NantOmics, LLC

Patent Trials and Appeals Board

Jan 7, 2022

2021000078 (P.T.A.B. Jan. 7, 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. 15/292,095 10/12/2016 Patrick Soon-Shiong 102402.0017US 7704 149345 7590 01/07/2022 Umberg Zipser, LLP 1920 Main Street, Suite 750 Irvine, CA 92614 EXAMINER CLOW, LORI A ART UNIT PAPER NUMBER 1631 NOTIFICATION DATE DELIVERY MODE 01/07/2022 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 PATRICK SOON-SHIONG, STEPHEN CHARLES BENZ, ANDREW NGUYEN, SHAHROOZ RABIZADEH, KAYVAN NIAZI, OLEKSANDR BUZKO, and JAY GARDNER NELSON ____________ Appeal 2021-000078 Application 15/292,095 Technology Center 1600 ____________ Before JOHN E. SCHNEIDER, DEBRA L. DENNETT, and RACHEL H. TOWNSEND, Administrative Patent Judges. DENNETT, Administrative Patent Judge. DECISION ON APPEAL1 STATEMENT OF THE CASE Pursuant to 35 U.S.C. § 134(a), Appellant2 appeals from the Examiner’s decision to reject claims 1-11 of Application 15/292,095, which 1 In our Decision, we refer to the Specification (“Spec.”) of Application No. 15/292,095 filed Oct. 12, 2016; the Final Office Action dated Jan. 23, 2020 (“Final Act.”); the Appeal Brief filed Apr. 15, 2020 (“Appeal Br.”); and the Examiner’s Answer dated June 12, 2020 (“Ans.”). Appellant did not file a Reply Brief. 2 “Appellant” refers to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real parties in interest as Patrick Soon-Shiong and NantOmics LLC. Appeal Br. 2. Appeal 2021-000078 Application 15/292,095 2 constitute all the claims pending in this application. We have jurisdiction under 35 U.S.C. § 6(b). For the reasons set forth below, we AFFIRM. The subject matter of the invention relates to genetically modified viruses as therapeutic modalities for treatment of cancer as it relates to viral delivery and expression of patient specific HLA-matched neoepitopes. Spec. ¶ 2. Claim 1, reproduced below from the Claims Appendix of the Appeal Brief with the disputed limitations italicized, represents the claimed subject matter: 1. A method of treating a tumor in a patient using immunotherapy that targets selectively patient- and tumor- specific neoepitopes, comprising: obtaining DNA sequence information encoding neoepitopes, wherein the DNA sequence information is obtained by comparing omics data from a sample of the tumor and matched normal tissue of the patient, wherein the neoepitopes are specific to both the patient and the tumor in the patient, wherein the neoepitopes are peptide sequences having a length of between 5 and 30 amino acids and include a mutation in the peptide sequences relative to an amino acid sequence in the matched normal tissue’s omics data; obtaining an HLA-type of the patient by comparing the omics data from the sample and a reference sequence, wherein the reference sequence includes a plurality of known and distinct HLA allele sequences; calculating, for the neoepitopes, respective binding affinities to the determined HLA-type of the patient to select a neoepitope that is a high-affinity binder to at least one MHC Class I sub-type or at least one MHC Class H sub-type of the HLA-type of the patient; Appeal 2021-000078 Application 15/292,095 3 generating at least four recombinant nucleic acids, each comprising a promoter operably coupled to first and second sequence elements; wherein the first sequence element comprises the nucleic acid sequence that encodes the neoepitope; and wherein the second sequence element comprises a nucleic acid sequence that encodes a signal peptide for the first sequence element, wherein the signal peptide directs the neoepitope toward presentation by the at least one MHC Class I sub-type or by at least one MHC Class II sub-type; and transducing a plurality of cells with the at least four recombinant nucleic acids. REFERENCES The Examiner relies on the following prior art in rejecting claims 1- 11 as obvious under 35 U.S.C. § 103(a): Name Reference Date Hacohen et al. (“Hacohen 2”) US 2011/0293637 A1 Dec. 2, 2011 Hacohen et al. (“Hacohen”) US 2016/0339090 A1 Nov. 24, 2016 Z. Iqbal et al., De novo assembly and genotyping of variants using colored de Bruijn graphs, 44 Nature Genetics 226-233 (2012) (“Iqbal”) F. Duan et al., Genomic and bioinformatics profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity, 211 J. Exp. Med. 2231-2248 (2014) (“Duan”) REJECTIONS The Examiner maintains the following rejections of claims under 35 U.S.C. § 103: (1) claims 1-5, 7, 8, 10, and 11 over Hacohen as evidenced by Hacohen 2; (2) claim 6 over Hacohen as evidenced by Hacohen 2, further in Appeal 2021-000078 Application 15/292,095 4 view of Iqbal; and (3) claim 9 over Hacohen as evidenced by Hacohen 