DETAILED ACTION
Applicant’s response to the Election/Restriction Requirement received on 6/15/26 has been entered. Claims 1-20 are pending in the instant application.
Applicant’s election with traverse of Group I and the species of an immune competent cell as the carrier and BAP1 as the cancer driver neoepitope is acknowledged. While applicant indicates that the election has been made with traverse, the applicant does not actually provide any specific arguments traversing the grounds for restriction, or for either election of species requirement. As such, applicant’s traversal has not been found persuasive and the restriction requirement and both election of species requirements are deemed proper and made FINAL.
Claims 2, 5, 8-10, 17, and 19-20 are hereby withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 6/15/26. Claims 1, 3-4, 6-7, 11-16, and 18 are therefore currently under examination based on the elected species of an immune competent cell as the carrier and BAP1 as the cancer driver neoepitope.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . An action on the merits follows.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/25/25 is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the information disclosure statement has been considered by the examiner, and an initialed and signed copy of the 1449 is attached to this action.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-4, 6-7, and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent 2018/0153975 (June 7, 2018), hereafter referred to as Fritsch et al., with an effective filing date of 5/2/15, in view of Yankelevich et al. (2012) Pediatr. Blood Cancer, Vol. 59, 1198-1205.
Fritsch et al. teaches an extracellular ligand binding domains which recognize a tumor-specific neoepitope comprising a tumor-specific mutation which is useful for treating a tumor in a population of subjects, where the extracellular ligand binding domain is a therapeutic antibody developed against the tumor specific neoepitope (Fritsch et al., paragraphs 287, 716, 773). Fritsch et al. further teaches that the antibody is an Fv or scFv (Fritsch et al., paragraph 716). Fritsch et al. teaches that the tumor-specific neoepitope recognized by the antibody is capable of binding to an HLA molecule present in the subject to be treated with a Kd of less than 500 nM, or a Kd less than 150 nM (Fristch et al., paragraphs 16, 21, and 758). Fritsch et al. further teaches that the tumor-specific neoepitope comprises a tumor specific mutation such as a point mutation, which is a type of missense mutation, where the neoepitope is 15-35 amino acids, 8-11 amino acids or 9-10 amino acids in length (Fritsch et al., paragraphs 55-58). More specifically, Fritsch et al. teaches to obtain neoepitopes derived from point mutations of the BAP1 polypeptide associated with various specific cancers, specifically solid tumors such as kidney renal clear cell carcinoma (MIRC) and ovarian serous cystadenocarcinoma (Fritsch et al., paragraphs 119 and 131).
Fritsch et al. differs from the instant invention by not teaching to combine the antibody which binds to tumor-specific neoepitope comprising a tumor specific mutation with a carrier that is a CD8+ T cell. Yankelevich et al. supplements Fritsch et al. by teaching that while anti-tumor specific antibodies have shown efficacy in treating tumors, the clinical efficacy of naked anti-tumor antibodies may be limited by post-chemotherapy immunosuppression of effector cells mediating ADCC in the patient (Yankelevich et al., page 1198). Yankelvich et al. teaches the generation of a bispecific antibody comprising an anti-CD3 antibody and an anti-tumor antibody followed by coating the surface of cytotoxic T cells present in peripheral blood mononuclear cells, which include CD8+ T cells, with the bispecific antibody to generate “armed” T cells (Yankelevich et al., page 1198-1199). It is also noted that Yankelevich et al. also teaches an admixture of the anti-tumor antibody and PBMCs (Yankelevich et al., page 1199). In both cases, Yankelevich et al. teaches that the antibody T cell combinations are in media, which is a pharmaceutically acceptable carrier for injection or infusion (Yankelevich et al., page 1199). Yankelevich et al. demonstrates that the “armed” T cells coated with the bispecific ant-tumor antibody significantly enhanced tumor cell killing compared to the anti-tumor antibody alone, or PBMC mixed with control antibody (Yankelevich et al. page 1200, Figure 5). Yankelevich et al. also shows that while the mixture of the anti-tumor antibody and the T cells increased cytotoxicity compared to controls, the “armed” T cells exhibited higher cytotoxicity (Yankelevich et al., page 1200, Figure 5).
