CARBOXAMIDE COMPOUNDS AS PGE2 RECEPTOR ANTAGONISTS

NON-FINAL REJECTION This application is a 35 U.S.C. 371 (national stage) application of PCT/CN2023/077578, filed Feb. 22, 2023, which claims benefit of priority to Provisional Applications 63/475,462, filed Nov. 10, 2022; 63/473,258, filed May 16, 2022; and 63/372,204, filed Feb. 24, 2022. Claims 16-31, as amended, are pending. 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 Applicant' s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Information Disclosure Statement The information disclosure statement (IDS) submitted on Aug. 23, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. Election/Restrictions Applicant's election with traverse of Group I, drawn to compounds, and the compound species of Example 221, in the reply filed on Sep. 22, 2026 is acknowledged. The traversal is on the ground(s) that it should be no undue burden on the Examiner to consider all claims in the single application (Remarks, p. 2). This is not found persuasive because search burden is not a consideration in unity of invention practice under 35 U.S.C. § 371 and 37 C.F.R. 1.499. See also MPEP §§ 1850, 1893.03(d), and 1896. The requirement is still deemed proper and is therefore made FINAL. The compound of Example 221, having the structural formula shown below, Elected Species (Example 221) Formula (I) PNG media_image1.png 202 368 media_image1.png Greyscale PNG media_image2.png 166 380 media_image2.png Greyscale reads on formula (I) as recited by claims 16, 24, 26, and 28 wherein PNG media_image3.png 132 202 media_image3.png Greyscale is PNG media_image4.png 120 160 media_image4.png Greyscale , Y1 is -CRaR1a, where Ra and R1a are each hydrogen (-CH2-); Ar1 is -C0-alkylene-aryl (phenyl), substituted with one Re, where Re is C1-6 fluoroalkyl (CF3); R5 is hydrogen; r is 1; Y2 is absent and Ar2 is directly connected to X2; Ar2 is -C0-alkylene-aryl (phenyl); Y is CR3, and R2 and R3 are each hydrogen; PNG media_image5.png 106 146 media_image5.png Greyscale is PNG media_image6.png 106 144 media_image6.png Greyscale , n is 0, or n is 1 and X is absent; Y3 is –(CRa2)m- and m is 0; and R1 is -COOH. The compound of Example 221 does not read on claims 17-23 (wherein ring B-Y3-R1 is benzoic acid); claims 25 and 31 (wherein Ar2-Y2 is attached para rather than meta from the amide linker); and claim 27 (wherein Formulae XIII, XIV, XV, XVI, and XVII exclude cyclohexyl from ring B). Claims 17-23, 25, 27, and 29-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on Sep. 22, 2026. Because the elected compound is free of the prior art, search and examination has been extended to the next species. See MPEP § 803.02. Claims 16, 24, 26, and 28 are currently pending and under consideration. Claim Rejections – Improper Markush Grouping Claims 16 and 28 are rejected on the basis that they contain improper Markush groupings 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 groupings of claims 16 and 28 are 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: Claim 16 is drawn to compounds of formula (I), which encompasses approximately 5,150 distinct core structures formed by the combinations of variable ring A (206 options) and variable ring B (25 options). Further, substituents Y1-Ar1 and Y2-Ar2 encompass any cyclic group, as well as many non-cyclic substituents attached to ring A by linkers of 0-7 atoms in length, giving rise to thousands more variations for each of the thousands of structural cores. Similarly, claim 28 recites over 1000 compound species, again lacking any common structural core. As noted in the Restriction Requirement (¶ 8), the claimed compounds are so divergent that the only shared structural feature across all compounds of the invention is an amide linker. This makes it unlikely that all compounds of formula (I) share a common biological activity or mechanism, and also makes any meaningful search of formula (I) impossible. In response to this rejection, Applicants should either amend the claims to recite only groupings of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature (for example, as seen in claim 24, drawn to the subgenus of Formula (IX); or present a sufficient showing that the species recited in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1). 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 § 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. Claims 16, 24, and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nozawa et al. (US Pub. 2011/0144153, cited on the IDS dated 8/23/2024). Nozawa et al. exemplify the compound of Example 69 (Table 154, p. 95), having the structural formula, Nozawa et al. Compound of Example 69 Formula I of claim 16 PNG media_image7.png 258 456 media_image7.png Greyscale PNG media_image2.png 166 380 media_image2.png Greyscale which reads on formula (I) as recited by claims 16, 24, and 26, wherein PNG media_image3.png 132 202 media_image3.png Greyscale is PNG media_image8.png 130 162 media_image8.png Greyscale , Y1 is -CRaR1a, where Ra and R1a are each hydrogen (-CH2-); Ar1 is -C0-alkylene-aryl (phenyl), substituted with one Re, where Re is halogen (chloro); R5 and R6 are each hydrogen; r is 1; Y2 is absent and Ar2 is directly connected to X2; Ar2 is -C1-haloalkyl (CF3); Y is CR3, and R2 and R3 are each hydrogen; PNG media_image5.png 106 146 media_image5.png Greyscale is PNG media_image6.png 106 144 media_image6.png Greyscale , n is 0, or n is 1 and X is absent; Y3 is –(CRa2)m- and m is 0; and R1 is -COOH. Nozawa et al. Compound of Example 69 Formula IX of claim 24 Formula IXB of claim 26 PNG media_image7.png 258 456 media_image7.png Greyscale PNG media_image9.png 140 346 media_image9.png Greyscale Further, compound 69 of Nozawa et al. reads on formula (IX) as recited by claim 24, and formula (IXB) as recited by claim 26, wherein X4 and X5 are each CR6, and R6 is hydrogen. Thus, Nozawa et al. anticipates claims 16, 24, and 26. Claim Objections Applicant is advised that should claim 24 be found allowable, claim 26 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://portal.uspto.gov/external/portal. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). /SARA E. TOWNSLEY/Examiner, Art Unit 1629