TORAY INDUSTRIES, INC.Download PDFPatent Trials and Appeals BoardApr 26, 20212020006221 (P.T.A.B. Apr. 26, 2021) Copy Citation 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. 15/567,496 10/18/2017 Akira KURIHARA 1254-0599PUS1 6315 2292 7590 04/26/2021 BIRCH STEWART KOLASCH & BIRCH, LLP 8110 Gatehouse Road Suite 100 East Falls Church, VA 22042-1248 EXAMINER AEDER, SEAN E ART UNIT PAPER NUMBER 1642 NOTIFICATION DATE DELIVERY MODE 04/26/2021 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): mailroom@bskb.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte AKIRA KURIHARA, HYONGI CHON, TAKAYUKI FUJITA, and FUMIYOSHI OKANO Appeal 2020-006221 Application 15/567,496 Technology Center 1600 Before RICHARD M. LEBOVITZ, JOHN G. NEW, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims directed to a method for treating cancer that is not a brain cancer as being obvious and for lack of written description. Oral argument was heard April 8, 2021. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM IN PART. 1 We use the term “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as TORAY INDUSTRIES, INC. (Appeal Br. 3.) Appeal 2020-006221 Application 15/567,496 2 STATEMENT OF THE CASE According to Appellant’s Specification “various types of antibody medicines for treating cancer, targeting a specific antigen protein on cancer cells have been known in the world.” (Spec. ¶ 4.) “Most of the target antigen proteins provide certain levels of medicinal effects as a cancer- specific therapeutic agent and attract attention; however they express also on a plurality of normal cells.” (Id.) Thus, treatments with antibodies targeting such antigens are of concern because normal cells as well as cancer cells “are damaged as a result of administration of [such] antibodies.” (Id.) Appellant’s invention is directed to targeting a cancer antigen that is a transmembrane protein having a portion thereof expressed on the surface of cancer cells with an antibody against an extracellular region of that antigen. (Id. ¶¶ 8–9.) Claim 7, reproduced below, is illustrative of the claimed subject matter: 7. A method for treating cancer, said method comprising: administering to a subject a therapeutically effective amount of an antibody capable of binding to the extracellular region of CSPG5 protein expressed on the surface of cancer cells to treat the cancer, wherein the CSPG5 protein comprises the amino acid sequence of SEQ ID NO: 8, 4, 6, 10, or 12, wherein the antibody has a cytotoxic effect, wherein the cytotoxic effect comprises antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC), with the proviso that the cancer is not a brain tumor. (Appeal Br. 30.) Appeal 2020-006221 Application 15/567,496 3 REFERENCE The prior art relied upon by the Examiner is: Name Reference Date Cairns US 2008/0124331 A1 May 29, 2008 REJECTIONS The following grounds of rejection by the Examiner are before us on review: Claims 7, 10, 11, and 14–30 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. Claims 7, 10, 11 and 14–30 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Cairns. DISCUSSION I. Written Description The Examiner finds that “[t]he specification does not disclose, and the art does not teach, the genus of antibodies as broadly encompassed in the claims.” (Final Action 3.) The Examiner explains that “[t]he claimed method requires use of a product defined by functions (an antibody that both binds to a recited polypeptide and has a cytotoxic effect of ADCC and/or CDC).” (Id. at 5.) Moreover, the Examiner finds that “[t]he claims lack a correlation between the structure of an antibody that both binds to a recited polypeptide and has a cytotoxic effect of ADCC and/or CDC.” (Id.) And, the Examiner finds that “[w]ithout a correlation between structure and Appeal 2020-006221 Application 15/567,496 4 function, the claims define the antibody to be used in the claimed invention by function.” (Id.) The Examiner acknowledges that the Specification discloses 18 monoclonal antibodies that bind the CSPG5 extracellular domain (“ECD”) and that there are several polyclonal antibodies