CTNF 18/273,579 CTNF 97111 DETAILED ACTION 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. Claim Status To expedite the compact prosecution, the Examiner is pursuing the claims field 16 April 2026, in which Applicant claims 1-20. Therefore, claims 1-20 are pending in the application. Election/Restrictions Applicant’s election of Group I: Claims 1-8, 15 directed to a method of treating an autoimmune disease caused by pathogenic Th1 cells comprising administering one or more agents capable of inhibiting the expression, activity and/or function of a disease related gene or genes in the reply filed on 16 April 2026 is acknowledged. Claims 9-14 and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant argues that Carballido Herrera (US20090208997A1) do not reasonable teach the claimed method of treating an autoimmune disease caused by pathogenic Th1 cells comprising administering one or more agents capable of inhibiting the expression of GPR18, activity and/or function of one or more disease related genes. This is not found persuasive because the shared technical feature lacks novelty as evidenced by the obviousness rejection set forth below which satisfied the limitations of group I, thereby demonstrating that the special technical feature lacks novelty. Therefore, claims 1-8, 15 are under current examination. Priority This application was filed 07/21/2023 and is a 371 application of PCT/US22/133 31 filed on 01/21/2022, which claims benefit to the Provisional Application 63140458 filed on 01/22/2021. Thus, the earliest possible priority for the instant application is 01/22/2021 . Information Disclosure Statement The information disclosure statement (IDS) submitted on 07/21/2023, 04/16/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action. Abstract Objection The abstract of the disclosure filed 07/21/2023 is objected to because the abstract is only 37 words in length, and it is not submitted as a single paragraph on a separate sheet as required. Therefore, submitted abstract is considered non-compliant. Applicant is reminded of the proper language and format for an abstract of the disclosure. MPEP § 608.01(b)(I) sets forth guidelines for the preparation of patent abstracts. MPEP § 608.01(b)(I)(C) states that "the abstract for a national stage application filed under 35 U.S.C. 371 may be found on the front page of the Patent Cooperation Treaty publication (i.e., pamphlet). See MPEP § 1893.03(e)." 06-16 AIA However, MPEP §608.01(b)(I) also sets forth guidelines for the abstract. MPEP § 608.01(b)(I)(C) states that “the abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.” The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided. Therefore, appropriate correction is required. Claim Rejections - 35 USC § 112(a) (Written description) 07-30-01 AIA 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 Claims 1-7, 15 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 contains subject matter that 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, at the time the application was filed, had possession of the claimed invention. Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so 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. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002). Accordingly, to satisfy the written description requirement, the 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 . Vas-Cath, Inc. v. Mahurkar , 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163. REQUIREMENTS TO ESTABLISH ACTUAL REDUCTION TO PRACTICE "In an interference proceeding, a party seeking to establish an actual reduction to practice must satisfy a two-prong test: (1) the party constructed an embodiment or performed a process that met every element of the interference count, and (2) the embodiment or process operated for its intended purpose." Eaton v. Evans, 204 F.3d 1094, 1097, 53 USPQ2d 1696, 1698 (Fed. Cir. 2000). The same evidence sufficient for a constructive reduction to practice may be insufficient to establish an actual reduction to practice, which requires a showing of the invention in a physical or tangible form that shows every element of the count. Wetmore v. Quick, 536 F.2d 937, 942, 190 USPQ 223, 227 (CCPA 1976). For an actual reduction to practice, the invention must have been sufficiently tested to demonstrate that it will work for its intended purpose, but it need not be in a commercially satisfactory stage of development. See, e.g., Scott v. Finney, 34 F.3d 1058, 1062, 32 USPQ2d 1115, 1118-19 (Fed. Cir. 1994) (citing numerous cases wherein the character of the testing necessary to support an actual reduction to practice varied with the complexity of the invention and the problem it solved). If a