CURATORS OF THE UNIVERSITY OF MISSOURI

Patent Trials and Appeals BoardMar 26, 2021

2020004892 (P.T.A.B. Mar. 26, 2021)

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. 14/773,497 09/08/2015 Habib Zaghouani 88936-8004.US01 5634 113677 7590 03/26/2021 Perkins Coie LLP - CHI General PO Box 1247 Seattle, WA 98111-1247 EXAMINER EWOLDT, GERALD R ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 03/26/2021 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): patentprocurement@perkinscoie.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ________________ Ex parte HABIB ZAGHOUANI1 ________________ Appeal 2020-004892 Application 14/773,497 Technology Center 1600 ________________ Before ULRIKE W. JENKS, JOHN G. NEW, and RACHEL H. TOWNSEND, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 We use the term “Appellant” to refer to the “applicant” as defined in 37 C.F.R. § 1.142. Appellant identifies The Curators of The University of Missouri as the real party-in-interest. App. Br. 1. Appeal 2020-004892 Application 14/773,497 2 SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 15, 17, 18, 22–25, and 30–35 as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of C.J.M. Loomans et al., Endothelial Progenitor Cell Dysfunction: A Novel Concept in the Pathogenesis of Vascular Complications of Type 1 Diabetes, 53 DIABETES 195–99 (2004) (“Loomans”) and Zaghouani et al. (US 7,744,876 B2, June 29, 2010) (“Zaghouani”). We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. NATURE OF THE CLAIMED INVENTION Appellant’s claimed invention is directed to methods and compositions of treating or preventing diabetes mellitus by administering to a subject a composition comprising an amount of stem and/or progenitor cells and at least one antigen-specific therapy. Spec. Abstr. REPRESENTATIVE CLAIM Independent claim 15 is representative of the claims on appeal and recites: 15. A composition comprising an amount of purified autologous endothelial progenitor cells and an amount of at least one immunoglobulin-polypeptide chimera, wherein the immunoglobulin-peptide chimera expresses a disease-specific T- or B-cell epitope. App. Br. Claims App’x 2. Appeal 2020-004892 Application 14/773,497 3 ISSUES AND ANALYSES We decline to adopt the Examiner’s findings, reasoning, and conclusion that the claims on appeal are prima facie obvious over the combined cited prior art. We address the arguments raised by Appellant below. Issue Appellant argues that the Examiner erred by failing to consider all of the evidence and the full scope and content of the cited prior art. App. Br. 5.2 Analysis The Examiner finds that Loomans teaches autologous endothelial progenitor cell (“EPC”) transplantation for type 1 diabetes (“T1D”). Final Act. 2 (citing Loomans 198). However, the Examiner finds that Loomans does not teach a composition further comprising an immunoglobulin- polypeptide chimera (Ig-C) that expresses a disease-specific T cell epitope. Id. The Examiner finds that Zaghouani teaches a composition comprising an Ig-C, in which a T cell epitope is inserted into the D segment of a CDR3 loop. Final Act. 2 (citing Zaghouani cols. 9–10, ll. 48–65, col. 4 ll. 64–67). The Examiner finds that Zaghouani further teaches that the epitopes comprise SEQ ID NOS: 1–3, and that the compositions may be soluble or 2 With the exception of page 1, Appellant’s Brief lacks page numbering. We designate the page numbers in sequence from page 1. Appeal 2020-004892 Application 14/773,497 4 aggregated. Id. (citing Zaghouani col. 21, ll. 36–46, col. 11, ll. 12–14). The Examiner also finds that Zaghouani teaches that the composition is capable of preventing the activation of diabetogenic T-cells specific for the inserted peptide. Id. (citing Zaghouani col. 11, ll. 1–11). The Examiner concludes that it would have been prima facie obvious to a person of ordinary skill in the art to produce a composition comprising the Ig-C of Zaghouani in combination with the EPCs of Loomans for the treatment of type 1 diabetes. Final Act. 2. The Examiner reasons that a skilled artisan would have realized that the combined composition would provide an elegant combination therapy and superior results for the treatment of type 1 diabetes, including both the benefits of EPC treatment and the protection from diabetogenic T cells. Id. Appellant argues that, in the Second Non-Final Office Action filed on January 3, 2019, the Examiner relied on S. Kang et al., Endothelial Progenitor Cell Cotransplantation Enhances Islet Engraftment by Rapid Revascularization, 61 DIABETES 866–76 (2012) (“Kang”).3 App. Br. 5. Appellant points to the Response to that Non-Final Action, including the declaration of the inventor, Dr. Habib Zaghouani, filed March 27, 2019 (the “First Zaghouani Declaration”), which argued that Kang teaches away from Appellant’s claimed invention. Id. at 5–6. In response, Appellant asserts, 3 Appellant identifies the Kang reference as “U.S. 7,744,876.” See App. Br. 5–6. However that patent number is, in fact, Zaghouani, which still forms the basis of the rejection of the present appeal. We interpret this as an error on Appellant’s part, and we consider Kang as the reference identified in the Second