DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Election/Restrictions Applicant’s election without traverse of Group I, (drawn to a method of inducing ferroptosis comprising therapeutic GPR68 ), in the reply filed on 02/02/2026 is acknowledged. Claim 1 -30 are pending of which claims 23-30 (Group II , III and IV ) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected INVENTION, there being no allowable generic or linking claim. The restriction requirement is still deemed proper and is made Final. Claims 1- 14 are pending and have been examined on the merits. Please note, for clarity of the record, Applicant ’s election of compound OGM1 , 5-ethyl-5'naphthalen-l-ylspiro[ lH -indole -3,2'-3H-l,3,4-thiadiazole]-2-one , having the following structure: Per MPEP 803.02, the Examiner determined that the elected species is not allowable over the prior art, therefore, the examination of the Markush claim was not extended. Applicant also elects the patient species as cancer patient . T herefore , claims 1 5 -22 drawn to nonelected species, are withdrawn from further consideration. Claim Objections The specification (page 62, OGM17) is objected to because chemical structure OGM17 has a benzene substituent “-OCH” instead of “-OCH 3 .” Applicant is required to amend the specification to correct the typographical error , so that the disclosure accurately reflect the described compound. Claim Rejections - 35 USC § 112 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- 14 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 1 recites a method of inducing ferroptosis comprising therapeutic GPR68 inhibiting 1,2-dihydro-3'H-spiro[ indole-3,2'-[1,3,4] thiadiazole ]-2-one agent of Formula I with various substituents such as R 1 , R 2 , R 3 and R 4 . However, the specification disclose s only limited substitution for the R 1 substituent groups. For example, the specification describes R 1 naphthalene substituted with a methoxy or hydrogen and R 1 quinoline bearing only hydrogen. Similarly, the specification provides only limited examples of substitution for the R 3 and R 4 positions, and does not adequately demonstrate possession of the full range of the substituents options as recited in the instant claims. T herefore, a POSITA would conclude that Applicant does not possess the full genus of compounds defined by R 1 , R 2 , R 3 , and R 4 substituents. Claims 4 -5 recite a method of treating a subject with cancer, encompassing a broad range of cancers, including but not limited to germ cell tumor, blastomas, ovarian cancer, kidney cancer and neuroendocrine prostate cancer. However, the specification lacks description, disclosure, and experimental data relating to these cancer types. While the specification provides support for certain cancers (e.g., leukemia, glioblastoma, as an example), there is no representative examples of germ cell tumor or ovarian cancer. Therefore, given the unpredictability of cancer biology and treatment response , a POSITA would recognize that the specification does not describe treatment across the full scope of cancers, and therefore Applicant was not in possession of the claimed genus at the time of filing. Claim 11 recites “ method of claim 3 further comprising administering an ATF4 activating agent to the subject to overcome therapeutic resistance .” However, the specification does not identify, describe, or provide examples of ATF4 activating agents, nor does it describe administering such agents to a subject. The specification does not provide representative species of activating compounds, and give at least general dosing guidance of their therapeutic use for a cancer patient. Therefore, a POSITA would infer that Applicant was not in possession of the claimed method at the time of filing. This is supported by the specification (page 39) disclosing the following: Therefore, the lack of description of the claimed subject matter at the time of filing, suggest that Applicant did not possess supporting data to claim on “administering an ATF4 activating agent to the subject to overcome therapeutic resistance.” Claims 12-14 recite methos comprising administration of a GRP68 inhibitor in combination with a cancer immunotherapy agent, wherein the combination promotes anti-cancer immunity. However, the specification fails to provide any description, guidance, or example of the use of immunotherapy agent such as ipilimumab or nivolumab either alone or in combination as part of a therapeutic regimen. The specification is silent of the use of any immunotherapy agents in combination with any disclosed compound (e.g., OGM2) as part of treatment protocol. There is no disclosure that would inform a POSITA how to use immunotherapy agents, either alone or in combination, to achieve a therapeutic effect in cancer treatment. Therefore, the lack of description of the claimed subject matter at the time of filing, suggest