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 national stage entry of PCT/IN2020/050549 filed on June 24, 2020.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in India on June 26, 2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Response to Amendment
Applicant’s amendment filed on February 10, 2026 amending claims 1-2, 4, 7, 9-10, and canceling claim 5 has been entered. Claims 1-4 and 6-10 are currently pending.
Election/Restrictions
Applicant has amended the claims to remove Applicant’s elected species of a compound of formula I which was compound 1043. In view of the removal of Applicant’s elected species the search has been expanded to include the next closest species which is compound 1069 having the following structure:
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1-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)-3-(4-(3-methylmorpholino)phenyl)imidazolidin-2-one and examined herewith. In view of Applicant’s elected species being deleted from claim 4, claim 4 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group and species, there being no allowable generic or linking claim.
Claims 1-3 and 6-10 are currently being examined as they read on compound 1069.
Response to Arguments
Due to Applicant’s amendments to claims 7 and 9, the previous rejection of claims 7 and 9 under 35 USC 112(b) is hereby withdrawn.
Applicant’s amendment to claim 10 is not sufficient to overcome the previous rejection under 35 USC 112(b) because of the use of “including” in line 2. The transitional term "including," which is synonymous with "comprising", "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Thus it is unclear how diabetic complications include or comprise the conditions as claimed since the diabetic complications are the conditions as claimed or they are not. Thus a modified rejection of claim 10 under 35 USC 112(b) is detailed below.
Due to Applicant’s amendments to the claims, specifically deleting Applicant’s elected species of a compound of formula I which was compound 1043, the previous rejection under 35 USC 102(a)(1) over Xu is hereby withdrawn. Applicant’s arguments with respect to said rejection are moot in view of the withdrawal of the rejection. However, since a new rejection necessitated by Applicant’s amendments to the claims under 35 USC 103 over Xu et al. is detailed below, Applicant’s arguments as they pertain to the new rejection are being addressed.
Applicant argues that the present invention relates to a new class of apoptosis signal-regulating kinase 1 (ASK1) inhibitors, specifically novel 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)-pyridin-2-yl) imidazolidin-4-one derivatives, wherein these compounds are designed to inhibit ASK1, a MAP3K enzyme implicated in cellular stress responses and associated with progressive liver diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Applicant argues that the compounds show strong ASK1 inhibition and desirable biochemical and cellular assay profiles, supporting their potential use in treating fibrotic liver diseases, metabolic syndromes, and other ASK1-mediated disorders. Applicant argues that the compounds disclosed in Xu differ fundamentally from the present invention because Xu relates to urea-based ASK1 inhibitors, where the defining structural element is a urea functional group linking aromatic or heteroaromatic systems. Applicant argues that in contrast, the present invention describes imidazolidin-4-one derivatives bearing a triazolyl-substituted pyridine, with no urea linkage and no structural similarity to the scaffolds of Xu. Applicant argues that while Xu focuses on aryl/heteroaryl urea frameworks, the present invention provides novel heterocyclic compounds incorporating a triazole-pyridine-imidazolidinone arrangement not taught, suggested, or motivated by Xu and thus the compounds differ in chemical class, substitution pattern, ring system, mechanism of assembly, and structural motif.
These arguments are found not persuasive since the claims of the instant application are drawn to ASK1 inhibitors having the following structure
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and Xu specifically discloses ASK1 inhibitor compounds of formula (IF) having the following structure:
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and compounds of formula (IE) having the following structure
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wherein R1 may be selected as substituted phenyl; wherein the R1 substituent may be selected as morpholinyl which may be substituted with alkyl; and R2 may be selected as C1-C6 alkyl ([0069]-[0070] and claims 21-24). Xu teaches that alkyl groups include straight chain alkyl such as methyl and branched chain alkyl such as isopropyl [0017]. Xu specifically discloses compounds having the same core structure as the compounds as claimed wherein R2 of Xu is isopropyl or other substituents that correspond with the groups at the same position on the compounds as claimed (see compounds V-02-V27 on Table 3 on pages 106-112 and compounds III-05-III-10 on Table 2 pages 101-102). Thus Xu also specifically teaches, discloses and claims 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)-pyridin-2-yl) imidazolidin-4-one derivatives like the compounds as claimed.
It has been well established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches, when viewed in light of the admitted knowledge in the art, to a person of ordinary skill in the art. In re Boe, 355 F.2d 961,148 USPQ 507, 510 (CCPA 1966); In re Lambedi, 545 F.2d 747, 750, 192 USPQ 279,280 (CCPA 1976): In re FracalossL 681 F.2d 792,794, 215 USPQ 569, 570 (CCPA 1982)4 In re Kaslow, 707 F.2d 1366, 13:4,217 USPQ 1089, 1095 (Fed. Cir. 1983). Furthermore, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Thus Applicant’s arguments are found not persuasive. Applicant’s amendments necessitate the new rejection under 35 USC 103 detailed below.
