Inc., New York, pp. 3-4 (1983); Gerald B. Dermer, Another Anniversary for the War on Cancer, 12 BIO/TECHNOLOGY 320 (1994); and Gura, Systems for Identifying New Drugs Are Often Faulty, 278 SCIENCE 1041-1042 (1997). Appeal 2011-000919 Application 11/818,783 3 the instant application is claiming a method of administering compositions that prophetically inhibit[ ] the growth, invasion and metastasis of melanoma tumors, breast cancer tumors, and fibrosarcoma tumors in vivo without providing any in vivo data and the compositions of the claimed method are not structurally similar to compositions which have known ability to inhibit the growth, invasion, and metastasis of any tumors in vivo, hence the claimed invention is not enabled. (Id. at 8, emphasis omitted.) Appellants argue that the in vitro results provided in the Specification (Appeal Br. 7), combined with the disclosed instructions regarding how to use Des A fibrin to inhibit malignant tumors in a patient (id. at 8-9), enable those skilled in the art to practice the claimed method without undue experimentation (id. at 10). Appellants also argue that the evidence shows that, “[i]n the present case, the in vitro method correlates with an in vivo method” (id.). Appellants cite Oku,2 Caltagirone,3 and Fujii4 as evidence of a correlation between in vitro and in vivo results obtained with B16-BL6 melanoma cells (id. at 10-12), and cite Dehn5 and Wang6 as showing a 2 Tohru Oko et al., Antimetastatic and Antitumor Effect of a Recombinant Human Tissue Inhibitor of Metalloproteinases-2 in Murine Melanoma Models, 20 BIOL. PHARM. BULL. 843-849 (1997). 3 Sara Caltagirone et al., Flavonoids Apigenin and Quercetin Inhibit Melanoma Growth and Metastatic Potential, 87 INT. J. CANCER 595-600 (2000). 4 Hideki Fujii et al., Inhibition of Tumor Invasion and Metastasis by Peptidic Mimetics of Arg-Gly Asp (RGD) Derived from the Cell Recognition Site of Fibronectin, 8 ONCOLOGY RESEARCH 333-342 (1996). 5 Donna L. Dehn et al., Development of a New Isogenic Cell-Xenograft System for Evaluation of NAD(P)H:Quinone Oxidoreductase-Directed Antitumor Quinones: Evaluation of the Activity of RH1, 10 CLINICAL CANCER RESEARCH 3147-3155 (2004). Appeal 2011-000919 Application 11/818,783 4 similar correlation for breast cancer cells and HT-1080 fibrosarcoma cells, respectively (id. at 13-14). “[T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting a prima facie case of unpatentability.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). When the rejection is for nonenablement, the burden is to “set[ ] forth a reasonable explanation as to why [the Examiner] believes that the scope of protection provided by that claim is not adequately enabled by the description of the invention provided in the specification of the application.” In re Wright, 999 F.2d 1557, 1561- 62 (Fed. Cir. 1993). “After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument.” Oetiker, 977 F.2d at 1445. We conclude that the Examiner’s rejection is not supported by a preponderance of the evidence. The Examiner has provided evidence that cancer researchers recognize that anti-tumor activity in cell culture is no guarantee that a compound will ultimately provide a clinically useful drug. See, e.g., Gura 1041, left col. Nonetheless, “[u]sefulness in patent law, and in particular in the context of pharmaceutical inventions, necessarily includes the expectation of further research and development.” In re Brana, 51 F.3d 1560, 1568 (Fed. Cir. 1995) (Although the Brana court referred to 6 Jieyi Wang et al., Tumor Suppression by a Rationally Designed Reversible Inhibitor of Methionine Aminopeptidase-2, 63 CANCER RESEARCH 7861- 7869 (2003). Appeal 2011-000919 Application 11/818,783 5 usefulness, the rejection on appeal was based on nonenablement. See 51 F.3d at 1564.) Gura, in fact, discloses that testing in cultured cells is an art-accepted method of identifying promising anti-cancer drugs. See Gura 1042, left col. (“The limitations of animal models have spurred the NCI, among others, to test drug candidates in cultures of human cells.”). Thus, Gura provides evidence that the type and amount of experimentation required to advance a candidate drug from in vitro assays through the testing and approval process to a clinically useful drug is expected in the field of anti-cancer research. The Examiner’s conclusion of nonenablement is also undercut by the evidence cited in the Appeal Brief. Appellants cite three papers showing that the effects of a compound on B16-BL6 melanoma cells in an in vitro invasion and migration assay were indicative of in vivo results. See Oku 845, Caltagirone 598, and Fujii 339. Appellants also cite a paper showing that a tested compound inhibited proliferation of HT-1080 fibrosarcoma cells in vitro as well as in vivo. See Wang 7864 (Table 2) and 7865, right column. The B16-BL6 and HT-1080 cell lines are the same melanoma and fibrosarcoma cells lines used in the Specification’s examples (see Spec. 21: 10-21). Finally, Appellants cite a paper showing that a tested compound showed anticancer activity both in vitro and in vivo against a human breast adenocarcinoma cell line. See Dehn 3153, right col. (“The in vivo evaluation of RH1 validated the in vitro studies.”). Appellants argue that the cells used by Dehn are similar to those used in the examples of the Specification (Appeal Br. 13), which the Examiner does not dispute (see Answer 12-13). Appeal 2011-000919 Application 11/818,783 6 The Examiner does, however, discount the evidentiary value of Appellants’ papers on the basis that the anti-cancer effects of the compounds used, or similar compounds, “were well known prior to publication of the five articles” (Answer 13). The Examiner’s point is a valid one, in that a correlation between in vitro and in vivo results would be expected for a compound already known to have in vivo anti-cancer activity. However, the Examiner has not provided evidence or persuasive technical reasoning to support concluding that the Specification’s in vitro results obtained specifically with Des A fibrin would not have been expected to be predictive of in vivo results with the same compound. In summary, we conclude that the Examiner has not shown by a preponderance of the evidence that practicing the claimed method would require undue experimentation. We therefore reverse the rejection of claims 9-11 for nonenablement. REVERSED lp