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. Applicant’s election of the invention of Group I in the reply filed on 6-24-25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Upon consideration of the claim amendments filed 6-24-25 it was determined that the restriction requirement mailed 4-1-25 no longer reflects the subject matter of claims 1-15; rather, claims 1-15 are now drawn to the following groups of invention: I. Claims 1- 8 , drawn to method of treating HvG disease in a patient, comprising administering to said patient a human Treg cell expressing a fusion protein which is a chimeric antigen receptor (CAR) which contains an scFv domain specific for human HLA-A*02 (CAR-A*02) and which Treg cell is genetically manipulated to express FOXP3 , classified in A61P 37/06 . II. Claims 9-13, drawn to in vitro method s for introducing suppressor activity specific for HLA-A*02 in Treg cells, by introducing a nucleic acid sequence encoding the fusion protein CAR-A*02 as defined in claim 1 into Treg cells, wherein said cells do not contain or express HLA-A*02, and expressing the fusion protein and further genetically manipulating said cells to express FOXP3 , classified in C12N 15/00. III. Claims 14-15 drawn to a nucleic acid sequence encoding a fusion protein which is a chimeric antigen receptor (CAR) which contains an scFv domain specific for human HLA-A*02 (CAR-A*02), P2A and a C-terminally fused FOXP3, in one unified fusion protein, and to viral vectors thereof, classified in C12N 15/62. Applicant’s representative was contacted on 8-21-25 and informed of the new groups of invention set forth above. On 8-28-25 applicant’s representative elected the invention of Group I without traverse. Claims 1-15 are pending. Claims 1-8 are under examination. Claim 9-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse on 8-28-25 as set forth in the attached interview summary. A certified copy of the ‘08.2 has been received in priority application 16310312. A certified copy of the ‘21.8 has been received in related (but not by priority) application 17442759 . 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. Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for: A method of treating HvG disease in a patient, comprising administering to said patient a human Treg cell which: (i) expresses a fusion protein which is a chimeric antigen receptor (CAR) which contains an scFv domain specific for human HLA-A*02 (CAR-A*02), (ii) is genetically manipulated to express FOXP3, and (iii) is HLA- A*02 negative, wherein the patient is HLA-A*02 negative and contains or is intended to contain a solid tissue transplant which is HLA-A*02 positive, does not reasonably provide enablement for practicing the breadth of the claimed invention, e.g., in the context of patients that are HLA-A*02 positive, or by making use of CAR-A*02 expressing Treg cells which are themselves HLA- A*02 positive. The Abstract states: “A fusion protein for use in the treatment of HvG disease in a patient having received a transplant, for use in suppressing the host's immune response directed against the transplant. The fusion protein is adapted for use in suppressing the immune rejection of a transplant which contains or expresses HLA-A *02 or SLA-01 *0401 in a recipient patient who is negative for HLA-A*02 or SLA-01*0401, i.e. the patient prior to transplantation does not express HLA-A*02 or SLA-01*0401. The fusion protein is a chimeric antigen receptor (CAR), which upon expression in regulatory T-cells (Treg) causes a specific suppressor activity of the regulatory T-cells in the presence of HLA-A *02 or SLA-01 *0401.” Similar teachings are also set forth at page 4, 1 st paragraph and at page 5-6, bridging paragraph. Consistent with the teachings of the specification, the skilled would not know how to practice the breadth of the method of treatment of claim 1 and dependent claims thereof insofar as the patient being treated is positive for HLA-A*02 in that the administered Treg cells comprising a fusion protein having specificity for HLA-A*02 (CAR-A*02) would no longer target, e.g., HLA-A*02+ transplanted cells, or an HLA-A*02+ tissue or organs. The specification does not enable any person skilled in the art to treat HvG disease in a patient where nearly all cells of said patient would be expected to be HLA-A*02 positive. For example, in the instance where HLA-A*02 positive or HLA-A*02 negative allogenic donor cells, tissue or organ are transplanted into an HLA-A*02 positive recipient, the ordinarily skilled artisan would not expect, and would not know how to induce or direct the administered CAR-A*02 expressing Treg cells to traffic to and exert an immune-suppressive effect on the allogenic but HLA-A*02 negative donor cells, tissue or organ cells in particular. Likewise, if the administered human Treg expressing a fusion protein which is a chimeric antigen receptor (CAR) which contains an scFv domain specific for human HLA-A*02 (CAR-A*02) were to be a Treg cell which itself expresses human HLA-A*02 then the administer Tregs could be self-suppressive, e.g., via expression of IL-10 (see page 20, 2 nd full paragraph; see also Chaudhry et al., Immunity. 2011 Apr 22;34(4):566-78, at Introduction and Discussion; O’Garra et al., Nat Rev Immunol. 