device is so simple, and its purpose and efficacy so obvious, construction alone is sufficient to demonstrate workability. King Instrument Corp. v. Otari Corp., 767 F.2d 853, 860, 226 USPQ 402, 407 (Fed. Cir. 1985). For additional cases pertaining to the requirements necessary to establish actual reduction to practice see DSL Dynamic Sciences, Ltd. v. Union Switch & Signal, Inc., 928 F.2d 1122, 1126, 18 USPQ2d 1152, 1155 (Fed. Cir. 1991) ("events occurring after an alleged actual reduction to practice can call into question whether reduction to practice has in fact occurred"); Fitzgerald v. Arbib, 268 F.2d 763, 765-66, 122 USPQ 530, 531-32 (CCPA 1959) ("the reduction to practice of a three-dimensional design invention requires the production of an article embodying that design" in "other than a mere drawing"); Birmingham v. Randall, 171 F.2d 957, 80 USPQ 371, 372 (CCPA 1948) (To establish an actual reduction to practice of an invention directed to a method of making a product, it is not enough to show that the method was performed. "[S]uch an invention is not reduced to practice until it is established that the product made by the process is satisfactory, and [ ] this may require successful testing of the product."). See MPEP 2138.05. Claim 1 encompasses a genus of any agent to inhibit expression, activity and/or function of any of the genes . However, the specification doesn't have adequate support in the disclosure for the any agent to inhibit expression, activity and/or function of any of the genes . The specification discloses that the methods of treating and autoimmune disease administrating one or more therapeutic agents against one or more of the targets identified, wherein the one or more agents comprises a small molecule inhibitor, small molecule degrader (e.g., ATTEC, AUTAC, LYTAC, or PROTAC), genetic modifying agent, antibody, antibody fragment, antibody-like protein scaffold, aptamer, protein, or any combination thereof [0008], [0076], [0083-0096]. However, specification does not disclose that any agent to inhibit expression, activity and/or function of any of the genes can be treated in a subject with instant method. Therefore, the specification fails to identify the any agent to inhibit expression. Claim 4 encompasses a genus of any agent administrating with Th1 cells for treating the autoimmune disease. However, the specification doesn't have adequate support in the disclosure for the generic species that characterize the genus of any agent that capable of inhibiting the expression. As discussed above, specification does not disclose that any agent administrating with Th1 to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease. Therefore, the specification fails to identify the any agent to inhibit expression. Furthermore, the specification discloses that the expression of IL-23R in Th1 cells reached similar levels as in pathogenic Th1 7 cells that were differentiated with the cytokine combination IL-1[Symbol font/0x62] + IL-6 + IL-23 (Fig. 1a). When Applicants further added IL-23 to the differentiation condition (IL-12 + IL-21 + IL-23), it slightly increased the expression of IL-23R compared to IL-12 + IL-21, and it is known that IL-23 can increase the expression of its own receptor (Fig. 1a and Fig. 5). Differentiation of naive T cells with IL-12 or IL-18 alone induced minimal expression of IL-23R (Fig. 5) ([0325] ¶ of SPEC). However, the specification does not show any embodiments that meet all the limitations of the claim reduced to practice (e.g., any agent to inhibit expression, activity and/or function of any of the genes; a CRISPR-Cas base editing system) . Therefore, an actual reduction to practice of an invention directed to a method of treating is not established at the time of filling. The successful testing of the method of the current invention is not shows reduced to practice , therefore, it is not established that the product made by the process is satisfactory. See MPEP 2163(I)-(II) and 2163.02. The genus of agent is very large, including many small molecule inhibitors (FDA approved and otherwise), as well as antibodies, aptamers, etc. and any moiety capable of inhibiting expression of any gene . For example, antibody inhibitors are known in the art as per Cai et al. (Nature Immunology volume 9, pages176–185 (2008); cited in PTO892). Small molecule inhibitors can be found in several review articles, including: Morales et al. (Therapeutic exploitation of GPR18: beyond the cannabinoids; Journal of medicinal chemistry , 63 (23), pp.14216-14227, 2020; cited in PTO892) and Santa Cruz Inc. et al. (CD160 Inhibitors; cited in PTO892). Therefore, prior arts do not support merely any agent to inhibit