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 .
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.
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.
Claim(s) 25-28, 39, 41-42, and 44-56 are rejected under 35 U.S.C. 103 as being unpatentable over WO17/170348 in view of WO20/046767 and US2020/0255410.
The claims of the instant application are drawn to compositions comprising a FLT3 inhibitor compound of formula I; a B-cell lymphoma (Bcl-2) inhibitor – which is ultimately venetoclax; and optionally an additional hypomethylating agent which is ultimately azacitidine. The agents are claimed to be in the same or separate dosages and administered together or separately. Also claimed are methods of treating cancer with the same wherein the cancer is optionally AML or AML having various specified mutations.
‘348 is drawn to treating AML having various mutations with combinations comprising a FLT3 inhibitor and the hypomethylating agent azacitidine (see [0004]-[0009]). The methods are taught to be practiced in AML mutant FLT3 polynucleotide-positive AML; or FLT3 internal tandem duplication (ITD) AML; or AML with FLT3 point mutation (see [0015]). The combinations are taught to be administered simultaneously or sequentially in a single dose or separate dosages and can be administered orally or by infusion (parenterally) (see [0019]). What is not taught is to add the additional Bcl-2 inhibitor as claimed herein nor the compound of formula I as the FLT3 inhibitor.
‘410 teaches compounds of formula I, including the species set forth in claim 27 (see example 8 – [0260] and table 2) are effective as FLT3 inhibitors in treating AML diseases as claimed herein.
‘767 teaches methods of treating the same AML diseases with combinations of azacitidine, venetoclax, and a FLT3 inhibitor (see page 10, lines 26-28).
It would have been obvious to combine the FLT3 inhibitors of ‘410 with the Bcl-2 inhibitor venetoclax and the hypomethylating agents azacitidine with these references before them since they are suggested to be combined by the same. ‘767 teaches methods of treating the same AML diseases with combinations of azacitidine, venetoclax, and a FLT3 inhibitor; ‘348 teaches methods combining FLT3 inhibitors and hypomethylating agents (azacitidine); and ‘410 teaches formula I is an effective FLT3 inhibitors. If applicants are relying on unexpected results to overcome a case of obviousness, the results should be commensurate in scope with the claims. It is noted that applicants have only shown the combination of Formula 3, venetoclax, and azacitidine as providing the improved results when compared to the individual agents.
Claim(s) 25-28, 39, 41-42, and 44-56 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020/171646 (see US 12,433,867 for English language equivalent) in view of Kennedy et al. (Frontiers of Oncology, vol. 10, 23, Dec. 2020, 20 pages – Citation 012 on applicant’s IDS filed 10/15/25).
‘646 teaches combinations of FLT3 inhibitors of formula I herein together with hypomethylating agents such as azacitidine (see claims 1-2). ‘646 teaches treating the same AML diseases having the same mutations (see claims 6-9). What is not taught is to add the additional Bcl-2 inhibitors as claimed herein.
Kennedy states that venetoclax, an inhibitor of Bcl-2, is particularly intriguing in combination with FLT3 inhibitors (see page 8). Kennedy notes that preclinical studies show that FLT3-ITD mutated blasts have higher Bcl-2 expression compared to FLT3-WT blasts and upregulation of antiapoptotic proteins is a mechanism of FLT3 resistance. In preclinical mouse models, venetoclax has demonstrated synergistic antileukemia activity with midostaurin, gilteritinib, and quizartinib (FLT3 inhibitors). Kennedy also notes the use of hypomethylating agents such as azacitidine to be used in combination with FLT3 inhibitors.
It would have been obvious to combine the FLT3 inhibitors of ‘646 with the Bcl-2 inhibitors such as venetoclax of Kennedy with these references before them; and also add the hypomethylating agents such as azacitidine as taught by both and use in the same methods of treating AML as claimed herein. Kennedy notes that combinations of FLT3 inhibitors and Bcl-2 inhibitors are intriguing based on their activity, and ‘646 teaches the same FLT3 inhibitors as claimed herein.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 25-28, 39, 41-42, and 44-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,433,867 in view of Kennedy et al. (Frontiers of Oncology, vol. 10, 23, Dec. 2020, 20 pages – Citation 012 on applicant’s IDS filed 10/15/25).
‘867 claims methods of treating AML with combinations of FLT3 inhibitors of formula I herein together with hypomethylating agents such as azacitidine (see claims 1-2). ‘646 teaches treating the same AML diseases having the same mutations (see claims 6-9). What is not taught is to add the additional Bcl-2 inhibitors as claimed herein.
Kennedy states that venetoclax, an inhibitor of Bcl-2, is particularly intriguing in combination with FLT3 inhibitors (see page 8). Kennedy notes that preclinical studies show that FLT3-ITD mutated blasts have higher Bcl-2 expression compared to FLT3-WT blasts and upregulation of antiapoptotic proteins is a mechanism of FLT3 resistance. In preclinical mouse models, venetoclax has demonstrated synergistic antileukemia activity with midostaurin, gilteritinib, and quizartinib (FLT3 inhibitors). Kennedy also notes the use of hypomethylating agents such as azacitidine to be used in combination with FLT3 inhibitors.
It would have been obvious to combine the FLT3 inhibitors of ‘646 with the Bcl-2 inhibitors such as venetoclax of Kennedy with these references before them; and also add the hypomethylating agents such as azacitidine as taught by both and use in the same methods of treating AML as claimed herein. Kennedy notes that combinations of FLT3 inhibitors and Bcl-2 inhibitors are intriguing based on their activity, and ‘646 teaches the same FLT3 inhibitors as claimed herein.
Claims 25-28, 39, 41-42, and 44-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-23 of copending Application No. 19/291,109 in view of Kennedy et al. (Frontiers of Oncology, vol. 10, 23, Dec. 2020, 20 pages – Citation 012 on applicant’s IDS filed 10/15/25).
‘109 claims combinations of FLT3 inhibitors of formula I herein together with hypomethylating agents such as azacitidine (see claims 1-2). ‘109 teaches treating the same AML diseases having the same mutations (see claims 14-18). What is not taught is to add the additional Bcl-2 inhibitors as claimed herein.
Kennedy states that venetoclax, an inhibitor of Bcl-2, is particularly intriguing in combination with FLT3 inhibitors (see page 8). Kennedy notes that preclinical studies show that FLT3-ITD mutated blasts have higher Bcl-2 expression compared to FLT3-WT blasts and upregulation of antiapoptotic proteins is a mechanism of FLT3 resistance. In preclinical mouse models, venetoclax has demonstrated synergistic antileukemia activity with midostaurin, gilteritinib, and quizartinib (FLT3 inhibitors). Kennedy also notes the use of hypomethylating agents such as azacitidine to be used in combination with FLT3 inhibitors.
It would have been obvious to combine the FLT3 inhibitors of ‘646 with the Bcl-2 inhibitors such as venetoclax of Kennedy with these references before them; and also add the hypomethylating agents such as azacitidine as taught by both and use in the same methods of treating AML as claimed herein. Kennedy notes that combinations of FLT3 inhibitors and Bcl-2 inhibitors are intriguing based on their activity, and ‘646 teaches the same FLT3 inhibitors as claimed herein.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TRAVISS C MCINTOSH III whose telephone number is (571)272-0657. The examiner can normally be reached Monday-Friday 9AM-5:30PM EST.
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/TRAVISS C MCINTOSH III/Primary Examiner, Art Unit 1693
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