CTNF 18/560,791 CTNF 81569 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION Status of Application/Election/Restrictions 08-25-01 AIA Applicant’s election without traverse of Group I (claims 1-2, 39-40, 48-49, 60, 65, 67, 72-73, 75-77 and 95), anti-HLA G antigen binding domain for species of binding molecule, IL15 for species of cytokine, TGFBR2 for species modified endogenous gene, glioblastoma for species of cancer, and MEM G/9 antibody for antibody clone in the reply filed on May 27, 2026 is acknowledged. Claims 3-38, 41-47, 50-59, 61-64, 66, 68-71, 74, 78-94 and 96-110 are canceled. Claims 1-2, 39-40, 48-49, 60, 65, 67, 72-73, 75-77 and 95 are pending in this application. Claim 39 is withdrawn without traverse (filed 05/27/2026) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 27, 2026. Claims 1-2, 40, 48-49, 60, 65, 67, 72-73, 75-77 and 95 are under examination with respect to anti-HLA-G antigen binding domain, IL-15, TGFRB2 and MEM G/9 antibody in this office action. Specification 07-29 AIA The disclosure is objected to because of the following informalities: The use of the term “Alex-Fluor647” (p. 87, [0303]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks . Appropriate correction is required. Claim Objections 07-29-01 AIA Claim s 1-2, 67 and 76 are objected to because of the following informalities: The recitations “HLA”, “KIR2DL4” “CD8” “CD3” “IL-15… or IL7” “NK” “NKG2A….CD38” recited in claims 1-2, 39, 67 and 76 are not unique or common abbreviations in the art. Applicants are required to spell out “HLA”, “KIR2DL4” “CD8” “CD3” “IL-15… or IL7” “NK” “NKG2A….CD38” recited in claims 1-2, 39, 67 and 76 at the first usage . Appropriate correction is required. Improper Markush Grouping 7. Claims 1-2, 40, 48-49, 60, 65, 67, 72-73, 75-77 and 95 on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch , 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi , 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use . A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117. The Markush grouping of a KIR2DL4 extracellular domain and an anti-HLA-G antigen-binding region of an anti-HLA-G specific antibody recited in claim 1, the Markush grouping of different genes recited in claim 76 or the Markush grouping of different polynucleotide sequences recited in claim 95 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The recited alternative species do not share a single structural similarity, as each species of KIR2DL4 extracellular domain and an anti-HLA-G antigen-binding region, each species of genes recited in claim 76 or each species of polynucleotide sequences of SEQ ID NOs: recited in claim 95 has a different chemical structure because it comprises different amino acid sequences or different nucleic acid sequences. Thus, the KIR2DL4 extracellular domain and the anti-HLA-G antigen-binding region of an anti- HLA-G antibody recited in claim 1 or the different genes recited in claim 76 and the different polynucleotide sequences recited in claim 95 do not share a single structural similarity or biological activity. See MPEP § 706.03(y). To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. Claim Rejections - 35 USC § 112 07-30-02 AIA 8. 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. 07-34-01 AIA Claim s 75-76 are 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 pre-AIA the applicant regards as the invention. Claims 75-76 are indefinite because the term “modified” in claim 75 is unclear which renders the claim indefinite. The term “modified” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what modification on the recited one or more endogenous genes in the immune cells and what effects on endogenous genes and immune cells. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “modification” on the endogenous genes and what is encompassed within the definition of “one or more endogenous genes in the immune cells has been modified”. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as “one or more endogenous genes in the immune cells has been modified” recited in the claim. Thus, the claim is indefinite. Claim 76 is indefinite as depending from an indefinite claim. Claim Rejections - 35 USC § 112 07-30-01 AIA 9. 