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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to a cocrystal of a compound of formula (I) and fumaric acid, and a pharmaceutical composition comprising said compound and one or more pharmaceutically acceptable excipient; and a crystalline form in the reply filed on October 14, 2025 is acknowledged; and a crystalline form characterized by an X-ray powder diffraction pattern comprising at least three peaks at 2θ angles of: 5.0±0.2, 10.0±0.2, 10.5±0.2, 15.0±0.2, 18.7±0.2, and 19.8±0.2 as the elected species of cocrystal of a compound of formula (I) and fumaric acid. The traversal is on the ground(s) that the groups of inventions share the same or corresponding technical feature, i.e., a compound of formula (I) and fumaric acid or ionized form thereof. This is not found persuasive, because based on the fact that technical feature shared among the groups of inventions is a compound of formula (I) and fumaric acid, said technical feature still lack unity of invention in view of the prior art rejections set forth below.
Claims 20, 23-24, 28, 31-37, 40 and 49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 14, 2025.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on March 5, 2024, wherein claims 4-5, 20, 24 and 33-35 are unchanged; claims 9-10, 12, 14, 17-19, 23, 28, 31-32, 36-37, 40, and 48-49 are amended; claims 1-3, 6-8, 11, 13, 15-16, 21-22, 25-27, 29-30, 38-39, 41-47 and 50-54 are cancelled.
Claims 4-5, 9-10, 12, 14, 17-20, 23-24, 28, 31-37, 40 and 49 are pending.
Claims 20, 23-24, 28, 31-37, 40 and 49 are withdrawn.
Claims 4-5, 9-10, 12, 14, 17-19 and 48 are under examination in accordance with the elected species.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 1/24/2024, 7/10/2025, 8/22/2025, 12/10/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Priority
The instant application 18/257,962 filed on June 16, 2023 is a 371 of PCT/IB2021/061895 filed
on December 17, 2021, which claims priority to, and the benefits of Foreign Application No.
IN202041055174 filed on December 18, 2020.
Claim Objections
Claims 10, 12, 14, 17-19 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 Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 4-5, 9 and 48 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 4 recites “[a] cocrystal of a compound of formula (I):
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and fumaric acid”; instant claim 5 recites “[t]he cocrystal of claim 4, wherein molar ratio of compound of formula (I) to fumaric acid is 1:1”; and instant claim 9 recites “[t]he cocrystal of claim 4, characterized by a X-ray powder diffraction pattern comprising at least three peaks at 2θ angels selected from:
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”. However, the instant specification only describes one species of cocrystal of a compound of formula (I) and fumaric acid, Form 1, having an X-ray powder diffraction pattern in Table 1 and Fig. 2. The specification does not disclose other cocrystal species of a compound of formula (I) and fumaric acid.
Regarding the requirement for adequate written description of chemical entities, Applicant's attention is directed to the MPEP §2163. In particular, Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), holds that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plain for obtaining the claimed chemical invention." Eli Lilly, 119 F.3d at 1566. The Federal Circuit has adopted the standard set forth in the Patent and Trademark Office ("PTO") Guidelines for Examination of Patent Applications under the 35 U.S.C. 112.I "Written Description" Requirement ("Guidelines"), 66 Fed. Reg. 1099 (Jan. 5,2001), which state that the written description requirement can be met by "showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter alia, "functional characteristics when coupled with a known or disclosed correlation between function and structure ..." Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106 (emphasis added)). Moreover, although Eli Lilly and Enzo were decided within the factual context of DNA sequences, this does not preclude extending the reasoning of those cases to chemical structures in general. Univ. of Rochester v G.D. Searle & Co., 249 Supp. 2d 216, 225 (W.D.N.Y. 2003).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In the present case, the specification only describes one cocrystal species of a compound of formula (I) and fumaric acid, specifically, the specification describes a crystalline form I prepared in Example 1 with an X-ray powder diffraction pattern described in Table 1 and Fig. 2, a differential scanning calorimetry (DSC) in Fig. 2, a thermogravimetric analysis in Fig 4, and a dynamic vapor sorption in Fig. 8. However, the instant claims pertain to the full scope of cocrystal of a compound of formula (I) and fumaric acid, including those at least 3 peaks at the claimed 2θ angles in the X-ray powder diffraction pattern. To the extent that said cocrystal has 3 peaks in the X-ray powder diffraction pattern, it is insufficient to identify a specific cocrystal species. A single X-ray diffraction peak only provide one piece of information, thus, a complete pattern containing at least four strongest reflections (major peaks) is often required to reveal the crystal's unique fingerprint. In order to sufficiently identify a specific cocrystal structure of a compound, at least four major peak positions are required to determine arrangements of all atoms within its unit cell, including lattice parameters, crystal system, and space group.
