DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority This application was filed June 17, 2022 , and is a 371 application of PCT/ US2020/066256 filed on Dec. 18, 2020 , which claims benefit to the provisional application 63/115,592 filed on Nov. 18, 2020 , and the provisional application 63/025,735 filed on May 15, 2020, and the provisional application 62/950 , 063 filed on Dec. 18, 2019. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc. , 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994) The disclosures of the prior-filed applications fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The cited priority provisional application, 62/950063 filed on Dec. 18, 2019, appears to not disclose a guide RNA targeting the cytokine inducible SH2 containing protein (CISH). Should applicant disagree, applicant is invited to point with particularity by application, page and line number where support for these concepts exist in prior applications, including the earliest non-provisional and Provisional applications. However, in the lack of any such indication where support exists for these concepts and prior applications, priority to such applications is denied, and the claims of the instant invention are accorded the filing date of the instant application, which is 15 May 2020 . Election/Restrictions Applicant’s election without traverse of Group II (claims 30-36) , drawn to a method of making the cell with a genomic edit of CISH and ADORA2A, the method comprising contacting the cell with one or more of: an RNA-guided nuclease and a guide RNA comprising a targeting domain sequence comprising the nucleotide sequence according any one of SEQ ID: 258-364, 1155, 1162, 29-257, 1157, 1161, 827-1143, 1159, and 1163 , and species election of I) cell type is pluripotent or human pluripotent stem cell; 2) pluripotent marker is Oct4; 3) endogenous is CD56 (NCAM); 4) Genomic edit: A characterized by an exogenous nucleic acid expression construct that comprises a nucleic acid sequence encoding: . FcγR III (CD16) or a variant of FcγRIII (CD16); B. genomic edit that results in a loss of function of ADORA2A; 5. Guide RNA and SEQ ID NO: A. CISH and SEQ ID NO: 1162; B. TGFβR11 and SEQ ID NO: 1161; C. ADORA2A and SEQ ID NO: 1159, without traverse in the reply filed on August 28, 2025, is acknowledged. Claim Status Applicant’s response filed on August 28, 2025, Claims 30, 32-35, and 83-95 are pending, and claims 1-29, 31 and 36-82 were cancelled , and claims 83-95 are new. Currently, claims 30, 32-35, and 83-95 are under consideration in this office action. Information Disclosure Statement The information disclosure statement (IDS) submitted on August 9, 2022; November 30, 2022, May 17, 2023, and September 17, 2024, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 30 , 85 , and 94 -95 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al., (US2015 / 0291966A1, published June 2019 , cited IDS 8/09/2022 ). The instant claims recite “ a guide RNA targeting Cytokine Inducible SH2 Containing Protein (CISH) , and a guide RNA targeting TGF beta receptor II (TGFβRII) ” . According to Technology Center 1600 procedure the examiner is instructed to interpret this type of claim language broadly: Claim language such as claim 30 and 8 5 encompasses nucleic acids that comprise any portion of CISH and TGFβRII . Regarding Claim s 30 , Zhang discloses a method of making a genetically engineered cell (see e.g. abstract, claim 1, Example 14) , the method comprising contacting a cell with an RNA-guided nuclease (see e.g. para. 32, fig. 57) and a guide RNA targeting Cytokine Inducible SH2 Containing Protein (CISH) (para. 339, 348, 351) ; an RNA-guided nuclease and a guide RNA targeting TGF beta receptor II (TGFβRII) (para. 344, 348, Table B) ; wherein the genetically engineered cell comprises a genetic edit that that results in loss of function of CISH and a genetic edit that results in loss of function of TGFβRII (see e.g. para. 363) . Regarding Claim 85 and 95 , Zhang discloses further comprising contacting the cell with an RNA guided nuclease and a guide RNA targeting adenosine A2a receptor (ADORA2A)(see e.g. para. 350-351); and wherein the genetically engineered cell further comprises a genetic edit that that results in loss of function of ADORA2A (see e.g. para. 363). Regarding Claim 94, Zhang discloses further comprising genetically modifying the cell to express an exogenous nucleic acid sequence encoding: a variant of FcγRIII (CD16) (see e.g. para. 351). Thus, the prior art of Zhang et al., anticipates the instant claims. Claims 30 and 8 4 rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Zhang et al., (WO2019126709A1, published June 2019 , cited IDS 8/9/2022 ) . The instant claims recite “ a guide RNA targeting Cytokine Inducible SH2 Containing Protein (CISH), and a guide RNA targeting TGF beta receptor II (TGFβRII)”. According to Technology Center 1600 procedure the examiner is instructed to interpret this type of claim language broadly: Claim language such as claim 30 and 8 4 encompasses