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 .
Priority
The present Application, filed April 20, 2023, is a national stage entry under 35 U.S.C. § 371 of International Patent Application No. PCT/US2021/055644, filed October 19, 2021, which claims the benefit of U.S. Provisional Patent Application No. 63/094,826, filed October 21, 2020.
Status of the Claims
In the amendment filed January 29, 2026, claims 11, 12, 16-18, and 23-26 are canceled and new claims 400-406 are added. Claims 3-10 and 13-15 are amended. Claims 3-10, 13-15, and 400-406 are currently pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 29, 2026 is acknowledged.
Previous Rejections and/or Objections
Any objections and/or rejections raised in the previous Office Action but not reiterated below are considered to have been withdrawn.
Declaration Under 35 U.S.C. § 1.132
The Declaration of Dr. Francis Burrows (hereinafter, “the Burrows Declaration”), filed under 35 U.S.C. § 1.132 on January 26, 2026, is acknowledged.
Response to Arguments
Applicant’s arguments made in conjunction with Applicant’s response, filed January 29, 2026, to the Non-Final Office Action filed September 29, 2025, are noted. The Arguments are moot in view of the new modified grounds for rejection, below. However, Applicant’s argument that the claimed methods yield unexpected results, presented on pg. 14 of Applicant’s response, are of relevance.
Applicant referring to the Burrows Declaration, notes that the non-patent publication, Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial, Lancet Oncol., 25, pgs. 1310-1324 (2024) by Wang et al. (hereinafter, “Wang”) teaches a patient having AML, lacking an NPM1 mutation and a MLL rearrangement (as in instant claim 3) but having mutations in both of SETD2 and RUNX1, exhibited exceptional responsiveness to the menin inhibitor ziftomenib. As noted, details of this are further discussed in the Burrows Declaration. Applicant argues that this constitutes an expected result not suggested by the cited references, and supports the nonobviousness of the amended claims that include one or more mutations in SETD2 and RUNX1.
While the result mentioned from Wang may be promising, it is noted that it is from a single individual, making it hard to ascertain whether or to what extent the observed response is related to the genetic profile. Moreover, the patient reference from the Wang study had mutations in both SETD2 and RUNX1, whereas the instant claims, with the exception of claim 406, require a mutation in only one of these genes. For this reason, the unexpected result of Wang, while preliminary, is found to militate in favor of nonobviousness of new claim 406, which requires a mutation in both SETD2 and RUNX1. Applicant’s argument regarding unexpected results is not found persuasive with respect to claims 3-10, 13-15, and 400-405, which require a mutation in only one of these genes, because the scope of the claims is not commensurate with the conditions of the unexpected result. This reasoning applies to the modified rejections for obviousness under 35 USC 103, and for nonstatutory double patenting.
Applicant’s other arguments, as noted, are moot in light of the modified reasons for rejection.
Claim Rejections-- 35 USC § 103 – 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.
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.
Claims 3, 5, and 7-8 are unpatentable over Armstrong and Yokota:
Claims 3, 5, and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication No. 2019/0307750 to Armstrong (hereinafter, “Armstrong”), in view of the non-patent publication, The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies, Molecules and Cells, 43, pgs. 145-152 (2020) by Yokota et al. (hereinafter, “Yokota”).
Claim 3 recites a method for treating a hematological malignancy or Ewing's sarcoma (ES) in a subject who does not exhibit a mutation in nucleophosmin (NPM1) gene or who does not exhibit a rearranged mixed-lineage leukemia (MLL-r) gene, the method comprising administering to the subject a menin inhibitor. Amended claim 3 further recites wherein the subject exhibits a mutation in SET domain containing 2 (SETD2) gene or a mutation in runt-related transcription factor 1 (RUNX1) gene.
Armstrong teaches a method for treating a leukemia, such as acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML), comprising administering to the patient an inhibitor of interaction between MLL and menin (a menin inhibitor – see paragraphs [0031]-[0032]). Armstrong further teaches that, in some embodiments, the leukemia (i.e. the subject) does not exhibit an MLL-rearrangement (paragraph [0073]). Armstrong thus teaches treating a hematological malignancy in a subject who does not exhibit MLL-rearrangement, the method comprising administering a menin inhibitor. Armstrong does not expressly teach that the subject exhibits one of the recited mutations, but it would have been an obvious extension of the method of Armstrong to include such patients because RUNX1 mutations were known in the art as a common subset of leukemia patients. See, for example, Yokota.
Yokota presents a review of clinical and molecular characteristics of RUNX1 mutations (Abstract), including their frequency in various hematological malignancies such as ALL and other leukemias (Abstract, pg. 146). Yokota teaches, for example, that RUNX1 mutations are found in about 7-18% of AML cases, with higher frequencies in certain subtypes (e.g. up to 33% in intermediate-risk patients as opposed to 0% in low-risk patients; and with variations based on hematopoietic lineage, such as 40% in M0 cases) – see RUNX1 Mutation-Related AML, pg. 146). It would have been obvious to include patient populations, not only naturally encompassed by the general leukemic patient populations of Armstrong, but constituting an appreciable percentage of ALL and AML patients. This is particularly so given that there is no clear evidence of record to indicate any particular functional or outcome-based difference in the claimed subpopulation (e.g. those leukemic patients having a RUNX1 mutation). As such, the limitation merely identifies a known large subset of patients encompassed in the prior art treatment, and is not supported by evidence of criticality or surprising results, claim 3 is obvious.
