DETAILED ACTION
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
This application is a divisional of U.S. Patent Application No. 18/987,568, filed December 19, 2024; which is a divisional of U.S. Patent Application No. 17/689,741, filed March 8, 2022; which is a continuation of U.S. Patent Application No. 16/685,841, filed on November 15, 2019; which claims the benefit of priority to U.S. Provisional Application No. 62/768,802, filed November 16, 2018.
Information Disclosure Statement
The Information Disclosure Statement filed 09/10/2026 has been considered by the Examiner. The submissions is in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
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 1 is 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 claim is indefinite because the claim recites a “method of preparing a compound of Formula (5M),” whereas the recited crystallization step provides a “co-crystal of the compound of Formula (5M) and chiral acid.” Thus, it is unclear whether the claimed method is directed to preparing the compound of Formula (5M) itself or preparing a co-crystal comprising the compound of Formula (5M) and the chiral acid.
Response to Arguments
Applicant’s arguments filed 9/10/2026 with respect to the ODP rejection have been fully considered and are persuasive with regard to co-crystal as defined in the specification preclude the formation of a salt of the claimed co-crystal. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Sanchez-Guadarrama et al. (Crystal Growth & Design (2016) 16 (1): 307–314. https://doi.org/10.1021/acs.cgd.5b01254), teaching that chiral acids can serve as coformers to produce separable diastereomeric co-crystal during chiral resolution.
Double Patenting
New Rejection
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.
A. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 15, 16, 19, 21 and 22 of U.S. Patent No. 12,441,729 in view of Chenard et al. (US 6,323,208 B1) and Sanchez-Guadarrama et al. (Crystal Growth & Design (2016) 16 (1): 307–314. https://doi.org/10.1021/acs.cgd.5b01254.)
Claimed invention
Claim 1 is drawn to a process of preparing a compound of Formula (5M)
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comprising
mixing compound of Formula 4
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with a chiral acid, and
crystallizing the mixture of Formula (4) and the chiral acid to provide a cocrystal compound of Formula (5M) and the chiral acid.
Patent/Reference claims
The patent claims teach a process of preparing Compound A
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(A) and using it to make Compound F
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(F), a pharmaceutically acceptable salt, atropisomer, or a pharmaceutically acceptable salt of an atropisomer thereof.
While the patent claims teach that atropisomer forms of Compound F
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can be made from Compound A
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, the patent claims do not teach mixing Compound A with a chiral acid and crystallizing the mixture to provide a cocrystal comprising the desired atropisomer and the chiral acid.
However, the process of forming cocrystals by mixing a chiral acid such as tartaric acid with another compound in order to resolve atropisomers of the compounds was already known. For example, Chenard teaches racemic mixtures of atropisomers that contain an acidic or basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids (for example, tartaric acid) when the racemate contains a basic moiety or with optically pure bases (for example a-methylbenzyl amine) when the racemate contains an acidic moiety. Repeated recrystallizations of these diastereomeric salts will allow the single pure atropisomer to be obtained. The single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. See Chenard, col. 13, third paragraph.
Sanchez-Guadarrama teaches chiral resolution of a racemic active pharmaceutical ingredient by co-crystallization with a chiral acid. Specifically, Sanchez-Guadarrama teaches that racemic praziquantel forms a diastomeric co-crystal pair with L-malic acid, including separate cocrystals of the individual and that the stereoisomers may be separated by fractional crystallization. Sanchez-Guadarrama further teaches that chiral resolution by co-crystallization may employ enantiopure conformers including, inter alia, L-malic acid, L-lactic acid, L-tartaric acid, and concludes that the procedure may be extended to other APIs and chiral substances.
It would have been obvious to a POSA to resolve the atropisomer mixture of Compound F using an optically pure chiral acid and crystallization, as taught by Chanani, because such resolution was known to provide a single pure atropisomer. It further would have been obvious to employ the chiral-acid co-crystallization technique of Sanchez-Guadarrama because Sanchez-Guadarrama teaches that chiral acids can serve as coformers to produce separable diastereomeric co-crystal during chiral resolution. Thus, the combined teachings would have suggested crystallizing the atropisomeric mixture with a chiral acid to obtain the desired atropisomer as a co-crystal with the chiral acid.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
B. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 14-16 of U.S. Patent No. 12,473,281 in view of Chenard et al. (US 6,323,208 B1) and Sanchez-Guadarrama et al. (Crystal Growth & Design (2016) 16 (1): 307–314. https://doi.org/10.1021/acs.cgd.5b01254.)
