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 .
All previous objections and rejections not reiterated herein were overcome by claim amendments and arguments, filed January 15th, 2026, have been fully considered and found persuasive. As such all objections and rejections not reiterated herein have been withdrawn.
This Office Action is in response to the amendment and arguments filed January 15th, 2026. Claims 5 – 6, and 30 are currently pending in the application. Accordingly, claims 5 – 6, and 30 are being examined on the merits.
Claim Objections
Claim 6 is 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 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 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.
Claims 5 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over VELICELEBI et al. (WO2016138472A1, PTO-1449), in view of Whitten et al. (US 20110263612, PTO-1449).
VELICELEBI et al. discloses an intracellular calcium signaling inhibitor which includes instant compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide (free base), or a pharmaceutically acceptable salt, solvate thereof. See page 2, para [0005]; page 3 para [0006]; claims 7, 26; para [0009]; page 21.
VELICELEBI et al. does not teach that the compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide is crystalline.
VELICELEBI et al. does not teach wherein crystalline N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide is crystalline Form A with at least one property as in instant claim 30.
Whitten et al. teaches compounds that modulate intracellular calcium. The compounds therein encompass instant compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide. See Formula (VI), claims 2-7. See page 158, Example 46, compound 119 (see structure below); page 197, compounds 17-20; claim 15, pages 214, 216. It is taught that the compounds therein were obtained as a solid (see paras [0850]-[0851]) or crystalline solid obtained by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane) (see paras [0863], [0868]).
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It would have been obvious to a person of ordinary skill in the art to obtain N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide taught by VELICELEBI et al. in crystalline form because Whitten et al. teaches compounds of Formula (VI) which encompasses instant compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide, and Whitten et al. teaches that the compounds therein which are similar to instant compounds are obtained in crystalline form by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane).
VELICELEBI et al. in view of Whitten et al. renders obvious obtaining N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide in crystalline form by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane); and said crystalline form will be substantially free of N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide crystalline Form B which has at least one of the properties as in instant claim 30.
Note: Instant specification teaches Form A is obtained by slow evaporation, slow cooling, anti-solvent addition; and that Form B is obtained by polymer induced crystallization. See Table 2. Whitten et al. does not use polymer induced crystallization and thus Form B is not obtained by Whitten et al. method of obtaining crystalline compounds.
Response to Arguments
Applicant’s arguments, see applicant’s remarks page 5 paragraph 1, filed January 15th, 2026, with respect to the prior art rejection of claim 6 have been fully considered and are persuasive. The prior art rejection of claim 6 has been withdrawn.
Applicant's arguments filed January 15th, 2026, with respect to the prior art rejection of claims 5 and 30 have been fully considered but they are not persuasive.
Applicant argues that not all solid compounds produce polymorphs, thus, a person of skill in the art did not know, or have reason to know, that N-(5-(6-chloro-2,2-difluorobenzo[d][l,3]dioxol-5-yl)pyrazin- 2-yl)-2-fluoro-6-methylbenzamide is polymorphic. See page Applicant’s remarks page 5 paragraph 1. Moreover, Applicant argues that there is no evidence that a person of skill in the art would have a reasonable expectation of success in producing a crystalline form of this compound, let alone crystalline Form A or crystalline Form A substantially free of N-(5-( 6-chloro-2,2-difluorobenzo[ d][ 1,3 ]dioxol-5-yl)pyrazin-2-yl)-2-fluoro- 6-methylbenzamide crystalline Form B of the present invention, based on the disclosures of Velicelebi in view of Whitten. See page Applicant’s remarks page 5 paragraph 1.
In regards to claim 5, the claim only requires N-(5-( 6-chloro-2,2-difluorobenzo[ d][ 1,3 ]dioxol-5-yl)pyrazin-2-yl)-2-fluoro- 6-methylbenzamide to be in a crystalline form. Thus claim 5 does not require that the crystalline structure to have the XRPD peaks as recited in either claim 6 or claim 30. Hence, the prior art teachings of Velicelebi in view of Whitten as delineated above, taught that the compound species 119, which is N-(5-( 6-chloro-2,2-difluorobenzo[ d][ 1,3 ]dioxol-5-yl)pyrazin-2-yl)-2-fluoro- 6-methylbenzamide, was purified using Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane) which resulted in a crystalline product. Thus the teachings of Velicelebi in view of Whitten renders obvious claim 5.
Regarding claim 30; the claim only requires that the crystalline form of N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide to be substantially free of N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide crystalline Form B which has the characteristics as delineated in claim 30. Furthermore, as pointed in the examined specification the only way to form crystalline Form B was to use polymer induced crystallization. Thus since the prior art of Velicelebi in view of Whitten as delineated above does not teach that technique; the resulting crystallin form is free of Form B and would not have the characteristics of Form B which has the characteristics as delineated in claim 30.
Additionally, in response to the Applicant’s argument about no evidence that a person of skill in the art would have a reasonable expectation of success in producing a crystalline form of this compound the technique of crystallization is very common in the pharmaceutical arts. Moreover, as taught above by Whitten, N-(5-( 6-chloro-2,2-difluorobenzo[ d][ 1,3 ]dioxol-5-yl)pyrazin-2-yl)-2-fluoro- 6-methylbenzamide was known in the prior art to form crystals in solvent systems of 0 – 20% ethyl acetate in hexane. Thus, one of ordinary skill in the art would have had a reasonable expectation for forming crystals since the prior art taught it would be possible and in fact did make crystals. Furthermore, obviousness does not require absolute predictability, but at least some degree of predictability is required. See MPEP 2143.02 (II).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 5 and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 10,821,109; over claims 1-16 of US 11,311,535; over claims 1-17 of US 11,439,639, in view of Whitten et al. (US 20110263612, PTO-1449). Instant claims are drawn to a compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide or a pharmaceutically acceptable salt thereof, wherein the compound is crystalline; wherein the compound is free of crystalline Form B which has at least one property as in claim 30.
