Ex Parte Schwager

Patent Trial and Appeal BoardAug 25, 2016

13140492 (P.T.A.B. Aug. 25, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 13/140,492 06/17/2011 110 7590 08/26/2016 DANN, DORFMAN, HERRELL & SKILLMAN 1601 MARKET STREET SUITE 2400 PHILADELPHIA, PA 19103-2307 Kathrin Schwager 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. 5026-P0479 l USOl/KDR 8091 EXAMINER HADDAD, MAHER M ART UNIT PAPER NUMBER 1644 MAILDATE DELIVERY MODE 08/26/2016 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 KATHRIN SCHWAGER 1 Appeal2014-002384 Application 13/140,492 Technology Center 1600 Before ERIC B. GRIMES, MELANIE L. McCOLLUM, and JACQUELINE T. HARLOW, Administrative Patent Judges. McCOLLUM, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. Â§ 134 involving claims to an endometriosis treatment method. The Examiner has rejected the claims as obvious. We have jurisdiction under 35 U.S.C. Â§ 6(b). We reverse. STATEMENT OF THE CASE According to the Specification, "[ e ]ndometriosis is a common medical condition in women, and is characterized by growth beyond or outside the uterus of tissue resembling endometrium, which normally lines the uterus" 1 Appellant identifies the real party in interest as Philogen S.P.A. (App. Br. 1). Appeal2014-002384 Application 13/140,492 (Spec. 6: 22-24 ). The Specification also states that "ED-A of fibronectin is indicated as a vascular marker of endometriosis" (id. at 9: 11-12). The Specification discloses "a specific binding member, e.g. an antibody molecule, that binds the ... ED-A[] isoform of fibronectin ... for use in a method of treatment of endometriosis" (id. at 9: 23-26). The Specification also discloses that "the specific binding member may be conjugated to a cytokine, such as IL-10" (id. at 17: 23-24). Claims 15, 17, 89, 92, and 94-96 are on appeal (App. Br. 3). We will focus on claims 15 and 94, which read as follows: 15. A method of treating endometriosis in a patient, the method comprising administering to a patient a therapeutically effective amount of a medicament comprising a specific binding member which binds the ED-A isoform of fibronectin operably linked to IL-10, wherein said specific binding member is an anti-EDA antibody comprising: (i) a VH domain comprising comprising [sic] a framework and a set of complementarity determining regions HCDRl, HCDR2 and HCDR3, HCDRl comprises amino acid sequence SEQ ID NO: 42, HCDR2 comprises amino acid sequence SEQ ID NO: 56, HCDR3 Comprises amino acid sequence SEQ ID NO: 60; and (ii) a VL domain comprising a set of complementarity determining regions LCDRl, LCDR2 and LCDR3 and a framework, wherein LCDRl has amino acid sequence SEQ ID NO: 102, LCDR2 has amino acid sequence SEQ ID NO: 114, and LCDR3 has amino acid sequence SEQ ID NO: 118. 94. The method of claim 15, wherein the binding member is a small immunoprotein (SIP). (Id. at 16: Claims Appendix.) 2 Appeal2014-002384 Application 13/140,492 Claims 15, 17, 89, 92, 95, and 96 stand rejected under 35 U.S.C. Â§ 103(a) as obvious over Neri2 in view Varma3 and Tagashira4 (Ans. 2). Claim 94 stands rejected under 35 U.S.C. Â§ 103(a) as obvious over Neri in view Varma, Tagashira, and Corvinus5 (Ans. 4). I The Examiner relies on Neri for teaching: a method of delivering a molecule to the neovasculature ( angiogenesis) of tumor metastases in a human or animal comprising administering to the human or animal an antibody which binds the ED-A isoform of fibronectin, including F8 antibody comprising the claimed CDR sequences, wherein the antibody is conjugated to detectable label, a radioisotope, and/or has biocidal or cytotoxic activity, wherein the VH/VL, domain framework is a human germline framework comprising the claimed sequences, wherein the antibody is scFv, diabody ... , wherein the biocidal or cytotoxic molecule is cytokine. (Ans. 2.) The Examiner also finds that Neri "teaches that both endometrium (the proliferative phase and some vessels of the ovaries) and metastatic neovasculature (angiogenesis) were strongly positively stained with the flag- tagged parent anti-ED-A antibody (anti-EDA)" and that Neri "evaluated different anti-ED-A antibodies and shows that F8 has the best dissociation 2 Neri et al., WO 2008/120101 A2, Oct. 9, 2008. 3 Rajesh Varma et al., Endometriosis and the Neoplastic Process, 127 REPRODUCTION 293-304 (2004). 