DETAILED ACTION
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.
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.
Claim 1-5, 7, 10, 11, 13, 15-18 and 20.are rejected under 35 U.S.C. 103 as being unpatentable over Shumway (WO 2014/085216) in view of Weisberg (Leukemia, 2015, 29, 27-37).
Scope of prior art
Shumway teaches WEE1 inhibitor in combination with AKT inhibitor in a method of treating cancer (page 40, lines 13-21) and MK-1775 as a WEE1 inhibitor (page 4 last paragraph). List of cancers includes melanoma (page 8, line 4).
Ascertaining the difference
Shumway fails to teach synergistic effect of the combined administration.
Secondary reference
Weisberg teaches that RAS-expressing malignancies including melanoma can be treated by a combination of WEE1 inhibitor MK-1775 and an inhibitor of mTOR. Weisberg also teaches synergy resulting from the combination treatment (page 30, column 2 last paragraph). Weisberg further teaches that mTOR and AKT are part of the same PI3K/AKT/mTOR pathway and indicate that inhibition of components of that pathway other than the exemplified mTOR also result in synergy in RAS expressing cells (page 32, second column first paragraph). On page 32, first column, second paragraph, Weisberg teaches that AKT is at least in part responsible for the observed synergy.
Obviousness
One skilled in the art prior to the earliest effective filing date of the instant invention would have found it obvious to try to treat melanoma in a subject in need thereof by administering a combination of WEE1 inhibitor MK-1775 and AKT inhibitor as suggested by Shumway. One would have found it obvious to administer the combination to RAS-expressing melanoma with an expectation that the combination would produce a synergistic effect. Synergy is expected based on the teachings Weisberg. Weisberg establishes that WEE1 inhibition when combined with inhibition of PI3K/AKT/mTOR pathway produces synergistic results. Since AKT is a part of the PI3K/AKT/mTOR pathway, one would expect that a combination of WEE1 inhibitor and AKT inhibitor in RAS positive melanoma would result in synergistic effect. Thus, it would have been obvious to combine WEE1 inhibitor and AKT inhibitor because it has been suggested by Shumway, and one would expect a synergistic effect of the combination in RAS positive melanoma because it has been described by Weisberg.
Regarding limitation directed to the 3:1 ratio of ATK and WEE1 inhibitors:
A person of ordinary skill would have found it obvious to determine by routine experimentation the optimal amount of each inhibitor to use in the combination treatment. Applicants can overcome this rejection by a showing of unexpected results derived from the specifically claimed ratio.
Regarding limitations directed to composition and commercial package:
In order to practice the method of treating malignancies, a skilled artisan would have found it obvious to prepare a composition comprising the active components and to prepare a commercial package for use by medical practitioners.
Claims 2, 6, 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shumway (WO 2014/085216) in view of Weisberg (Leukemia, 2015, 29, 27-37) as applied to claims 1 and 10 above, and further in view of Tomkinson (US 9,487,525).
Scope of Shumway and Weisberg and motivation for combining the two are discussed in the rejection above.
Ascertaining the difference
Shumway fails to teach AZD5363 as an AKT inhibitor.
Secondary reference
Tomkinson teaches that AZD5363 is an AKT inhibitor useful in treatment of melanoma.
Obviousness
One skilled in the art prior to the earliest effective filing date of the instant invention would have found it obvious to try to treat melanoma by administering to a subject in need thereof a combination of WEE1 inhibitor MK-1775 and an AKT inhibitor with an expectation that the combination would produce a synergistic effect. One would have also found it obvious to use AZD5363 as an AKT inhibitor in the proposed combination because AZD5363 has been described in the art a therapeutic agent for melanoma. The resulting combination of MK-1775 and AZD5363 would be expected to produce a synergistic effect because it has been suggested by Weisberg that MK-1775 in combination with an inhibitor of PI3K/AKT/mTOR pathway produces synergistic results. Suggestion and motivation to utilize the combination for treatment of melanoma is provided by Shumway. Expectation of success is provided by Weisberg when he teaches synergy observed from inhibition of WEE1 and PI3K/AKT/mTOR pathway.
Reply to applicant’s remarks
Remarks filed on 9/19/25 have been fully considered and found to be not convincing.
In the remarks applicants argue that simultaneous administration of the WEE1 and ATK inhibitors led to dramatically improved results with lower toxicity that was observed using sequential administration. Applicants reference paragraphs [00302] – [00315] of the specification and corresponding figures 4C and 4D to support the argument. This argument is not persuasive because in order to reap the benefit of the expected synergy described by Weisberg, the two agents have to be administered at the same time. For synergy to exist both agents need to be carrying out their biological activity. The portions of the specification cited by applicants compares simultaneous administration to sequential administration where Wee1 inhibitor is administered for 3 days followed by ATK inhibitor administered for 4 days. If the agents are not administered at the same time, there is no opportunity for them to interact in the synergistic manner, so it’s not surprising that synergy was not observed in sequential administration method. Lastly, Shumway teaches Wee1 inhibitor in combination with inhibitor of ATK. A reasonable interpretation of “in combination with” is that the agents are administered together.
Conclusion
Claims 1-7, 10-13, 15-18 and 20 are pending
Claims 1-7, 10-13, 15-18 and 20 are rejected
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.
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628