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 .
DETAILED ACTION
Status of 18/127,160
Claims 1, 3, 5-7, 10-14, and 16-22 are currently pending.
Priority
Instant application 18/127,160, filed 3/28/2023, claims priority as follows:
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The Examiner notes the translated, foreign priority documents were submitted on 6/5/2026. Support for the instant claims is found in the documents and thus, the instant claims are granted the effective filing date of 9/30/2020.
Information Disclosure Statement
All references from the IDS’s submitted on 3/28/2023, 11/22/2023, 7/2/2024, 8/30/2024, 12/2/2024, and 6/3/2025 have been considered unless marked with a strikethrough.
Response to Arguments/Amendments
The amendment filed 6/5/2026 has been entered. Claims 1, 3, 5-7, 10-14, 16-18, and 20 have been amended. Claims 2, 4, 8-9, and 15 have been cancelled, and claims 21-22 have been added, but are not considered new matter.
In the Non-Final dated 3/5/2026, the abstract was objected to for minor informalities. In response, Applicant has submitted a corrected abstract that overcomes the objection. The objection is withdrawn.
Claim 9 was objected to for a minor informality in the Non-Final dated 3/5/2026. Upon cancellation of the claim, the objection is overcome and withdrawn.
In the Non-Final dated 3/5/2026, claims 3-6 and 8-9 were rejected under 35 U.S.C. 112(b). In response, Applicant has struck through the term “preferably” in claims 3-6 and has cancelled claims 8-9, which overcomes the rejection. Thus, the rejection is withdrawn.
Claims 1-6, 8-11, and 13-17 were rejected under 35 U.S.C. 112(a) in the Non-Final dated 3/5/2026. Upon amendment to the claims to omit the term, “prodrug”, the rejection is overcome and withdrawn.
In the Non-Final dated 3/5/2026, claims 1-6, 8-11, and 13-17 were rejected under 35 U.S.C. 103. In response, Applicant has amended instant claim 1 to recite a compound of instant Formula II:
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Which is a narrower genus than that of instant Formula I:
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previously recited in the claim set of 3/28/2023. Applicant additionally argues that the compounds I-1, I-4, I-5, I-14, I-27, I-28, I-29, and I-30 of the instant disclosure, which are compounds of instant Formula II, exhibit significantly higher antagonistic activity against the hP2X3 receptor than reference compounds in comparative assays. There are only two reference compounds of the instant disclosure, Reference compound 1 and Reference compound 2, which are the non-fluorinated counterparts of instant compounds I-I and I-19 . The Examiner notes in a head to head comparison of Reference compound 1 and instant compound I-1, instant compound I-1 is 3x more potent than Reference compound 1 in hP2X3 inhibitory assays. However, of the 18 examples in the hP2X3 inhibitory assays, there are 9 examples of compounds of the instant disclosure with a hP2X3 IC50 higher than that of Reference compound 1. Stated differently, only half of the compounds of the instant disclosure demonstrate improved inhibitory activity than that of Reference compound 1 in hP2X3 IC50 assays. Thus, a sweeping generalization that the compounds of the instant disclosure, of Formula II, are superior to Reference compound 1 and Reference compound 2, and thus of the compounds of Evotec, cannot be made. The experimental results don’t substantiate that the compounds of the instant disclosure, represented by instant Formula II, do not all have improved biological activity, pharmacokinetic properties, antitussive effects, and pharmacologic activity.
Moreover, Applicant argues that the IC50 determination methods of Evotec differ from those of the instant disclosure, and thus are not directly comparable. Reference Compound 1 of the instant disclosure, which is also Example 11 of Evotec, and Reference Compound 2 of the instant disclosure, which is also Example 348 of Evotec, were subjected to the same biological assay conditions as the compounds of the instant disclosure, and are thus comparable. The Examiner agrees with Applicants on this point.
Further Applicant argues that Evotec fails to teach or suggest the specific type, position, and number of halogen substituents, and that Gillis is merely a literature review of fluorinated molecules and is not universally applicable to all drug candidates. Gillis additionally does not provide neither the guidance on structural optimization of hP2X3 antagonists nor the specific suggestion regarding fluorine substitution sites for the compounds disclosed in Evotec, and thus, no relevant teachings can be derived.