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. 07-31-01 AIA Claim s 1-2, 40, 48-49, 60, 65, 67, 72-73, 75-77 and 95 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. Claims 1-2, 40, 48-49, 60, 65, 67, 72-73, 75-77 and 95 are drawn to A polynucleotide that encodes an anti-HLA-G chimeric antigen receptor (CAR), the CAR comprising (a) a KIR2DL4 extracellular domain or an anti-HLA-G antigen binding region of an HLA-G specific antibody, (b) a transmembrane domain, and (c) an intracellular domain that is not a KIR2DL4 intracellular domain. The claims encompass a genus of polynucleotide that encodes an anti-HLA-G CAR, comprising (a) a KIR2DL4 extracellular domain or an anti-HLA-G antigen binding region of an HLA-G specific antibody (elected), (b) a transmembrane domain, and (c) an intracellular domain that is not a KIR2DL4 intracellular domain. The claims also encompass a genus of an anti-HLA-G antigen binding region, a genus of anti-HLA-G specific antibody, a genus of transmembrane domain, and a genus of intracellular domain that is not a KIR2DL4 intracellular domain. Applicant has not disclosed sufficient species for the broad genus of polynucleotide encoding an anti-HLA-G CAR, the broad genus of anti-HLA-G CAR, the broad genus of anti-HLA-G antigen binding region, the broad genus of anti-HLA-G antibody, the broad genus of transmembrane domain, the broad genus of intracellular domain that is not a KIR2DL4 intracellular domain. The specification only describes an anti-HLA-G CAR comprising a CD8 signal peptide, a KIR2DL4 EC, a CD28 TMD, a CD3 zeta ICD, and IL-15; an anti-HLA-G CAR comprising a CD8 signal peptide, a KIR2DL4 EC, a CD8 TMD, a CD3 zeta ICD, a CD28 costimulatory domain and IL-15; an anti-HLA-G CAR comprising inducible caspase 9, a CAR comprising MEM-G/11 antibody (from the N terminal to the C terminal: VH-VL), a CD28 Hinge, a CD28 Costimulatory domain, CD3 zeta and IL-15; an anti-HLA-G CAR comprising inducible caspase 9, a CAR comprising MEM-G/11 antibody (from the N terminal to the C terminal: VH-VL), a CD28 Hinge, a DAP10 Costimulatory domain, CD3 zeta and IL-15; an anti-HLA-G CAR comprising inducible caspase 9, a CAR comprising 87G antibody (from the N terminal to the C terminal: VH-VL), a CD28 Hinge, a CD28 Costimulatory domain and CD3 zeta and IL-15; an anti-HLA-G CAR comprising inducible caspase 9, a CAR comprising MEM-G/11 antibody (from the N terminal to the C terminal: VH-VL), a CD28 Hinge, a DAP10 Costimulatory domain and CD3 zeta and IL-15 and their corresponding DNA and amino acid sequences (see below and para. [0166]-[0181]). CD8SP- CD8SP- iC9 iC9 iC9- iC9- KIR2DL4EC- coKIR2L4EC- MEM MEM 87G 87G CD28TMD- CD8TMD- VHVL- VHVL- VHVL- VHVL CD3zeta- 28Z 28Hing- 28Hinge- 28Hinge- 28Hing- IL15 15 CD28- DAP10- CD28- DAP10- CD3z CD3Z CD3Z- CD3Z- __________________________________________ IL15 IL15 IL15 IL15 DNA SEQ ID NO: 1 3 74 76 78 80 Amino acid SEQ ID NO: 2 4 75 77 79 81 The specification teaches that co-culturing the HLA-G CAR NK cells transfected with HLA-G CAR construct MG1 or MG22 with OCI-AML3 cells or GSC20 spheroid cells at 1:1 or 4:1 or 2:1 showed reduction in mean fluorescence intensity of the OCI-AML3 cells or GSC20 cells over the time and secretion of TNF- a compared to non-transfected NK cells (see [0303], Figures 5-9). However, the specification provides no structural and functional relationship between the HLA-G CAR construct MG1 or MG22 shown in Examples and figures 5-9 and an anti-HLA-G CAR having polynucleotide of instant SEQ ID NO:74, 76, 78 or 80. In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming. M.P.E.P. § 2163 instructs: An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . . An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . . An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” This standard has not been met in this case. While the specification describes reduction of fluorescence intensity of OCI-AML3 cells or GSC20 cells in the OCI-AML3 cells or GSC20 cells cocultured