NantOmics, LLC et al.

Patent Trials and Appeals Board

Jan 28, 2022

2021003896 (P.T.A.B. Jan. 28, 2022)

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. 16/073,105 07/26/2018 Andrew Nguyen 102402.0026US 4992 149345 7590 01/28/2022 Umberg Zipser, LLP 1920 Main Street, Suite 750 Irvine, CA 92614 EXAMINER CLOW, LORI A ART UNIT PAPER NUMBER 1631 NOTIFICATION DATE DELIVERY MODE 01/28/2022 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): ipsupport@umbergzipser.com patents@umbergzipser.com rdean@umbergzipser.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ANDREW NGUYEN, JOHN ZACHARY SANBORN, STEPHEN CHARLES BENZ, KAYVAN NIAZI, SHAHROOZ RABIZADEH, PATRICK SOON-SHIONG, and CHARLES JOSEPH VASKE Appeal 2021-003896 Application 16/073,105 Technology Center 1600 Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, 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 to methods of treating cancer patients with immune therapy as being anticipated. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM IN PART. 1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as Nant Holdings IP, LLC and NantOmics LLC. (Appeal Br. 2.) Appeal 2021-003896 Application 16/073,105 2 STATEMENT OF THE CASE Appellant’s Specification states: Cancer immunotherapies targeting certain antigens common to a specific cancer have led to remarkable responses in some patients. Unfortunately, many patients failed to respond to such immunotherapy despite apparent expression of the same antigen. (Spec. ¶ 5.) One reason posited for failure to respond is that “intracellular antigen processing and HLA variability among patients may have led to insufficient processing of the antigen and/or antigen display, leading to a therapeutically ineffective or lacking response.” (Id.) Appellant’s Specification notes that “[t]o increase the selection of targets for immune therapy, random mutations have more recently been considered since some random mutations in tumor cells may give rise to unique tumor specific antigens (neoepitopes).” (Id. ¶ 6.) “Unfortunately, current data appear to suggest that all or almost all cancer neoepitopes are unique to a patient and specific tumor and therefore fail to provide any specific indication as to which neoepitope may be useful for an immunotherapeutic agent that is therapeutically effective.” (Id.) Appellant’s Specification indicates that “[t]he inventive subject matter is directed to various composition[s] and methods for selecting neoepitopes for immune therapy targeting neoepitopes that are not only expressed and presented on a tumor cell, but that also confer a functional advantage to the tumor cell.” (Id. ¶ 9.) Claims 33, 46-56, and 69 are on appeal. Claims 33 and 69, reproduced below, are illustrative of the claimed subject matter: Appeal 2021-003896 Application 16/073,105 3 33. A method of treating a cancer in a patient using immune therapy, comprising: obtaining from a patient omics data from a tumor tissue and a matched normal tissue, and using the omics data to determine a plurality of expressed missense based patient- and tumor-specific neoepitopes; deriving from the expressed missense based patient- and tumor-specific neoepitopes a cancer driver neoepitope; and administering to the patient an immune therapeutic agent that comprises a synthetic antibody having binding specificity to the cancer driver neoepitope. 69. A method of treating a cancer in a patient using immune therapy, comprising: obtaining from a patient omics data from a tumor tissue and a matched normal tissue, and using the omics data to determine a plurality of expressed missense based patient- and tumor-specific neoepitopes; deriving from the expressed missense based patient- and tumor-specific neoepitopes a cancer driver neoepitope; and administering to the patient an immune therapeutic agent that comprises a recombinant virus comprising a nucleic acid encoding the cancer driver neoepitope. (Appeal Br. 19, 21.) Claim 33 differs from claim 69 in the recitation of the immune therapeutic agent that is administered. In claim 33, that agent comprises a synthetic antibody having binding specificity to the cancer driver neoepitope. In claim 69, on the other hand, the therapeutic agent comprises a recombinant virus comprising a nucleic acid encoding the cancer driver neoepitope. Appeal 2021-003896 Application 16/073,105 4 The prior art relied upon by the Examiner is: Name Reference Date Sanborn et al. US 2012/0059670 A1 Mar. 8, 2012 Hacohen et al. US 