Ex Parte RennertDownload PDFPatent Trial and Appeal BoardJul 26, 201612548366 (P.T.A.B. Jul. 26, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/548,366 08/26/2009 26168 7590 07/28/2016 FISH & RICHARDSON (BIOGEN) P.O. BOX 1022 MINNEAPOLIS, MN 55440-1022 FIRST NAMED INVENTOR Paul D. Rennert 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 13751-0055002/Al84US 6978 0 EXAMINER HADDAD, MAHER M ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 07/28/2016 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address( es): P ATDOCTC@fr.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD ExpartePAULD. RENNERT Appeal2013-007648 Application 12/548,366 Technology Center 1600 Before ERIC B. GRIMES, CHRISTOPHER G. PAULRAJ, and TA WEN CHANG, Administrative Patent Judges. PAULRAJ, Administrative Patent Judge. DECISION ON APPEAL rri"1 • • "1 1 "1 ,..,, ,_ T T r"I ~ n "I ,..,, Al • "1 • "1 • • • "1 "1 ims 1s an appear unaer j) u.~.L. s U4 mvo1vmg crnnns to a memoa of treating graft-versus-host disease (GVHD). The Examiner rejected the claims for lack of enablement. We have jurisdiction under 3 5 U.S. C. § 6(b ). We reverse. STATEMENT OF THE CASE Background The invention at issue relates to a method of inhibiting GVHD by administering an effective amount of a KIM-1 antagonist (Spec. 3:29-30). 1 Appellant identifies the Real Party in Interest as Biogen Idec MA Inc. (see Appeal Br. 1). Appeal2013-007648 Application 12/548,366 The Specification notes that "KIM-1 (Kidney Injury Molecule-I) is a type l cell membrane glycoprotein" with an extracellular portion ( ectodomain) that "contains a six-cysteine immunoglobulin-like domain and a T/SP rich domain characteristic of mucin-like 0-glycosylated proteins" (Id. at 1:7-10). "KIM-1 is a member of a gene family known as the TIM ( T cell [mmunoglobulin and Mucin domain) family" (Id. at 1: 17-18). According to the Specification, "[i]t has been discovered that treatment of a mammal with a KIM-1 antagonist alters the interaction of T cells with other immune system cells," and furthermore "blockade of the binding of KIM-1 to its receptor reduces secretion of IFN-y by immune cells engaged in an antigen response in the mixed lymphocyte response (MLR) assay" (Id. at 2:2-9). The Specification further discloses that "[m]uch of the damage in graft-versus-host disease (GVHD) results directly from actions of donor T cells that become activated in the host (in response to host antigens), once grafted, e.g., in a bone marrow transplant," and "[b]y virtue of its ability to interfere with T cell activation, the present invention is useful for inhibiting GVHD" (Id. at 9: 18-21 ). The Claim Claims 42 and 43 are under appeal, and are reproduced in the Claims Appendix of the Appeal Brief. Independent claim 42 is representative and reads as follows: 42. A method of treating an immunological disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising an antagonist antibody or antigen-binding fragment thereof that binds to KIM-1, wherein the immunological disorder is graft- versus-host disease. 2 Appeal2013-007648 Application 12/548,366 (Br. 8). The Re} ection The Examiner has rejected claims 42 and 43 under 35 U.S.C. § 112, first paragraph as lacking enablement (Ans. 3-15). PRINCIPLES OF LAW In order for a medical treatment claim to satisfy the enablement requirement of Section 112, one of ordinary skill in the art must be able to effectively use the claimed treatment method in order to achieve the desired therapeutic result. See, e.g., In re '318 Patent Infringement Litig., 583 F.3d 1317, 1325-27 (Fed. Cir. 2009); Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1322-25 (Fed. Cir. 2005). When the claims are directed to a treatment using a particular drug, "[ w ]hat is necessary to satisfy the how-to- use requirement of§ 112 is the disclosure of some activity coupled with knowledge as to the use of this activity." In re Cortright, 165 F.3d 1353, 1360 (Fed. Cir. 1999) (citation omitted). The Examiner must set forth a reasonable basis to question the enablement of the claimed invention. In re Wright, 999 F.2d 1557, 1562 (Fed. Cir. 1993) ANALYSIS The rejection is maintained at least in part based upon the Examiner's assertion that "[t]he influence of a scientific theory should depend on its empirical and demonstrable aspects and not its underlying logic" (Ans. 5). The Examiner finds that "[t]he specification fails to provide empirical data to show that the claimed method would work in vivo to treat GVHD" (Id.). In response, Appellant argues that "[t]he inventor of the present application discovered that treatment of a mammal with a KIM-1 antagonist alters the 3 Appeal2013-007648 Application 12/548,366 interaction of T cells with other immune system cells and thereby strongly suppresses an IgG response to an antigen (see Ex. 5)" and "the working examples demonstrate that antagonism of KIM-1 reduces secretion of interferon-gamma by immune cells engaged in an antigen response in the mixed lymphocyte response assay" and "is therapeutically effective in an in vivo mouse model of inflammatory bowel disease" (Appeal Br. 2). On the record before us, we determine that the Examiner has not established a prima facie case for lack of enablement of the claimed invention. The Specification includes data showing that administration of an anti-KIM-I antagonist (i.e., KIM-1-Fc fusion protein) to mice blocks the production of IgG 1 isotype in response to a challenge with sheep red blood cells (SRBC), and nearly eliminates IgG