In the absence of a sufficient recitation of a representative number of species for the claimed genus, while applicant is in possession of crystalline form I, a fumarate slat of (S, E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide, with an X-ray powder diffraction pattern as shown in Fig. 2 and Table 1, it is not apparent that Applicant was actually in possession of the full scope of the cocrystal species of a compound of Formula 1 and a fumarate acid based on the limited disclosure at the time the application was filed.
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 (i.e., changing from AIA to pre-AIA ) 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 4-5 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al. (WO 2022/084930 A2; cited in the IDS filed on 1/24/2024), in view of Gupta et al. (Molecules [Basel, Switzerland], 2018. Vol. 23, 7:1 719), as evidenced by Anderson (Academic Press, 2012: pp. 329-364).
Kumar et al. teaches a compound 44A, (S)-(E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide, is an isomer of (E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino )-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide having the structure of:
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(see e.g., claim 18, Compound No. 44A; p. 52-54, “Synthesis of Compound-44A & 44B” section). Please note the compound 44A of Kumar et al. is a compound of formula (I) instantly claimed. Kumar et al. further teaches said compound, or a pharmaceutically acceptable salt or a stereoisomer thereof is a compound of formula (I) useful for inhibiting CDK7 (see e.g., claims 1 and 18; page 55, line 1). Kumar et al. further teaches the term "pharmaceutically acceptable salt" refers to a product obtained by reaction of the compound of the present invention with a suitable acid or a base; Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as, inter alia, fumarate (see e.g., p. 8, line 28 to p. 9, line 4). Kumar et al. further teaches a pharmaceutical composition comprising the compound as disclosed therein, optionally admixed with a pharmaceutically acceptable carrier or diluent (see e.g., p. 34, line 6-8). Kumar et al. further teaches the phrase "pharmaceutically acceptable carrier" as used herein means a pharmaceutically acceptable material, composition or vehicle, such as excipient (see e.g., p. 36, line 1-3).
Kumar et al. does not teach the elected cocrystal species of a compound of formula (I) and fumaric acid.
Gupta et al. teaches salt formation approaches have widely been utilized to increase solubility, and therefore, the dissolution rate of a drug (see e.g., p. 5, line 1-2 under “2.8 Solubility and dissolution rate” section). Gupta et al. further teaches hydrochloride, mesylate, hydrobromide, acetate, and fumarate are the most common counterions that are used for basic chemical entities in the past 20 years; and increases in aqueous solubility have been achieved by most of these counterions (see e.g., p. 5, line 3 under “2.8 Solubility and dissolution rate” section to p. 6, line 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by forming a pharmaceutically acceptable salt of compound 44A of Kumar et al. with a fumarate as the suitable acid as taught by Gupta et al. One would have been motivated to do so, because Kumar et al. teaches compound 44A or a pharmaceutically acceptable salt thereof are both useful for inhibiting CDK7, and further teaches a pharmaceutically acceptable salt is obtained by reaction of the compound with a suitable acid, such as fumarate; and Gupta et al. further teaches fumarate is one of the most common counterions used in the salt formation to increase solubility and dissolution rate of a drug. Please note salt formation is commonly mentioned as reactive crystallization and the product crystallizes as it is formed, as evidenced by Anderson (see e.g., page 340, “VI. Reactive crystallization”). One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that a fumarate and a compound 44A can successfully form a pharmaceutically salt of compound 44A useful inhibiting CDK7, and that renders obvious the cocrystal instantly claimed.