2016/0101170 A1 Apr. 14, 2016 Claus Lundegaard et al. Prediction of epitopes using neural network based methods, 374 J Immunol. Methods, 26-34 2011 Rubio-Perez et al. In Silico Prescription of Anticancer Drugs to Cohorts of 28 Tumor Types Reveals Targeting Opportunities, 27 Cancer Cell, 382-96 2015 The following grounds of rejection by the Examiner are before us on review: Claims 33, 46-55, and 69 under 35 U.S.C. § 102(a)(2) as being anticipated by Hacohen as evidenced by Lundegaard and Sanborn. Claim 56 under 35 U.S.C. § 103 as unpatentable over Hacohen and Rubio-Perez. DISCUSSION The Examiner found that Hacohen discloses a method for making a vaccine for a subject diagnosed with cancer that includes identifying mutations in the tumor and analyzing the mutations to identify a subset of mutations, including missense mutations, in the tumor and producing a personalized vaccine therefrom. (Ans. 4 (citing Hacohen Abstr.); Final Action 4 (citing Hacohen Abstr.).) In addition, the Examiner found that as Appeal 2021-003896 Application 16/073,105 5 part of the foregoing, the method includes sequencing to identify mutated neoantigens (including missense mutations) that are uniquely present in the tumor as compared to normal patient sample and where the neoantigens can include driver gene derived neoantigens. (Ans. 4 (citing Hacohen ¶¶ 104, 121); Final Action 4 (citing Hacohen ¶¶ 104, 121).) The Examiner additionally found that Hacohen discloses that the immune therapeutic to be administered to the subject can include a peptide containing the tumor specific mutation, where the mutation is a driver mutation, including a tumor specific driver mutation. (Ans. 4-5 (citing Hacohen ¶ 140); Final Action 4-5 (citing Hacohen ¶ 140).) The Examiner also found that Hacohen teaches that other therapeutic molecules may be administered along with the peptide, including checkpoint blockade antibodies, for example anti-CTLA or anti-PD-L1 antibodies. (Ans. 5 (citing Hacohen ¶¶ 275, 304-05); Final Action 5 (citing Hacohen ¶¶ 275, 304-05).) Addressing claim 69, the Examiner further found that in addition to the foregoing disclosures, Hacohen also discloses “administration of immune therapeutic agents that include recombinant virus [0154]; [0165]; [0166]; [0173]; and [0175], as example.” (Ans. 6; Final Action 6.) Independent claim 69 We address claim 69 first. Appellant argues in the Appeal Brief that the Examiner’s rejection of claim 69 is in error because the rejection was “cursory” and failed to delineate how the method was anticipated by Hacohen. (Appeal Br. 16.) We do not find this argument persuasive. The Examiner’s rejection, which we have set forth above, adequately explained the teachings of Hacohen as they relate to the limitations of claim 69. As the Examiner explained in the Answer: Appeal 2021-003896 Application 16/073,105 6 The first two steps of instant claim 69 are identical to the first two steps of claim 33. Thus, as set forth in the rejection pertaining to claim 33, Hacohen teaches said embodiments. The third claim step is directed to administering to the patient an immune therapeutic agent, which is also the same as the third step of claim 33. In independent claim 69, that “therapeutic agent” is a “recombinant virus comprising a nucleic acid encoding the cancer driver neoepitope”.The citations from Hacohen as present in the rejection most certainly disclose that a therapeutic agent may be administered to a patient that comprises a recombinant virus comprising a nucleic acid encoding the cancer driver neoepitope. See Hacohen at [0154] teaching expression vectors comprising isolated polynucleotides wherein neoantigenic peptides may be provided in the form of RNA or DNA molecules encoding the desired neoantigenic peptides. Further disclosed are viral expression systems, such as adenoviral expression vector systems. This is one of numerous examples as disclosed in Hacohen. (Ans. 14-15.) Appellant does not dispute any of the Examiner’s findings with respect to claim 69 and thus failed to marshal evidence or argument sufficient to rebut the Examiner’s finding of anticipation. We affirm the Examiner’s rejection of claim 69 as being anticipated by Hacohen for the reasons articulated by the Examiner. Independent claim 33 Regarding claim 33, Appellant argues, among other things, that “nothing in Hacohen teaches or even suggests administration of the presently claimed synthetic antibody that binds to a cancer driver neoepitope” (Appeal Br. 