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 .
Detailed Action
This Office Action is in response to the Applicant’s reply received 11/06/2025. Claims 1, 2, 19-33 are pending and are considered on the merits.
Response to Applicant’s Arguments and Amendments
In the response submitted by the Applicant the following 35 U.S.C § 103 (a) rejections are withdrawn:
Claims 1-3, 6, 7, 11, 19, and 21 were rejected under 35 U.S.C. 103 as being obvious over Bernards et al. (WO 2015/178770, in IDS 7/29/22).
Claim(s) 4, 10, 12, 16 and 20 were rejected under 35 U.S.C. 103 as being unpatentable over Bernards et al. (WO 2015/178770, in IDS 7/29/22) as applied to claims 1-3, 6, 7, 11, 19, and 21 above, and further in view of Caponigro et al. (US 2019/0105303, in IDS 7/29/22) in light of support by Kim et al. (Mol. Cells 2014).
Claim(s) 22 were rejected under 35 U.S.C. 103 as being unpatentable over Bernards et al. (WO 2015/178770, in IDS 7/29/22) as applied to claims 1-3, 6, 7, 11, 19, and 21 above, and further in view of Fischer et al. (Saudi J Gastroenterol 2012, in IDS 7/29/22).
The Applicant’s amendments limiting the MAPK pathway inhibitors to a combination of binimetinib and encorafenib while not administering cetuximab to the subject necessitated the above withdrawals since these inhibitors are not disclosed by Bernards et al. (WO 2015/178770). All arguments drawn to these rejections are now considered moot.
New Rejections Necessitated by Amendment
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.
Claim(s) 1, 2, and 21-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Caponigro et al. (US 2019/0105303, in IDS 7/29/22).
Caponigro et al. teach treating cancer including pancreatic cancer with a BRAF V600E mutation and the subject expresses a wild-type KRAS [0158 and 0164]. They teach administering a combination of encorafenib (a BRAF inhibitor) and binimetinib (a MEK inhibitor) with an EGFR inhibitor other than cetuximab, which includes getifinib, erlotinimb, lapatinib, dacomitinib, neratinib, vanetanib, or panitumumab [0045].
The Applicant has amended the claims to exclude the administration of cetuximab. However MPEP 2123 state:
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments.
In this case, since Caponigro et al. offers many alternatives to cetuximab, then it would be obvious to use one of those, rather than cetuximab, and therefore meet the negative limitation in claim 1.
Caponigro et al. teach that the patient was previously treated with another anticancer treatment including 1st or 2nd line systemic anticancer therapy with cytotoxic agents, tumor resection, or radiation therapy [0052, 0157]. Therefore it would be obvious to use this on a subject’s pancreatic cancer that is intolerant to at least one line of therapy for metastatic disease and one shows metastatic disease recures less than or equal to 12 weeks after completion of 1st or 2nd line systemic anticancer therapy.
Caponigro et al. teach;
encorafenib is administered orally once daily at a dose of 100-400 mg (0053);
binimetinib is administered twice daily at a dose of 10-85 mg (0053);
encorafenib (a BRAF inhibitor) can be administered for up to 6 days to 6 weeks and the dose may be reduced depending on the severity of reaction [0128];
binimetinib (a MEK inhibitor) can be administered for up to 14 days to 4 weeks and the dose may be reduced depending on the severity of reaction [0129].
Both encorafenib and binimetinib can be administered in 28 day cycles until stopped by disease progression, unacceptable toxicity, consent withdrawal, initiation of subsequent anticancer therapy or death [0295 and 384].
Therefore it would be obvious for one of ordinary skill in the art to administer encorafenib and binimetinib for 28 day cycles at least twice based on disease progress, patient acceptance of toxicity, initiation of an alternative cancer therapy or death. The doses of each drug per cycle can be reduced based on severity of reaction. One of ordinary skill in the art would recognize the dosage and administrations claimed as a matter of routine optimization to minimize toxic reactions while continuing to treat pancreatic cancer based on the values provided by Caponigro et al. (MPEP 2144.05 II).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Caponigro et al. (US 2019/0105303, in IDS 7/29/22) as applied to claims 1, 2, and 21-33 above, and further in view of Bernards et al. (WO 2015/178770, in IDS 7/29/22) in light of support by Kim et al. (Mol. Cells 2014).
Caponigro et al. render obvious treating pancreatic cancer with a BRAF V600E mutation and the subject expresses a wild-type KRAS [0158 and 0164] by administering a combination of encorafenib (a BRAF inhibitor) and binimetinib (a MEK inhibitor) [0045]. They do not expressly teach their pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This would be obvious in view of Barnards et al. who teach PANC1 cells are sensitive to MEK inhibition (Barnards, [017]). Kim et al. teach that PANC1 cells are a pancreatic ductal adenocarcinoma (PDAC) cell line as supported by Kim et al. (pg. 889, col 1, 1st full paragraph). Therefore it would be obvious to use the pancreatic cancer therapy of Caponigro on BRAF V600E mutated PDAC cells since Barnards et al. teach these are susceptible to MEK inhibition.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 19 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Caponigro et al. (US 2019/0105303, in IDS 7/29/22) as applied to claims 1, 2, and 21-33 above, and further in view of Ning et al. (J of Pancreatology 2019).
Caponigro et al. render obvious treating pancreatic cancer with a BRAF V600E mutation and the subject expresses a wild-type KRAS [0158 and 0164] by administering a combination of encorafenib (a BRAF inhibitor) and binimetinib (a MEK inhibitor) [0045]. They do not expressly teach further administering a PD-1 or PD-L1 inhibitor. However this would be obvious in view of Ning et al. suggest combining PD-1 immunotherapy in combination with other immunotherapies, chemotherapies, or radiotherapies to treat PDAC pancreatic cancer (Ning, Prospection, last page). Table 1 teach several PD-1 inhibitors including nivolumab, pembrolizumab, and pembrolizumab are used in combination with other therapies in current clinical trials.
MPEP 2044.06 I renders obvious combining two compositions taught in the prior art as useful for the same purpose. It would be obvious for one of ordinary skill in the art to combined any of the PD-1 inhibitors taught by Ning et al. with encorafenib and binimetinib since all three are taught to be useful to treat pancreatic cancer. Furthermore it would be obvious to use this composition to treat PDAC since Ning et al. teach that PD-1 inhibitors in combination with other chemotherapies are suitable to treat this version of pancreatic cancer.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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.
In response to this office action the applicant should specifically point out the support for any amendments made to the disclosure, including the claims (MPEP 714.02 and 2163.06).
CONTACT INFORMATION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THANE E UNDERDAHL whose telephone number is (303) 297-4299. The examiner can normally be reached Monday through Thursday, M-F 8-5 MST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at (571) 272-3311.The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THANE UNDERDAHL/Primary Examiner, Art Unit 1699