Regarding the limitation of “wherein molar ratio of compound of formula (I) to fumaric acid is 1:1” in claim 2, It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by forming a pharmaceutically acceptable salt of compound 44A of Kumar et al. with a fumarate as the suitable acid as taught by Gupta et al. One would have been motivated to do so, because Kumar et al. teaches compound 44A or a pharmaceutically acceptable salt thereof are both useful for inhibiting CDK7, and further teaches a pharmaceutically acceptable salt is obtained by reaction of the compound with a suitable acid, such as fumarate; and Gupta et al. further teaches fumarate is one of the most common counterions used in the salt formation to increase solubility and dissolution rate of a drug. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the incorporation of fumarate in its entirety (100% by weight) as a counterion with the compound 44A of Kumar et al. in its entirety (100% by weight) would have successfully form a pharmaceutically acceptable salt of compound 44A, and that gives at least a 1:1 ratio that can include a molar ratio.
Regarding the limitation of “a pharmaceutical composition comprising the compound of formula (I) fumarate…and one or more pharmaceutically acceptable excipient” in claim 48, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to combine the fumarate salt of compound 44A of Kumar et al. and Gupta et al. sets forth above with an excipient as the pharmaceutically acceptable carrier to arrive at the claimed invention. One would have been motivated to do so, because Kumar et al. teaches the compound of formula (I) can admixed with a pharmaceutically acceptable carrier, such as excipient, to arrive at a pharmaceutical composition. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that a fumarate salt of compound 44A combined with a pharmaceutically acceptable excipient would have successfully arrive at a pharmaceutical composition without any appreciable loss of activity.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed.
Claims 4-5 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Samajdar et al. (WO 2016/193939 A1; cited in the IDS filed on 1/24/2024), in view of Gupta et al. (Molecules [Basel, Switzerland], 2018. Vol. 23, 7:1 719), as evidenced by Anderson (Academic Press, 2012: pp. 329-364).
Samajdar et al. teaches a compound 44, (E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl) amino)-3-methyl-1-oxobutan-2-yl) phenyl) pyridin-2-yl)-4-morpholinobut-2-enamide, having the structure of:
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, or a pharmaceutically acceptable salt or a stereoisomer thereof is an exemplary compound of formula (I) useful for inhibiting CDK7 kinase activity (see e.g., p. 25, Compound No. 44; p. 28, last line; p. 102, 1st line under the “biochemical assay for CDK7” section; and Table 5). Samajdar et al. further teaches a pharmaceutical composition comprising the compound 44 or a pharmaceutically acceptable salt or a stereoisomer thereof and at least one pharmaceutically acceptable excipient (see e.g., claims 17-18). Samajdar et al. further teaches the term "stereoisomers" refers to any enantiomers, diastereoisomers, or geometrical isomers of the compounds of Formula (I), (IA), (IB), (IC), (ID), (IE), (IF) and (IG), wherever they are chiral or when they bear one or more double bonds; when the compounds of the formula (I), (IA), (IB), (IC), (ID), (IE), (IF) and (IG) are chiral, they can exist in racemic or in optically active form; individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art; and the present invention includes all isomers as well as the appropriate mixtures thereof (see e.g., p. 9, line 22 to p. 10, line 9).
Samajdar et al. does not teach the elected cocrystal species of a compound of formula (I) and fumaric acid.
Gupta et al. teaches salt formation approaches have widely been utilized to increase solubility, and therefore, the dissolution rate of a drug (see e.g., p. 5, line 1-2 under “2.8 Solubility and dissolution rate” section). Gupta et al. further teaches hydrochloride, mesylate, hydrobromide, acetate, and fumarate are the most common counterions that are used for basic chemical entities in the past 20 years; and increases in aqueous solubility have been achieved by most of these counterions (see e.g., p. 5, line 3 under “2.8 Solubility and dissolution rate” section to p. 6, line 2).
