Cannabinoid Receptor Modulating Compounds

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 Instant application 18/709949 filed on 05/14/2024 claims benefit as follows: CONTINUING DATA: PNG media_image1.png 33 367 media_image1.png Greyscale Status of the Application Claims 1-3, 5-9, 11-15 and 17-23 are pending. Information Disclosure Statement The information disclosure statement (IDS) submitted on 05/14/2024 was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Election/Restrictions Applicant’s species election without traverse of compound 20 PNG media_image2.png 185 190 media_image2.png Greyscale in the reply filed on 08/05/2026 is acknowledged. Examination will begin with the elected species. In accordance with the MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id. As per MPEP 803.02, the Examiner will attempt to determine whether the entire scope of the claims is patentable. Applicants' elected species, as shown above, does make a contribution over the prior art. Therefore, according to MPEP 803.02: should the elected species appear allowable; the search of the Markush-type claim will be extended. The search and examination should be continued until either (1) prior art is found that anticipates or renders obvious a species that falls within the scope of a proper Markush grouping that includes the elected species, or (2) it is determined that no prior art rejection of any species that falls within the scope of a proper Markush grouping that includes the elected species can be made. The Examiner need not extend the search beyond a proper Markush grouping. Species Election A careful review of the prior art has indicated that elected species is free of the prior art. A claim directed to the elected species in independent form would be free of prior art. The examiner has moved onto alternative species embodied within the general formula recited in the instant claim 1, and subsequent examination is based on this species expansion. Claims 2 ,6, 8, 13, 17, 18 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/05/2026. Claim Objections Claim 1 is objected to because of the following informalities: The claim recites” A compound comprising a structure of Formula I…” The examiner suggests “A compound of Formula I…” in the interests of clarity. Appropriate correction is required. Claim Interpretation The term “substantially” has been defined in instant specification (see para. [0092] and [0093]): PNG media_image3.png 195 669 media_image3.png Greyscale Therefore, the term “substantially (R) stereochemistry”, recited in instant claim 14, is interpreted as greater than 50% enantiomeric excess of enantiomer (R) and the term “substantially (S) stereochemistry”, recited in instant claim 15, is interpreted as greater than 50% enantiomeric excess of enantiomer (S). 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 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, 3, 5, 7, 9, 11, 12, 14, 15, 19, 21, 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over WO-03/026648-A1 (made of record on the IDS) in view of Meanwell (Nicholas A. Meanwell, Top Med Chem (2015) 9: 283–382; the reference has been provided with the previous office action). WO-03/026648-A1 discloses and claims compounds of Formula Ib: PNG media_image4.png 189 146 media_image4.png Greyscale as potent cannabinoid receptor antagonists (see abstract): PNG media_image5.png 126 376 media_image5.png Greyscale For example, WO-03/026648-A1 discloses example 36 (see page 13, CAS Registry Number 505031-20-9): PNG media_image6.png 218 362 media_image6.png Greyscale PNG media_image7.png 56 571 media_image7.png Greyscale In example 36, the positions corresponding to instant variables of instant Formula I: PNG media_image8.png 134 97 media_image8.png Greyscale are as follows: X is PNG media_image9.png 131 116 media_image9.png Greyscale wherein R1c is halogen (Cl), R1a, R1b, R1d and R1e are each hydrogen, Y1 is PNG media_image9.png 131 116 media_image9.png Greyscale wherein R1a-e are each hydrogen, Y2 is hydrogen, Z1 and Z2 are each hydrogen, A is SO2-R4 wherein R4 is PNG media_image10.png 89 73 media_image10.png Greyscale wherein R20a and R20b are each linear C1 alkyl (methyl), and Q is S-CH3. The instant claims recite a proviso that when Q is -S-R3, R3 is not linear or branched alkyl. Therefore, the above compound differs from compounds of instant Formula I only in the position corresponding to instant Q variable. However, applying KSR prong (B) - Simple substitution of one known element for another to obtain predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the alkyl group present in example 36 with an alkyl group substituted with halogen(s) to arrive at compounds embraced by instant Formula I and use the compounds for the same purpose as disclosed in WO-03/026648-A1. For example, one of ordinary skill would substitute the hydrogen(s) in the C1 alkyl group of R3 with fluorine atom(s) to arrive at a substituted alkyl as recited in the present claims. As evidenced by [0026] of the specification, all permissible substituents of organic compounds reads on the phrase “substituted” which includes the halogen fluorine. Meanwell teaches that fluorine is an isostere of hydrogen (see section 2.1, page 285). Further, Meanwell teaches that introduction of fluorine to replace a hydrogen atom can influence potency (see last paragraph on page 285). One of ordinary skill would have been motivated to prepare further examples of cannabinoid receptor antagonists and would expect retention of activity after said H-F substitution. Regarding instant claims 14 and 15, one of ordinary skill in the art would have been motivated to prepare both stereoisomers because WO-03/026648-A1 teaches stereoisomers and compounds of formula 1b* having a chirality center present at the position marked with * in instant Formula I (see page 4): PNG media_image11.png 150 635 media_image11.png Greyscale PNG media_image12.png 226 617 media_image12.png Greyscale Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm. 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, Clinton A Brooks can be reached at (571)270-7682. 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. /I.S./Examiner, Art Unit 1621 /GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621