4 Yukiko Tagashira et al., Interleukin-I 0 Attenuates TNF-a-induced Interleukin-6 Production in Endometriotic Stromal Cells, 91 FERTILITY & STERILITY 2185-92 (May 2009 (published online Aug. 8, 2008)). 5 Corvinus et al., US 2008/0248038 Al, Oct. 9, 2008. 3 Appeal2014-002384 Application 13/140,492 constant KD~3.l x10-9" (id.). In addition, the Examiner finds that Neri "differ[ s] from the claimed invention only in the recitation that the target delivery is endometriosis and F8-IL- l 0 linked antibody in claim 15" (id.). The Examiner relies on Varma for teaching "that recent studies of endometriosis suggest endometriosis can be viewed as a neoplastic process" (id.). In particular, the Examiner finds that Varma teaches "that like uterine and breast cancer, endometriosis behaves as an estrogen-dependent neoplasm" and "that significantly, both cancer and endometriosis share some of the mediators implicated in this 'inflammatory angiogenesis' model" (id. at 2-3). The Examiner also finds that Varma teaches: Pre-clinical studies have shown that endostatin effectively inhibits tumor growth and shrinks existing tumor blood vessels. Phase 1 clinical cancer trials of endostatin and angiostatin are ongoing, and preliminary results show minimal toxicities. Anti- angiogenic strategies for treating endometriosis exist, but are still at the experimental phase. Soluble truncated receptor (Flt-I) and an affinity-purified antibody to human VEGF-A, significantly inhibited the growth of endometrial explants in a mouse in vivo model of endometriosis by disrupting the vascular supply. Gene transfection (using a replication-deficient adenovirus vector AdAngiostatin) of the endogenous angiogenesis inhibitor angiostatin to the peritoneum of a mouse was successful in treating a mouse in vivo model of endometriosis. (Id. at 3.) In addition, the Examiner finds that Varma teaches "that Tissue invasion and metastasis are similar in endo[ m ]etriosis" and "provides examples of agents under investigation for endometriosis and cancer using the cancer hallmark model" (id.). The Examiner relies on Tagashira for teaching "that IL-10 attenuates TNF-a-induced IL-6 mRNA expression and protein production by activating 4 Appeal2014-002384 Application 13/140,492 STAT3 in endometriotic cells" and that "the results suggest that IL-10 plays a significant role in regulating the inflammatory environment in patients with endometriosis and may also provide a therapeutic modality for endometriosis" (id.). (Id.) The Examiner concludes: Those of skill in the art would have had reason to conjugate[] IL-10 taught by Tagashira et al to the anti-EDA antibody, F8, taught by [Neri] to target deliver the anti-EDA antibody conjugated to IL-10 to the endometriosis, because, EDA is marker of both neovascular structures of endometrium and metastatic neovasculature as taught by [Neri], and thus a therapeutic target with F8-IL 10 antibody-cytokine conjugate .... Alternatively, given that endometriosis and tumor metastases share some of the mediators implicated in angiogenesis taught by Varma et al, it would have been obvious to one skilled in the art at the time the invention was made to target endometriosis for imaging/diagnosing and treatment with the referenced anti-EDA antibody as taught by [Neri] conjugated to IL-10 taught by Tagashira et al because IL-10 plays a significant role in regulating the inflammatory environment in patients with endometriosis and may also provide a therapeutic modality for endometriosis. Those of skill in the art would have had reason to use the IL-10 of the Tagashira et al reference as a substitute for the endometriosis treatment taught [Neri] because, like the bioactive molecules taught in [Neri], IL-10 attenuates TNF-a-induced IL-6 mRNA expression and protein production and hence treat endometriosis. 5 Appeal2014-002384 Application 13/140,492 Analysis Neri relates to "a method of treating a tumour metastases in an individual comprising administering to the individual a therapeutically effective amount of a medicament comprising a binding member, e.g. an antibody molecule, which binds the ED-A isoform of fibronectin" (Neri 4: 22-26). In particular, Neri discloses: [A ]spects of the present invention employ a conjugate or fusion between a binding member of the invention and a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. For example, the biocidal or cytotoxic molecule may be interleukin-2 (IL-2), doxorubicin, interleukin-12 (IL-12), Interferon-y (IFN-y), Tumour Necrosis Factor a (TNFa) or tissue factor (preferably truncated). Such conjugates may be used therapeutically, e.g. for treatment of tumour metastases and/or tumour as referred to herein. Tagashira discloses: "IL-10 attenuates TNF-a-induced IL-6 mRNA expression and protein production by activating STAT3 in endometriotic cells. Collectively, the results suggest that IL-10 plays a significant role in regulating the inflammatory environment in patients with endometriosis and may also provide a therapeutic modality for endometriosis." (Tagashira 2191.) However, we agree with Appellant that the Examiner has not adequately explained why it would have been obvious to link IL-10 to Neri's ED-A antibody and use the resulting product to treat endometriosis. In particular, the Examiner relies on the disclosure in Neri stating: The most striking discrimination between liver structures and metastatic neovasculature was observed for the ED-A and ED-B 6 Appeal2014-002384 Application 13/140,492 domains of fibronectin. In both cases, a strong and specific staining of the metastatic blood vessels was observed, while normal liver and virtually all normal organs (exception made for the endometrium in the proliferative phase and some vessels of the ovaries) scored negative in this immunohistochemical analysis (Figure 3A).[6J Importantly, ED-A was also found to be strongly expressed in the neo-vasculature of human lung metastases and liver metastases (Figure 4). (Neri 57: 12-21 (emphasis added).) However, we agree with Appellant that the Examiner does not adequately explain why a teaching that the endometrium in the proliferative phase is not negative for anti-ED-A antibody staining suggests that such an antibody would be a good targeting moiety for endometriosis (App. Br. 5-6; see also Decl.7 iJ 7). The Examiner also relies on the teachings in Varma (Ans. 2-3, 8, 16- 17, 19, and 23-24). However, we agree with Appellant that the Examiner does not adequately explain how Varma suggests that Neri's antibody would be a good target for endometriosis (App. Br. 6-7). Conclusion The Examiner has not set forth a prima facie case that Neri, Varma, and Tagashira suggest the method of claim 15. We therefore reverse the 6 This teaching states that the endometrium in the proliferative phase is an exception to the general rule that normal organs are negative for anti-ED-A staining. However, we agree with Appellant that this does not demonstrate that endometrium in the proliferative phase, much less endometriosis, provides strongly positive staining (Reply Br. 2-3). 7 Declaration of Professor Petraglia Under 37 C.F .R. Â§ 1.132 dated April 22, 2013. 7 Appeal2014-002384 Application 13/140,492 obviousness rejection of claim 15 and of claims 17, 89, 92, 95, and 96, which depend from (or we are considering to depend from8) claim 15. II In rejecting claim 94, which depends from claim 15, the Examiner relies on the teachings of Neri, Varma, and Tagashira as discussed above (Ans. 4). The Examiner finds that the "combined reference teachings differ from the claimed invention only in the recitation that binding member is a small immunoprotein (SIP) in claim 94" (id.). The Examiner relies on Corvinus for teaching an Ll9-SIP (id.). The Examiner concludes that "[t]hose skilled in the art would have been motivated to use F8 antibody taught by [Neri] in the SIP technology format taught by [ Corvinus] in [a] method of treating endometriosis because SIP is the functional equivalent of F8 and scFv, i.e., would target the endometrium" (id.). Appellant argues that Corvinus "fails to compensate for the fundamental deficiencies noted above in the disclosures of [Neri], Varma and Tagashira" (App. Br. 14). We conclude that the Examiner has not set forth a prima facie case that Corvinus suggests that Neri's antibody would 8 An Amendment was filed on September 18, 2013, which changes the dependency of claim 89 from a cancelled claim to claim 15. It is not clear from the record whether this Amendment has been entered. However, given that the Examiner has made no comment on the inclusion of this change to claim 89 in Appellant's Claims Appendix (App. Br. 16), we are assuming, for the purpose of this appeal, that this change has been entered. 8 Appeal2014-002384 Application 13/140,492 be good for targeting a treatment to endometriosis. We therefore reverse the obviousness rejection of claim 94. REVERSED 9