In the present case, Samajdar et al. teaches a compound 44 that can exist in racemic form, and individual stereoisomers of said compound can be obtained by preparation of mixtures of enantiomeric products followed by separation. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by separating the individual stereoisomers of compound 44 of Samajdar et al., and then form a pharmaceutically acceptable salt of each stereoisomer with a fumarate as the counterions as taught by of Gupta et al. One would have been motivated to do so, because Samajdar et al. teaches compound 44 or a stereoisomers or a pharmaceutically acceptable salt thereof are all useful for inhibiting CDK7 kinase, and further teaches the compound can exists in racemic form and individual stereoisomers can be obtained using the method known in the art, such as preparation of mixtures of enantiomeric products followed by separation; and Gupta et al. teaches fumarate is one of the most common counterions used in the salt formation to increase solubility and dissolution rate of a drug. Please note salt formation is commonly mentioned as reactive crystallization and the product crystallizes as it is formed, as evidenced by Anderson (see e.g., page 340, “VI. Reactive crystallization”). One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that each individual stereoisomer of compound 44 can successfully be separate to form a pharmaceutically acceptable salt using a fumarate as the counterion, and that renders obvious the cocrystal instantly claimed.
Regarding the limitation of “wherein molar ratio of compound of formula (I) to fumaric acid is 1:1” in claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by separating the individual stereoisomers of compound 44 of Samajdar et al., and then form a pharmaceutically acceptable salt of each stereoisomer with a fumarate as the counterions as taught by of Gupta et al. One would have been motivated to do so, because Samajdar et al. teaches compound 44 or a stereoisomers or a pharmaceutically acceptable salt thereof are all useful for inhibiting CDK7 kinase, and further teaches the compound can exists in racemic form and individual stereoisomers can be obtained using the method known in the art, such as preparation of mixtures of enantiomeric products followed by separation; and Gupta et al. teaches fumarate is one of the most common counterions used in the salt formation to increase solubility and dissolution rate of a drug. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the incorporation of fumarate in its entirety (100% by weight) as a counterion with the compound 44 of Samajdar et al. in its entirety (100% by weight) would have successfully form a pharmaceutically acceptable salt, and that gives at least a 1:1 ratio that can include a molar ratio.
Regarding the limitation of “a pharmaceutical composition comprising the compound of formula (I) fumarate…and one or more pharmaceutically acceptable excipient” in claim 48, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to combine the fumarate salt of each individual stereoisomers of compound 44, as taught by Samajdar et al. and Gupta et al., sets forth above with at least one pharmaceutically acceptable excipient to arrive at the claimed invention. One would have been motivated to do so, because Samajdar et al. teaches the compound 44 or a pharmaceutically acceptable salt or a stereoisomer thereof and at least one pharmaceutically acceptable excipient can be combined to arrive at a pharmaceutical composition. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that a fumarate salt of each individual stereoisomers of compound 44 combined with at least one pharmaceutically acceptable excipient would have successfully arrive at a pharmaceutical composition without any appreciable loss of activity.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed.
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 4-5 and 48 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 12 of U.S. Patent No. 10,689,347 B2 in view of Gupta et al. (Molecules [Basel, Switzerland], 2018. Vol. 23, 7:1 719), as evidenced by Anderson (Academic Press, 2012: pp. 329-364).
The claims of the reference patent are drawn to a compound having the structure:
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or a pharmaceutically acceptable salt, or an enantiomer thereof; which the compound is an enantiomer of (E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier or excipient.
The claims of the reference patent does not teach the elected cocrystal species of a compound of formula (I) and fumaric acid.
Gupta et al. teaches salt formation approaches have widely been utilized to increase solubility, and therefore, the dissolution rate of a drug (see e.g., p. 5, line 1-2 under “2.8 Solubility and dissolution rate” section). Gupta et al. further teaches hydrochloride, mesylate, hydrobromide, acetate, and fumarate are the most common counterions that are used for basic chemical entities in the past 20 years; and increases in aqueous solubility have been achieved by most of these counterions (see e.g., p. 5, line 3 under “2.8 Solubility and dissolution rate” section to p. 6, line 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by forming a pharmaceutically acceptable salt of each enantiomer of (E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl) amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide with a fumarate as the counterions as taught by Gupta et al. One would have been motivated to do so, because the reference patent teaches the compound can be an enantiomer or a pharmaceutically acceptable salt thereof; and Gupta et al. teaches fumarate is one of the most commonly used counterions for salt formation in order to increase solubility and the dissolution rate of a drug. Please note salt formation is commonly mentioned as reactive crystallization and the product crystallizes as it is formed, as evidenced by Anderson (see e.g., page 340, “VI. Reactive crystallization”). One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that a fumarate and each enantiomer of (E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide can successfully form a pharmaceutically salt form with improved solubility, and that renders obvious the cocrystal instantly claimed.