with the HLA-G CAR NK cells transfected with HLA-G CAR construct MG1 or MG22, the specification fails to provide sufficient descriptive information as to what the structures of HLA-G CAR construct MG1 or MG22 are. While the specification describes a polynucleotide having SEQ ID NO:74 encoding iC9-MEMVHVL-28Hing-CD28-CD3z-IL15; a polynucleotide having SEQ ID NO: 76 encoding iC9-MEMVHVL-28Hing-DAP10-CD3z-IL15; a polynucleotide having SEQ ID NO: 78 encoding iC9-87GVHVL-28Hing-CD28-CD3z-IL15; and a polynucleotide having SEQ ID NO: 80 encoding iC9-87GVHVL-28Hing-DAP10-CD3z-IL15 (see para. [0166]-[0181]), the specification provides no well-established structural and functional relationship between the HLA-G CAR construct MG1 or MG22 shown in Examples and figures 5-9 and an anti-HLA-G CAR having a polynucleotide of instant SEQ ID NO:74, 76, 78 or 80 or the claimed genus of polynucleotide encoding an anti-HLA-G CAR recited in claim 1. The specification also fails to provide well-established structural and functional relationship between the HLA-G CAR construct MG1 or MG22 shown in Examples and figures 5-9 or an anti-HLA-G CAR having a polynucleotide of instant SEQ ID NO:74, 76, 78 or 80 and the claimed genus of anti-HLA-G antigen binding region, the claimed genus of anti-HLA-G antibody, the claimed genus of transmembrane domain or the claimed genus of intracellular domain that is not a KIR2DL4 intracellular domain. The specification provides no identification of any particular portion of the structure that must be conserved. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of polynucleotide encoding an anti-HLA-G CAR, the claimed genus of anti-HLA-G CAR, the claimed genus of anti-HLA-G antigen binding region, the claimed genus of anti-HLA-G antibody, the claimed genus of transmembrane domain or the claimed genus of intracellular domain that is not a KIR2DL4 intracellular domain. There is no description of the conserved regions which are critical to the function of the genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of structure of the genus of polynucleotide encoding an anti-HLA-G CAR, the genus of anti-HLA-G CAR, the genus of anti-HLA-G antigen binding region, the genus of anti-HLA-G antibody, the genus of transmembrane domain or the genus of intracellular domain that is not a KIR2DL4 intracellular domain to the function of the HLA-G CAR construct MG1 or MG22 shown in Examples and figures 5-9 or an anti-HLA-G CAR having a polynucleotide of instant SEQ ID NO:74, 76, 78 or 80. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other polynucleotides encoding an anti-HLA-G CAR recited in claim 1, other anti-HLA-G CARs, other anti-HLA-G antigen binding regions, other anti-HLA-G antibodies, other transmembrane domains or other intracellular domain that is not a KIR2DL4 intracellular domain that can be used in the claimed anti-HLA-G CAR recited in claim 1 might be. Since the common characteristics/features of other polynucleotides encoding an anti-HLA-G CAR recited in claim 1, other anti-HLA-G CARs, other anti-HLA-G antigen binding regions, other anti-HLA-G antibodies, other transmembrane domains or other intracellular domain that is not a KIR2DL4 intracellular domain are unknown, a skilled artisan cannot contemplate the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of polynucleotides encoding an anti-HLA-G CAR recited in claim 1, the genus anti-HLA-G CARs, the genus of anti-HLA-G antigen binding regions, the genus of anti-HLA-G antibodies, other transmembrane domains and the genus of intracellular domain that is not a KIR2DL4 intracellular domain. As stated in M.P.E.P. § 2163(II)(A)(3), a specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321,1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) (“[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim.”); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) (“[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose.”); Mahurkar v. C.R. Bard, Inc. , 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves). Whereas a reduction to practice of an uncomplicated invention such