TRUXILLIC ACID MONOESTER-DERIVATIVES AS SELECTIVE FABP5 INHIBITORS AND PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

§103 §112 §DOUBLEPATENT

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 . Amended claims 1-2, 6, 8, 11, 20-21, 25, 32, 35-36, 43, 46 and withdrawn claims 47-48, 55, 57 and 62-64 are pending. binding affinity to FABP This action takes into consideration discussion with Attorney on 10/01/2026 with regards to amendments for favorable office action. 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. Claim(s) 1, 2, 6, 8, 11, 20, 21, 25, 32, 35, 36, 43, and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yan, European Journal of Medicinal Chemistry (2018), 154, 233-252 and Ojima, WO2017156354. Yan teach, Table at page 241 PNG media_image1.png 584 474 media_image1.png Greyscale PNG media_image2.png 366 386 media_image2.png Greyscale Ojima also teach compounds with binding affinity to FABP PNG media_image3.png 352 662 media_image3.png Greyscale More specifically Ojima teaches substructure formulae of the above formula at claim 10 page 15, and also specific species at pages 15-17, 86-89. From Ojima page 69 teaches how to make: PNG media_image4.png 372 534 media_image4.png Greyscale (Also see section under Objection) The Difference: While the core structure of the above Ojima formula, that is structure without the multiple R groups and of Yan and the instant claims are the same, Ojima and Yan do not teach the compounds of the instant formula, because as recited in the claims, the multiple provisos in the instant claims exclude specific selective combination the R groups disclosed in Yan and Ojima. The key word here is ‘combination’ (more on this later with an example). These provisos are recited with ‘other than’ claim language to avoid anticipatory rejections of claims. The position taken by the Examiner is that the compounds of instant claims including that of species claim 43 represent ‘selective combination’ (more on this later with an example) of R group substituent combinations. Substituents such as the R groups recited and exemplified in the cited references and in the instant claims are routinely used to decorate core templates of biologically active compounds to optimize desired physical and chemical properties. The limitations of dependent claims are further selection of combination of R group possibilities. The first word ‘SAR’ in the title of cited Yan means ‘structure-activity-relationship’, the elementary medicinal chemistry principle illustrated in the last four columns of Yan Table. The actual values in these columns are irrelevant since the claims examined are drawn to products. It is acknowledged that Yan and Ojima are focused on the antinociceptive activity of the compounds and Yan and Ojima are silent with respect any and all inherent property of the compounds. Even though the elected claims are drawn to product, disclosure throughout the specification are considered including the intended use of the compounds. That said the following Examination guidelines is relevant in this context: MPEP 2112 Requirements of Rejection Based on Inherency; Burden of Proof [R-10.2019], "[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." Provisos and selective combination:. Consider the elected species (Remarks 03/16/2026 page 2) that is included in claims and the Ojima compound shown below: PNG media_image5.png 110 160 media_image5.png Greyscale PNG media_image6.png 106 134 media_image6.png Greyscale Elected species Ojima at page 87 claim 37 The difference is methoxy (OMe) group in the compound for which protection is sought. This group OMe explicitly is included in other exemplified species (plural) in the instant claims (see claim numbered pages 16-17) and in Ojima claims (numbered pages 87-88) with other combinations of R possibilities. This is an example of deliberate exclusion of otherwise same prior art compound structure to avoid rejection under 35 USC § 102. As such the position taken is that the invention is a selective combination of the inventions by the prior arts done in a manner obvious to one of ordinary skill in the art. Patent for the combination of known elements wherein their functions remain the same withdraws “what is already known into field of its monopoly and diminishes resources available to skilled men”. Sakraida v. Ag Pro, Inc.189 USPQ 449, 425 US 273, (1976). Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office Response to Applicant’s Remarks filed 08/12/2026: The focus of the Remarks is/are, PNG media_image7.png 158 636 media_image7.png Greyscale PNG media_image8.png 50 634 media_image8.png Greyscale PNG media_image9.png 72 638 media_image9.png Greyscale PNG media_image10.png 72 628 media_image10.png Greyscale PNG media_image11.png 78 628 media_image11.png Greyscale Applicants arguments are not persuasive. Firstly the rejection is not under 35 USC § 102. With regards to ‘substituents, ’R-group substituents noted by the Applicant are result-effective variables. As explained in the previous action, substituents such as the R groups recited and exemplified in the cited references and in the instant claims, are routinely used to decorate core templates of biologically active compounds to optimize desired physical and chemical properties. The core template is not prior art. With regards to ‘combination’, as explained in the previous action, the invention is a selective combination of the inventions by the prior arts done in a manner obvious to one of ordinary skill