9) and the Examiner has not presented how the use “of known antibodies (e.g., anti-PDL1, anti-CTLA). . . anticipate[s] the presently claimed method that includes ‘administering to the patient a synthetic antibody having binding specificity to the cancer driver Appeal 2021-003896 Application 16/073,105 7 neoepitope’” (Appeal Br. 11). We agree with Appellant that anticipation by Hacohen has not been established by the Examiner. We do not address any issues of obviousness as to this claim because the Examiner did not reject the claim under that statutory ground. The PTAB serves as a board of review, not a de novo examination tribunal. See 35 U.S.C. 6(b). As Appellant notes, claim 33 requires that the synthetic antibody that is administered have “binding specificity to the cancer driver neoepitope.” According to the Examiner “checkpoint blockade antibodies target cancer driver neoepitopes (see Hacohen [0275]).” (Ans. 10.) The Examiner’s citation to Hacohen paragraph 275 does not support the Examiner’s finding of fact. The paragraph is as follows: The tumor specific neo-antigen peptides and pharmaceutical compositions described herein can also be administered in combination with another therapeutic molecule. The therapeutic molecule can be any compound used to mitigate neoplasia, or symptoms thereof. Examples of such compounds include, but are not limited to, chemotherapeutic agents, anti- angiogenesis agents, checkpoint blockade antibodies or other molecules that reduce immune-suppression, and the like. (Hacohen ¶ 275.) In short, paragraph 275 states that checkpoint blockade antibodies can mitigate neoplasia by reducing immune-suppression. The Examiner has not explained how such a statement establishes that checkpoint blockade antibodies necessarily have “binding specificity” to any particular cancer driver neoepitope. The Examiner further explains that the method taught by Hacohen is concerned with identifying neoepitopes to target for therapy, including any such neoepitopes in cancer driver genes. (Ans. 12-13 (citing Hacohen ¶ 140).) The Examiner states: Appeal 2021-003896 Application 16/073,105 8 Thus, for argument sake, if, for example, the identified neoepitope happens to exist in an oncogenic driver gene, as may be elucidated in a patient as a neoepitope in a gene of interest, one may administer an immune therapeutic agent, such as ip[i]limumab. Said antibody therapy would be expected to demonstrate a binding specificity to the driver neoepitope. (Id. at 13.) We understand ipilimumab to be a monoclonal antibody that targets CTLA-4. It is not apparent from the Examiner’s hypothetical that CTLA-4 is an oncogenic driver gene. The mere fact that ipilimumab would be expected to have some binding affinity to CTLA-4 and mitigate a neoplasia does not establish the antibody would have binding affinity to an oncogenic driver gene, much less the claim requirement for the antibody to have “binding specificity to the cancer driver neoepitope.” It is true, as the Examiner points out, that Appellant’s method claim recites the transition phrase “comprising,” which “indicates that the claim is open-ended and allows for additional steps,” Invitrogen Corp. v. Biocrest Mfg., L.P., 327 F.3d 1364, 1368 (Fed. Cir. 2003), and Hacohen provides for “‘combination’ therapies . . . wherein the administration includes not only tumor neoantigens (neoepitopes), but also other therapeutic agents [0038].” (Ans. 10.) However, the Examiner has not explained how the administration of checkpoint antibodies meets the claim requirement that the administered antibody has binding specificity to “the cancer driver neoepitope.” As such, we reverse the Examiner’s rejection of claim 33 as being anticipated by Hacohen. Claims 46-55 depend from claim 33, and thus, we also reverse the Examiner’s rejection of these claims as being anticipated by Hacohen. The Examiner’s additional reliance on Rubio-Perez in the rejection of claim 56 for obviousness was not for the purpose of establishing that Appeal 2021-003896 Application 16/073,105 9 checkpoint antibodies have binding specificity to cancer driver neoepitopes. Consequently, the Examiner’s rejection of this claim for obviousness is also reversed for the reasons discussed with respect to claim 33. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 33, 46-55, 69 102(a)(2) Hacohen 69 33, 46-55 56 103 Hacohen, Rubio- Perez 56 Overall Outcome 69 33, 46-56 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED IN PART