FABI INHIBITORS FOR GRAM-NEGATIVE PATHOGENS

§102 §103 §112

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 . Response to Arguments Applicant’s response from 7/21/2026 is acknowledged. Claim Rejections - 35 USC § 112 In view of Applicant’s claim amendments this rejection is hereby withdrawn. Claim Rejections - 35 USC § 103 In view of Applicant’s claim amendments, the search was expanded across the breadth of Applicant’s new claims. The Examiner disagrees with Applicant that the prior art does not teach a halo substitution on the benzofuran ring. The art of record Pauls teaches this substitution. Further, a substitution of H for F is a known bioisostere substitution in the art. Accordingly, a modified rejection and a new rejection have been made below. Claims 1, 4-7, 17 and 23 are pending, and have been examined herewith. Claim Rejections - 35 USC § 102 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)(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, 4-7, 17 and 23 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2021/123372 A1 to Gerusz et al. (“Gerusz”, of record). Gerusz provides compounds of the general formula (I) or a pharmaceutically acceptable prodrugs, salts and/or solvates thereof, wherein LHS is selected from the group consisting of LHSa and LHSb And wherein, the asterisk (*) marks the point of attachment. PNG media_image1.png 444 464 media_image1.png Greyscale These compounds exhibit antibacterial activity against Gram-negative and Gram-positive bacteria, especially S. aureus, E. coli, K. pneumoniae and A. baumannii. Pharmaceutical compositions containing these compounds, therapeutic uses thereof and methods for manufacturing the same are also provided. A disclosed compound of Gerusz is Applicant’s compound of claim 17. PNG media_image2.png 104 288 media_image2.png Greyscale (p. 99). 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, 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. Claims 1, 4-7, 17 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Muñoz et al., Facilitating Compound Entry as a Means to Discover Antibiotics for Gram-Negative Bacteria, Acc Chem Res, 2021 Mar 16;54(6):1322-1333, Epub 2021 Feb 26 (“Muñoz”, of record), further in view of US 2009/0156578 A1 to Pauls et al. (“Pauls”). Muñoz describes the discovery and successful applications of a promising strategy for enhancing the accumulation of Gram-positive-only antibiotics as a means of imbuing compounds with broad-spectrum activity. Per Muñoz, “we describe a set of important criteria to consider when selecting candidate Gram-positive-only antibiotics for conversion to Gram-negative-active versions via the eNTRy rules. As detailed herein, using this blueprint the spectrum of activity was expanded for three antibiotic classes that engage three different biological targets: DNA gyrase inhibitor 6DNM, FabI inhibitor Debio-1452, and FMN riboswitch inhibitor Ribocil C.” (Abstract). See cf Figure 3. PNG media_image3.png 253 466 media_image3.png Greyscale Muñoz describes the importance of having a primary amine for accumulation in E. coli, with charge on the amine being a primary factor in accumulating- as in the compound above. It is noted that Debio-1452-NH3 describes a compound, only charged, as in Applicant’s claim 17. However, the description of a primary amine underneath the compound also describes the same compound as in Applicant’s claim 17. Muñoz does not specifically disclose a F substitution on the methylbenzofuran ring, as in Applicant’s elected species of compound. It is noted, however, that H versus F substitution is a well known bioisostere substitution in the art. Further, there is art on compounds with the general structure of Formula (I), which are designated to have this F substitution, as further disclosed in Pauls. Regarding claims 1 and 6, Pauls teaches a fab1 inhibitor (para [0007], [0531]) compound of formula I or a salt thereof, wherein G1 is CH2; Q is CHRa, where Ra is H; X is C=O; R1 is H; R2 is C1-alkyl; R3 is H and R4 is methyl (para [0825], Example 76). PNG media_image4.png 96 257 media_image4.png Greyscale Regarding claim 23, Pauls further teaches treating a subject with a bacterial illness by way of targeting bacterial enzymes. (Abstract, [0004-5]).1 Pauls further discloses stereoisomers of the compounds. ([0045], [0086]). Pauls further a broader structure, wherein, as in Applicant’s elected species a F substitution can be made. Namely, this is Applicant’s elected species with the F depicted. PNG media_image5.png 187 653 media_image5.png Greyscale This is the broader structure of Pauls: PNG media_image6.png 312 326 media_image6.png Greyscale Claim 2 recites A, where R8 can be F, and L can be O. PNG media_image7.png 119 146 media_image7.png Greyscale Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to combine the teachings of Muñoz and Pauls in order to practice Applicant’s claimed invention with a reasonable expectation of success. The skilled artisan would have been motivated to do so because Applicant’s claimed species is disclosed as nearly the same compound in Muñoz, which further specifically outlines the benefit of a primary amino group in the structure for having antibacterial activity. The skilled artisan would have been further motivated to modify the compound with an F substitution on the methylbenzofuran ring, as in Applicant’s elected species of compound. Motivation to do so is because H versus F substitution is a well-known bioisostere substitution in the art. Further, Pauls further teaches compounds with the general structure of Formula (I), which are designated to have this F substitution. Other relevant art The Examiner also restates that references in the various PCT search reports disclose relevant art with compounds within the broader scope of claim 1. As does art from Applicant’s IDS, e.g. WO 2020/099341 A1 to Gerusz et al. (“Gerusz”, of record). Gerusz relates to antibiotic compounds for the treatment of N. gonorrhoeae infections and related infections of Formula (I). (Abstract). PNG media_image8.png 128 260 media_image8.png Greyscale Within this formula is also formula IV. PNG media_image9.png 379 767 media_image9.png Greyscale Per the definition of substituents: PNG media_image10.png 180 642 media_image10.png Greyscale PNG media_image11.png 630 754 media_image11.png Greyscale PNG media_image12.png 39 565 media_image12.png Greyscale This encompasses a compound of Applicant’s claim 1. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. (p. 4-6). Any inquiry concerning this communication or earlier communications from the examiner should be directed to SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00. 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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. /SVETLANA M IVANOVA/ Primary Examiner, Art Unit 1627 1 It is noted that claims 1, 6 and 23, although not for Applicant’s elected species for which an obviousness rejection applies, are otherwise rejectable under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 2009/0156578 A1 to Pauls et al. (“Pauls”).