2007 Jun;7(6):425-8, at Fig. 1 and at paragraph bridging 1 st and 2 nd text cols. on page 425, both cited herewith). In sum, in view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims, it would take undue trial and error experimentation to practice the claimed invention. 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. Claim(s) 4 is rejected under 35 U.S.C. 103 as being unpatentable over Boardman et al. ( American Journal of Transplantation 2017; 17: 931–943 ) in view of Allan et al. ( Mol Ther . 2008 Jan;16(1):194-202 ) (cited on an IDS ) and Fransson et al. ( J Neuroinflammation. 2012 May 30;9:112 ) (cited herewith) . In the final paragraph of their Introduction Boardman teaches “ We redirected human CD4+CD25+ CD127 lo FOXP3 + Tregs toward an MHC class I molecule (HLA-A2), an alloantigen that is ubiquitously expressed in an allograft, with the hypothesis that they would be more potent than polyclonal Tregs at protecting from graft rejection, upon adoptive transfer. ” (see page 932, right col., 1 st paragraph). At page 937, right col., last full paragraph – page 939, left col., 1 st full paragraph, Boardman describes a murine human skin xeno -graft transplant model system wherein human Tregs expressing an anti-HLA-A2 CAR were able to protect the human skin xenograft from co-administered human HLA-A2 - PBMC more effectively than human Tregs expressing a control ΔCAR or than polyclonal Tregs (see also at page 943, right col., 2 nd full paragraph and Figure S4). Boardman concludes in the paragraph bridging pages 938-39, “ Together, these results suggested that CAR expression facilitated preferential homing and retention of the Tregs in the HLA-A2+ allografts , ” and in the paragraph bridging pages 9 40 - 41 , “ Similarly, we have shown that CAR Tregs redirected toward HLA-A2 preferentially transmigrate through alloantigen-expressing endothelial cells and exhibit a favored homing and retention in allografts. ” The final paragraph of the Discussion of Boardman concludes, “ In conclusion, polyclonal Treg therapy is currently being investigated clinically by us and others as a means of limiting graft rejection. However, to avoid the risk of pan - immunosuppression and provide a tailored therapy, the successful generation and expansion of alloantigen - specific Tregs is required. We demonstrated that clinically applicable CAR technology may be used to generate donor antigen-specific Tregs that suppress alloimmune responses, providing a future direction for Treg therapy in the pursuit of transplant tolerance in solid organ transplantation. ” However, Boardman does not explicitly teach the methods of claims 4 and 5 drawn to “ A method of treating HvG disease in a patient, comprising administering to said patient a human Treg cell expressing a fusion protein which is a chimeric antigen receptor (CAR) which contains an scFv domain specific for human HLA-A*02 (CAR-A*02) and which Treg cell is genetically manipulated to express FOXP3 , wherein expression of FOXP3 with the fusion protein CAR-A*02 is by expression of a fusion of P2A with C-terminally fused FOXP3 in one unified fusion protein . ” Allan teaches genetic modification of CD4+ T-cells to constitutively express exogenous FoxP3 by lentiviral gene transfer (see Fig. 1A) ensures that the T-cells maintain FoxP3 expression , and in turn stable suppressive capacity over many weeks, which is advantageous for Treg immunotherapy (see page 199, col. bridging paragraph and page 199-200 bridging paragraph ). In the penultimate paragraph of their Introduction, Fransson teaches: “ Cultured Tregs may change their suppressive phenotype posttreatment, and this might be detrimental for patients. For example, Xu and coworkers have reported that Tregs in the absence of TGFβ can differentiate into Th17 cells, which are considered an integral cause of autoimmune manifestations in MS [15]. Since FoxP3 is fundamental for the differentiation and maintenance of Tregs, a stable expression of FoxP3 by genetic engineering may block Treg conversion into effector cells and thereby provide a safer option for patients . In a model of arthritis, FoxP3 was coexpressed with an antigen-specific TCR to achieve multiple stable targeting Tregs [16]. By co-expressing FoxP3 with a chimeric antigen receptor (CAR) [17] targeting myelin oligodendrocyte glycoprotein (MOG) in naive CD4+ T cells we can generate sufficient numbers of stable Tregs that localize to the CNS . The role of the CARαMOG receptor is to attach the Treg to the vicinity of MOG+ oligodendrocytes to prevent immune attacks against these cells. ” (see page 2, emphasis added). At page 2, right col, 2 nd full paragraph, Fransson further teaches production of their construct for the co-expression of their CARαMOG and FoxP3 : “ The CARαMOG-FoxP3 vector (Figure 1A) was constructed as follows: a single chain variable fragment (scFv) was cloned from hybridoma … The murine FoxP3 gene was inserted into the construct and separated from the CAR gene by a 2A peptide (described in reference [19]) …. The amino acid sequence for the CARαMOG receptor is given in Additional file 1: Figure S1 ” (see also Figs. 1(A) and S1). Given the teachings of Boardman in view of