as a simple mechanical or electrical device can be achieved by merely providing a diagram of the device wherein one skilled in the relevant art can predict the likely operability of the device by reviewing the diagram, the operability of the claimed invention cannot be predicted by merely reviewing diagrams or illustrations. To demonstrate the reduction to practice of the claimed genus of polynucleotide tide encoding an anti-HLA-G CAR recited in claim 1 requires either a working embodiment, a demonstration of operability of a polynucleotide tide encoding an anti-HLA-G CAR recited in claim 1 or a polynucleotide of instant SEQ ID NO:74, 76, 78 or 80 capable of acting or function as the HLA-G CAR construct MG1 or MG22 shown in Examples and figures 5-9. In the instant case, Applicant has provided none of these. Consequently, Applicant has failed to demonstrate possession of the claimed genus of polynucleotide encoding an anti-HLA-G CAR recited in claim 1 or vectors or immune cells thereof required thereby as of the earliest effective filing date of the instant application. With respect to the demonstration of a reduction to practice of a generic invention, M.P.E.P. § 2163(II)(A)(3)(ii) states that 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, reduction to drawings, 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, 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). The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that; “ It appears to be well settled that a single species can rarely, if ever, afford support fora generic claim. In re Soil, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867,117 F.21 270,48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.” In the instant case, Applicant has failed to demonstrate a reduction to practice of a representative number species of the genus of polynucleotide encoding an anti-HLA-G CAR recited in claim 1 or vectors or immune cells thereof. The experimental results described in the specification consist primarily of the characterization of the HLA-G CAR construct MG1 or MG22 in HLA-G CAR NK cells, and the effects of HLA-G CAR NK cells transfected with HLA-G CAR construct MG1 or MG22 on the reduction of fluorescence intensity of the OCI-AML3 cells or GSC20 cells cocultured with the HLA-G CAR NK cells transfected with HLA-G CAR construct MG1 or MG22 as shown in Examples and figures 5-9. Those results do not support a conclusion that Applicant was in possession of the claimed polynucleotide encoding an anti-HLA-G CAR recited in claim 1 or vectors or immune cells thereof because the specification provides no detailed structure of the HLA-G CAR construct MG1 or MG22 transfected in NK cells as shown in Examples and figures 5-9. The specification provides no well-established structural and functional relationship between the HLA-G CAR construct MG1 or MG22 shown in Examples and figures 5-9 and an anti-HLA-G CAR having a polynucleotide of instant SEQ ID NO:74, 76, 78 or 80. The specification also provides no well-established structural and functional relationship between the HLA-G CAR construct MG1 or MG22 shown in Examples and figures 5-9 and the claimed genus of polynucleotide encoding an anti-HLA-G CAR recited in claim 1. The specification also provides no well-established structural and functional relationship between the anti-HLA-G CAR having a polynucleotide of instant SEQ ID NO:74, 76, 78 or 80 and the claimed genus of anti-HLA-G CAR recited in claim 1, or the claimed genus of antigen binding region, the claimed genus of anti-HLA-G antibody, the claimed genus of transmembrane domain or the claimed genus of intracellular domain that is not a KIR2DL4 intracellular domain. Based on MPEP § 2161.01 and §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”. Vas-Cath Inc. v. Mahurkar , 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention . The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed. ” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polynucleotides encoding an anti-HLA-G CAR recited in claim 1, the genus anti-HLA-G CARs, the genus of anti-HLA-G antigen binding regions, the genus of anti-HLA-G antibodies, other transmembrane domains and the genus of intracellular domain that is not a KIR2DL4 intracellular domain, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel , 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. , 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird , 30 USPQ2d 1481 at 1483. Therefore, the claimed polynucleotide, the claimed vector, the claimed immune cell and the claimed composition have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163 . 