and a single monoclonal antibody known in the art that bind to the CSPG5 ECD but that “the specification only mentions one CSPG5-binding antibody that has a cytotoxic effect (‘monoclonal antibody #1’).” (Final Action 3.) The Examiner notes, with respect to “monoclonal antibody #1,” that the Specification does not indicate that it has been deposited and it does not identify the polypeptide sequence of it. (Id.) Thus, according to the Examiner, the Specification fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed. (Id. at 6.) We disagree with the Examiner that the claimed method is not adequately described. Although Appellant’s claim is not to an antibody or genus of antibodies itself (Appeal Br. 10), we agree with the Examiner that to comply with the written description requirement of 35 U.S.C. § 112, an adequate description of the method of using the claimed genus of antibodies to treat cancer requires an adequate written description of the genus of antibodies. “Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the Appeal 2020-006221 Application 15/567,496 5 compound sufficient to distinguish infringing compounds from non- infringing compounds, or infringing methods from non-infringing methods.” Univ. of Rochester v. GD Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004). Furthermore, we note that for claims that include a genus of antibodies that may be used in a method of treatment, when the genus is claimed using functional language to define a desired result, “the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349 (Fed. Cir. 2010) (en banc). A number of factors must be considered “for evaluating the adequacy of the disclosure [of generic claims], including ‘the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.’” Id. at 1351 (quoting Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005).) Appellant’s Specification teaches that CSPG5 protein molecules that include SEQ ID Nos: 8, 4, 6, 10, or 12 are expressed on the surface of a variety of cancer cells and that an antibody that binds to the ECD of such protein molecules damages the cancer cell expressing the protein. (Spec. ¶¶ 9, 17.) The Specification demonstrates that a polyclonal antibody as well as a monoclonal antibody to the ECD region of the foregoing protein shows cytotoxic activity. (Id. ¶ 13 (referring to Figure 4, Figure 5), ¶¶ 113–114 (Example 4), ¶¶ 121–122 (Example 7).) Additionally, Mr. Okano, one of the inventors of the claimed invention, attested in a declaration that the biological activity of the claimed Appeal 2020-006221 Application 15/567,496 6 invention is not predicated on binding at a specific location of the ECD of CSPG5, but rather the subsequent cytotoxic activity is driven by the antibody Fc domain once the antibody binds. (Okano I Declaration dated May 22, 2019, 2.) Dr. Shahir Rizk agreed. (Declaration Under 37 C.F.R. § 1.132 of Dr. Shahir Rizk dated November 8, 2019 (“Rizk Declaration”) ¶ 23.) Dr. Rizk2 explains that, in his view, the antibodies that bind specifically to the ECD region of the CSPG5 protein that includes SEQ ID Nos: 8, 4, 6, 10, or 12 are not required to neutralize activity of that protein or bind with a specific affinity or have specific functional behavior such as blocking binding to achieve the claimed ADCC and/or CDC function. (Id. ¶¶ 7, 23–24, 27.) As the Examiner noted, antibodies that bind the ECD of CSPG5 were known in the field prior to the application filing date. Moreover, Appellant described in its Specification 18 additional monoclonal antibodies that bind the ECD of CSPG5 comprising at least one of the claimed SEQ ID NOs. (See Okano I Declaration 2 (citing Spec. ¶ 118).) Furthermore, Mr. Okano testified that the generation and isolation of monoclonal antibodies through hybridoma technology was considered routine in the art at the time the claimed invention was made. (Okano I Declaration 2.) Dr. Rizk attested to the same. (Rizk Declaration ¶ 11.) Given the foregoing facts, we find Appellant’s disclosure of numerous antibodies that bind to the ECD of CSPG5 sufficient to show possession of 2 Dr. Rizk