Claim 2 of ‘109 is drawn to a compound N-(5-(6-chloro-2,2- difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide (instant compound) or a salt thereof.
Claims of ‘535, ‘639 teach use of compound N-(5-(6-chloro-2,2- difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide (instant compound) or a salt thereof.
‘109, ‘535 or ‘639 do not teach that the compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide is crystalline.
‘109, ‘535, or ‘639 do not teach wherein crystalline N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide is crystalline Form A with at least one property as in instant claim 30.
Whitten et al. teaches compounds that modulate intracellular calcium. The compounds therein encompass instant compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide. See Formula (VI), claims 2-7. See page 158, Example 46, compound 119 (see structure above); page 197, compounds 17-20; claim 15, pages 214, 216. It is taught that the compounds therein were obtained as a solid (see paras [0850]-[0851]) or crystalline solid obtained by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane) (see paras [0863]).
It would have been obvious to a person of ordinary skill in the art to obtain N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide in crystalline form because Whitten et al. teaches compounds of Formula (VI) which encompasses instant compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide, and Whitten et al. teaches that the compounds therein which are similar to instant compounds are obtained in crystalline form by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane).
Further, ‘109, ‘535, or ‘639 in view of Whitten et al. renders obvious obtaining N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide in crystalline form by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane); and said crystalline form will be substantially free of N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide crystalline Form B which has at least one of the properties as in instant claim 30.
Note: Instant specification teaches Form A is obtained by slow evaporation, slow cooling, anti-solvent addition; and that Form B is obtained by polymer induced crystallization. See Table 2. Whitten et al. does not use polymer induced crystallization and thus Form B is not obtained by Whitten et al. method of obtaining crystalline compounds.
Claims 5, and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-12, 14, 17-19, 25, 26 of copending Application No. 17/906,229; unpatentable over claims 1, 4-10, 12-15 of copending Application No. 18/056,973; unpatentable over claims 1-4, 6, 15-16, 18, 25, 28, 31, 35 of copending Application No. 18/777,901, unpatentable over claims 3-19 of copending Application No. 18/593,518; unpatentable over claim 43 of copending Application No. 18/252,695; in view of Whitten et al. (US 20110263612, PTO-1449).
Instant claims are drawn to a compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide or a pharmaceutically acceptable salt thereof, wherein the compound is crystalline; wherein the compound is free of crystalline Form B which has at least one property as in claim 30.
Claims of ‘695 teach a method of making compound N-(5-(6-chloro-2,2- difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide (instant compound).
Claims of ‘229, ‘973, ‘901, ‘518 teach use of compound N-(5-(6-chloro-2,2- difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide (instant compound) or a salt thereof.
‘229, ‘973, ‘901, ‘518 or ‘695 do not teach that the compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide is crystalline.
‘229, ‘973, ‘901, ‘518 or ‘695 do not teach wherein crystalline N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide is crystalline Form A with at least one property as in instant claim 30.
Whitten et al. teaches compounds that modulate intracellular calcium. The compounds therein encompass instant compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide. See Formula (VI), claims 2-7. See page 158, Example 46, compound 119 (see structure above); page 197, compounds 17-20; claim 15, pages 214, 216. It is taught that the compounds therein were obtained as a solid (see paras [0850]-[0851]) or crystalline solid obtained by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane) (see paras [0863]);
It would have been obvious to a person of ordinary skill in the art to obtain N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide in crystalline form because Whitten et al. teaches compounds of Formula (VI) which encompasses instant compound N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide, and Whitten et al. teaches that the compounds therein which are similar to instant compounds are obtained in crystalline form by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane).
Further, ‘229, ‘973, ‘901, ‘518 or ‘695 in view of Whitten et al. renders obvious obtaining N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide in crystalline form by Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane); and said crystalline form will be substantially free of N-(5-(6-chloro-2,2-difluorobenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluoro-6-methylbenzamide crystalline Form B which has at least one of the properties as in instant claim 30.
Note: Instant specification teaches Form A is obtained by slow evaporation, slow cooling, anti-solvent addition; and that Form B is obtained by polymer induced crystallization. See Table 2. Whitten et al. does not use polymer induced crystallization and thus Form B is not obtained by Whitten et al. method of obtaining crystalline compounds.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed January 15th, 2026 have been fully considered but they are not persuasive.
Applicant’s arguments, see applicant’s remarks page 5 paragraph 1, filed January 15th, 2026, with respect to the NSDP and provisional NSDP rejections of claim 6 have been fully considered and are persuasive. The NSDP and provisional NSDP rejections of claim 6 has been withdrawn.
Applicant's arguments filed January 15th, 2026, with respect to the NSDP and provisional NSDP rejections of claims 5 and 30 have been fully considered but they are not persuasive.
Applicant argues that the provisional NSDP and NSDP rejections be held in abeyance until allowable subject matter has been identified. See Applicant’s remarks page 6 paragraph 4.
The examiner contends that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. See MPEP 804. (I)(B)(1).
Moreover, a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. Replies with an omission should be treated as provided in MPEP § 714.03. See MPEP 804. (I)(B)(1).
Conclusion
Claims 5 and 13 are rejected. Claim 6 is objected.
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 DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney 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.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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