Ex Parte Zaghouani et alDownload PDFPatent Trial and Appeal BoardJun 26, 201311290070 (P.T.A.B. Jun. 26, 2013) Copy Citation 1 UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte HABIB ZAGHOUANI and RANDAL KEITH GREGG __________ Appeal 2012-003459 Application 11/290,070 Technology Center 1600 __________ Before ERIC GRIMES, LORA M. GREEN, and SHERIDAN K. SNEDDEN, Administrative Patent Judges. SNEDDEN, Administrative Patent Judge. DECISION ON APPEAL This appeal1 under 35 U.S.C. § 134 involves claims directed to a method of delaying the onset of type 1 diabetes in a pre-diabetic subject. The Examiner entered rejections under 35 U.S.C. §112, first paragraph, for lack of enablement, and under the judicially-created doctrine of obviousness-type double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We affirm the obviousness-type double patenting rejections. 1 Appellants identify the Real Party in Interest as The Curators of The University of Missouri (App. Br. 2). Appeal 2012-003459 Application 11/290,070 2 STATEMENT OF THE CASE Claims 1-4, 6, 7, 10-12 and 14-16 are on appeal. Claim 1, the only independent claim on appeal, is representative and reads as follows: 1. A method of delaying the onset of type 1 diabetes in a pre-diabetic subject, the method comprising administering to the pre-diabetic subject a pharmaceutically acceptable composition comprising at least one soluble immunoglobulin having a variable region and at least one peptide inserted within the variable region, wherein the at least one peptide is GAD2 represented by SEQ ID NO: 3, and wherein the composition is administered to the subject in one or more dosage administrations. The claims stand rejected as follows: I. Claims 1-4, 6, 7, 10-12 and 14-16 under 35 U.S.C. §112, first paragraph, for lack of enablement. The Examiner has also provisionally rejected claims 1-4, 6, 7, 10-12 and 14-16 under the judicially-created doctrine of obviousness-type double patenting as being unpatentable over claims 1-4, 6 and 7 of US Application No. 11/425,084 and over claims 1-5, 7, 13, 15-19 and 22-26 of US Application No. 10/681,788. Appellants have not traversed the merits of this rejection (App. Br. 21-22). We therefore summarily affirm each of these rejections. See MANUAL OF PATENT EXAMINING PROCEDURE § 1205.02 (“If a ground of rejection stated by the examiner is not addressed in the appellant’s brief, that ground of rejection will be summarily sustained by the Board.”). Appeal 2012-003459 Application 11/290,070 3 I. ENABLEMENT The Examiner rejected claims 1-4, 6, 7, 10-12, and 14-16 under 35 U.S.C. § 112, first paragraph, on the basis that “the specification does not enable the induction of immune tolerance in humans for the delaying of the onset of type 1 diabetes (T1D)” (Ans. 6). The Examiner finds that there is no question that immune tolerance has been established in numerous inbred small animal models. Unfortunately said results have not translated to larger outbred animal populations. (Ans. 12.) The Examiner supports the rejection with reliance on Marketletter,2 Pozzilli,3 and Skyler4 as evidence that treatments based on the induction of immune tolerance failed in human clinical trials despite providing successful results in inducing tolerance in small in-bred animal models. Marketletter discusses the failure of the drugs Myloral (for multiple sclerosis, MS) and Colloral (for rheumatoid arthritis, RA) in Phase III clinical trials (id. at 8). Pozzilli summarizes an unsuccessful human trial where oral insulin was tested for its ability to act as a tolerogen in patients with Type 1 Diabetes mellitus (id.). Skyler reported the failure of another human trial involving the administration of insulin for the prevention of Type 1 Diabetes (id.). 2 Autoimmune shares collapse on Colloral data in rheumatoid arthritis. Marketletter. MARKETLETTER PUBS (UK) 1999. 3 POZZILLI, P., et al. No effect of oral insulin on residual beta-cell function in recent-onset Type I diabetes (the IMDIAB VII). DIABETOL. 2000; 43:1000-1004. 4 SKYLER, J.S., et al. Effects of Oral Insulin in Relatives of Patients With Type 1 Diabetes. DIABETES CARE. 2005; 28:1068-1076. Appeal 2012-003459 Application 11/290,070 4 The Examiner relies on Dong,5 Goodnow,6 Kraus,7 and Bell8 to support the contention that practice of the instant claims would require undue experimentation because the field of immune tolerance is not predictable (id. at 8-9). The Examiner references Leslie,9 van der Worp,10 and von Herrath11 to support the contention that mice models are not predictive of the effectiveness of treatment strategies in human trials (id. at 12 and 15). Finally, the Examiner relies on Petersen12 and Bieg13 to support the contention that “the art shows that it would be improper to try to predict what would occur in all diabetic subjects based only on the single NOD mouse H-2 I-Ag7 model” (id. at 13). Petersen discloses “that neither GAD65 nor BSA autoimmunity is important for the development of diabetes in BB 5 DONG, V.M., et al. Transplantation tolerance: The concept and its applicability. PED. TRANSPLAN. 1999; 3:181-192. 6 GOODNOW, C.C., Pathways for self tolerance and the treatment of autoimmune diseases. THE LANCET. 2001; 357:2115-2121. 7 KRAUS, T.A. and MAYER, L., Oral tolerance and inflammatory bowel disease. CURR. OPIN. GASTROENTEROL. 2005; 21:692-696. 8 BELL, J.J., et al. In Trans T Cell Tolerance Diminishes Autoantibody Responses and Exacerbates Experimental Allergic Encephalomyelitis. J. IMMUNOL. 2008; 180:1508-1516. 9 LESLIE, M., Immunology Uncaged. SCIENCE. 2010; 327:1573. 10 VAN DER WORP, H.B., et al. Can Animal Models of Disease Reliably Inform Human Studies? PLOS MED. 2010;7(3) :1-8. 