production by memory B cells in response to a subsequent SRBC challenge (Spec. 35-37, Ex. 5; Figs. 3-7). Further, the Specification discloses an in vitro experiment using a Mixed Lymphocyte Reaction (MLR) assay, and demonstrates that treatment with an antagonist anti-KIM-I antibody and KIM-1-Ig fusion protein significantly reduced the level of IFNy secreted into the supernatant without affecting the level ofIL-2 or TNF secretion (Spec. 44--46, Ex. 11; Figs. 8-13). Thus, contrary to the Examiner's assertion, we find that the experimental data provided in the Specification supports the enablement of the claimed invention. We address the Examiner's other reasons for maintaining the rejection. First, we are unpersuaded by the Examiner's assertion that "while the specification teaches that KIM-1 is located in T cells, its ligand has not been identified at the time the invention was made" and "[t]he in vivo effect 4 Appeal2013-007648 Application 12/548,366 of any KIM-1 antagonist that inhibits any KIM-1/ligand( s ), as encompassed by the instant claims, is highly unpredictable ... and can range from increasing to decreasing T cell responses" (Ans. 5). The claimed method of treatment does not require the identification of the ligand ofKIM-1. Rather, claim 42 only requires "administering to the subject an effective amount of a composition comprising an antagonist antibody or antigen-binding fragment thereof that binds to KIM-1," and Appellant's Specification makes clear that the relevant activity to be suppressed or inhibited by the anti-KIM-I antagonist is the production or secretion of IFNy (Spec. 12, 11. 10-17 ("A KIM-1 antagonist can be used advantageously to reduce IFNy production in diseases where IFNy production is excessive or inappropriate.")). The Specification teaches the use of MLR assays to determine whether an anti- KIM-1 antagonist reduces the level of IFN y secreted into the supernatant (Spec 44--46 (Ex. 11) ). Second, we are also unpersuaded by the Examiner's assertion that "independent studies of the functions of KIM-1 in CD4 +cn25+ regulatory T cells provided conflicting results in two transplantation models" (Ans. 6). The Examiner relies upon references published after the filing date of the present application to support that assertion. However, "[i]n general, the examiner should not use post-filing date references to demonstrate that the patent is non-enabling," with the exception that "a later-dated reference provides evidence of what one skilled in the art would have known on or before the effective filing date of the patent application." See MPEP § 2164.05(a) (citing In re Hogan, 559 F.2d 595, 605 (CCPA 1977)). Here, the Examiner has not shown how the post-filing date references are relevant to 5 Appeal2013-007648 Application 12/548,366 establishing what the skilled artisan would have known on or before the priority date of the present application. Moreover, even if considered, the teachings of the cited references are not inconsistent with the claimed invention in which an anti-KIM-I antagonist is used to treat GVHD. For example, the Examiner notes that "Yuan (Proc Natl Acad Sci USA 2009, 30;106(26):10734-9, of record) teach that treatment with an antagonist anti-KIM- I mAb (RMTI-10 mAb) aids in the induction of transplant tolerance via blockage of pro inflammatory cytokine IL-17 production" (Ans. 6). The "induction of transplant tolerance" with an anti-KIM-I antagonist would appear to be consistent with using an anti-KIM-I antagonist to treat GVHD. The Examiner further notes that "Degauque et al (J. Clin. Invest. 2008; 118(2): 735-741, of record) teach that agonist KIM-I-specific mAbs (3B3 mAb) serve to prevent allogeneic transplant tolerance" (Ans. 6). The use of an agonist that promotes KIM-1 activity to "prevent allogenic transplant tolerance" would also appear to be consistent with using an anti- KIM-1 antagonist (that suppresses KIM-1 activity) to treat GVHD. The Examiner also notes that "Barlow (Clinical & Experimental Allergy, 41, 1012-1021, 2011, of record) "teach that anti-Timl (KIM-1) antibodies recognizing the same epitope (clones 3B3 and RMTl-10), but with different avidities for Tim 1, have been reported to elicit opposite functional effects (see page 1013, 1st col., ,-i l)" (Ans. 6). Barlow, however, does not address whether the anti-Timl (KIM-1) antibodies were antagonistic, and thus the relevance of Barlow's teaching to the claimed invention is unclear. By contrast, Appellants have introduced into the record 6 Appeal2013-007648 Application 12/548,366 Sonar et al. (2010) J. Clin. lnvest. 120(8):2767-81, which teaches that TIM- I antagonists can suppress Th2 cell proliferation and cytokine production, and thereby provide potential therapeutic benefit in immune-mediated disorders (Appeal Br. 6). Finally, we are unpersuaded by the Examiner's reliance upon Brok et al. (J. Immunol., 151(11):6451-6459, 1993, of record) ("Brok") for its teaching that "IFNy prevents graft-versus-host disease after allogeneic bone marrow transplantation in mice" (Ans. 6). Brok teaches "the mechanism of the effect of prolonged IFN-y injections is the suppression of endogenous IFN-y" (Brok, 6456). This is consistent with the mechanism taught in the Specification in which anti-KIM-I antibodies suppress endogenous IFN-y production in order to prevent GVHD. We therefore reverse the rejection of claims 42 and 43 under 35 U.S.C. § 112, first paragraph as lacking enablement. REVERSED 7 Copy with citationCopy as parenthetical citation