CTFR 17/919,376 CTFR 100014 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION Status of the Claims Claims 16-17 currently pending. Claims 28-38 are rejected. Information Disclosure Statement The Information Disclosure Statement (IDS) dated 04/01/2026 has been considered. Response to Amendment/Arguments The amendment filed 03/19/2026 is compliant with the requirements of 37 CFR 1.121(c), accordingly the amendment has been entered. Applicant’s arguments have been fully considered and are addressed below: 35 USC § 103 Rejection The rejection of claims 16-17 and 28-38 under 35 USC 103 for being obvious over Skolc et al. in view of Bruns et al. has been overcome by the amendments to said claims. The rejection has been withdrawn. The rejection of claims 16-17 and 28-38 under 35 USC 103 for being obvious over Valade et al. in view of Bruns et al. has been overcome by the amendments to said claims. The rejection has been withdrawn. Scope of the Elected Invention In accordance with the MPEP 803.02, examination of the Markush-type claims has been extended, as necessitated by amendment, to the scope of formula (Ib) or (IIb) wherein R3 is chloro, R2 is hydrogen and R5 is substituted alkyl, which was not found allowable over the prior art. Incidental to this search, additional species were found and are included in the rejection under 35 USC 103 below to advance prosecution. New Claim Rejection - 35 USC § 103 07-20-aia AIA 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. 07-23-aia AIA 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. 07-21-aia AIA Claims 1 6-17 and 28-38 are re jected under 35 U.S.C. 103 as being unpatentable over Zh ang et al. in WO 2018/057973 in view of Breda et al. “Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites” PNAS, 2016, 113(19) pp. 5435-5440. De termining the scope and contents of the prior art. (See MPEP § 2141.01) Zhang et al. teach a variety of novel compounds which inhibit indoleamine-2,3- dioxygenase (IDO), specifically indoleamine 2,3-dioxygenase 1 (IDO1), and tryptophan-2,3- dioxygenase (TDO). See para. [0003]. Zhang et al. states that the compounds are useful for the treatment of neurological diseases including Parkinson’s disease, per instant claims 17 and 38. See paragraphs [0014] - [0016]. Zhang identifies six compounds in particular, P-0002, P-0136, P-0198, P-0191, P-0012, and P-0029, that are 4,6-indazoles that have improved inhibitory activity against IDO and/or TDO over their 5,7 indazole analogs. See pages 385-387. All six compounds inhibited TDO in both a biochemical/enzymatic assay and a cellular assay at IC50 values between 0.0001 and 10 uM. See para. [0574] and Table 2 beginning on page 355. The compounds are embraced by instant formula (IIa) PNG media_image1.png 103 128 media_image1.png Greyscale of claim 16 wherein: R3 is chloro (see also claims 28-31), R2 and R4 are each hydrogen (see also claims 28, 31-34), and R5 is substituted C1 or C4 alkyl for P-0002, P-0136, P-0198 and P-0191 (see also claims 35-37), substituted C7 cycloalkyl for P-0012 (see also claims 35-36), or substituted 9 membered heterocycloalkyl for P-0029 (see also claim 35). Their structures are provided herein for reference: PNG media_image2.png 152 545 media_image2.png Greyscale on p. 209, PNG media_image3.png 136 609 media_image3.png Greyscale on p. 231, PNG media_image4.png 174 551 media_image4.png Greyscale on p. 244, PNG media_image5.png 143 549 media_image5.png Greyscale on p. 243, PNG media_image6.png 152 547 media_image6.png Greyscale on p. 191, and PNG media_image7.png 139 546 media_image7.png Greyscale on p. 213. Breda et al. teach that chemical inhibition of TDO using indole compound 680C91, which has the structure PNG media_image8.png 152 156 media_image8.png Greyscale , is associated with "a significant amelioration in climbing performance" compared with controls in fly models of both Parkinson's and Alzheimer's diseases. See p. 5437, right column, last paragraph. See also Figure 5B on page 5439: PNG media_image9.png 365 567 media_image9.png Greyscale . Applicant is advised that numerous compounds are embraced by instant formula (IIa) or (IIb) including, for instance, compound Examples P-0001 through P-0049, P-0051 through P-0053, P-0055, P-0056, P-0089 through P-0097, P-0100 through P-0128, P-0130 through P-0144, P-0147 through P-0168, P-0170, P-0175 through P-0274, P-0276, P-0281 through P-0291, P-0294, P-0295, P-0297 through P-0371, P-0373 through P-0489, P-0491 through P-0526, P-0529 through P-0576, P-0579 through P-0602, P-0604, P-0605, P-0645, P-0650 through P-0656, P-0658, P-0659, P-0662 through P-0681. See Table 1 beginning on page 209. Majority of the compounds inhibit TDO in enzyme and cell-based assays. See Table 2 beginning on page 355. Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02) The prior art does not teach explicit embodiments wherein the compounds cited above are administered to a subject in need for treatment of a disease such as Parkinson’s disease. Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2144) It would have been obvious to a person having ordinary skill in the art to pursue the prior art compounds above taught by Zhang et al. in a treatment for Parkinson’s disease given the results of another TDO inhibitor, 680C91, in the in vivo assay performed by Breda et al. Since the indicated compounds are known TDO inhibitors, and Breda et al. teach that TDO inhibitors are useful in treating Parkinson's disease in animal models, it would have been obvious to a skilled artisan to administer the known indazole compounds as indicated in the present claims. Moreover, the skilled artisan would have a reasonable expectation of success in doing so since Breda et al. teach inhibition of TDO using a chemical inhibitor is neuroprotective in Parkinson's disease fly models. Breda et al. provides further motivation stating: "These results, together with supportive studies in flies and rodents, raise the possibility that inhibition of TDO and KMO—or combinatorial treatment—may offer therapeutic advantages." See page 5439, left column, first paragraph. Thus, claims 16-17 and 28-38 are obvious in view of the prior art . Conclusion Claims 16-17 and 28-38 are rejected. 07-40 AIA 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 extension fee 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 date of this final action. Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jalisa H. Ferguson whose telephone number is (703)756-1489. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm. 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, Amy L. Clark can be reached on (571) 272-1310. 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. /J.H.F./Examiner, Art Unit 1626 /KAMAL A SAEED/Primary Examiner, Art Unit 1626 Application/Control Number: 17/919,376 Page 2 Art Unit: 1626 Application/Control Number: 17/919,376 Page 3 Art Unit: 1626 Application/Control Number: 17/919,376 Page 4 Art Unit: 1626
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