Allan and Fransson , it would have been obvious to one of ordinary skill in the art, and one of ordinary skill in the art would have been motivated to treat HvG in a patient, e.g., in an HLA-A2 - patient that is receiving a cell or organ transplant which is HLA-A*02 positive , by administering to said patient a human Treg cell expressing a CAR containing an scFv specific for HLA-A*02 as described by Boardman, but to further genetically modify said CAR containing Treg cell to co-express, via fusion to a “2A peptide,” the Fox3 protein (as taught by Fransson ), which maintains the suppressive state of the Treg cell consistent with the teachings of Allan (and further with Fransson ). One reason the skilled artisan would have been motivated to modify the αHLA-A2 binding CAR of Boardman set forth in Fig. 1A to allow for further co-expression of a 2A peptide joined to FoxP3 is because Figs 1A and S1 of Fransson provide an obvious template for achieving such a goal. In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made. 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 - 2 and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 13 and 26 of copending Application No. 17494610 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claim 4 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 13 and 26 of copending Application No. 17494610 (reference application) in view of Allan et al. (Mol Ther . 2008 Jan;16(1):194-202) and Fransson et al. (J Neuroinflammation. 2012 May 30;9:112) . This is a provisional nonstatutory double patenting rejection. The reference claims do not anticipate instant claim 4 because the reference claims fail to teach that expression of FOXP3 with the fusion protein CAR-A*02 is by expression of a fusion of P2A with C-terminally fused FOXP3 in one unified fusion protein. However, Allan teaches genetic modification of CD4+ T-cells to constitutively express exogenous FoxP3 by lentiviral gene transfer (see Fig. 1A) ensures that the T-cells maintain FoxP3 expression, and in turn stable suppressive capacity over many weeks, which is advantageous for Treg immunotherapy (see page 199, col. bridging paragraph and page 199-200 bridging paragraph). In the penultimate paragraph of their Introduction, Fransson teaches: “Cultured Tregs may change their suppressive phenotype posttreatment, and this might be detrimental for patients. For example, Xu and coworkers have reported that Tregs in the absence of TGFβ can differentiate into Th17 cells, which are considered an integral cause of autoimmune manifestations in MS [15]. Since FoxP3 is fundamental for the differentiation and maintenance of Tregs, a stable expression of FoxP3 by genetic engineering may block Treg conversion into effector cells and thereby provide a safer option for patients . In a model of arthritis, FoxP3 was coexpressed with an antigen-specific TCR to achieve multiple stable targeting Tregs [16]. By co-expressing FoxP3 with a chimeric antigen receptor (CAR) [17] targeting myelin oligodendrocyte glycoprotein (MOG) in naive CD4+ T cells we can generate sufficient numbers of stable Tregs that localize to the CNS . The role of the CARαMOG receptor is to attach the Treg to the vicinity of MOG+ oligodendrocytes to prevent immune attacks against these cells.” (see page 2, emphasis added). At page 2, right col, 2 nd full paragraph, Fransson further teaches production of their construct for the co-expression of their CARαMOG and FoxP3: “The CARαMOG-FoxP3 vector (Figure 1A) was constructed as follows: a single chain variable fragment (scFv) was cloned from hybridoma… The murine FoxP3 gene was inserted into the construct and separated from the CAR gene by a 2A peptide (described in reference [19])…. The amino acid sequence for the CARαMOG receptor is given in Additional file 1: Figure S1” (see also Figs. 1(A) and S1). Given the knowledge in the prior art reflected in the teachings of Allan and Fransson , it would have been obvious to one of ordinary skill in the art contemplat ing treating HvG disease in a patient by administering genetically modified Treg cells as recited in the method of reference claim 1 that not only should the Treg cell be genetically manipulated to express FOXP3 (see reference claim 1 2 ) , e.g., a FoxP3 that is expressed constitutively (see reference claim 13), but a yet further obvious step would be to additionally genetically modify said CAR containing Treg cell to co-express, via fusion to a “2A peptide,” the Fox3 protein (as taught by Fransson ), which maintains the suppressive state of the Treg cell consistent with the teachings of Allan (and further with Fransson ). One reason the skilled artisan would have been motivated to co-express the CAR and FoxP3 of the reference claims by fusing the former to the latter via a 2A peptide was because Figs 1A and S1 of Fransson provide an obvious template for achieving such a goal. In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ZACHARY S SKELDING whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-9033 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9-5 EST . 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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. /ZACHARY S SKELDING/ Primary Examiner, Art Unit 1644