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 .
Status of claims
Pending claims 1-13 have been examined on the merits.
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 1-13 are rejected under 35 U.S.C. 112(b) or pre‐AIA 35 U.S.C. 112, 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation (1) for the definitions of X2 and G1 on numbered page 3 of the September 30, 2024 claim set: “…a (C1-C4) alkyl group” (X2) and “…a (C1-C4) alkylene group” (G1), respectively, and the claim also recites “in particular a methyl group” (X2) or in particular a methylene group”, respectively, which is the narrower statement of the range/limitation; claim 1 also recites the broad recitation (2) for the definitions of G3 and G7 on numbered page 4 of the September 30, 2024 claim set: “…a (C1-C4) alkyl group” (G3 and G7) and the claim also recites “in particular a methyl group” (G3 and G7), which is the narrower statement of the range/limitation; claim 1 recites the broad recitation (3) for the definition of G7 on numbered page 5 of the September 30, 2024 claim set: “…a (C1-C3) alkoxy group” and the claim also recites “in particular a methoxy group” which is the narrower statement of the range/limitation; claim 1 also recites the broad recitation (4) for the definition of F8 embedded in the definition of F1 on numbered page 5 of the September 30, 2024 claim set: “…F8 is a (C1-C4) alkyl group,” and the claim also recites “in particular a methyl group” which is the narrower statement of the range/limitation; claim 1 further recites the broad recitation (5) for the definition of F2 on numbered page 5 of the September 30, 2024 claim set: “a (C4-C8) cycloalkyl group” and the claim also recites “in particular a cyclohexyl group or a cyclopentyl group”, which is the narrower statement of the range/limitation; and etc. Similar, broad limitations followed by narrower limitations occur in the definitions of F3 (numbered page 6), F4 (numbered page 6) for multiple recited moieties therein, F5 (numbered page 6), F6 (numbered page 6), and at the definition of F7 (numbered page 6). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Furthermore, claims 2-4, 6-7, and 11 contain the same ambiguous “in particular” language, often at multiple locations in each of these claims in their respective limitations. The rejection therefore applies independently to these claims as well.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation R11 is a (C6-C10) aryl group or a heteroaryl group containing between 4 and 9 carbon atoms…, and the claim also recites preferably in ortho positions which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the 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 (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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-6 and 8-13 are rejected under 35 U.S.C. 103 as being unpatentable over Dey et al. WO2022246459, Kaneda et al. Am J Cancer Res. 2020 Dec 1;10(12):4399-4415 (IDS 02/21/2025) in view of Fett et al., WO2021204823 (IDS, 02/21/2025).
Regarding claim 1-6 and 8-12, Dey (abstract; page 4) teaches a method of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of such combinations comprising: (i) one or more YAP/TAZ-TEAD inhibitors; and (ii) one or more KRAS inhibitors. Dey (page 89 and 99) teaches one or more KRAS inhibitors comprise adagrasib (Compound K3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt. Adagrasib is chemically described as 2-((S)-4-(7-(8-chloronaphthalen-1-yl)-2-(((S)-1-methylpyrrolidin-2- yl)methoxy)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)-1-(2-fluoroacryloyl)piperazin-2- yl)acetonitrile, wherein R6 is methyl; R7 is chlorine; RA is fluorine; and RB is hydrogen.
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Regarding other KRAS inhibitors, Dey (pages 78-79) also discloses sotorasib (Compound K1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt. Sotorasib is chemically described as 4-((S)-4-acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6- hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one,
wherein RD and RC are hydrogen; R12 is methyl and R11 is pyridine substituted with isopropyl
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and methyl; R8 is hydrogen; R9 is fluorine; L2 is a bond; R10 is phenyl substituted with fluorine and hydroxy.
Regarding KRAS G12C inhibitor and disease state, Dey (page 132-133) further discloses:
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Dey does not explicitly refer to the KRAS inhibitors as “KRAS G12C inhibitor,” but the inhibitors are effective against cancers having a KRAS G12C mutation. See paragraph [0307] of Dey, pasted above. Therefore, a POSITA would reasonably understand and characterize the inhibitors as KRAS G12C inhibitors based on the disclosed therapeutic activity against KRAS G12C-mutant cancers. Moreover, while Dey (page 6-7; page 100-104) describes multiple combinations of TEAD inhibitor with KRAS inhibitor, Dey does not explicitly disclose the exact claimed TEAD inhibitor administered with either sotorasib or adagrasib or both for the therapeutic regimen.
Kaneda (page 4399-4400) teaches K-975, a potent and selective TEAD inhibitor that inhibits YAP1/TAZ-TEAD signaling, suppresses cancer cell proliferation, and provides antitumor activity in mesothelioma xenograft models. Kaneda (page 4405) discloses K-975 having the following structure,
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wherein, with respect to the instant claims, X2 is methyl and X1 is chlorine.
Kaneda (page 4404) further teaches that K-975 may be combined with another anticancer agent, indicating K-975 is suitable for use in combination anticancer therapy. Therefore, a POSITA would have been motivated to substitute the TEAD inhibitors taught by Kaneda for those by Dey as a predictable selection of known TEAD inhibitors for use in the same KRAS G12C inhibitor/TEAD inhibitor combination therapy, with the reasonable expectation of identifying an effective treatment for cancer.
Additionally, as disclosed in claim 6, Fett (page 1-3 and 80-81) teaches structurally distinct TEAD inhibitor, compared to Kaneda, that inhibits YAP1/TAZ-TEAD pathway, and resistance to prior anti-cancer therapy. Fett (page 6 and 11) discloses a compound N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide or a pharmaceutically acceptable salt thereof; wherein q is 0; G1 is a bond; G2 is phenyl substituted with trifluromethyl; G7 is hydrogen; G11
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is hydrogen; G4 is hydrogen; G8 is hydrogen. Fett (page 81) further teaches that TEAD inhibitors may be administered in combination with other anticancer agents. In view of Dey (abstract; page 4) teaches combination therapy comprising: (i) one or more YAP/TAZ-TEAD inhibitors; and (ii) one or more KRAS inhibitors; therefore, a POSITA would have been motivated to combine the teachings of Dey, Kaneda and Fett to prepare a therapeutic combination comprising a at least one KRAS G12C inhibitor and at least one TEAD inhibitor to arrive at the claimed invention, with a reasonable expectation of successfully treating cancer. Furthermore, It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding dose frequency, Dey (page 128) discloses the following:
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Regarding KRAS G12C- mediated cancers, Dey (page 133) teaches the following:
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Regarding claim 13, The instruction for use of the compound is not considered a limitation as it is not functionally related. Therefore, the subject matter in this claim is treated the same as claim 1 and rejected for the same reason. See MPEP 2112.01
Subject Matter Free of the Art of Record
The subject matter of claim 7 is free of the art of record. The closest prior art reference is Fett et al., WO 2021/204823. While Fett teaches TEAD inhibitors containing a pyrroline core, Fett does not explicitly disclose a compound comprising a pyrrolidine core. There is no motivation for an ordinary skill in the art to modify the teaching of Fett to arrive at the claimed compounds. The claim is not allowable until the other rejections set forth above are overcome.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.P.E./
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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