07-06 AIA 15-10-15 10. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 11. 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 – 07-08-aia AIA (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. 07-12-aia AIA (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. 07-15 AIA Claim s 1-2, 60, 65, 67, 72-73 and 75-77 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Loustau et al. (WO2020/043899, published March 5, 2020, priority Aug 30, 2018; also issued as US11505608; US11117971; US11325977; US12297275, cited previously) . Claims 1-2, 60, 65, 67, 72-73 and 75-77 are drawn to a polynucleotide that encodes an anti-HLA-G chimeric antigen receptor (CAR), the CAR comprising (a) a KIR2DL4 extracellular domain or an anti-HLA-G antigen binding region of an HLA-G specific antibody (elected), (b) a transmembrane domain, and (c) an intracellular domain that is not a KIR2DL4 intracellular domain. Loustau et al. (WO2020/043899) discloses a polynucleotide encoding an anti-HLA-G CAR as in claim 1 (p. 6; p.43-53), wherein the polynucleotide encoding the anti-HLA-G CAR comprises an anti-HLA-G antigen binding region of an anti-HLA-G specific antibody, a transmembrane domain (TMD) and an intracellular domain (ICD) that is not a KIR2DL4 intracellular domain, or comprises from N to C terminus: (a) a peptide signal sequence, b) an anti-HLA-G antibody or an antigen-binding fragment thereof, c) optionally a spacer domain, d) a TMD, e) an ICD, and optionally f) a cleavable linker and optionally g) a truncated human CD29 domain (see p. 3-6; p. 8, lines 13-24; p. 17, lines16-33; p. 23-24; p. 26, line 18-p. 40, line 18; p. 43, line 19-p. 51, line 24; p51-55; p.53-56; p.60-65; p. 83-85; p. 86-89; p. 90-93, claims 1-23), which meet the limitations recited in instant claims 1-2, 40, 48-49, 60, 65, 67, 72-73, 75-77 and 95. Loustau discloses a vector comprising the claimed polynucleotide as in claim 60 (p. 6; p.43-53), an immune cell including NK cells including different NK cells: Natural Killer T (NKT) cells, cytokine-induced killer (CIK) cells, tumor-infiltrating lymphocytes (TILs), lymphokine-activated killer (LAK) cells, NK-92 (ATCC® CRL-2407™), NK-92MI (ATCC® CRL-2408™) (i.e. NK cells genetically modified to continuously express human IL-2) or immune cells with one or more modified endogenous genes as in claims 65, 67, 72-73 and 75-77 (p. 6; p.53-56; p.60-65; p. 83-85; p. 86-89; p. 90-93, claims 1-23) and a pharmaceutical comprising the claimed polynucleotide, the claimed vector or the claimed immune cell (p. 6; p. 8; p.53-56; p.61-63; p.65-68).Loustau teaches that the TMD is selected from CD28, CD3 or CD8; the ICD comprises CD3 zeta signaling domain and at least one costimulatory domain including CD28, 41BB and DAP10; and the cleavable linker including P2A, T2A, E2A, B2A or F2A (p. 3-6; p. 32-41). Loustau teaches that the anti-HLA-G antibody or antigen-binding fragment thereof includes anti-HLA-G scFv comprising a VH having SEQ ID NO:1 or at least 90% to SEQ ID NO:1 and a VL having SEQ ID NO:2 or at least 90% identity to SEQ ID NO:2; or comprising a VH having SEQ ID NO:3 or at least 90% identity to SEQ ID NO:3 and a VL having SEQ ID NO:4 or at least 90% identity to SEQ ID NO:4 (see p.3-6; p. 23-24; p. 26, line 18-p. 40, line 18; p. 43, line 19-p. 51, line 24; p51-55). Thus, claims 1-2, 60, 65, 67, 72-73 and 75-77 are anticipated by Loustau . Claim Rejections - 35 USC § 103 07-20-aia AIA 12. 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 of this title, 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. 