2, further in view of Duan. Final Act. 3-9. DISCUSSION We review the appealed rejections for error based upon the issues identified by Appellant and in light of the arguments and evidence produced thereon. Ex parte Frye, 94 USPQ2d 1072, 1075 (BPAI 2010) (precedential), (cited with approval in In re Jung, 637 F.3d 1356, 1365 (Fed. Cir. 2011)) (“[I]t has long been the Board’s practice to require an applicant to identify the alleged error in the [E]xaminer’s rejections.”). After considering the evidence presented in this Appeal and each of Appellant’s arguments, we are not persuaded that Appellant identifies reversible error. Thus, we affirm the Examiner’s rejections for the reasons expressed in the Final Office Action and the Answer. We add the following primarily for emphasis. Rejection of claims 1-5, 7, 8, 10, and 11 as obvious over Hacohen as evidenced by Hacohen 2 Appellant argues for reversal of the rejection of this group of claims on the basis of limitations present in independent claim 1, the sole independent claim. Appeal Br. 5-6. Therefore, we limit our discussion to claim 1, which represents the claimed subject matter to this ground of rejection. 37 C.F.R. § 41.37(c)(1)(iv) (2017). The Examiner finds that Hacohen teaches each and every limitation of claim 1. Final Act. 3-5. Of relevance to this appeal, the Examiner finds Hacohen includes teachings of class I and II receptors that undergo conformational change in response to signals [0088]; recombinant vectors for DNA expression including DNA encoding the tumor specific neoantigenic peptides that are Appeal 2021-000078 Application 15/292,095 5 constructed of operative linkage to suitable transcriptional or translational regulatory elements generally comprised of promoters and/or enhancers, the coding sequence and appropriate transcription or translation initiation and termination sequences as detailed in [0128]; Hacohen teaches compositions comprising at least four different neoantigens [012]; [634 ], [635]. Id. at 5. Appellant first argues that Hacohen does not teach at least four neoepitopes as recited in claim 1, more specifically that “the claims require that the four neoepitopes have ‘a length between 5 and 30 amino acids’ and that each of the four neoepitopes be present in four different nucleic acid vectors.” Appeal Br. 5. Appellant contends that Hacohen does not teach that neoantigens are in four different recombinant nucleic acids, each having its own signal peptide. Id. Appellant next argues that Hacohen does not teach signal peptides as disclosed in the claims. Id. According to Appellant, the signal peptides recited in the claims are those that direct the neoepitope toward presentation by the at least one MHC Class I sub-type or by the at least one MHC Class II sub-type. Id. at 6. For the reasons well explained by the Examiner in the Answer, Appellant’s arguments are not persuasive. See Ans. 10-13. With respect to Appellant’s first argument, the Examiner points out that “Hacohen . . . describe[s] that the neoplasia vaccine comprises tumor- specific neoantigens that include two, three, four, or five or more neoantigenic peptides.” Ans. 11; Hacohen ¶ 13; see also id. ¶¶ 39, 43, 46. In addition, Hacohen teaches that multiple compositions may be administered at the same or different times. Ans. 11; Hacohen ¶¶ 142, 182, 199; see also id. ¶ 12 (“sub-compositions can be administered to different Appeal 2021-000078 Application 15/292,095 6 places on the subject or patient; for instance, a composition comprising 20 different neoantigens, can be administered in four (4) subcompositions, each containing 5 of the 20 different neoantigens”). Thus, Hacohen teaches treating neoplasia, including tumors, by administration of at least four different neoantigens, each of which has a different neoepitope. Hacohen, ¶¶ 5, 12, 105 (discussing determining mutated epitopes by sequencing). Hacohen teaches that the antigenic peptides include between 5 to 50, 15 to 35, or 15 to 75 amino acids. Id., ¶ 13. The claimed amino acid ranges read on Hacohen’s disclosure. The therapeutic agents of the vaccines that include neoantigenic peptides can be formulated as separate compositions that are given at the same time or at different times. Id., ¶¶ 142, 182, 199. Hacohen describes administering a complete vaccine consisting of four distinct pools of up to five synthetic peptides. Id., ¶¶ 633-34. Claim 1’s “at least four recombinant nucleic acids” read on Hacohen’s disclosure. Given the above, Appellant’s arguments that Hacohen does not teach the at least four neoepitopes as recited in claim 1 is unpersuasive. With respect to Appellant’s second argument, the Examiner