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 .
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.
Current Status of 18/826,792
This Office Action is responsive to the amended claims received 1 November 2024.
Claims 2-4, 6-8, 10, 12-17, 21-22, 24-27, and 59 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications 63/581,469 (filed 8 September 2023) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
The Examiner has determined, for the purposes of the instant action, that the effective filing date of the instant claims is 6 September 2024, because sufficient support was not found in earlier-filed documents.
Information Disclosure Statement
The information disclosure statements (IDS) received on 3 June 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, these information disclosure statements are being considered by the examiner.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application for the following reasons: In Figures 2D-2G and 12A-12B, it is not currently possible to determine which curve relates to which of the legend items. Applicant may choose to increase the size of the data markers
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim Objections
Claim 25 is objected to because of the following informalities: The word “or” appears within the middle of the list of items in claim 25. There does not appear to be any particular reason for this, so it seems to be grammatically incorrect. Applicant may choose to delete this “or”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2-4, 6-8, 10, 12-15, 17, and 24-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
WANG (Wang, J.; Hu, K.; Guo, J.; et al. “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” NATURE COMMUNICATIONS | 7:11363, 2016).
WANG teaches that ROCK inhibition using a combination of fasudil and BI-2536 caused apoptosis and cell cycle arrest in KRAS-mutant cancer cell lines (discussion section). WANG teaches that this fasudil combination also caused tumor regression in an LSL-KRAS G12D mutant mouse model of lung cancer (discussion section). WANG teaches that the mouse model was produced by obtaining non-small cell lung cancer (NSCLC) samples from patients and implanting them into mice (animal studies section). Figure 5 of WANG teaches that treatment of the NSCLC mouse model animals with fasudil and BI-2536 resulted in lower tumor weights, as compared to vehicle administration. WANG teaches the administration of the fasudil and BI-2536 combination for the treatment of cancerous cells with multiple specific KRAS mutations (KRAS V12 on Pg. 2 6th paragraph and KRAS G12D in Figure 5) and for the treatment of cancerous cells generally having a KRAS mutation (Pg. 4 2nd-3rd paragraphs).
The Examiner does not see specific inhibitors of expression or function listed within the instant specification for each and every one of the proteins listed within claim 2. Paragraph [00171] of the instant specification states that “an inhibitor described herein may decrease the expression or function of…” and then goes on to list all of the proteins in the instant claims. Because of these facts, the Examiner is interpreting the instant claims in light of the instant specification in the following manner: the specific inhibitors listed in instant claim 13 are understood to decrease the expression or function of every one of the proteins discussed within the instant claims.
Regarding claims 17 and 25-26: Claims 17 and 25-26 further limit the identity of the KRAS inhibitor within the intended use of claim 2. The teachings of WANG allow for the intended use described within instant claim 2.
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.
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 2-4, 6-8, 10, 12-17, and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over:
WANG (Wang, J.; Hu, K.; Guo, J.; et al. “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” NATURE COMMUNICATIONS | 7:11363, 2016)
in view of:
QUNAJ (Qunaj, L.; May, M.S.; Neugut, A.I.; et al. “Prognostic and therapeutic impact of the KRAS G12C mutation in colorectal cancer” Front. Oncol. 13:1252516, 2023).
Regarding claim 16: WANG teaches that ROCK inhibition using a combination of fasudil and BI-2536 caused apoptosis and cell cycle arrest in KRAS-mutant cancer cell lines (discussion section). WANG teaches that this fasudil combination also caused tumor regression in an LSL-KRAS G12D mutant mouse model of lung cancer (discussion section). WANG teaches that the mouse model was produced by obtaining non-small cell lung cancer (NSCLC) samples from patients and implanting them into mice (animal studies section). Figure 5 of WANG teaches that treatment of the NSCLC mouse model animals with fasudil and BI-2536 resulted in lower tumor weights, as compared to vehicle administration. WANG teaches the administration of the fasudil and BI-2536 combination for the treatment of cancerous cells with multiple specific KRAS mutations (KRAS V12 on Pg. 2 6th paragraph and KRAS G12D in Figure 5) and for the treatment of cancerous cells generally having a KRAS mutation (Pg. 4 2nd-3rd paragraphs).
WANG does not directly teach the treatment of cells with G12C mutations, although WANG does mention G12C mutations within the introduction.
QUNAJ teaches, in Figure 1, that the KRAS G12C mutation is known to occur in 1 % of pancreatic ductal adenocarcinomas, 12 % of non-small cell lung cancers, and 3 % of colorectal cancers.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the administration of fasudil and BI-2536 for the general treatment of mutant KRAS cancers (taught by WANG) with the KRAS G12C mutant NSCLC (taught by QUNAJ), for the purpose of treating as many types of mutant KRAS cancers as possible. The artisan would have expected success with this combination, because WANG and QUNAJ both provide teachings related to the same condition, being NSCLC.