Ultimately, Applicants arguments have been considered, and are persuasive because the Examiner agrees one of ordinary skill in the art would not be directed to place a fluorine on the internal aryl ring at the site adjacent to the thiazole and the amide from the teachings of Evotec and Gillis. Neither Evotec nor Gillis provides the guidance on structural optimization of hP2X3 antagonists with fluorine aryl substitutions necessary for one of ordinary skill in the art to arrive at the limitations of the instant claims. The amendments to the claims and the arguments presented herein overcome the rejection, and thus, the rejection is withdrawn.
Claims 1-6, 8-11, and 13-17 were rejected on the ground(s) of nonstatutory double patenting in the Non-Final dated 3/5/2026. Applicant requested that the double patenting rejection be held in abeyance until the ‘218 application issues as a patent or the present application is indicated to be otherwise in condition for allowance. This request is acknowledged. However, Applicant is reminded that the Office cannot hold a rejection in abeyance and “[i]n order to be entitled to reconsideration or further examination, the applicant or patent owner must reply to the Office action. The reply by the applicant or patent owner must be reduced to a writing which distinctly and specifically points out the supposed errors in the examiner's action and must reply to every ground of objection and rejection in the prior Office action.” Because Applicant has failed to present an amendment or argument that overcomes the present rejection, the provisional rejection is maintained. Any future submissions that fail to address the merits of the non-statutory double patenting rejection might be deemed to be non-responsive. The claims of the rejection have been updated to reflect Applicant’s claim changes.
Additionally, Applicant’s amendments necessitated a new objection presented in this Office Action.
Election/Restriction
Applicant’s election of Group I, claims 1-17, drawn to compounds and compositions of Formula I, without traverse in the reply filed 11/7/2025 is acknowledged. Applicant’s election of compound I-27:
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In the same reply, is also acknowledged.
Examination will begin with the elected species. In accordance with 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 examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
In the Non-Final dated 3/5/2026, the elected species was searched and prior art was identified. In response, Applicant has presented arguments and amendments that overcome the 103 rejection, but do not overcome the double patenting rejection. In the interest of compact prosecution, the search was expanded to the full scope of Formula II. Claims 1, 3, 5-7, 10-14, 16-17, and 21-22 are the subject of this Office Action. Claims 18-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species and/or group, there being no allowable generic or linking claim. The Examiner notes the method claims are not in condition for allowance as they contain 112(a) issues.
MAINTAINED REJECTIONS
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.
Claims 1, 3, 5-6, 10-11, 13-14, 16-17, and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 15 of copending Application No. 18/850,218 (herein after the “‘218 Application”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘218 Application teach a crystalline form of the elected species. Further, claim 15 of the ‘218 Application additionally teaches a pharmaceutical composition of the crystalline form.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
NEW OBJECTIONS NECESSITATED BY AMENDMENT
Claim Objections
Claims 7 and 12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 16 is objected to for pixelated and illegible images. Upon amendment to the claim 16, the compound images of the claim are now unable to be interpreted. Appropriate correction is required.
Close Prior Art Not Cited
Close prior art identified during the search is Evotec AG (WO 2016/091776 A1, cited in the IDS of 3/28/2023, herein after “Evotec”), which teaches 1,3-thiazol-2-yl substituted benzamides as compounds active against P2X3 (abstract and Table, starting on page 646). Specifically, Evotec teaches Example 163 (page 489, lines 13-22):
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Which was found to have a 5 nm IC50 against hP2X3, in addition to selectivity for the hP2X3 receptor over the hP2X2/3 receptor (Table, page 653). Example 163 partially maps to the elected species and instant Formula II:
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When R1 is unsubstituted C1 alkyl, L is –(CH2)n-, where n is 0, and R2 is a Ra-substituted C4 alkyl, wherein the Ra substitution is an -OH. With respect to claim 17, Evotec teaches the addition of the compound to buffer, which indicates a pharmaceutical composition (page 645, lines 30-32). However, Example 163 and the compounds of Evotec do not contain a fluorine at the internal aryl position adjacent to the thiazole and amide substituents as recited by Formula II of the instant claims.
Conclusion
Claims 1, 3, 5-6, 10-11, 13-14, 16-17, and 21-22 are rejected. Claims 7, 12, and 16 are objected to. Claims 18-20 remain withdrawn.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton 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.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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