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 .
Response to Arguments
Applicant's arguments filed 10/09/2025 have been fully considered but they are not persuasive. Applicant argues the teachings of Cooke does not describe the use of the combination of Compound A and trametinib for the treatment of NSCLC with one or more Class II BRAF mutations or more or Class III BRAF mutation (page 1). Applicant additionally argues Welsch teaches an extensive list of MEK and RAF inhibitors and it would have been hindsight bias to choose the Cooke reference. It is noted from previous office action Cooke teaches the claimed invention combination to treat typical and atypical BRAF NSCLC mutations, which includes Class I-III mutations and Welsch teaches different combinations of MEK and RAF inhibitors which include claimed invention to treat claimed particular NSCLC Class II and Class III BRAF mutations.
Applicant has overcome the 112b rejection of claim 5 by the cancelation of the claim. Claims 1, 3-4, 6-8, 13-16, 20, 23 and 32 is now evaluated on its merits.
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.
Claims 1, 3-4, 6-8, 13-16, 20, 23 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Cooke (WO 2018203219 A1) in view of Welsch et al. (WO 2018213302 A1).
Regarding claims 1, 3-4, 6-8, 13-16, 20, 23 and 32, Cooke teaches a method for the treatment of non-small-cell lung cancer (NSCLC) comprising administration of a therapeutically effective amount of a combination therapy of formula (I)
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and a MEK inhibitor selected from a list which includes trametinib (Page 6, lines 10-15, 27-32). Accordingly, compound of formula (I), or a pharmaceutically acceptable salt thereof, and Compound of formula (II), or a pharmaceutically acceptable salt thereof, in combination with a MEK inhibitor, and in particular with trametinib, or a pharmaceutically acceptable salt or solvate thereof, for treating solid tumors, particularly tumors that harbor one or more MAPK pathway alterations, e.g. BRAF-mutant, KRAS-mutant and NRAS-mutant cancers (Page 25 lines 7-16).
Cooke teaches the treatment of oral dosage form (relevant to claims 7-8 and 13) (page 7, last para.) separately, simultaneously or sequentially (relevant to claim 20) to patients with NSCLC BRAF mutations of NSCLC having at least one V600E or other BRAF mutation, whether typical or atypical, i.e. BRAFV600E-mutant NSCLC or BRAF non- V600E-mutant NSCLC (relevant to claims 1, 6 and 23) (page 27, lines 14-17). Cooke additionally teaches the daily dose of Compound (I) administered twice a day and trametinib administered once daily in the amounts of Table:
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(relevant to claims 14-16) (Page 56, last para.), and the treatment led to the reduction or stabilization of tumor size or cancerous cell count (Page 20, 1st para).
Cooke fails to teach the combination therapy to treat the specific Class II and Class III BRAF mutant NSCLC from the list of claims 3-4.
Welsch teaches a method for the treatment of non-V600E/K BRAF cancers of melanoma, colorectal and non-small cell lung cancer (NSCLC) (para. 0019) comprising administration of an effective amount of an ERK inhibitor. Welsch teaches the method further comprises a MEK inhibitor, a RAF inhibitor, an HDAC inhibitor, and combinations thereof (para. 0021). Of the therapeutics the ERK inhibitor can be selected from a list of inhibitors that includes LTT-462 (para. 0008), RAF inhibitor from a list that includes LXH254
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(para. 0135) and MEK inhibitor from a list that includes trametinib (para. 0051). Of the non-V600E/K BRAF Welsch teaches G466E, G464R, G464V, L597R, D594A, D594E, D594G, D594H and K601E (relevant to claims 3-4) (para. 10-14). Welsch additionally teaches the pharmaceutical combination in oral dosage form (para. 0217), administered separately at appropriate intervals (para. 0210) and reduction of the tumor size or cancerous cell count (para. 0228).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have administered to a patient with Class II or Class III BRAF NSCLC mutation a pharmaceutical combination comprising
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in a total daily dosage from 400-800 mg and trametinib in an amount of 0.5 to 2mg. One would have been motivated to do so from the teachings of Cooke and Welsch on the therapeutics of
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and trametinib used to treat non-V600E/K BRAF mutant NSCLC). Cooke teaches the claimed mg range of claimed compound A and trametinib to treat atypical BRAF mutation NSCLC, which includes Class II-III, while Welsch teaches the claimed Class II and Class III BRAF mutant NSCLC (non-V600E/K BRAF mutant NSCLC) to be treated with claimed compound and trametinib. One would have combined the RAF inhibitor of
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and MEK inhibitor of trametinib with the claimed range from the teachings of Cooke with the teaching of Welsch of LXH254 and trametinib to treat a Class II and Class III BRAF mutant NSCLC.
Conclusion
THIS ACTION IS MADE FINAL. 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 MIKHAIL O'DONNEL ROBINSON whose telephone number is (571)270-0777. The examiner can normally be reached Monday-Friday 7:30am-5:30pm.
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627