DETAILED ACTION
Claims 1-3, 5-7, 10, 12, 15-18, 20-21, 23-25, and 28-30 are pending.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 5-7, 10, 12, 15-18, 20-21, 23-25, and 28 in the Reply filed on 7/7/2026, is acknowledged.
Claims 29-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply.
Applicant’s election of species of Acute Myeloid Leukemia, SNDX-5613, and venetoclax claims 1-3, 5-7, 18, 20-21, 23-25, and 28 in the Reply filed on 7/7/2026, is acknowledged.
Claims 10, 12, 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-3, 5-7, 18, 20-21, 23-25, and 28 are present for Examination and the subject of the Office Action below.
Priority
The instant application filed 11/10/2023 is a National Stage entry of PCT/US22/29002, with an International Filing Date of 5/12/2022. PCT/US22/29002 claims Priority from Provisional Application 63187753, filed 5/12/2021.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 11/10/2023, 6/7/2024, and 1/9/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the Examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 5-7, 18, 20-21, 23-24, and 28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement with evidence from Adato et al. “Quantitative Analysis of Dierential Expression,” Cancers 2020, 12, 1572.
of HOX Genes in Multiple Cancers The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 states, “a method of treating cancer with a HOX gene signature.”
Applicant states, “[a]s used herein, a HOX gene signature is set of genes that their expressions are altered—driven by altered HOX gene expression that affect initiation, development, progression of cancer, or a combination thereof. HOX gene signatures are well-known in the art.”
Applicant states, “[m]utations or activations in the HOX genes can lead to an increased risk of cancer, as well as affecting cancer development and/or progression. HOX gene alterations play a role in angiogenesis, autophagy, differentiation, apoptosis, proliferation, invasion, metastasis and metabolism. Cancers with a HOX gene signature include breast cancer, multiple myeloma, ovarian cancer, renal cancer, colon cancer, colorectal cancer, prostate cancer, gastric cancer, non-small cell lung cancer, glioblastoma, cervical cancer, chondrosarcoma, osteosarcoma, neuroblastoma, and hematological malignancies such as leukemias.”
The genus, all cancers with a HOX gene signature includes more than breast cancer, multiple myeloma, ovarian cancer, renal cancer, colon cancer, colorectal cancer, prostate cancer, gastric cancer, non-small cell lung cancer, glioblastoma, cervical cancer, chondrosarcoma, osteosarcoma, neuroblastoma, and hematological malignancies such as leukemias. Looking to the art, Adato shows that in all the cancers analyzed, HOX genes were altered in some way. Therefore, Applicant’s claim reads on all cancer, given the Applicant has not defined a specific cutoff of alteration of expression from normal. Given the art, alteration in HOX is present in all cancers.
Applicant has only shown synergy in treating cancer in the genus of leukemia, Applicant has not demonstrated treatment of other hematological cancers or any cancers of a broader genus to be in possession of the genus of claim 1. There are no blaze marks to provide teaching to the other parts of the genus of all cancers. Applicant can overcome this rejection by limiting the claims to the genus of leukemia.
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.
Claims 1-2, 5-7, 18, 20-21, 23-25, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn et al. “Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia,” Cancer Discov. 2016 October; 6(10): 1166–1181; Kontro et al. “HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia,” Leukemia (2017) 31, 301–309; and Claremon WO2017112768A1 published June 29, 2017.
Claim 1 is directed to a method of treating cancer with a HOX gene signature in a subject in need thereof, comprising administering to the subject a synergistic combination of a therapeutically effective amount of a menin inhibitor and a therapeutically effective amount of a Bcl-2 inhibitor.
Kuhn teaches treating NPM1 Mutant Leukemia with menin inhibitors including MI-503, a novel menin-MLL1 inhibitor.
Kontro teaches treating NPM1 Mutant Acute Myeloid Leukemia with a Bcl-2 inhibitor, venetoclax (ABT-199).
Claremon teaches menin inhibitors including those of instant claim 6 and 7, and teach them as treatments for AML (claim 48), and in combination with Bcl-2 inhibitors including venetoclax (page 41, lines 20-24).
Given the generic teaching in the art that menin inhibitors can be combined with Bcl-2 inhibitors (Claremon) and since the art teaches using them individually in the exact same cancer, NPM1 Mutant Acute Myeloid Leukemia (Kuhn & Kontro) one would find it obvious to use the 2 compounds together to treat the same indication.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Regarding instant claim 2, directed to “wherein the menin inhibitor and the Bcl-2 inhibitor are orally administered simultaneously or sequentially.” The art shows that venetoclax is an oral drug, and MI-503 is an oral drug.
Regarding instant claim 5, directed to wherein the therapeutically effective amount of the menin inhibitor, the therapeutically effective amount of the Bcl-2 inhibitor, or both, is reduced compared to the therapeutically effective amount for administration as a single agent.” When combining therapies, one would expect additive effects and would thereby reduce the dose.
Claim 6 and Claim 7 are directed to “the menin inhibitor is 5-fluoro-N,N-diisopropyl-2-((4-(7-((trans-4- (methylsulfonamido)cyclohexyl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)pyrimidin-5- yl)oxy)benzamide, or N-ethyl-2-((4-(7-((trans-4-(ethylsulfonamido)cyclohexyl)methyl)-2,7- diazaspiro [3.5]nonan-2-yl)pyrimidin-5-yl)oxy)-5-fluoro-N-isopropylbenzamide and is administered once or twice per day in a daily dose of 200 mg to 600 mg; the Bcl-2 inhibitor is venetoclax administered at a daily dose of 20 mg for a first week, at a daily dose of 50 mg for a second week, at a daily dose of 100 mg for a third week, at a daily dose of 200 mg for a fourth week and at a daily dose of 400 mg for a fifth week and subsequent weeks; or a combination thereof.
Claremon teaches the synthesis and use of SNDX-5613, which is the claimed compound required by instant claims 6 and 7. As to the dose of the compounds, venetoclax is taught in the same dosage range, and SNDX-5613 is taught in the art as a larger range (Claremon page 45, lines 1-15) and to be adjusted to efficacy. AS such the dosing is obvious.
Regarding claim 18 directed to wherein the subject has been treated previously with venetoclax for a cancer and the subject progressed on the prior venetoclax treatment, or the subject has been treated previously with venetoclax and developed resistance to venetoclax. This is obvious as one could pick either treatment as the starting point, and then switch when the drug failed or resistance occurred. Given they both treat the same type of cancer they would be ideal to give in this sequential manner.
Regarding claims 20, 21, 23, 24, 25, and 28 are all directed to AML taught in the art, which is the cancer both references teach. As such, this cancer is obvious.
Allowable Subject Matter
Claims 3 and 25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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