Therefore, in view of the enhanced tumor cell killing achieved using either a mixture of an anti-tumor antibody and T cells, including CD8+ T cells, or “armed” T cells coated with a bispecific antibody comprising an anti-tumor antibody and an anti-CD3 antibody compared to use of the anti-tumor antibody alone as taught by Yankelevich et al., it would have been prima facie obvious to the skilled artisan at the time of filing to either mix the therapeutic antibody specific for a missense tumor specific neoepitope such as BAP1 as taught by Fritsch et al. with CD8+ T cells, or to coat the T cells with a bispecific antibody generated by conjugating the antibody specific for a missense tumor specific neoepitope such as BAP1 as taught by Fritsch et al. with an anti-CD3 antibody in order to generate an immune therapeutic composition with increased tumor cell killing with a reasonable expectation of success.
Claims 1, 3-4, 6-7, and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Khalili et al. (2012) OncoImmunol., Vol. 1(8), 1281-1289, in view of Wang et al. (2014) Annu. Rev. Med., Vol. 65,33-48, Cohen et al. (2013) Antibodies, Vol. 2, 517-534, and Yankelevich et al. (2012) Pediatr. Blood Cancer, Vol. 59, 1198-1205.
Khalili et al. teaches the identification of HLA binding tumor antigen peptide epitopes derived from missense gene mutations present in a database of somatic mutations in cancer patients, including a specific 9mer HLA binding missense tumor antigen peptide epitope derived from BAP1 with the sequence FQFVSYVPI with a binding affinity for HLA-A02:01 of 21 nM or RTMEAFQFV with binding affinity of 15 nM, (Khalili et al., abstract, page 1274, and Tables 1 and 2). Khalili et al. further teaches that these patient specific missense tumor antigen peptides can serve as the targets for T-cell therapy and as ligands for TCR-like antibodies (Khalili et al., page 1288).
While Khalili et al. teaches that the identified HLA binding missense tumor antigen peptide epitopes are tumor specific, Khalili et al. does not specifically identify which cancers are associated with BAP1 mutations. However, such as known in the prior art. Wang et al. teaches that BAP1 is tumor specific antigen associated with various solid tumors such as mesothelioma, uveal melanoma, and renal clear cell carcinoma (Wang et al., Table 1, and Figure 3). As such, Wang et al. demonstrates that the gene encoding BAP1 cancer driver gene is expressed in a solid tumor.
Khalili et al., while teaching that missense tumor antigen peptides can serve as the targets for T-cell therapy and as ligands for TCR-like antibodies, does not provide the specifics for generating anti-tumor TCR-like antibodies, or teach to combine anti-tumor TCR-like antibodies with an immune competent cell such as CD8+ T cell. Cohen et al. supplements Khalili et al. by teaching that TCR-like antibodies are antibodies that recognize a target peptide bound to an MHC molecule (MHC/peptide complex) which can be generated by screening a hybridoma library or phage display Fab library using a specific MHC/peptide complex followed by affinity maturation strategies of identified and isolated antibodies to generate high-affinity TCR-like fab, scfvs, and full antibodies (Cohen et al., pages 520-521). Cohen et al. reports the successful generation of TCR-like antibodies against numerous tumor antigen specific peptide/MHC complexes (Cohen et al., page 521).
Yankelevich et al. supplements Khalili et al. and Cohen et al. by teaching that while anti-tumor specific antibodies have shown efficacy in treating tumors, the clinical efficacy of naked anti-tumor antibodies may be limited by post-chemotherapy immunosuppression of effector cells mediating ADCC in the patient (Yankelevich et al., page 1198). Yankelvich et al. teaches the generation of a bispecific antibody comprising an anti-CD3 antibody and an anti-tumor antibody followed by coating the surface of cytotoxic T cells present in peripheral blood mononuclear cells, which include CD8+ T cells, with the bispecific antibody to generate “armed” T cells (Yankelevich et al., page 1198-1199). It is also noted that Yankelevich et al. also teaches an admixture of the anti-tumor antibody and PBMCs (Yankelevich et al., page 1199). In both cases, Yankelevich et al. teaches that the antibody T cell combinations are in media, which is a pharmaceutically acceptable carrier for injection or infusion (Yankelevich et al., page 1199). Yankelevich et al. demonstrates that the “armed” T cells coated with the bispecific ant-tumor antibody significantly enhanced tumor cell killing compared to the anti-tumor antibody alone, or PBMC mixed with control antibody (Yankelevich et al. page 1200, Figure 5). Yankelevich et al. also shows that while the mixture of the anti-tumor antibody and the T cells increased cytotoxicity compared to controls, the “armed” T cells exhibited higher cytotoxicity (Yankelevich et al., page 1200, Figure 5).