Non-Final Action of January 3, 2019. See Non-Final Act. 2. Appeal 2020-004892 Application 14/773,497 5 the Examiner dropped the Kang reference from its rejection without comment or consideration and relies instead upon Loomans and Zaghouani. Id. at 6. Appellant notes that the Examiner, in the Third Non-Final Office Action, filed May 1, 2019, stated that “Applicant’s remarks and the 1.132 declaration have been rendered moot by the new rejection,” and were thus improperly not considered.4 Id. Appellant asserts that evidence of teaching away by the prior art is not moot: the Kang reference still forms part of the relevant scope and content of the prior art and that, together with the evidence presented in the First Zaghouani Declaration 1, must be considered by the Examiner. Id. We are not persuaded that the Examiner has established a prima facie case of obviousness over the combined teachings of the cited prior art. The test for obviousness “is what the combined teachings of the references would have suggested to those of ordinary skill in the art.” In re Keller, 642 F.2d 413, 425 (C.C.P.A. 1981). Loomans initially observes that T1D is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia, and hypothesizes that EPC function in T1D patients may be adversely affected by the disease. Loomans Abstr. Loomans teaches that when EPCs isolated from patients with T1D were cultured under normoglycemic conditions, angiogenic differences between EPCs derived from T1D patients and control EPCs persisted. Id. Loomans 4 Appellant mistakenly identifies this as occurring in the Second Non-Final Office Action of January 3, 2019. See App. Br. 6. Appeal 2020-004892 Application 14/773,497 6 teaches that these findings demonstrate that adverse metabolic stress factors in T1D may be associated with reduced EPC numbers and angiogenicity. Id. However, Loomans concludes by observing that: Finally, the notion that EPC dysfunction exists in certain patient categories, such as type 1 diabetes, may have implications for currently explored cell-based clinical strategies to enhance tissue perfusion in patients with ischemic coronary and peripheral artery disease. EPCs or MNCs isolated from these patients for autologous cell transplantation may retain their dysfunctional characteristics in vivo and as a consequence display a reduced capacity to augment therapeutic neovascularization. Therefore, it could be useful to set progenitor quality criteria and perform EPC function tests (such as assays for angiogenic growth factor secretion, adhesion, or migration) in order to obtain optimal cells for transplantation. Loomans 198 (emphases added; internal references omitted). In other words, Loomans suggests assaying for EPC angiogenic function when screening cells for transplantation in patients with ischemic coronary and peripheral artery disease, and not transplantation of EPCs into patients with T1D, as the Examiner finds. Indeed, Loomans suggests that EPCs from patients with T1D are inappropriate for transplantation, and should be screened out, due to their reduced vascular regenerative properties. This is the only suggestion of transplanting EPCs in Loomans. Zaghouani teaches a “composition comprising an immunoglobulin, or portion thereof, linked to a protein fragment or peptide wherein the immunoglobulin, or portion thereof, is capable of binding to an Fc receptor.” Zaghouani col. 3, ll. 43–47. Zaghouani teaches that its composition comprises an immunosuppressive factor for the down regulation of diabetogenic T-cells for endocytic presentation that exhibit superior Appeal 2020-004892 Application 14/773,497 7 performance for the treatment of T1D. Id. at col. 7, ll. 54–59. The purpose of the composition is thus to suppress the activity of the T-cells that are implicated in causing T1D. Id. There is therefore no nexus between the teachings of Loomans and Zaghouani such that a person of ordinary skill in the art would be motivated to combine the references with a reasonable expectation of success. Simply put, Loomans suggests screening out EPCs exhibiting deficient angiogenic function (such as those from patients with T1D) when transplanting the cells to patients with ischemic coronary and peripheral artery disease. Loomans neither teaches nor suggests transplanting EPCs to patients with T1D, as the Examiner finds. Zaghouani teaches administering its composition of an immunoglobulin, or portion thereof, linked to a protein fragment or peptide capable of binding to an Fc receptor, to downregulate diabetogenic T cells. We can therefore discern no motivation, nor any reasonable expectation of success, for a skilled artisan to combine the teachings of the references to arrive at the claimed composition. We consequently reverse the Examiner’s rejection of the claims. Because we find this conclusion dispositive of the appeal, we do not reach Appellant’s additional arguments. CONCLUSION The Examiner’s rejection of claims 15, 17, 18, 22–25, and 30–35 under 35 U.S.C. § 103(a) is reversed. REVERSED Appeal 2020-004892 Application 14/773,497 8 Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 15, 17, 18, 22–25, 30– 35 103(a) Loomans, Zaghouani 15, 17, 18, 22– 25, 30–35