11 VON HERRATH, M. and NEPOM, G.T., Animal models of human type 1 diabetes. NATURE IMMUNOL. 2009; 10(2) :129-132. 12 PETERSEN, J.S., et al. Treatment with GAD65 or BSA Does Not Protect Against Diabetes in BB Rats. AUTOIMMUNITY. 1997; 25:129-138. 13 BIEG, S., et al., GAD65 and Insulin B Chain peptide (9-23) are not Primary Autoantigens in the Type 1 Diabetes Syndrome of the BB Rat. AUTOIMMUNITY. 1999; 31:15-24. Appeal 2012-003459 Application 11/290,070 5 rats, in contrast to the situation in NOD mice, and ... that extrapolation from only one animal model to autoimmune diabetes in general may not be appropriate” (Petersen, abstract). Bieg reports on a study that “provides evidence against the hypothesis that GAD65 ... [is a] primary diabetogenic autoantigen[] in BB rats because immunization with these antigens and GAD65-induced immune deviation did not alter the development of diabetes” (Bieg, abstract). Appellants contend that “[a]t most, the references properly relied on by the Examiner are only tangentially related to the presently claimed invention and/or simply do not cast any doubt, let alone any reasonable doubt, on the presently claimed invention” and that “[t]his is simply not enough to establish a prima facie case of lack of enablement” (App. Br. 16.) Appellants further provide “data demonstrating delay of onset of diabetes in pre-diabetic mice in the gold standard NOD mouse model,” citing the Zaghouani Declaration,14 and “complete experimental results in a published article,” citing Jain.15 The Zaghouani Declaration provides a summary of results of experiments conducted by co-inventor Habib Zaghouani “examining the impact of administration, initiated at the pre- diabetic stage, of soluble Ig-GAD2 to NOD mice over a period of 56 weeks” (Zaghouani Declaration 1, ¶ 6). In the study, 14 Declaration of Habib Zaghouani under 37 C.F.R. § 1.132, entered in the record in the Response filed on July 16, 2009 (Appellants Exhibit T). 15 JAIN, R., et al. Innocuous IFNy induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. JEM. 2008; 205(1): 207-218. Appeal 2012-003459 Application 11/290,070 6 NOD mice were assessed for blood glucose beginning at week 12 of age. Those mice that reached glucose levels of 160 - 250 mg/dl between week 14 to 25 received the following Ig-GAD2 regimen: 500 µg of soluble Ig-GAD2 i.p. daily for 5 days and then weekly injections thereafter for either 15 or 25 weeks. (id. 1-2, ¶ 7). “60% of mice undergoing the 15-week treatment regimen were protected against diabetes throughout the 25 week post-hyperglycemia monitoring period” (id. 2, ¶ 8). “When the regimen was extended to 25 weeks, 100% of the Ig-GAD2 treated animals were protected (Figure 1 A, right panel) and normoglycemia was restored in all mice (Figure 1 B, right panel). This status persisted throughout the duration of the study, which was terminated when the mice were 52 to 56 weeks of age.” (Id. at 2. ¶ 9; see also, Jain at 208 and Figure 2). After review of the evidence on this record, we find that Appellants have the better position. The reasons articulated by the Examiner pertain to the general field of immune tolerance and the difficulties faced by others in bringing therapies to market, such as a need for improved animal models. However, this is not sufficient basis for requiring proof of operability. In re Chilowsky, 229 F.2d 457, 462 (CCPA 1956). Further, clinical efficacy is not required to enable the claims on appeal. See CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1338 (Fed. Cir. 2003) (“Enablement does not require an inventor to meet lofty standards for success in the commercial marketplace.”); In re Brana, 51 F.3d 1560, 1569 (Fed. Cir. 1995) (“Usefulness in patent law, and in particular in the context of pharmaceutical inventions, necessarily includes the expectation of further research and development.”). Accordingly, we are not persuaded by the Examiner’s contention that the disclosure is speculative and that the recited various Appeal 2012-003459 Application 11/290,070 7 difficulties which might be encountered in practice of the invention would result in undue experimentation. Second, even if we assume for the sake of argument that the Examiner made out a prima facie case of nonenablement, we conclude that Appellants have provided sufficient evidence to overcome it. Appellants have provided evidence in the form of a Rule 132 declaration by co-inventor Habib Zaghouani and published data in Jain to support their position that a soluble Ig-GAD2 fusion protein, containing a peptide derived from GAD65 related to the recited GAD peptide represented as SEQ ID NO: 3 (cf. Specification 32, ¶ [0119] and Jain at 215, right col.), is operable in a mouse model for human Type 1 diabetes. In our opinion, Appellants have thus demonstrated the workability and utility of their invention and the principles on which it operates. SUMMARY We reverse the rejection of claims 1-4, 6, 7, 10-12 and 14-16 under 35 U.S.C. §112, first paragraph, for lack of enablement. We affirm the rejection of claims 1-4, 6, 7, 10-12 and 14-16 under the judicially-created doctrine of obviousness-type double patenting as being unpatentable over claims 1-4, 6 and 7 of US Application No. 11/425,084. We affirm the rejection of claims 1-4, 6, 7, 10-12 and 14-16 under the judicially-created doctrine of obviousness-type double patenting as being unpatentable over claims 1-5, 7, 13, 15-19 and 22-26 of US Application No. 10/681,788. Appeal 2012-003459 Application 11/290,070 8 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED lp Copy with citationCopy as parenthetical citation