Therefore, in view of motivation to make anti-tumor TCR-like antibodies specific for BAP1 missense neoepitopes taught by Khalili et al., the specific guidance for making anti-tumor TCR-like antibodies provided by Cohen et al., and the teachings and motivation for enhancing tumor cell killing achieved using either a mixture of an anti-tumor antibody and T cells, including CD8+ T cells, or “armed” T cells coated with a bispecific antibody comprising an anti-tumor antibody and an anti-CD3 antibody compared to use of the anti-tumor antibody alone as taught by Yankelevich et al., it would have been prima facie obvious to the skilled artisan at the time of filing to either mix a therapeutic anti-tumor TCR-like antibody specific for a missense tumor specific neoepitope such as BAP1 as taught by Fritsch et al. with CD8+ T cells, or to coat the T cells with a bispecific antibody generated by conjugating the TCR-like antibody specific for a missense tumor specific neoepitope such as BAP1 as taught by Fritsch et al. with an anti-CD3 antibody in order to generate an immune therapeutic composition with increased tumor cell killing with a reasonable expectation of success.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 18 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 18 recites, “[t]he immune therapeutic composition of claim 1, further comprising a non-immune therapeutic drug that targets a protein comprising the cancer driver neoepitope”. It is unclear what types of drugs qualify as “non-immune” therapeutic drug. The phrase “non-immune” is not defined in the specification. It is unclear whether “non-immune” refers to a drug which does not activate the immune system, or which is not targeted by the immune system, i.e. non-immunogenic, or whether the applicant intends to claim a class of drugs which do not include any components related to the immune system. It is noted that the specification does not clarify this issue as not actual description of any such drug is provided. As such, the metes and bounds of the claim cannot be determined.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 18 is 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 18 recites, “[t]he immune therapeutic composition of claim 1, further comprising a non-immune therapeutic drug that targets a protein comprising the cancer driver neoepitope”. The as filed specification does not provide sufficient written description for the genus of non-immune therapeutic drug that targets a BAP1 protein comprising the cancer driver neoepitope. The specification does not specifically define what constitutes a “non-immune” therapeutic drug that targets a protein comprising a cancer driver neoepitope. The specification identifies various cancer driver neoepitopes as epitopes derived from cancer specific proteins that comprise cancer specific and/or patient specific mutations, particularly missense mutations, including the elected species of BAP1. However, the specification, aside from including the phrase “a non-immune therapeutic drug that targets a protein comprising a cancer driver neoepitope”, provides no description of any “non-immune” drug that is capable of targeting any protein comprising a cancer driver neoepitope, let alone a “non-immune” drug which targets BAP1. The specification does not disclose any drug class by either name or mechanism which affects BAP1, nor does it disclose any species of any such drug. It is further noted that the specification does not provide any working examples which disclose or utilize any “non-immune” drug capable of targeting BAP1.
As set forth in MPEP 2163: To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.’" Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612. In regards to the written description requirement for genuses, MPEP 2163 states: The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). In the instant case, the specification provides none of the requisite description for the genus of “non-immune” therapeutic drugs that target a protein comprising a cancer driver neoepitope. As discussed above, the specification neither defines, identifies, or characterizes by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, any “non-immune” drug which targets the BAP1 protein or any other protein comprising a cancer driver neoepitope and thus fails to demonstrate that applicant was in possession of the claimed genus of “non-immune” drugs.
It is further noted that the art at the time of filing does not teach a class of drugs which are “non-immune” and which can therapeutically target the BAP1 protein. Murali et al., in a review of the state of research into BAP1 and its associated with tumors, teaches that the specific functions of BAP1, particularly in relation to tumorigenesis, are still being elucidated (Murali et al. (2013) Pathology, Vol. 45(2), 116-126, see pages 116-117). More to the point, Murali et al. does not teach any targeted therapies directed towards the BAP1 protein and further states that early data regarding the potential usefulness of histone deacetylase inhibitors in uveal melanoma cell lines suggests that BAP1 may not serve as a primary drug target for therapeutic agents (Murali et al., page 124). Thus, it is clear that at the time of filing drugs which therapeutically target BAP1 were neither well-developed nor readily available.
As such, since “non-immune” therapeutic drugs targeting the BAP1 protein were neither conventional, predictable, or readily available at the time of filing, the knowledge and level of skill in the art at the time of filing would not have permitted the ordinary artisan to immediately envisage the claimed “non-immune” therapeutic drugs capable of targeting the BAP1 protein from the generic description provided by the specification. Therefore, in view of these considerations, and the above analysis as a whole, the skilled artisan would not have viewed the teachings of the specification as sufficient to show that the applicant was in possession of the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-4, 6-7, and 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claims 1-17 of U.S. Patent No. 11,421,016, hereafter referred to as the ‘016 patent, OR claims 1-17 of U.S. Patent 11,725,186, hereafter referred to as the ‘186 patent, in view of U.S. Patent 2018/0153975 (June 7, 2018), hereafter referred to as Fritsch et al., with an effective filing date of 5/2/15.