07-23-aia AIA The factual inquiries set forth in Graham v. John Deere Co. , 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 40 and 48-49 are rejected under 35 U.S.C. 103 as being unpatentable over Loustau et al. (WO2020/043899; also issued as US11505608; US11117971; US11325977; US12297275) . Loustau is set forth above. Loustau does not explicitly teach that the polynucleotide further encodes a cytokine including IL-15 as in claims 40 and 48-49. However, Loustau teaches that the anti-HLA-G CAR expressing cells can be administered in combination with other components such as cytokines or other cell populations that are immunostimulatory for enhancing the effect of the anti-HLA-G CAR expressing cells including anti-HLA-G CAR expressing-T cells or -NK cells for better treatment of cancer and anti-cancer therapy (see p.75-77); and the T cell or NK cell populations can be expanded using IL-2, IL-15, IL-15/IL-15RA complex, IL-18 and IL-12 (see p.62-63). A person of ordinary skill in the art would have recognized that selecting and applying the known benefits of including sequences encoding cytokines including IL-15 in the anti-HLA-G CAR and the anti-HLA-G CAR expressing cells for enhancing the effect of the anti-HLA-G CAR expressing cells including anti-HLA-G CAR expressing-T cells or -NK cells and expanding the T cell or NK cell populations disclosed by Loustau to the polynucleotide encoding the anti-HLA-G CAR disclosed by Loustau would have yielded the predictable result of a polynucleotide encoding anti-HLA-G CAR and a cytokine including IL-15 and resulted in an improved product for better treatment of cancer and anti-cancer therapy. Using and including a polynucleotide encoding a cytokine including IL-15 in the polynucleotide encoding the anti-HLA-G CAR and the anti-HLA-G CAR expressing immune cells including T cells or NK cells disclosed by Loustau would generate the claimed polynucleotide encoding the claimed anti-HLA-G CAR and further comprising a cytokine including IL-15, and enhance the effect of the anti-HLA-G CAR expressing cells including anti-HLA-G CAR expressing-T cells or -NK cells and expanding the T cell or NK cell populations disclosed by Loustau, and expand application of the polynucleotide encoding the anti-HLA-G CAR and the anti-HLA-G CAR expressing immune cells disclosed by Loustau, and would increase patient’s satisfaction with better treatment of cancer or anti-cancer therapy. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known benefits of including sequences encoding cytokines including IL-15 in the anti-HLA-G CAR and the anti-HLA-G CAR expressing cells for enhancing the effect of the anti-HLA-G CAR expressing cells including anti-HLA-G CAR expressing-T cells or -NK cells and expanding the T cell or NK cell populations disclosed by Loustau to the polynucleotide encoding the anti-HLA-G CAR disclosed by Loustau and yield the predictable result of a polynucleotide encoding the claimed anti-HLA-G CAR and further comprising a cytokine including IL-15 to enhance the effect of the anti-HLA-G CAR expressing cells including anti-HLA-G CAR expressing-T cells or -NK cells and expand the T cell or NK cell populations disclosed by Loustau for better treatment of cancer or anti-cancer therapy . Claim Rejections - 35 USC § 103 07-22-aia AIA 13. Claim 76 is rejected under 35 U.S.C. 103 as being unpatentable over Loustau et al. (WO2020/043899; also issued as US11505608; US11117971; US11325977; US12297275) as applied to claim s 40 and 48-49 above and further in view of Cao et al (US11866494, issued Jan 9, 2024, priority Aug 31,2018) and Inderberg et al. (US2019/0336529, published Nov 17, 2019, priority May 9, 2016) . Loustau is set forth above but does not explicitly teach that genes recited in claim 76. Cao et al (US11866494) teaches that the modified immune cells comprising a CAR and a modified tumor antigen including NKG2A, LAG3, PD1, PDL-1, PDL-2, ADAM12, CD25, CD40, ICAM1, CD95, CD80, CD86,IL-11R, CD5, CD7, CD38, or a combination thereof as in claim 76 (see col. 13, lines 55-61; col.15, lines 16-30; col. 18, line 8-22). Inderberg et