expression, activity and/or function of any of the genes . Rather, arts disclose several agent (e.g., antibodies, aptamers, etc.) is involved to inhibit expression, activity and/or function of any of the genes . Accordingly, arts do not identify or support the use of any agent as claimed. Furthermore, an actual reduction to practice of instant invention directed to a method is not established at the time of filling and POSITA cannot predictably identify a method that exercise in this invention of pathogenic Th1 cells, wherein the Th1 cells is comprising specific agent to inhibit expression, activity and/or function of any of the genes associated with treating autoimmune disease that exercise in this invention. The Examiner concludes that the disclosure of any species of agent does not constitute a “representative number of species” to show possession of the broad genus presently claimed. Accordingly, the claimed genus of agent is involved to inhibit expression, activity and/or function of any of the genes doesn't have an adequate written description. Specifically, doesn't have an adequate written description on actual reduction to practice of instant invention directed to a method of treating a product is not established at the time of filling. The successful testing of the product of the current invention is not shows reduced to practice, therefore, it is not established that the method steps are satisfactory. Therefore, the Applicant did not sufficiently possess the broader invention as claimed in claim 1 and dependent claims 2-7 and 15. Claim Rejections - 35 USC § 112(a) (Scope of Enablement) 07-30-01 AIA 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, 4-7 and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while enabling the scope for or more agents inhibit the expression, activity and/or function of CD160 or GPR18 as recited in claims 2-3 , does not reasonably provide enablement for any agent and CRISPR editing system enable to treating an autoimmune disease as recited in claims 1, 4-7 and 15 . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” ( Wands , 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention. Furthermore, MPEP 2164.03 as set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). THE BREADTH OF THE CLAIMS The breadth of the claims 1 and 4-7 broadly encompasses the scope to any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease. THE NATURE OF THE INVENTION The nature of the invention is reprograming the Th1 cells by culturing the cell with any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease. THE STATE OF THE PRIOR ART The genus of agent is very large, including many small molecule inhibitors (FDA approved and otherwise), as well as antibodies, aptamers, etc. and any moiety capable of inhibiting expression of any gene . For example, antibody inhibitors are known in the art as per Cai et al. (Nature Immunology volume 9, pages176–185 (2008); cited in PTO892). Small molecule inhibitors can be found in several review articles, including: Morales et al. (Therapeutic exploitation of GPR18: beyond the cannabinoids; Journal of medicinal chemistry , 63 (23), pp.14216-14227, 2020; cited in PTO892) and Santa Cruz Inc. (CD160 Inhibitors; attached the PDF). Therefore, prior arts do not support merely any agent to inhibit expression, activity and/or function of any of the genes . Rather, arts disclose several agent (e.g., antibodies, aptamers, etc.) is involved to inhibit expression, activity and/or function of any of the genes . Accordingly, arts do not identify or support the use of any agent as claimed. Separately, Biton et al. (WO2019018440A1; cited in IDS filed 7/21/2023; hereinafter “Biton”) discloses treatment of an autoimmune condition (i.e., inflammatory bowel disease (IBD) ) ([0323]-[0325], claims 16-17 of Biton), involves vectors wherein the genetic modifying agent (i.e., CRISPR-Cas base editing system) comprises for delivering or introducing in a cell Cas and/or RNA capable of guiding Cas to a target locus (i.e. guide RNA) ([0189], [0190], [0261], [0022] of Biton). Therefore, the prior art does not provide any evidence to support the any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease. THE LEVEL OF ORDINARY SKILL IN THE ART An ordinary artisan in the area of cell biology and drug development would have experience to reprograming the T cells for treating cancer. Reprograming the Th1 cells, while it is complex, is routine in the art. The process of reprograming Th1 cells by culturing the cell with one or more agents capable of inhibiting the expression of GPR18 is well known. Additionally, while developing reprogram Th1 cells with any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease, as