that Applicant did not possess supporting data for the full scope of the claimed cancer genus. The specification’s failures to disclose a proper representative number of species across the claimed genus, and provide direction or guidance for the use thereof supports the conclusion that the specification lacks adequate written description of the claimed subject matter indicating that Applicant was not in possession of the entirety of the claimed genus at the time of filling of the instant application in view of the disclosure of the application as filed. Claim Rejections - 35 USC § 103 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 (i.e., changing from AIA to pre-AIA) 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. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action . The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claims 1- 5 are rejected under 35 U.S.C. 103 as being unpatentable over Gunes et al. WO 2014/041125 in view of Tarangelo et al. Oncotarget , vol. 9, no. 37, May 2018, pp. 24572–73 . Regarding claims 1- 5 , Gunes (abstract, page 1-3 ; page 52, lines 13-17 ) teaches p21 inhibitors to treat various disease such as breast cancer, kidney carcinoma, prostate cancer, cervical cancer, ovarian cancer , reading on the instant claim . Gunes (page 60, Table 1) teaches compound 5-Ethyl-5’naphthalen-1-ylspiro[1H-indole-3,2’-3H-1,3,4-thiadiazole]-2-one , which is identical to the elected species of the instant claims. Gunes ( page 22, lines 12-17; page 20, lines 32-34; page 52, lines 9-13; page 57, lines 5-22 ) teaches administration of an effective amount of the compound to a subject in need thereof . Gunes , however, does not explicitly teach a method of inducing ferroptosis and GPR68 inhibit ors. However, it is important to note that the claimed method differs only in reciting that the therapeutic effect occurs th r ough induction of ferroptosis via GPR68 inhibition. However, this represents a newly discovered mechanism of action for a known compound and known therapeutic use, which does not render the claimed method non-obvious. Therefore, “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.” See MPEP 2112(III). In addition, “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). ” See MPEP 2112 . Given that the claimed compound and Gumes’ compound are identical in structure and utility , thus, they cannot possess mutually exclusive properties, and a method of inducing ferroptosis and GPR68 inhibitors is deemed to be inherently disclosed. See MPEP 2112.01. This is supported by Tarangelo (page 24572 - 24572 ) teaches p53 -p21 pathway is involved in controlling ferroptosis in cancer cells, in part because p21 promotes conservation of intracellular glutathione during ferroptosis, thereby suppressing the accumulation of toxic lipid reactive oxygen species (lipid ROS) and prolonging cell survival. Therefore, it would have been obvious to a POSITA to combine the teachings of Gunes and Tarangelo and recognize that a p21 inhibitor would be expected to induce ferroptosis in cancer cells, and thus, useful for treating cancer via ferroptosis mechanisms. Thus, a POSITA would also recognize Gunes’s compound to also be a GPR68 inhibitor. Claims 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Gunes and Tarangelo as applied to claims 1-5 above, and in further view of Zhang et al., Theranostics . 2021 Jan 1;11(7):3167-3182 and Ye et al., ACS Chem Biol . 2020 Feb 21;15(2):469-484. The combined teachings of Gunes and Tarangelo disclose a compound identical to the elected species to induce ferroptosis for treatment in a subject in need thereof. The combined teachings, however, do not disclose a chemotherapeutic agent such as temozolomide or doxorubicin, and radiation. Regarding claim 6-7, and as applied to claim 1-5 above, Zhang (page 3168) teaches ferroptosis inducing agents enhance chemotherapy efficacy , including chemotherapeutic agents such as doxorubicin, by increasing reactive oxygen species and lipid peroxidation in cancer cells. Therefore, it would have been obvious to a POSITA to combine the teachings of Gunes in view of Tarangelo and Zhang to arrive at the claimed invention. This is because the combine d teachings of Gunes , Tarangelo and Zhang would have motivated a POSITA to apply the same rationale to increase the cell sensitization, because of the expectation that such approach would enhance anti-cancer efficacy through known ferroptosis- mediated sensitization. Regarding claim 8 -10 , Zhang (page 3175-3180) teaches a ferroptosis-inducing agent (e.g., Holo-lactoferrin) sensitizes cancer cells in the presence of radiation, suggesting the combined treatment is more potent th r ough increased ROS, ferroptosis, and DNA damage. Zhang, however, does not explicitly teach synergistic effect between ferroptosis-inducing agent and radiation. Nonetheless, Ye (abstract; page 471-480) teaches ferroptosis