has a Ph.D. in Biochemistry from Duke University, holds faculty appointments at the Indiana University School of Medicine as an Adjunct Assistant Professor of Biochemistry and Molecular Biology, and Indiana University South Bend as an Assistant Professor of Biochemistry and has practical experience with antibodies. (Rizk Declaration ¶ 3.) Appeal 2020-006221 Application 15/567,496 7 the genus of antibodies embraced by the claim, i.e., that bind the ECD of the CSPG5 protein which comprises the amino acid sequence of SEQ ID NO: 8, 4, 6, 10, or 12, and also has the claimed ADCC and/or CDC function. Therefore, we do not affirm the Examiner’s rejection of claims 7, 10, 11, and 14–30 under 35 U.S.C. § 112, first paragraph for failing to comply with the written description requirement. II. Obviousness The Examiner finds that Cairns teaches a surface-expressed tumor- associated antigenic target polypeptide TAT165, that has SEQ ID NO: 126 which is nearly identical to SEQ ID NO: 4 of Appellant’s Specification. (Final Action 11; Ans. 20.) The Examiner notes that Cairns teaches “TAT165 is expressed in glioma and glioblastoma, which are tumors that arise in both brain and spine.” (Ans. 20.) The Examiner further finds that Cairns “claims antibodies that bind the extracellular domain of SEQ ID NO:126, which preferably exhibit ‘effector functions’ such as those that promote death of cancer cells (claims 2 and 24, [0712] and [0727]-[0728], in particular).” (Final Action 11.) Moreover, the Examiner finds that “Cairns teaches methods of preparing and obtaining TAT antibodies (Example 12, in particular[.])” (Ans. 23.) The Examiner also finds that Cairns teaches “modifying Fc regions of said antibodies in order to generate antibodies that induce an ADCC or CDC cytotoxic response ([0794] and [0932], in particular).” (Final Action 11.) And, the Examiner finds that Cairns teaches “methods of assessing ADCC activity of antibodies ([0728], in particular), [as well as] methods of assessing CDC activity of antibodies ([0731], in particular).” (Ans. 23.) Appeal 2020-006221 Application 15/567,496 8 In addition, the Examiner finds Cairns teaches treating cancer such as lymphoma, leukemia or breast cancer, by administering an antibody that binds SEQ ID NO:126. (Final Action 11 (citing Cairns ¶¶ 38, 732, 1088, and claim 25); Ans. 23.) The Examiner, however, recognizes that Cairns “does not demonstrate that an antibody that binds the extracellular domain of instant SEQ ID NO: 4 or SEQ ID NO: 8 and generates a cytotoxic response has actually been administered to a subject with cancer.” (Final Action 12.) The Examiner concludes that it would have been obvious to one of ordinary skill in the art to carry out the method “envisioned by Cairns” with a reasonable expectation of success. (Id.) We agree with the Examiner’s findings and conclusion of obviousness. There is no dispute that SEQ ID NO:126, which is a polypeptide derived from SEQ ID NO:48, is 99.7% identical to Appellant’s SEQ ID NO:4. Cairns teaches an isolated antibody that binds to an ECD of any one of SEQ ID NOS: 79–154. (Cairns ¶¶ 102, 105 (claim 16).) In addition, Cairns teaches methods of producing such antibodies. (See, e.g., id. ¶¶ 1130–1137.) And, Cairns claims an antibody that binds the ECD of SEQ ID NO:126. (Id. at claim 2.) Also, Cairns teaches that the anti-TAT antibodies can induce cytotoxicity via ADCC or CDC. (Cairns ¶ 932.) And Cairns teaches how to assay for such antibodies and to enhance such activity. (See, e.g., id. ¶¶ 728, 731, 794, 1143–1149.) Furthermore, Cairns teaches that TAT165 is upregulated in glioma and glioblastoma as compared to normal brain tissue. (Id. ¶¶ 1005, 1085.) And Cairns teaches treating cancer in mammals by Appeal 2020-006221 Application 15/567,496 9 administering antibodies to the disclosed TAT polypeptides. (Id. ¶¶ 38, 46, 217, 223, 236, 324, 325.) According to Appellant, “Cairns does not determine the protein topology or the cellular localization of any polypeptide translated from the nucleic acid of SEQ ID NO:48,” and Cairns only mentions the possibility of generating