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 .
Current Status of 18/078,269
This Office Action is responsive to the amended claims and Applicant remarks of 05/19/2026. Claims 1, 3, 7, 10-11, 13, 17, 19, 22, 31-32, 36, 38, 41-43, 49-50, 52-52, 58-60, 64-66, 68, 71, 74, 76, 78, and 81-82 are pending and have been examined on the merits.
Priority
The instant application claims priority to U.S. Provisional Patent Application No. 63/287,866, filed 12/09/2021 and U.S. Provisional Patent Application No. 63/393,440, filed 07/29/2022.
Applicants have not presented arguments or evidence in response to the priority determination set forth in the Office Action of 08/01/2025. The reasons set forth in this action regarding the priority of the claims remain unchanged. Accordingly the effective filing dates of the claims remain unchanged in the present action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/19/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicants have amended claims 1 and 3 to limit the scope of E1. The amended scope does not encompass the following compounds
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. These substituents are the E1 substituents of the compounds of references Sato, Horswill, Calderon, and Guo that were relied upon for the rejections of claims 1 and 3 under 35 U.S.C. §102. These compounds no longer anticipate the compounds of claims 1 and 3 due to these amendments. The previous rejections are withdrawn.
Applicants have also amended claim 1 to exclude methyl pyrazolyl from the allowed substituents of E1. Compound 130 of Kaldor was relied upon to make the rejections under 35 U.S.C. § 103 of claims 1 and 30-32 and possessed a trifluoromethyl pyrazolyl substituent at E1. The remaining pyrazolyl substituents of claim 1 require additional substitutions beyond substituting hydrogen for fluorine. These amendments limit the claims to nonobvious compounds from those disclosed in Kaldor. The previous rejection is withdrawn.
Claim Rejections - 35 USC § 103
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 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Sato (EP 1505064 A1) in view of Patani (Patani, George A., and Edmond J. LaVoie. "Bioisosterism: a rational approach in drug design." Chemical reviews 96.8 (1996): 3147-3176.).
Sato discloses compound 23
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(pg. 28). Compound 23 has the following substitutions reading the Markush groups of claims 1 and 3: X1, X5,and X6 are CH; X2 and X4 are N; X3 is C-N(R4)-L3-E3, R4 is H, L3 is a direct bond, and E3 is H; R1-R3 are H; L1 is a direct bond; E1 is a halo-substituted aryl; Z is L7-Z7, L7 is a direct bond, and E7 is an alky substituted heterocycle. The halo-substituted aryl group of E1 is not expressly listed in the allowed substituents of the instant claims. However, the claims do allow for E1 to be
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.
Patani teaches that bioisosteric replacement is a common strategy in drug design for the rational modification of promising lead compounds to elicit similar biological activity (pgs. 3147-3148, Introduction). The reference also teaches that halogens have been replaced with other electron withdrawing groups such as cyano and trifluoromethyl groups (pg. 3172, Halogen Bioisosteres). The reference therefore teaches that substitution of chlorine for a trifluoromethyl group is a routine modification that would be undertaken as part of routine lead compound screening.
Based on the teachings above, the artisan would have been motivated to replace the Cl substituent of Sato with a CF3 as part of routine bioisosteric screening. The artisan would have reasonably expected the resulting compound to retain similar biological activity because the core structure is maintained while only a peripheral electron-withdrawing group is modified.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Horswill (Horswill, J G et al. “PSNCBAM-1, a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats.” British journal of pharmacology vol. 152,5 (2007): 805-14. doi:10.1038/sj.bjp.0707347).
Horswill discloses the structure of PSNCBAM-1
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(pg. 806, left col, Figure 1). PSNCBAM-1 has the following substitutions anticipating the Markush group of claim 1: X2-X6 are CH; X1 is N; R1-R3 are H; L1 is a direct bond; E1 is a halo-substituted aryl; Z is L7-E7, L7 is a direct bond, and E7 is a heterocycle. The halo-substituted aryl group of E1 is not expressly listed in the allowed substituents of the instant claims. However, the claims do allow for E1 to be
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Patani teaches that bioisosteric replacement is a common strategy in drug design for the rational modification of promising lead compounds to elicit similar biological activity (pgs. 3147-3148, Introduction). The reference also teaches that halogens have been replaced with other electron withdrawing groups such as cyano and trifluoromethyl groups (pg. 3172, Halogen Bioisosteres). The reference therefore teaches that substitution of chlorine for a trifluoromethyl group is a routine modification that would be undertaken as part of routine lead compound screening.
Based on the teachings above, the artisan would have been motivated to replace the Cl substituent of Horswill with a CF3 as part of routine bioisosteric screening. The artisan would have reasonably expected the resulting compound to retain similar biological activity because the core structure is maintained while only a peripheral electron-withdrawing group is modified.
Conclusion
Claims 1 and 3 are rejected.
Claims 31-32, 36, 38, 41-43, 49-50, 52-53, 58-60, 64-66, 68, 71, 74, 76, 78, and 81-82 are objected to for being dependent upon a rejected base claim.
Claims 7, 10, 11, 13, 17, 19, and 22 are allowable.
The above claims are indicated as allowed for the following reasons:
While the references Kaldor (WO 2021/081375, found in IDS filed 08/15/2023) and Aversa (WO 2016/038582 A1, found in IDS filed 08/15/2023) teach RAF kinase inhibitors with similar structures, the references cannot be prior art due to the provisos of the claims. The compounds of the references disclose IC50 activity of RAF kinases. However, the references fail to provide sufficient motivation to perform the necessary substitutions to arrive at the instantly claimed compounds. Chemistry is an unpredictable art, and the cited references do not provide a reasonable expectation that the specific substitutions resulting from the proposed combination would retain RAF kinase inhibitory activity.
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 CONNOR KENNEDY ENGLISH whose telephone number is (571)270-0813. The examiner can normally be reached Monday Friday, 8 a.m. 5 p.m. ET..
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/C.K.E./ Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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