in the art. See Sakraida v. Ag Pro, Inc. The argument with regards to ‘efficacy, heRG toxicity and mutagenicity’ and ‘synergism with Taxane’: The arguments is/are specious at best. The claims examined are drawn to product and not method. although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). With regards to the alleged demonstration synergistic or otherwise advantageous combined effects, Applicant points to cell line ex vivo data Table 4 for two compounds SBFI-102 1y (SBFI-102) 1w (SBFI-103). These are buried deep in the base claim 1 recitation. Also see claim 43, where these are found along with the first compound in claim 43 (elected species which was discussed/compared with compound of cited Ojima at page 87 claim 37. Also Table 3 data is based on in silico method known in the applicant admitted to art. One of skill in the art, would use such predictive model to arrive at the above-mentioned prior art substituents (and combination of substituents) to decorate the prior-art core template of cited Ojima. Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103. 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. Claim(s) 1, 2, 6, 8, 11, 20, 21, 25, 32, 35, 36, 43, and 46 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10968163. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims contain overlapping subject matter. The formula of 10968163 falls under the scope of the claim 1 of instant case in a species (10968163) and genus relationship. With core invariable moiety being the same in both cases, the difference is the combination of various R groups decorating the core template. Instant claim PNG media_image12.png 216 218 media_image12.png Greyscale (numbered page 2) and also at page 17 PNG media_image13.png 166 178 media_image13.png Greyscale (of instant dependent claim) overlap with 10968163 base claim 1 PNG media_image14.png 248 254 media_image14.png Greyscale Claim(s) 1, 2, 6, 8, 11, 20, 21, 25, 32, 35, 36, 43, and 46 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11026910 . Although the claims at issue are not identical, they are not patentably distinct from each other because the claims contain overlapping subject matter. The formula of 11026910 falls under the scope of the claim 1 of instant case in a species (11026910 ) and genus relationship. With core invariable moiety being the same in both cases, the difference is the combination of various R groups decorating the core template. The language ‘enantiomerically enriched’ compounds of claim 1 of 11026910 PNG media_image15.png 236 236 media_image15.png Greyscale falls under the scope of the racemate of instant claim 1 formula. The rejection are held in abeyance as suggested by the Applicant. Claim(s) 1, 2, 6, 8, 11, 20, 21, 25, 32, 35, 36, 43, and 46 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 19 and 20 of U.S. Patent No. 9604904 further in view of Yan, European Journal of Medicinal Chemistry (2018), 154, 233-252 and Ojima, WO2017156354 (compounds with binding affinity to FABP) and Pires J Med Chem 58, 4066-4072. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims contain overlapping subject matter. Claims of 9604904 are drawn to compounds of the same invariable of the instantly claimed formula, with the difference being the provisos in the instant claims The difference is in the substituents decorating the said invariable core structure. As explained in the rejection under 35 USC § 103, Yan and Ojima teach these result-effective variables. Note the entirety of rationale presented under 35 USC § 103 is incorporated here. Applicant admitted to references see Published Application 20230365488, page 50, in particular Pires J Med Chem 58, 4066-4072 to specific these substituents to decorate the known template to arrive at the instant limitations. For same rationale discussed above, Claim(s) 1, 2, 6, 8, 11, 20, 21, 25, 32, 35, 36, 43, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-38, 40-42 of copending Application No. 18346363 (reference application) further in view of Yan, European Journal of Medicinal Chemistry (2018), 154, 233-252 and Ojima, WO2017156354 and Pires J Med Chem 58, 4066-4072.. Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. The art made of record and not relied upon is considered pertinent to applicant's disclosure. Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804 Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32 (2010) 324–330. 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 applicant regards as his invention. Claim(s) 1, 2, 6, 8, 11, 20, 21, 25, 32, 35, 36, 43, and 46 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. The phrase PNG media_image16.png 18 268 media_image16.png Greyscale render the claims vague as these claims are drawn to compounds with defined PNG media_image17.png 98 112 media_image17.png Greyscale (poartial structure from base claim 1). Clarification is needed whether in the context of above defined structure and further because Truxillic acids are found in are found in a variety of plants, for example in coca. OBJETION: Disclosure at page 87 Example 1 needs correction. The starting material cannot make the titled compound. Note the chemistry is same as that of Ojima page 69. THIS ACTION IS MADE FINAL. 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 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, Andrew Kosar can be reached at (571) 272-0913. 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. /NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625