antibodies which are directed against numerous identified sequences that might be useful for treatment of any number of diseases. (Appeal Br. 22.) Consequently, Appellant argues Cairns’ disclosure is just “a speculative invitation to research generally.” (Id.) Furthermore, Appellant argues that Cairns only mentions that TAT165 is expressed in glioma, glioblastoma, and brain tumor but “does not disclose preparing an antibody therefor, let alone data that an antibody against TAT165 is actually effective in treating cancer, let alone cancer that is not a brain tumor.” (Appeal Br. 22.) Thus, Appellant concludes that Cairns does not support a prima facie case of obviousness. (Id.) We do not find Appellant’s arguments persuasive. Whether or not Cairns determines the topology of the protein of SEQ ID NO:126, Cairns does, as noted above, describe and claim an isolated antibody to the ECD of that protein. Furthermore, because Cairns discloses that the TAT165 protein is overexpressed in gliomas, glioblastomas, and brain tumors as compared to normal cells, one of ordinary skill in the art would have been motivated to raise antibodies to that protein. Furthermore, we agree with the Examiner that “[o]ne of skill in the art would [have reasonably] predict[ed] that an antibody with ADCC and/or CDC activity that targets just any cancer cells expressing SEQ ID NO: 126 on the cancer cell surface would therapeutically Appeal 2020-006221 Application 15/567,496 10 treat the cancer because the cytotoxic activity of said antibodies would therapeutically kill cancer cells targeted by the antibodies.” (Ans. 21.) Cairns teaches that TAT165 is upregulated in glioma and glioblastoma. It is well known that glioma is a cancer that starts in the glial cells of the brain or spinal cord. There is no evidence of record that the glial cells of the spinal cord are different than the glial cells of the brain, and they are generally recognized as representing a continuum of central nervous system tissue. See A.B. Butler et al., Comparative Vertebrate Neuroanatomy:Evolution and adaptation, 40–41 (1996). Therefore, we conclude that Cairns’ disclosure that SEQ ID NO: 126 of TAT165 is upregulated in glioma would have provided one of ordinary skill in the art with motivation to treat cancerous glial cells of the spinal cord by administering an antibody to the ECD region of the protein containing SEQ ID NO: 126 of TAT165. Because a glial tumor of the spinal cord is not evidently different from a glial tumor of the brain, we affirm the Examiner’s obviousness rejection of claims 7, 10, 11, 14, 15, 20, and 27–29, which only require that the method is applied to treat cancer that is not a brain tumor. However, we reverse the Examiner’s obviousness rejection as to claims 16–19, 21–26, and 30 because those claims are directed to certain specific cancers as follows: claims 16 and 18 recite “wherein the cancer is leukemia,” claims 17 and 19 recite “wherein the cancer is malignant lymphoma,” claims 21 and 30 recite “wherein the cancer is selected from the group consisting of breast cancer, lung cancer, adenocarcinoma, mastocytoma, squamous cell carcinoma, melanoma, and neuroblastoma,” claim 22 Appeal 2020-006221 Application 15/567,496 11 depends from claim 21 and claims 23–26 depend from claim 22. The Examiner has not provided sufficient evidence to establish a prima facie case of obviousness for treating any of the specifically recited cancers of claims 16–19, 21, and 30. Also, for the reasons just discussed, we conclude that the Examiner has not provided sufficient evidence to establish a prima facie case of obviousness of claim 22, which depends from claim 21, or claims 23–26, which depend from claim 22. DECISION SUMMARY Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 7, 10, 11, 14–30 112, first paragraph Written Description 7, 10, 11, 14–30 7, 10, 11, 14–30 103 Cairns 7, 10, 11, 14, 15, 20, 27–29 16–19, 21– 26, 30 Overall Outcome 7, 10, 11, 14, 15, 20, 27–29 16–19, 21– 26, 30 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED IN PART Copy with citationCopy as parenthetical citation