Regarding the limitation of “wherein molar ratio of compound of formula (I) to fumaric acid is 1:1” in claim 2, It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by forming a pharmaceutically acceptable salt of each enantiomer of (E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide with a fumarate as the counterions as taught by Gupta et al. One would have been motivated to do so, because the reference patent teaches the compound can be an enantiomer or a pharmaceutically acceptable salt thereof; and Gupta et al. teaches fumarate is one of the most commonly used counterions for salt formation in order to increase solubility and the dissolution rate of a drug. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the incorporation of fumarate in its entirety (100% by weight) as an counterion with an enantiomer of (E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide in its entirety (100% by weight) would have successfully form a pharmaceutically acceptable salt, and that gives at least a 1:1 ratio that can include a molar ratio.
Therefore, the nonstatutory double patenting rejection applies.
Claims 4-5 and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18 and 22 of copending Application No. 18/032,919 in view of Gupta et al. (Molecules [Basel, Switzerland], 2018. Vol. 23, 7:1 719), as evidenced by Anderson (Academic Press, 2012: pp. 329-364).
The claims of the reference application are drawn to a method of treating or preventing cancer in a subject, comprising administering to the subject (S)-(E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide or a pharmaceutically acceptable salt thereof as the compound of formula (I) conjointly with an anti-microtubule agent (see e.g., claims 1 and 22).
The claims of the reference patent do not teach the elected cocrystal species of a compound of formula (I) and fumaric acid.
Gupta et al. teaches salt formation approaches have widely been utilized to increase solubility, and therefore, the dissolution rate of a drug (see e.g., p. 5, line 1-2 under “2.8 Solubility and dissolution rate” section). Gupta et al. further teaches hydrochloride, mesylate, hydrobromide, acetate, and fumarate are the most common counterions that are used for basic chemical entities in the past 20 years; and increases in aqueous solubility have been achieved by most of these counterions (see e.g., p. 5, line 3 under “2.8 Solubility and dissolution rate” section to p. 6, line 2).
In the present case, the conflicting claims recite a method of treating where the rejected claims cover a product; However, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by forming a pharmaceutically acceptable salt of (S)-(E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide, which is used in the method of reference application, with a fumarate as the counterions as taught by Gupta et al. One would have been motivated to do so, because Gupta et al. teaches fumarate is one of the most commonly used counterions for salt formation in order to increase solubility and the dissolution rate of a drug. Please note salt formation is commonly mentioned as reactive crystallization and the product crystallizes as it is formed, as evidenced by Anderson (see e.g., page 340, “VI. Reactive crystallization”). One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that a fumarate and a (S)-(E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide can successfully form a pharmaceutically salt form with improved solubility, and said compound can reasonably be combined with a pharmaceutically acceptable excipient to arrive at the pharmaceutical composition useful for treating or preventing cancer.
Regarding the limitation of “wherein molar ratio of compound of formula (I) to fumaric acid is 1:1” in claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by forming a pharmaceutically acceptable salt of (S)-(E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide, which is used in the method of reference application, with a fumarate as the counterions as taught by Gupta et al. One would have been motivated to do so, because Gupta et al. teaches fumarate is one of the most commonly used counterions for salt formation in order to increase solubility and the dissolution rate of a drug. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the incorporation of fumarate in its entirety (100% by weight) as an counterion with an (S)-(E)-N-(5-(3-(1-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-3-methyl-1-oxobutan-2-yl)phenyl)pyridin-2-yl)-4-morpholinobut-2-enamide in its entirety (100% by weight) would have successfully form a pharmaceutically acceptable salt, and that gives at least a 1:1 ratio that can include a molar ratio.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628