nucleic acids that comprise any portion of CISH and TGFβRII. Regarding Claims 30, Zhang discloses a method of making a genetically engineered cell (see e.g. abstract, claim s 1 -24 and 80 , para. 469 ), the method comprising contacting a cell with an RNA-guided nuclease (see e.g. para. 7 0, 95-104, 176, 179 ) and a guide RNA targeting Cytokine Inducible SH2 Containing Protein (CISH)(para. 1113 and 1330 ); an RNA-guided nuclease and a guide RNA targeting TGF beta receptor II (TGFβRII)(para. 1273 ); wherein the genetically engineered cell comprises a genetic edit that that results in loss of function of CISH and a genetic edit that results in loss of function of TGFβRII (see e.g. para. 744, 999 and claim 1, 20 ). Regarding Claim 84 , Zhang discloses wherein the RNA-guided nuclease and the guide RNA targeting CISH are delivered as a ribonucleoprotein (RNP); and the RNA-guided nuclease and the guide RNA targeting TGFβRII are delivered as a ribonucleoprotein (RNP)(see e.g. claims 10-16, 22 and 40-44). Thus, the prior art of Zhang et al., anticipates the instant claims. Claims 30, 32, 84- 85, 87-88, and 9 0 -95 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Henley et al., ( WO 2018/081476 A2, published May 2018 ). The instant claims recite “ a guide RNA targeting Cytokine Inducible SH2 Containing Protein (CISH), and a guide RNA targeting TGF beta receptor II (TGFβRII)”. According to Technology Center 1600 procedure the examiner is instructed to interpret this type of claim language broadly: Claim language such as claim 30 encompasses nucleic acids that comprise any portion of CISH and TGFβRII. Regarding Claims 30 and 84 , Henley discloses a method of making a genetically engineered cell (see e.g. abstract, claims 1- 3 ), the method comprising contacting a cell with an RNA-guided nuclease (see e.g. para. 373-379 ) and a guide RNA targeting Cytokine Inducible SH2 Containing Protein (CISH ) and TGF beta receptor II (TGFβRII)( see e.g. para. 383-398 ); wherein the genetically engineered cell comprises a genetic edit that that results in loss of function (i.e. disruption) of CISH and TGFβRII (i.e. TGFBRII) (see e.g. para. 284 , 296 , 320, and 334) . Further, Henley discloses the RNA-guided nuclease and the guide RNA targeting CISH and TGFβRII are delivered as a ribonucleoprotein (RNP)(see e.g. para. 393) . Regarding Claims 3 2 , Henley discloses wherein the RNA-guided nuclease is a Cas12a (i.e. Cpf1) variant (see e.g. para. 370, 397, 401 and 463). Regarding Claims 85 , 87, and 95 , Henley discloses further comprising contacting the cell with an RNA guided nuclease and a guide RNA targeting adenosine A2a receptor (ADORA2A)(see e.g. para. 334); and wherein the genetically engineered cell further comprises a genetic edit that that results in loss of function (i.e. suppressed) of ADORA2A (see e.g. para. 335). Further, Henley discloses the RNA-guided nuclease and the guide RNA targeting ADORA2A are delivered as a ribonucleoprotein (RNP)(see e.g. para. 393). Regarding Claim 88 , Henley discloses wherein the cell is a human pluripotent stem cell or a human induced pluripotent stem cell (iPSC) (see e.g. para. 355, 469) . Regarding Claims 90-92, Henley discloses the iPSC further comprising differentiating the cell to an immune cell (see e.g. para. 350). Further, Henley discloses the immune cell is a lymphocyte or a natural killer cell (see e.g. para. 350). Regarding Claims 93, Henley discloses the immune cell does not express endogenous CD4 or CD8 (see e.g. para. 351, 467 , claim 20 ). Regarding Claims 94, Henley discloses further genetically modifying the cell to express an exogenous nucleic acid sequence encoding: ( i ) a chimeric antigen receptor (CAR)(see e.g. para. 318-319) . Regarding Claims 95, Henley discloses further comprising genetically modifying the cell to lose function of ADORA2A or PD-1 (fig. 6, para. 320-321 and 393). Thus, the prior art of Henley et al., anticipates the instant claims. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 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. Claim s 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over Henley et al., (WO 2018/081476 A2, published May 2018), as applied to claims 30, 32, 84-85, 87-88, and 90-95 above, and further in view of Behlke et al. (US2018/0187176 A1, application US 15/821 , 736 , published 2018 , cited IDS 8/9/2022 ). The teachings of Henley apply here as indicated above. Regarding Claims 33-35, Henley discloses wherein the RNA-guided nuclease is a Cas12a (i.e. Cpf1) variant (see e.g. para. 370, 397, 401 and 463). Henley is silent regarding the Cas12a variant that comprises the amino acid sequence of SEQ ID NO: 1148 , which comprises the amino acid substitutions M537R, F870L, and H800A. However, the prior art of Behlke discloses SEQ ID NO: 19 (Results Dec. 9, 2025, Issued_Patents_AA , file us-17-786-753-1148.align150.rai, Results No. 6) which is 100% identical to SEQ ID NO: 1148 (see results below) , which comprises the amino acid substitutions M537R, F870L, and H800A (see e.g. para. 20-21, 50-51, 71-73, and Example 1) . Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Henley and substitute the Cas12a variant with the amino acid sequence of SEQ ID NO: 1148, which comprises the amino acid substitutions M537R, F870L, and H800A, as taught by Behlke because it would have been obvious to substitute one known element for another to obtain predictable results. A person of ordinary skill in the art would have had predictable results with a reasonable expectation of success because both Henley and Behlke disclose Cas12a variants for the same purpose and it is prima facie obvious to substitute equivalents known for the same purpose (see MPEP 2144.06). Furthermore, substituting the claimed Cas12a (i.e. Cpf1) SEQ ID NO: 1148 as taught by Behlke in the methods of Henley would have led to predictable results with a reasonable expectation of success because Behlke teaches improved CRISPR/Cpf1 system for mammalian cell lines (see e.g. abstract, col.4). Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary. left 63500 0 389890 0 0 Claims 89 is rejected under 35 U.S.C. 103 as being unpatentable over Henley et al., (WO 2018/081476 A2, published May 2018), as applied to claims 30, 32, 84-85, 87-88, and 90-95 above, and further in view of Lundberg et al., (WO2017/064546A1, published 2017, cited IDS 8/9/2022). The teachings of Henley apply here as indicated above. Regarding Claims 8 9 , Henley discloses wherein the cell is a human pluripotent stem cell or a human induced pluripotent stem cell (iPSC)(see e.g. para. 355, 469). Henley is silent regarding the cell expressing one or more pluripotent marker such as Oct4, Sox2, or Nanog. However, the prior art of Lund b erg discloses methods for making engineered cells with Cas12a (i.e. Cpf1) (see e.g. claims 1-25). Further, Lundberg discloses methods for generat ing iPSCs where somatic cells are provided with reprogramming factors such as Oct4, Sox2, and Nanog (see e.g. para. 140). Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods as taught by Henley to incorporate the pluripotency marker of Oct4, Sox2, or Nanog as taught by Lundberg because Lundberg discloses that a person of ordinary skill in the art would know that these pluripotency markers are needed for somatic cells to become pluripotent stem cells (see e.g. para. 140). Further, A person of ordinary skill in the art would have had a reasonable expectation of success because both Henley and Lundberg disclose methods for engineering cells with Cas12a (i.e. Cpf1) as discussed above. Furthermore, an artisan of ordinary skill in the art of (i.e. genomic editing with Cas12a ) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007). Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary. Closest Prior Art Art made of record but not relied upon for art rejection: Art cannot be applied to the claims as written without reading limitations into the claims. Nonetheless, the following prior art references teaches many of the element/steps inferred by the disclosure as filed. Regarding c laim 83 , directed to a guide RNA targeting CISH comprises a targeting domain sequence comprising the nucleotide sequence according to any one of SEQ ID NO: 1162 : the prior art of Vender et a l ., ( cited as US6812339B1, Application No. US09/949,016, Results date: 9/15/2025, database: Issued_Patents_NA , file type “ . rng ” , R esult 5 , see below) has SEQ ID NO: 202512 that has a 100% Query Match and 85% Local similarity to SEQ ID NO: 1162. left 140667 Regarding claim 83, directed to the guide RNA targeting TGFβRII comprises a targeting domain sequence comprising the nucleotide sequence according to any one of SEQ ID NO: 1161 : the prior art of Le a mon et al., (App. US13/458,739 , Results date: 9/15/2025, Database: Published_Applications_NA_Main , file “. rnpbm ” Result 3, see below) has SEQ ID NO: 58776 that has a 100% Query Match and 71% Local similarity to SEQ ID NO: 1161. Regarding claim 86, directed to wherein the guide RNA targeting ADORA2A comprises a targeting domain comprising the nucleotide sequence according to any one of SEQ ID NO: 1159. The prior art of Drmanac , Radoje , App. No. 09-918-995 (Publication No. 20030073623A1, Results date: 9/15/2025, database: Pending_Patents_NA_Main , file type “. rn pm ”, Result 8 (see below) has SEQ ID NO: 31055 that has a 100% Query Match and 8 0 % Local similarity to SEQ ID NO: 11 59 . Conclusion Claims 83 and 86 are objected to for being dependent on a rejected claim. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JOSEPHINE GONZALES whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-1794 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-Th: 9AM - 5:00PM (EST) . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Doug Schultz can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-0763 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. FILLIN "Examiner Stamp" \* MERGEFORMAT JOSEPHINE GONZALES Examiner Art Unit 1631 /JOSEPHINE GONZALES/ Examiner, Art Unit 1631 /JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631