Claimed invention
Claim 1 is drawn to a process of preparing a compound of Formula (5M)
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comprising
mixing compound of Formula 4
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with a chiral acid, and
crystallizing the mixture of Formula (4) and the chiral acid to provide a cocrystal compound of Formula (5M) and the chiral acid.
Patent/Reference claims
The patent claims teach a process that includes mixing Compound 4
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(4) with (+)-DBTA (i.e., a chiral acid) and arriving at Compound (4A)
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(4A) (i.e., a compound containing the atropisomer of Compound 4) and, after additional steps, eventually arriving at Compound (5M),
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(5M) (i.e., the atropisomer of Compound 4).
While the patent claims teach mixing Compound 4 with (+)-DBTA (i.e., a chiral acid) to make Compound (4A) (i.e., the atropisomer of Compound 4 and (+)-DBTA) and eventually make Compound (5M),
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(i.e., the atropisomer of Compound 4), the patent claims do not teach crystallizing the mixture to provide a cocrystal compound of Compound 4A and the chiral acid.
However, the process of forming cocrystals by mixing a chiral acid such as tartaric acid with another compound in order to resolve atropisomers of the compounds was already known. For example, Chenard teaches racemic mixtures of atropisomers that contain an acidic or basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids (for example, tartaric acid) when the racemate contains a basic moiety or with optically pure bases (for example a-methylbenzyl amine) when the racemate contains an acidic moiety. Repeated recrystallizations of these diastereomeric salts will allow the single pure atropisomer to be obtained. The single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. See Chenard, col. 13, third paragraph.
Sanchez-Guadarrama teaches chiral resolution of a racemic active pharmaceutical ingredient by co-crystallization with a chiral acid. Specifically, Sanchez-Guadarrama teaches that racemic praziquantel forms a diastomeric co-crystal pair with L-malic acid, including separate cocrystals of the individual and that the stereoisomers may be separated by fractional crystallization. Sanchez-Guadarrama further teaches that chiral resolution by co-crystallization may employ enantiopure conformers including, inter alia, L-malic acid, L-lactic acid, L-tartaric acid, and concludes that the procedure may be extended to other APIs and chiral substances.
It would have been obvious to a POSA to resolve the atropisomer mixture of Compound 4 using an optically pure chiral acid and crystallization, as taught by Chanani, because such resolution was known to provide a single pure atropisomer. It further would have been obvious to employ the chiral-acid co-crystallization technique of Sanchez-Guadarrama because Sanchez-Guadarrama teaches that chiral acids can serve as coformers to produce separable diastereomeric co-crystal during chiral resolution. Thus, the combined teachings would have suggested crystallizing Compound 4 with a chiral acid to obtain the desired atropisomer, including Compound 5M, as a co-crystal with the chiral acid.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
C. Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 21-22 of U.S. 12,735,419 in view of Sanchez-Guadarrama et al. (Crystal Growth & Design (2016) 16 (1): 307–314. https://doi.org/10.1021/acs.cgd.5b01254.)
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Claimed invention
Claim 1 is drawn to a process of preparing a compound of Formula (5M)
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comprising
mixing compound of Formula 4
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with a chiral acid, and
crystallizing the mixture of Formula (4) and the chiral acid to provide a cocrystal compound of Formula (5M) and the chiral acid.
Patent/Reference claims
The patent claims teach a process of preparing a racemized Compound A
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which is resolved using tartrate (chiral acid) to separate it into its respective atropisomers, i.e., (P)-compound A and (M)-compound A (i.e.,
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).
While the patent claims teach that racemized Compound A can be mixed with tartrate to form its (P)- and (M)-atropisomers (e.g.,
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), the patent claims do not teach crystallizing the mixture to provide a cocrystal compound of the (M)-atropisomer and the chiral acid.
Sanchez-Guadarrama teaches chiral resolution of a racemic active pharmaceutical ingredient by co-crystallization with a chiral acid. Specifically, Sanchez-Guadarrama teaches that racemic praziquantel forms a diastomeric co-crystal pair with L-malic acid, including separate cocrystals of the individual and that the stereoisomers may be separated by fractional crystallization. Sanchez-Guadarrama further teaches that chiral resolution by co-crystallization may employ enantiopure conformers including, inter alia, L-malic acid, L-lactic acid, L-tartaric acid, and concludes that the procedure may be extended to other APIs and chiral substances.
It would have been obvious to a POSA to employ the chiral-acid co-crystallization technique of Sanchez-Guadarrama in the chiral-resolution process already claimed in the reference patent, thereby crystalizing the mixture to provide a co-crystal of the desired atropisomer and the chiral acid.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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