points out that Hacohen teaches signaling peptides as secretory leader sequences that are operatively linked in an appropriate expression vector. Ans. 12 (citing Hacohen, ¶¶ 127-128 (“DNA for a signal peptide (secretory leader) is operatively linked to DNA for a polypeptide if it is expressed as a precursor which participates in the secretion of the polypeptide.”). Hacohen discloses a means of administering nucleic acids encoding the peptide of the invention using minigene constructs encoding multiple epitopes, including cytotoxic T cell (CTL) epitopes. Hacohen, ¶ 338. As the Examiner explains, Hacohen Appeal 2021-000078 Application 15/292,095 7 discusses administration of nucleic acids that encode neoepitopes of interest using gene constructs that include adjoining the neoepitopes to leader sequences (signal peptides) and other flanking sequences, including promoters to ensure expression in target cells. Ans. 12. The signaling sequence would be expected to be involved in directing the neoepitope to presentation, as the inherent function of signaling sequences is to provide for cell-specific direction. Id. Therefore, Appellant’s argument that Hacohen does not disclose the claimed signal peptide is unpersuasive. Moreover, as the Examiner also explains, claim 1 recites “generating at least four recombinant nucleic acids, each comprising a promoter operably coupled to first and second sequence elements.” Ans. 10; see also Appeal Br. 8 (Claims App.). Use of “comprising” in the claim permits elements in addition to those specified to be included in the composition of the claim. In re Crish, 393 F.3d 1253, 1257 (Fed. Cir. 2004) (“[I]t is well-established that ‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.’” (quoting Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501 (Fed.Cir.1997)). Here, elements in addition to a promoter and first and second sequence elements are permitted by the claim language. At least because Hacohen teaches that subcompositions each containing a subset of neoantigens can be administered, it teaches and/or suggests at least four recombinant nucleic acids each operably coupled to its own signal peptide. We sustain the rejection of claim 1 as obvious over Hacohen as evidenced by Hacohen 2. We sustain the rejection of dependent claims 2-5, 7, 8, 10, and 11 for the same reasons as discussed in relation to claim 1. Appeal 2021-000078 Application 15/292,095 8 Rejection of claim 6 as obvious over Hacohen as evidenced by Hacohen 2, further in view of Iqbal Appellant argues that claim 6 is patentable for reasons in addition to those argued for claim 1. Appeal Br. 6-7. Claim 6 depends from claim 1 and further requires “wherein the HLA-type of the patient is determined in silica using a de Bruijn graph.” Id. at 9 (Claims App.). The Examiner finds that Iqbal teaches a technique of genetic variant detections (HLA typing) using de Bruijn graphs, and it would have been obvious to one of ordinary skill in the art to have used varying techniques to determine the HLA-type of a patient. Final Act. 7-8. Hacohen contemplates multiple ways of typing HLA for neoepitope analysis. Id. at 8. Appellant responds that multiepitope treatment is surprisingly and unexpectedly efficient at inducing epitope spread and tumor regression. Appeal Br. 6. Appellant also argues that Hacohen does not teach the claimed signal peptide, and Iqbal does not cure this deficiency. Id. at 6-7. The signal peptide taught by Hacohen was discussed in relation to claim 1. Appellant’s arguments are unpersuasive of reversible error. We sustain the rejection of claim 6 over Hacohen as evidenced by Hacohen 2, in view of Iqbal. Rejection of claim 9 as obvious over Hacohen as evidenced by Hacohen 2, further in view of Duan Appellant argues that claim 9 is patentable for the same reasons as argued for claim 1, i.e., “Duan does not cure the deficiencies of Hacohen and Hacohen 2.” Appeal Br. 7. Claim 9 depends from claim 1 and further requires “further comprising a step of verifying, in a proxy cell, presentation of the neoepitope by the at least one MHC Class l sub-type or by at least one MHC Class II sub-type.” Id. at 9 (Claims App.). Appeal 2021-000078 Application 15/292,095 9 Appellant’s arguments, unsuccessful in overcoming the rejection of claim 1, are equally unsuccessful here. We sustain the rejection of claim 9 over Hacohen as evidenced by Hacohen 2, in view of Duan. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1-5, 7, 8, 10, 11 102 Hacohen, Hacohen 2 1-5, 7, 8, 10, 11 6 103 Hacohen, Hacohen 2, Iqbal 6 9 103 Hacohen, Hacohen 2, Duan 9 Overall Outcome 1-11 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). AFFIRMED