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
The instant application, filed 10/26/2022, is a national stage entry of PCT/US2021/029435, filed 04/27/2021, which claims domestic priority to U.S. provisional application 63/015,883, filed 04/27/2020.
Amendments and Claim Status
The following amendment filed on 03/31/2026 is acknowledged and entered.
Claims 1-2 are cancelled;
Claim 4 remains withdrawn according to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species;
Claims 3, 4, 11, 13, 16, 17, 19-23, 27-29, and 37 are pending.
Information Disclosure Statement
The Information Disclosure Statement filed on 03/31/2026 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered.
Response to arguments
Applicant’s arguments filed 03/31/2026 with respect to the claim rejections under 35 U.S.C. § 102 (a) have been fully considered.
With respect to the rejection of claims 3, 11, 13, 16, 17, 19-23, 27-29, and 37 under 35 U.S.C. § 102(a)(1) as being anticipated by NCT03875820, Applicant argues that the prior art disclosure NCT03875820 (Institute of Cancer Research. A Phase I Trial of Defactinib and VS-6766, publicly available March 15, 2019, cited on applicant IDS dated 06/22/2023) had not disclosed the method applied to the KRAS G12V mutant at the time of the filing of the instant claims. Applicant’s arguments are found persuasive. Accordingly, the previous rejection under 35 USC 102(a)(1) is hereby withdrawn. However, a new ground of rejection under 35 U.S.C. § 103 is detailed below in view of Hung (Cancers, Volume 12, Issue 837, published March 31, 2020), hereinafter Hung, focusing on the motivation to treat KRAS G12V with the disclosed method of NCT03875820, with motivation supplied by Hung. In combination, the references render obvious all of the limitations of the instant claims. Accordingly, this action is nonfinal. The updated reference includes only the teachings of the publicly available version 1 document, made publicly available prior to the filing of the instant claims.
Specification
The specification is objected to for the inclusion of two-dimensional structures of compounds of low resolution (pages 9-14 and 19-22). At present, the structures of the compounds vary greatly with respect to size, style, and the thickness of bonds represented in the structures. It is recommended that the compounds of the instant specification be redrawn with a single chemical representation software. This objection is specifically made to avoid confusion for person of ordinary skill in the art as to what compound is being represented.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 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.
Claim 3, 11, 13, 16, 17, 19-23, 27-29, and 37 are rejected under 35 U.S.C. § 103 as being unpatentable over NCT03875820 (Institute of Cancer Research. A Phase I Trial of Defactinib and VS-6766, publicly available March 12, 2019, cited on applicant IDS dated 06/22/2023), in view of Hung (Cancers, Volume 12, Issue 837, published March 31, 2020), hereinafter Hung. As multiple versions of the study disclosure are available, citations are made to version 1 of the clinical trial from March 2019, which includes the record history tab, study details, and researcher view sections of the clinical trial. This combined disclosure is included on the PTO-892 form and attached as non-patent literature to this office action.
The instant claims are drawn to a method of treating cancer, elected to be non-small cell lung cancer, having a KRAS G12V mutation, comprising administering to the subject an effective amount of a dual RAF/MEK inhibitor, elected to be VS-6766, and further comprising the administration of a FAK inhibitor, elected to be defactinib.
NCT03875820 teaches a method of treating patients with advanced solid tumors using the FAK inhibitor, VS-6063 also referred to as Defactinib (see instant claims 23, 27-29) and the dual RAF/MEK inhibitor RO5126776, also referred to as CH5126776 and VS-6766 (see instant claims 3 and 11) (pages 5 and 6 of the disclosure). The patient population consisted of 20 patients with KRAS mutant non-small cell lung cancer (page 9 of the disclosure, see instant claims 3 and 37). The clinical trial further teaches wherein the starting dose of VS-6766 is 3.2 mg twice a week (page 9 of the disclosure, see instant claims 13, 19, and 21). A cycle length for a duration of three weeks, and a single week when the drug is not administered is also taught (page 9 of the disclosure, see instant claims 16 and 17). It is taught that in KRAS Mutant non-small cell lung carcinoma patients, VS-6766 will be administered on a twice-weekly schedule for 3 weeks followed by 1 week off in every 4 week cycle, wherein the starting dose will be 3.2 mg given orally as a single daily dose, and can be escalated to a maximum of 4 mg (page 12 of the disclosure, see instant claims 13, 16, 17,19-22).
Although the clinical trial NCT03875820 teaches the method instantly claimed applied to KRAS mutant cancer, at the time of filing, the clinical trial had not yet addressed the specific KRAS G12V mutant non-small cell lung cancer in the study (see instant claims 3 and 37).
The deficiencies of NCT03875820 are remedied by Hung, who teaches that different substitutions at codon 12 of KRAS mutants activate downstream signaling programs that drive fundamentally different biology. Of the many possible mutations, Hung teaches that G12V produces a more aggressive metastatic phenotype both in vitro and in vivo, and this aggressiveness is mechanistically linked to suppression of Rho signaling and consequent activation of the Wnt/b catechin pathway (page 2). Hung further discloses that advanced non-small-cell lung carcinoma (NSCLC) patients with KRASG12V mutation had a significantly shorter progression-free survival (PFS) and patients with KRASG12V mutation were predictive of pleuro-pericardial metastasis (page 2). As such, Hung identifies KRAS G12V mutant non-small cell lung cancer as an unmet and urgent therapeutic need within the field.
Accordingly, prior to the effective filing date of the instant claims, a person having ordinary skill in the art would have been motivated to apply the clinical trial method to patients with KRAS G12V mutant non-small cell lung cancer because the clinical trial outlines a therapeutic regimen directed to KRAS mutant cancer in general, and Hung teaches that KRAS G12V mutations confer greater likelihood of progression and metastasis as well as poor survival rates, supplying a person of ordinary skill direct motivation to prioritize the G12V mutant subpopulation for treatment. A person having ordinary skill in the art would be directly motivated to target KRAS G12V non-small cell lung cancer in order to address the urgent need identified by Hung, in an effort to improve poor prognosis and survival rates. Therefore, since the clinical trial outlines a therapeutic regimen directed to KRAS mutant cancer in general, an ordinary skilled artisan would have been motivated to treat patients with KRAS G12V with a reasonable expectation of success. Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
No claims are allowed.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
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