can be synergistically induced when radiation is combined with ferroptosis inducers (e.g., IKE and RSL3), and such synergistic effect enhances cancer cell death. Therefore, it would have been obvious to a POSITA to combine the teachings of Gunes in view of Tarangelo , Zhang and Ye to exploit the ferroptosis-sensitizing effects via ferroptosis-inducers and radiation to synergically enhance therapeutic efficacy and arrive at the claimed invention. It is important to note, while the combine teachings of the prior art do not explicitly mention immunogenic cell death, it is well known in the art that ferroptosis regulated cell death pathway or releasing damage-associated molecular patterns, thus, a POSITA would expect that immunogenic cell death would have occurred downstream of this process. In addition, the acidic tumor microenvironment would be expected, as it is well known in the art that tumors and cancer cells produce a distinctively acidic microenvironment, thus, it would expect that f erroptosis to enhance under these conditions of oxidative stress and lipid peroxidation. Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Gunes and Tarangelo , as applied to claims 1-5 above, in view of Pardoll DM. Nat Rev Cancer . 2012 Mar 22;12(4):252-64. The combined teachings of Gunes and Tarangelo disclose a compound identical to the elected species to treat able to induce ferroptosis for treatment in a subject in need thereof. The combined teachings, however, do not disclose co-administration of ferroptosis inducers with immunotherapy agent such as ipilimumab. Regarding claim 12 -14 , and as applied to claims 1-5 above, Pardoll ( abstract; page 255) teaches that immune checkpoint blockade is a well-established form of cancer immunotherapy and also discloses the clinical use of checkpoint inhibitors to enhance anti-tumor immune response. Padroll ( page 255 ) identifies ipilimumab as an FDA-approved immunotherapy for melanoma, Phase II and Phase III trials ongoing for multiple cancers . Given the immunotherapy agents, such as ipilimumab are well-known in the art against cancer , therefore, a POSITA would recognize such benefit in cancer treatment, would select immunotherapy agents for co-administration with the combined teachings Gunes and Tarangelo to arrive at the claimed invention. Regarding anti-cancer immunity, Padoll (page 252-253; page 260-262 ), however, teaches that immune checkpoint blockade enhances endogenous anti-tumor immune response and that combining checkpoint inhibitors with other targeted therapies is expected to further promote anti-cancer immunity. Therefore, a POSITA would have been motivated to combine the teachings of Gunes , Tarangelo and Padoll with checkpoint inhibitors to enhance immune-mediated tumor clearance and arrive at the claimed invention . Subject Matter Free of the Art of Record The subject matter of claim 11 is free of the art of record. The closest prior art is Gunes et al. WO 2014/041125. While Gunes teach es compound of formula I, however there is no motivation for an ordinary skill in the art to modify the teaching of Gunes to arrive at the claimed composition . Th e claim is not allowable until the 103 and 112 rejection are overcome. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claims 1- 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12194027. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ' 027 are comparable to those of the instant claims. C laim 1 of US patent ' 027 discloses a method of treating or preventing a malignancy in a mammalian subject in need thereof, comprising administering to the subject compound OGM12, having the following structure, wherein R 1 is benzene substituted with a methoxy group; R 2 and R 3 are hydrogen; R 4 is fluorine; reading on instant claim s 1 -3 : Claim 2 of US patent '027 discloses malignancy is selected from a group selected from breast cancer, skin cancer, and glioblastoma, as an example, which is comparable to the instant claims 4-5. C laims 3-5 of US patent '027 discloses the composition further comprises At least one additional therapeutic agent , such as Temozolomide , which is comparable to instant claims 6-7. Therefore, it would have been obvious to a POSITA that US patent '027 and the instant claims are not patentably distinct because they both recite the same method of treating cancer using the same class of compounds. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT PIERRE PAUL ELENISTE whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0589 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 8:00 am - 5:00 pm (EST) . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT JAMES H ALSTRUM-ACEVEDO can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-5548 . 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. /P.P.E./ Examiner, Art Unit 1622 /JAMES H ALSTRUM-ACEVEDO/ Supervisory Patent Examiner, Art Unit 1622