The Examiner does not see specific inhibitors of expression or function listed within the instant specification for each and every one of the proteins listed within claim 2. Paragraph [00171] of the instant specification states that “an inhibitor described herein may decrease the expression or function of…” and then goes on to list all of the proteins in the instant claims. Because of these facts, the Examiner is interpreting the instant claims in light of the instant specification in the following manner: the specific inhibitors listed in instant claim 13 are understood to decrease the expression or function of every one of the proteins discussed within the instant claims.
Regarding claims 17 and 25-26: Claims 17 and 25-26 further limit the identity of the KRAS inhibitor within the intended use of claim 2. The teachings of WANG allow for the intended use described within instant claim 2.
Claims 2-4, 6-8, 10, 12-17, 24-27, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over:
WANG (Wang, J.; Hu, K.; Guo, J.; et al. “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” NATURE COMMUNICATIONS | 7:11363, 2016)
and in view of:
QUNAJ (Qunaj, L.; May, M.S.; Neugut, A.I.; et al. “Prognostic and therapeutic impact of the KRAS G12C mutation in colorectal cancer” Front. Oncol. 13:1252516, 2023)
and in view of:
OSTREM (Ostrem, J.M.; Peters, U.; Sos, M.L.; et al. “K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions” NATURE | VOL 503 | 28 NOVEMBER 2013).
Teachings of WANG and QUNAJ are described above.
Regarding claims 27 and 59: WANG teaches that fasudil was dissolved in sterile water and administered by oral gavage to mice (animal studies section).
WANG does not directly teach the administration of a KRAS inhibitor in combination with a compound that is an expression inhibitor, function inhibitor, or degrader of an instantly claimed protein. However, Wang does teach, within the introduction, that “small molecules that bind to allosteric regulatory sited on KRAS (G12C) have shown preclinical benefits”, and cites OSTREM.
QUNAJ teaches, in Figure 1, that the KRAS G12C mutation is known to occur in 12 % of non-small cell lung cancers, and the KRAS G12D mutation is known to occur in 5 % of non-small cell lung cancers.
OSTREM teaches compounds that were found to irreversibly bind to “a common oncogenic mutant, K-Ras(G12C)”, and did not affect the wild-type protein (abstract). OSTREM teaches that compound 12 therein is effective at decreasing the viability of KRAS G12C lung cancer cell lines (Pg. 550-551 and Figure 4).
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date to combine the fasudil and BI-2536 therapeutic combination (taught by WANG) with the KRAS (G12C) inhibitor compound 12 taught by OSTREM (and directly pointed to in the intro. section of WANG), for the purpose of increasing the efficacy of the therapeutic combination against KRAS G12 mutant cancers and mutant cancer cells. The artisan would have expected success in this combination because OSTREM and WANG both teach compounds useful for the treatment of lung cancer.
Claims 2-4, 6-8, 10, 12-15, 17, 21, and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over:
WANG (Wang, J.; Hu, K.; Guo, J.; et al. “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” NATURE COMMUNICATIONS | 7:11363)
and in view of:
DIFEDERICO (DiFederico, A.; DeGiglio, A.; Parisi, C; Gelsomino, F. “STK11/LKB1 and KEAP1 mutations in non-small cell lung cancer: Prognostic rather than predictive?” European Journal of Cancer 157 (2021) 108e113).
Teachings of WANG are described above.
Regarding claim 21: DIFEDERICO teaches that STK11/LKB1 and KEAP1 mutations were known to occur in 25-30 % and 11-27 % of advanced NSCLC respectively.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the administration of fasudil and BI-2536 for the general treatment of mutant KRAS cancers (taught by WANG) with the STK11/LKB1 and KEAP1 mutant NSCLC (taught by DIFEDERICO), for the purpose of treating as many types of mutant KRAS cancers as possible. The artisan would have expected success with this combination, because WANG and DIFEDERICO both provide teachings related to the same condition, being NSCLC.
Claims 2-4, 6-8, 10, 12-15, 17, 22, and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over:
WANG (Wang, J.; Hu, K.; Guo, J.; et al. “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” NATURE COMMUNICATIONS | 7:11363)
and in view of:
SIRHAN (Sirhan, Z.; Alojair, R.; Thyagarajan, A.; et al. “Therapeutic Implications of PTEN in Non-Small Cell Lung Cancer” Pharmaceutics 2023, 15, 2090).
Teachings of WANG are described above.
Regarding claim 22: SIRHAN teaches, in Table 2, that a loss of PTEN expression was known to be found in 42.4 % of NSCLC patients.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the administration of fasudil and BI-2536 for the general treatment of mutant KRAS cancers (taught by WANG) with the PTEN deletion mutant NSCLC (taught by SIRHAN), for the purpose of treating as many types of mutant KRAS cancers as possible. The artisan would have expected success with this combination, because WANG and SIRHAN both provide teachings related to the same condition, being NSCLC.
Conclusion
No claims are currently allowable.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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