al. (US2019/0336529) teach that frameshift mutations which inactivate TGFβRII occur in approximately 90% of microsatellite instable (MSI+) and approximately 15% of microsatellite stable (MSS, non-MSI+ or MSI−) colon cancers. These mutations largely occur in a mutation-vulnerable polyadenine tract in exon 3 of TGFβRII in colon cancer cells ([0005]; [0212]; [0215]; [0218]; [0276]; [0284]-[0285]). A person of ordinary skill in the art would have recognized that selecting and applying the known modified immune cells comprising modified endogenous genes including CAR expressing cells comprising modified endogenous genes disclosed by Cao and Inderberg to the anti-HLA-G CAR expressing immune cells including anti-HLA-G CAR expressing- T cells or -NK cells of Loustau would have yielded the predictable result of the anti-HLA-G CAR expressing- immune cells including anti-HLA-G CAR expressing-T cells or -NK cells comprising modified endogenous genes, and resulted in an improved product for better treatment of cancer and anti-cancer therapy because the modified immune cells including CAR expressing cells comprising modified endogenous genes including genes recited in claim 76 have been taught by Cao. Using and including the known modified immune cells including the CAR expressing cells comprising modified endogenous genes disclosed by Cao and Inderberg in the anti-HLA-G CAR expressing-immune cells including anti-HLA-G CAR expressing-T cells or -NK cells of Loustau would generate the claimed anti-HLA-G CAR expressing-immune cells including anti-HLA-G CAR expressing-T cells or -NK cells comprising modified endogenous genes recited in claim 76, and expand application of the anti-HLA-G CAR expressing-immune cells including anti-HLA-G CAR expressing-T cells or -NK cells of Loustau, and would increase patient’s satisfaction with better treatment of cancer or anti-cancer therapy. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known modified immune cells including modified endogenous genes in the CAR expressing cells disclosed by Cau and Inderberg to the anti-HLA-G CAR expressing-T cells or -NK cells of Loustau and yield the predictable result of the anti-HLA-G CAR expressing-T cells or -NK cells comprising modified endogenous genes recited in claim 76 for better treatment of cancer or anti-cancer therapy. Conclusion 14. NO CLAIM IS ALLOWED. 15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-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, Jeffrey Stucker can be reached at 571-272-0911. 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. Chang-Yu Wang June 13, 2026 /CHANG-YU WANG/Primary Examiner, Art Unit 1675 Application/Control Number: 18/560,791 Page 2 Art Unit: 1675 Application/Control Number: 18/560,791 Page 3 Art Unit: 1675 Application/Control Number: 18/560,791 Page 4 Art Unit: 1675 Application/Control Number: 18/560,791 Page 5 Art Unit: 1675 Application/Control Number: 18/560,791 Page 6 Art Unit: 1675 Application/Control Number: 18/560,791 Page 7 Art Unit: 1675 Application/Control Number: 18/560,791 Page 8 Art Unit: 1675 Application/Control Number: 18/560,791 Page 9 Art Unit: 1675 Application/Control Number: 18/560,791 Page 10 Art Unit: 1675 Application/Control Number: 18/560,791 Page 11 Art Unit: 1675 Application/Control Number: 18/560,791 Page 12 Art Unit: 1675 Application/Control Number: 18/560,791 Page 13 Art Unit: 1675 Application/Control Number: 18/560,791 Page 14 Art Unit: 1675 Application/Control Number: 18/560,791 Page 15 Art Unit: 1675 Application/Control Number: 18/560,791 Page 16 Art Unit: 1675 Application/Control Number: 18/560,791 Page 17 Art Unit: 1675 Application/Control Number: 18/560,791 Page 18 Art Unit: 1675 Application/Control Number: 18/560,791 Page 19 Art Unit: 1675 Application/Control Number: 18/560,791 Page 20 Art Unit: 1675 Application/Control Number: 18/560,791 Page 21 Art Unit: 1675 Application/Control Number: 18/560,791 Page 22 Art Unit: 1675 Application/Control Number: 18/560,791 Page 23 Art Unit: 1675 Application/Control Number: 18/560,791 Page 24 Art Unit: 1675
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