Accordingly, this action is FINAL.
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 10 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 transitional term "including," which is synonymous with "comprising", "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
Regarding claim 10, the use of “including” in line 2 renders the claim indefinite because it is unclear how diabetic complications include (which is synonymous with comprise) the conditions as claimed since the diabetic complications are either the conditions as claimed or they are not.
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.
Claims 1-3 and 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Xu WO 2019/099307 A1 (published May 23, 2019).
Claims 1-3 and 6-10 of the instant application claim a compound of formula I having the following structure
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such as compound 1069 having the following structure:
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and a pharmaceutical composition thereof.
Xu teaches compounds, compositions, and methods related to inhibition of apoptosis signal regulating kinase 1 (ASK1) [0002]. In particular, the compounds and compositions may be used to treat ASK1-mediated disorders and conditions, including, e.g., fibrotic diseases, acute and chronic liver diseases and kidney diseases (abstract [0002] and [0010]).
Xu specifically teaches compounds of formula (IF) having the following structure:
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wherein R1 may be selected as substituted phenyl; wherein the R1 substituent may be selected as morpholinyl which may be substituted with alkyl; and R2 may be selected as C1-C6 alkyl ([0069]-[0070] and claims 21-24). Xu teaches that alkyl groups include straight chain alkyl such as methyl and branched chain alkyl such as isopropyl [0017].
Xu teaches a composition is provided that includes any one of the aspects and embodiments of compounds disclosed therein and a pharmaceutically acceptable carrier [0074]. In a related aspect, a pharmaceutical composition is provided which includes an effective amount of the compound of any one of the aspects and embodiments of compounds for treating an ASK1-mediated disorder or condition which may be fibrotic diseases including liver fibrosis, lung fibrosis, kidney fibrosis and idiopathic pulmonary fibrosis (IPF), acute and chronic liver diseases including non-alcoholic steatohepatitis (NASH), kidney diseases, autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, and neurodegenerative diseases [0074].
Xu further teaches a method is provided that includes administering an effective amount of a compound of any one of the aspects and embodiments of the present compounds or administering a pharmaceutical composition comprising an effective amount of a compound of any one of the aspects and embodiments of the present compounds to a subject suffering from an ASK1-mediated disorder or condition including liver fibrosis, lung fibrosis, kidney fibrosis and IPF, acute and chronic liver diseases including NASH, kidney diseases, autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, and neurodegenerative diseases [0075]. For example, the disorder or condition may be liver fibrosis or NASH [0075].
Xu teaches that the pharmaceutical compositions and medicaments may be prepared by mixing one or more compounds of the present technology, and/or pharmaceutically acceptable salts thereof, with pharmaceutically acceptable carriers, excipients, binders, diluents or the like to prevent and treat disorders and conditions associated with or mediated by ASK1 [0079]. Xu teaches that such compositions can be in the form of, for example, granules, powders, tablets, capsules, syrup, suppositories, injections, emulsions, elixirs, suspensions or solutions, formulated for various routes of administration, for example, by oral, parenteral, topical, rectal, nasal, vaginal administration, or via implanted reservoir, wherein parenteral or systemic administration includes, but is not limited to, subcutaneous, intravenous, intraperitoneal, and intramuscular, injections [0079].
Xu specifically teaches compound V-11 having the following structure:
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wherein R1 is
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and R2 is
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to form
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(pages 106 and 108). Xu further specifically demonstrates that compound V-11 inhibits ASK1 with an EC50 ≤ 50 nM (page 115).
Xu does not specifically exemplify compound 1069 having the following structure:
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as claimed.
However, Xu specifically exemplifies compound V-11 which is similar in structure to compound 1069 and has the same function as claimed for compound 1069 which is to inhibit ASK1. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. “An obviousness rejection based on similarity in chemical structure and/or function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). In the instant case, a person or ordinary skill in the art would have been motivated to modify compound V-11 of Xu to arrive at compound 1069 as claimed since Xu specifically teaches that that the morpholinyl substituent may be optionally substituted with one or more secondary substituents such as unsubstituted alkyl wherein a suitable alkyl is methyl (claim 23 and [0070]). Thus, an ordinary skilled artisan would have been motivated to make the modifications to arrive at compound 1069 as claimed according to the direct teachings of Xu with a reasonable expectation of obtaining a compound with similar properties.
Thus the cited claims of the instant application are rendered obvious over the teachings of Xu.
Conclusion
Claims 1-3 and 6-10 are rejected. Claim 4 is withdrawn. Claim 5 is canceled. No claims are allowed.
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 KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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