DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/US22/24263 , filed 04/11/2022, which claims the priority benefit of PRO Application No. 63/173,796, filed 04/12/2021. Information Disclosure Statement The information disclosure statements (IDS) submitted on 10/18/2023 , 1 2/05/2023 , 12/13/2023 , 07/26/2024 , 01/03/2025 , 02/27/2025 , and 11/11/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Status of the Application Claims 2-4, 6-19, 21-24, 26-30, 32-39, 41-52, 56, 62-63, 65-66, 68-69, 71-72, 77-84, and 88-95 have been cancelled. Claim s 1, 5, 20, 25, 31, 40, 53-55, 57-61, 64, 67, 70, 73-76, and 85-87 are pending and currently under examination. Claim Objections Claim 87 is objected to because of the following informalities: the term “ dyregulation ” appears in claim 87, line 2 appears to be misspelled. Appropriate correction is required. 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. Claim s 1 and 5 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) ( en ban c ), the Federal Circuit noted the importance of an application's disclosure and stated, "the hallmark of written description is disclosure." A disclosure adequately describes an invention when it "reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Id. at 1351. "A 'mere wish or plan' for obtaining the claimed invention is not adequate written description." CentocorOrtho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011 ). What is required to meet the written description requirement "varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar , 418 F.3d 1349, 1357 (Fed. Cir. 2005). The Federal Circuit explained what is required to meet the written description requirement in Ariad Pharm., Inc. v. Eli Lilly & Co.: This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d at 575. Thus, we have recognized that determining whether a patent complies with the written description requirement will necessarily vary depending on the context. Capon v. Eshhar , 418 F.3d 1349, 1357-58 (Fed. Cir. 2005). Specifically, the level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the c omplexity and predictability of the relevant technology. Id. For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including "the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue." Id. at 1359. A written description of a chemical genus "requires a precise definition, such as by structure, formula, [or] chemical name" of the claimed subject matter sufficient to distinguish it from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997). The Federal Circuit reflected on Eli Lilly in Ariad while explaining how to sufficiently describe of a genus of compounds: We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001 )). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. A "representative number of species" must typify the entire claimed genus and account for variation between the species of the genus. [A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated. Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004). The present claims encompass any compound comprising the structure of formula I (Below). By contrast, the specification supports only a few compounds within this genus such as compounds of table 2. These few species cannot possibly typify the entire genus claimed or account for all of the variation between species of such a genus. For example, while the genus of " [a] compound of formula I wherein A is a pyrrole " encompasses any compound with an pyrrole ring or selenophene moiety at A . H owever, there are no existing example s of either species of formula I containing a pyrrole or selenophene at position A . Regarding formulas I, Ia , and Ib , R1 cite an alkyl at R1 and provide only two representative species of a C1-C2 alkyl at position R1and no species of a benzyl at R1. Support for the entirety of the claimed genus cannot be extrapolated from few species examples . For example, a compound search executed in CAplus would return over 200,000 structure hits using the limitations cited by the inst a nt claims which illustrates the exceedingly broad scope of the instant claims. See MPEP 2163. Chemistry and biotechnology are generally considered to be unpredictable and/or have unpredictable factors. See, e.g., In re Carleton, 599 F.2d 1021, 202 USPQ 165, 170 (CCPA 1979) ("Although there is a vast amount of knowledge about general relationships in the chemical arts, chemistry is still largely empirical, and there is often great difficulty in predicting precisely how a given compound will behave."). The pharmaceutical art, that is the use of a chemical compound to affect a desired physiological activity, is generally considered to be unpredictable and/or have unpredictable factors. See, e.g., In re Fisher, 427 F.2d 833, 839 (CCPA 1970) ("In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved (emphasis added); In re Bowden, 183 F.2d 115, 86 USPQ 419, 423 ("chemical reactions frequently are unpredictable"). Considering the unpredictability found in chemistry and biotechnology. Accordingly, when a claim presents a genus with substantial variation as that currently presented by Applicant, the disclosure must adequately reflect such variation with a representative number of species. The lack of any disclosure of examples may be considered in determining whether a claimed invention was adequately described. Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 1353 (Fed. Cir. 2011 ). A few species is not a "representative number of species" for unpredictable arts such as chemistry and biotechnology. See, e.g., Ariad, 598 F.3d at 1354-55 (claiming that the inventor has an obligation to disclose examples when the art is unpredictable). The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the entirety of the genus now claimed, i.e., additional complete or partial structures, other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or some combination thereof demonstrating possession of the entirety of the claimed genus. This rejection may be overcome by further resolving the structure s of formula I, claim 1 and formulas Ia and Ib in claim 5 . Claim Rejections - 35 USC § 112 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 appl icant regards as his invention. Claim s 40 and 53-55 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 40 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: The definition of R6 in claim 40 is not provided for the compound of formula Ic . A skilled artisan would be unable to determine which functional group applicant means by R 6 which renders the claim i nde finite as the claim is currently written. This rejection may be overcome by defining what the identity of R 6 is in claim 40. Claim 53 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: The definitions of R 5 and R 6 in claim 53 is not provided for the compound of formula II. A skilled artisan would be unable to determine which functional group applicant means by R 5 or R 6 which renders the claim indeterminate as the claim is currently written. This rejection may be overcome by defining what the identities of R 5 and R 6 are in claim 53. Claim 54 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: The definition of R 5 in claim 54 is not provided by the definitions of the compound of formula IIIa. A skilled artisan would be unable to determine which functional group applicant means by R 5 which renders the claim indeterminate as the claim is currently written. This rejection may be overcome by defining what the identity of R 5 is in claim 54. Claim 5 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: The definition of R 5 in claim 55 is not provided by the definitions of the compound of formula IIIa. A skilled artisan would be unable to determine which functional group applicant means by R 5 which renders the claim indeterminate as the claim is currently written. This rejection may be overcome by defining what the identity of R 5 is in claim 55. Claim Rejections - 35 USC § 102 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 1 , 5, 20, 25 , and 31 are rejected under 35 U.S.C. 102 (a)(1) and 102(a)(2) as being anticipated by Atal l ah ( WO 2016/196776 A2 ) . Atal l ah teaches the compound of A-114 on table 1 ( 5-[(3R)-3-( 4-cyclopropyl-2-fluorobenzamido) piperidin- 1 -yl]-3-[(3-pheny l -1,2-thiazol-5-yl)ammo]pyrazine-2-carboxamide ), which anticipates the compound s of formula I , Ia and Ib of the instant claims , where E is phenyl, A is thiazole, B is pyridine, D is piperidine and R1 is H. Atal l ah’s compound A-114 (Above) Applicants formula I (Left) Formula Ia (Center) Formula Ib (Right) Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 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. 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 . Claims 86 and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Atallah (WO 2016/196776 A2). The instant claims are directed to a pharmaceutical composition comprising a compound of formula I, claim 1 in a method of treating a disease or disorder characterized by TACC dyregulation in a subject comprising administering a compound of claim lor a pharmaceutically acceptable salt thereof to the subject. (sic) In addition to the disclosures of Atallah above, Atallah et al. teach “ a method for treating a cancer comprising administering to a patient in need a therapeutically effective amount of a compound of any one of formulas described herein or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, and/or pharmaceutically acceptable prodrug thereof” [0047] . Atallah teaches “Pharmaceutical compositions may be formulated in a conventional manner using one or more physiologically acceptable carriers including excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically” [00508]. It is noted from the specification that “In certain embodiments, the TACC mediated disease or disorder is cancer. In certain embodiments, the cancer is breast cancer, colon cancer, melanoma cancer, lung cancer, central nervous system cancer, ovarian cancer, leukemia cancer, renal cancer or prostate cancer”. (pg. 55) Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application , to administer Atallah’s compound of A-114 in a composition further comprising an excipient for the treatment of a disease or disorder characterized by TACC d ys regulation in a subject in need thereof because of Atallah’s teaching of pharmaceutical compositions for the treatment of cancer, including lymphoma . A person of ordinary skill in the art would have been motivated to administer a compound of A-114 for the treatment of a disease characterized by TACC dysregulation as taught by Atallah because a skilled artisan would have had a reasonable expectation of success in treating a disease characterized by TACC dysregulation because a compound administered for the treatment of cancer would also encompass a disease or disorder which is also characterized by TACC dysregulation . See MPEP 2144.01 and 2144.06 . 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 and 5 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim 1 of U.S. Patent No. 11,622,966 B2 . Although the claims at issue are not identical, they are not patentably distinct from each other because formula I of the reference satisfies the structural limitations of formulas I and Ib in instant claims 1 and 5 wherein R1 is H, A is isoxazole, E is anisole, B is pyrimidine, D is morpholine in regards to formula I and further where X1 is O, X2 is N and X3 is CR3 where R3 is H for formula Ib. Allowable Subject Matter Claims 57-6 1 , 64, 67, 70, 73-76 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Conclusion Claims 1, 5, 20, 25, 31, 40, 53-55, and 85-87 are rejected, claims 57-61, 64, 67, 70, 73-76 are objected to. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ERNESTO VALLE JR whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-5356 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 0730-1700 M-F EST, 1st Friday off . 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 Adam C Milligan can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-7674 . 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. /E.V./ Examiner, Art Unit 1623 /ADAM C MILLIGAN/ Supervisory Patent Examiner, Art Unit 1623