Both of the ‘016 patent claim and the ‘186 patent claims independently recite a method which generates a genus of pharmaceutical agents that encompass the immune therapeutic compositions as claimed. The ‘016 patent claims OR the ‘186 patent claims recite a method which produces a synthetic antibody that binds to a mutant cancer specific cancer neoepitope identified from patient and cancer specific omics data, in which the final step involves “coupling the synthetic antibody to a therapeutic or diagnostic agent to so obtain the pharmaceutical agent” (‘016 patent claim 1, OR ‘186 patent claim 1). Dependent claims 14-15 in each patent recites that the therapeutic agent is a cell, or a T cell. Dependent claim 3 of each patent recites that the peptide is between 7 and 11 amino acids.
The ’016 patent claims OR the ‘186 patent claims differ from the instant claims by not teaching that the mutant cancer specific cancer neoepitope is derived from BAP1. Fritsch et al. supplements the ‘106 patent claims OR the ‘186 patent claims by teaching similar antibodies which recognize a tumor-specific neoepitope capable of binding to an HLA molecule present in a subject to be treated with a Kd of less than 500 nM, or a Kd less than 150 nM (Fristch et al., paragraphs 16, 21, and 758). Fritsch et al. further teaches that the tumor-specific neoepitope comprises a tumor specific mutation such as a point mutation, which is a type of missense mutation, where the neoepitope is 15-35 amino acids, 8-11 amino acids or 9-10 amino acids in length (Fritsch et al., paragraphs 55-58). More specifically, Fritsch et al. teaches to obtain neoepitopes derived from point mutations of the BAP1 polypeptide associated with various specific cancers, specifically solid tumors such as kidney renal clear cell carcinoma (MIRC) and ovarian serous cystadenocarcinoma (Fritsch et al., paragraphs 119 and 131). Thus, Fritsch et al. provides motivation to generate an antibody specific for mutated patient-specific cancer specific BAP1 neoepitope. As such, based on the teachings and motivation provided by Fritsch et al., it would have been obvious to practice the method of the ‘016 patent claims or the method of the ‘186 patent claims to generate a synthetic antibody coupled to a therapeutic agent which is a T cell where the antibody recognizes and bind to mutated patient-specific cancer specific BAP1 neoepitope with a reasonable expectation of success.
Claims 1, 3-4, 6-7, and 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent 10,533,157, hereafter referred to as the ‘157 patent, in view of U.S. Patent 2018/0153975 (June 7, 2018), hereafter referred to as Fritsch et al., with an effective filing date of 5/2/15.
The ‘157 patent claims are drawn to genetically engineered natural killer cell which expresses a high-affinity Fcgamma receptor coupled to antibody that has binding specificity against a cancer neoepitope- see claims 1, 3, and 4. While the ‘157 patent claims broadly encompasses the narrower instant claims, the ‘157 patent claims do not recite the particular features of the cancer neoepitope recited in the instant claims. Fritsch et al. supplements the ‘157 patent claims by teaching similar antibodies which recognize a tumor-specific neoepitope. Fritsch et al. teaches mutant tumor specific neoepitopes capable of binding to an HLA molecule present in a subject to be treated with a Kd of less than 500 nM, or a Kd less than 150 nM (Fristch et al., paragraphs 16, 21, and 758). Fritsch et al. further teaches that the tumor-specific neoepitope comprises a tumor specific mutation such as a point mutation, which is a type of missense mutation, where the neoepitope is 15-35 amino acids, 8-11 amino acids or 9-10 amino acids in length (Fritsch et al., paragraphs 55-58). More specifically, Fritsch et al. teaches to obtain neoepitopes derived from point mutations of the BAP1 polypeptide associated with various specific cancers, specifically solid tumors such as kidney renal clear cell carcinoma (MIRC) and ovarian serous cystadenocarcinoma (Fritsch et al., paragraphs 119 and 131). Thus, Fritsch et al. provides motivation to generate an antibody specific for a mutated patient-specific cancer specific BAP1 neoepitope. As such, based on the teachings and motivation provided by Fritsch et al., it would have been obvious to couple an antibody which recognizes a mutated patient-specific cancer specific BAP1 neoepitope as taught by Fritsch et al. to genetically modified NK cells according to the ‘157 patent claims with a reasonable expectation of success.
No claims are allowed.
Any inquiry concerning this communication from the examiner should be directed to Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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