claimed, is generally not well-known or routine, given the complexity of certain biological systems. Thus, the level of ordinary skill in the art of reprograming the Th1 cells by culturing the cell with any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease is high, as an ordinary artisan in this art needs specialized knowledge of the complex nature of the reprogram Th1 cells. THE LEVEL OF PREDICTABILITY IN THE ART While the reprograming Th1 cells by culturing the cell with one or more agents capable of inhibiting the expression of GPR18 , activity and/or function of one or more disease related genes, wherein one or more agents comprises an antibody, small molecule, polypeptide, or any combination thereof is well known, the use any agent and CRISPR editing system to reprogram Th1 cells to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease within the scope of the claim is not predictable, for instance, Cai et al. Small molecule inhibitors can be found in several review articles, including: Morales et al. and Santa Cruz Inc. et al. Therefore, prior arts do not support merely any agent to inhibit expression, activity and/or function of any of the genes . Rather, arts disclose several agent (e.g., antibodies, aptamers, etc) is involved to inhibit expression, activity and/or function of any of the genes . Accordingly, arts do not identify or support the use of any agent as claimed. Separately, Biton et al. (WO2019018440A1; cited in IDS filed 7/21/2023; hereinafter “Biton”) does not support CRISPR editing system to inhibit expression, activity and/or function of any of the genes discloses treatment of an autoimmune condition. Thus, it is unpredictable whether any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease. The predictability of applying any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease encompassed by the instant claim would be low given that there doesn’t appear to a link between reprogram Th1 cells and the claimed conditions. THE AMOUNT OF GUIDANCE AND WORKING EXAMPLES DISCUSSION The specification shows that the expression of IL-23R in Th1 cells reached similar levels as in pathogenic Th1 7 cells that were differentiated with the cytokine combination IL-1[Symbol font/0x62] + IL-6 + IL-23 (Fig. 1a). When Applicants further added IL-23 to the differentiation condition (IL-12 + IL-21 + IL-23), it slightly increased the expression of IL-23R compared to IL-12 + IL-21, and it is known that IL-23 can increase the expression of its own receptor (Fig. 1a and Fig. 5). Differentiation of naive T cells with IL-12 or IL-18 alone induced minimal expression of IL-23R (Fig. 5) ([0325] ¶ of instant SPEC). Applicants identified receptor activation can be determined by detecting the phosphorylation (e.g., tyrosine or serine/threonine) of the receptor or of one of its down-stream substrates by immunoprecipitation followed by western blot analysis ([0100] ¶ of instant SPEC). However, specification does not provide preferred embodiment that enable to meet all the limitations of the claim reduced to practice (e.g., any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease). Therefore, an actual reduction to practice of an invention directed to a method of treating is not established at the time of filling. Therefore, POSITA would not able to reprogram Th1 cells at the time of filling, with any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease as disclosed in specification and claims 1, 4-7 and 15 . Accordingly, the specification and the prior art provide sufficient teachings only receptor activation can be determined by detecting the phosphorylation (e.g., tyrosine or serine/threonine) of the receptor or specific antibody to reprogram Th1 cells. CONCLUSION Since both the instant specification and the prior art at the effective filing date of the present application provide a guide to reprograming the Th1 cells by culturing the cell with receptor activation by detecting the phosphorylation (e.g., tyrosine or serine/threonine) of the receptor or specific antibody for treating the autoimmune of claims 1, 4-7 and 15 and since does not appear to be any other teaching in the specification and/or prior art that reprogram Th1 cells by culturing the cell any agent and CRISPR editing system to inhibit expression, activity and/or function of any of the genes for treating autoimmune disease, it would therefore be unpredictable to practice the invention to reprogram Th1 cells by culturing the cell with any agent and CRISPR editing system . The prior art provides no compensatory guidance, and since attempts to reprogram Th1 cells by culturing the cell with any agent and CRISPR editing system have been unsuccessful. In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims 1, 4-7 and 15 , it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention as recited. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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. 07-15 AIA Claim s 1, and 3-4 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Carballido Herrera et al. (US20090208997A1; cited in IDS filed 7/21/2023; hereinafter “Carballido Herrera”) . With respect to claims 1 and 3, Carballido Herrera teaches a method of treating an autoimmune disease caused by pathogenic Th1 cells comprising administering one or more agents capable of inhibiting the expression of GPR18 , activity and/or function of one or more disease related genes [0092], [0005]-[0006], [0084]-[0085]. With respect to claim 4, Carballido Herrera teaches that the one or more agents comprises an antibody, small molecule, polypeptide, or any combination thereof [0084-0085], [0089], Accordingly, Carballido Herrera anticipates the instant claims 1, and 3-4 . Claim Rejections - 35 USC § 103 07-20-aia AIA 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 1-7 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Carballido Herrera et al. (US2009/0208997A1; cited in IDS filed 7/21/2023; hereinafter “Carballido Herrera”), in view of Bouma et al. (Molecular Immunology 54 (2013) 472– 481; cited in PTO892; hereinafter “Bouma”) and Biton et al. (WO2019018440A1; cited in IDS filed 7/21/2023; hereinafter “Biton”) . As discussed above Carballido Herrera discloses the method of claims 1, 3 (a method of treating an autoimmune disease caused by pathogenic Th1 cells comprising administering one or more agents capable of inhibiting the expression of GPR18 , activity and/or function of one or more disease related genes). However, regarding claim 2 , Carballido Herrera discloses the method of claim 1, but Carballido Herrera does not specifically disclose wherein the one or more agents inhibit the expression, activity and/or function of CD160. With respect to claims 2, and 4, Bouma discloses a administering a CD160 inhibitor agent (e.g., thiopurine derivatives) capable of inhibiting the expression, activity and/or function of CD160 in helper T cells for treating Crohn’s disease (p. 477 right-hand col. 3 rd ¶) Since Carballido Herrera discloses treatment of psoriasis by inhibition of a gene associated with activated helper T cells, and Bouma discloses where administering a CD160 inhibitor for treating Crohn’s disease may be involved in helper T-cell activation. Accordingly, it would have been obvious to POSITA to modify the method, as disclosed by Carballido Herrera, to include or instead consider inhibition of CD160, as disclosed by Bouma, since this would allow targeted inhibition of an alternative gene associated with helper T cells activation in Crohn’s disease patient (p. 477 right-hand col. 3 rd ¶; Fig. 4 of Bouma), thereby increasing the applicability and therefore value of the method of Carballido Herrera. Regarding claims 5-7, Carballido Herrera does not disclose the genetic modifying agent comprises an RNA guided nuclease system. With respect to claims 5-7 and 15, Biton discloses treatment of an autoimmune condition (i.e., inflammatory bowel disease (IBD) ) ([0323]-[0325], claims 16-17 of Biton), involves vectors wherein the genetic modifying agent (i.e., CRISPR-Cas base editing system) comprises for delivering or introducing in a cell Cas and/or RNA capable of guiding Cas to a target locus (i.e. guide RNA) ([0189], [0190], [0261], [0022] of Biton). Therefore, the method of Biton is treating IBD comprising modulating the activity of one or more gastrointestinal tract cell types may express one or more IBD GWAS genes selected from GPR18 (claims 16-17 of Biton). Since Carballido Herrera discloses inhibition of GPR18 for treatment of autoimmune disease, and Biton discloses treatment of autoimmune IBD disease using an RNA-guided nuclease system, and where target cells may express GPR18, it would have been obvious to one of ordinary skill in the art to modify the method, as disclosed by Carballido Herrera, to include or instead consider RNA-guided nuclease editing, such as base editing, as disclosed by Biton, since this would afford an alternative method of inhibiting GPR18 by using a known CRISPR base-editing technology, thereby affording any potential improvement in patient clinical outcome for IBD disease ([0400] of Biton). Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary . 07-21-aia AIA Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over McGeachy et al. (Nature immunology, 10(3), pp.314-324, 2009; cited in IDS filed 7/21/2023; hereinafter “McGeachy”) . Regarding claim 8 , McGeachy discloses a method comprising adoptive transfer of Th1 cells modified to have decreased expression of IL-23R (Fig. 3; p. 316, col 1, 2 nd ¶; p. 318, col 2, 3 rd ¶). McGeachy suggests that the normal TH1 response in absence of IL-23R defects in activation noted in ll23ra-/- T cells are specific to TH-17-inducing conditions rather than to global activation of T cells (p. 321, col 2, 2 nd ¶). McGeachy does not specifically disclose a method of treating an autoimmune disease caused by pathogenic Th1 cells comprising administering Th1 cells modified to have decreased expression of IL-23R. However, McGeachy does disclose where IL23R polymorphisms are important in autoimmune diseases (p. 314, col 1, 1 st ¶) "TH-17 cells were initially shown to be a chief pathogenic cell type in models of autoimmunity, including experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis, and have since been identified in several human inflammatory diseases, including Crohn's disease and psoriasis. Likewise, polymorphisms in the gene encoding the IL-23 receptor (IL-23R), are important susceptibility factors for these disorders."), where IL23R affects disease model induction (p. 315, col 1, 2 nd ¶). MPEP 2143 states a combination of all the elements into a single embodiment would be apparent to an artisan skilled in cell therapy in light of the Supreme Court’s KSR decision (see MPEP 2143 Exemplary Rationale (A)). Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Since McGeachy discloses where IL23R polymorphisms are present in several autoimmune diseases, therapeutic administration of IL23R deficient Th1 cells, and where said cells retain normal response. Accordingly, it would have been obvious to POSITA to modify the method, as each of the elements disclosed by McGeachy, to include or instead consider treating an autoimmune disease by administering Th1 cells modified to have decreased expression of IL-23R, since this would allow transfer of functional Th1 cells to subjects with diseases characterized by pathogenic helper cells, thereby providing any restoration of Th1 cell activity and therefore any improvement in patient clinical outcome. Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary. Pertinent References 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure is the following: Regev et al. (WO2018218231; publication 29 November 2018; cited in PTO892) discloses an engineered T cell comprising (a) a genetically engineered antigen receptor that specifically binds to an antigen, which receptor may be a CAR; and (b) a disrupted gene encoding a PDL1, an agent for disruption of a gene encoding a PDL1, and/or disruption of a gene encoding PDL1, wherein the disruption of the gene may be mediated by a gene editing nuclease, a zinc finger nuclease (ZFN), CRISPR/Cas9 and/or TALEN. Further, also discloses that the immune effector cells comprising a CAR in combination with an agent (such as CRISPR, TALEN or ZFN) that increases the efficacy of the immune effector cells in the treatment of cancer, wherein the agent may inhibit an immune inhibitory molecule, such as PD1, PD-LI, CD160 [0419]. Conclusion No claims are allowed. Examiner Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (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, Christopher Babic can be reached on (571) 272-8507. 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633 /JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684 Application/Control Number: 18/273,579 Page 2 Art Unit: 1633 Application/Control Number: 18/273,579 Page 3 Art Unit: 1633 Application/Control Number: 18/273,579 Page 4 Art Unit: 1633 Application/Control Number: 18/273,579 Page 5 Art Unit: 1633 Application/Control Number: 18/273,579 Page 6 Art Unit: 1633 Application/Control Number: 18/273,579 Page 7 Art Unit: 1633 Application/Control Number: 18/273,579 Page 8 Art Unit: 1633 Application/Control Number: 18/273,579 Page 9 Art Unit: 1633 Application/Control Number: 18/273,579 Page 10 Art Unit: 1633 Application/Control Number: 18/273,579 Page 11 Art Unit: 1633 Application/Control Number: 18/273,579 Page 12 Art Unit: 1633 Application/Control Number: 18/273,579 Page 13 Art Unit: 1633 Application/Control Number: 18/273,579 Page 14 Art Unit: 1633 Application/Control Number: 18/273,579 Page 15 Art Unit: 1633 Application/Control Number: 18/273,579 Page 16 Art Unit: 1633 Application/Control Number: 18/273,579 Page 17 Art Unit: 1633 Application/Control Number: 18/273,579 Page 18 Art Unit: 1633 Application/Control Number: 18/273,579 Page 19 Art Unit: 1633 Application/Control Number: 18/273,579 Page 20 Art Unit: 1633 Application/Control Number: 18/273,579 Page 21 Art Unit: 1633
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