With respect to claim 5, Armstrong teaches that in particular embodiments, the leukemia is selected from the group consisting of an acute lymphocytic leukemia (ALL) and an acute myeloid leukemia (AML) – paragraph [0061].
Claim 7 recites the method of claim 3 wherein said subject exhibits an aberrant expression or activity of myeloid ecotropic viral insertion site 1 (MEIS1) gene or MEIS1 protein. Claim 8 recites wherein said aberrant expression or activity is overexpression or increased activity of MEIS1 protein. Armstrong teaches that the method is preferably directed to leukemia having a mutant nucleophosmin 1 (NPM1) gene (claim 15), and that MEIS1 is aberrantly expressed in NPM1mut AML (i.e. acute , which is the target of Armstrong (paragraph [0024]). With respect to claim 8, Armstrong teaches specifically that leukemic cells having an NPM1 mutation tend to overexpress Meis1 (paragraph [0015]). As such, at minimum it would have been obvious to apply the method of Armstrong to a subject that exhibits aberrant expression of MEIS1 gene (claim 7), and wherein that aberrant expression is overexpression of MEIS1 protein (claim 8).
Claim 4 is obvious over Armstrong, Yokota, and Cacatian:
Claim 4 is rejected under 35 U.S.C. § 103 as being unpatentable over Armstrong, in view of Yokota, further in view of International Patent Application Publication No. WO/2017/214367 by Cacatian et al. (hereinafter, “Cacatian”).
Claim 4 recites a method for treating a hematological malignancy or Ewing's sarcoma (ES) in a subject who exhibits neither a mutation in nucleophosmin (NPM I) gene nor a rearranged mixed-lineage leukemia (MLL-r) gene, the method comprising administering to the subject a menin inhibitor. Essentially this is the method of claim 3 but excludes both recited mutations from the subject pool.
Armstrong and Yokota are applied to claim 4 as to claim 3, above. As noted, Armstrong teaches wherein the subject does not exhibit a rearranged mixed-lineage leukemia (MLL-r) gene, but does not teach that the subject of the method lacks both an NPM I mutation and an MLL-r mutation. It would have been obvious, however, to apply the method of Armstrong to a subject lacking both types of mutation because it was known in the art that, in addition to the teachings of Armstrong, menin inhibitors can be effective in treating leukemias lacking a NPM1 mutation. See, for example Cacatian.
Cacatian teaches compounds that are inhibitors of the menin-MLL interaction (menin inhibitors) -see Abstract- and further teaches a method of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of one of the disclosed compounds (pg. 2, lines 20-22). Cacatian teaches that the cancer can be a hematological cancer, such as leukemia (pg. 45, lines 20-22). While Cacatian teaches that in some embodiments, the leukemia is an AML having an NPM1 gene(pg. 49, lines18-20), Cacatian does not require this in the broadest embodiments of leukemia treatment (e.g. pg. 45, lines 20-22; and pg. 48 line 28 through pg. 49, line 20). Furthermore, Cacatian teaches working examples in which the menin inhibitors are shown to inhibit proliferation of MV-4-11 cells [Assay 2: (cell proliferation assay) beginning at pg. 379]. Notably, MV-4-11 cells are leukemia cells that do not have an NPM1 mutation (see, for example, the non-patent publication, A Rapid Flow Cytometric Method for the Detection of NPM1 Mutated Patients with Acute Myeloid Leukemia (AML), Blood, 112, pgs. 529-530 (2008) by Oelschlaegel et al., for confirmation that MV4-11 cells have wild-type NPM1).
Armstrong thus teaches administration of a menin inhibitor to treat leukemia in a subject having a NPM1 mutation but not a MLL mutation, while Cacatian teaches administration of a menin inhibitor to treat leukemia in a subject having a MLL mutation, but not a NPM1 mutation; while Yokota renders it obvious to include subjects having a RUNX1 mutation.
Claim 6 is obvious over Armstrong, Yokota, and Cancer Genome:
Claim 6 is rejected under 35 U.S.C. § 103 as being unpatentable over Armstrong, in view of Yokota, further in view of the non-patent publication, Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia, N. Engl. J. Med., 368, pgs. 2059-2074 (2013) by The Cancer Genome Atlas Research Network (hereinafter, “Cancer Genome”). In particular, reference is made to the raw data from this publication, obtained at the url www.cbioportal.org/study/summary?id=laml_tcga_pub, and referred to as “Cancer Genome raw data”.
Claim 6 recites the method of claim 3 wherein the subject does not exhibit a mutation in mixed-lineage leukemia (MLL) gene. Armstrong and Yokota are applied as above. As noted, Armstrong teaches that the leukemia (i.e. the subject) does not exhibit a genetic mutation, alteration, and/or abnormality that is an MLL-translocation (MLL-t), an MLL-rearrangement (MLL-r), or an MLL-partial tandem duplication (MLL-PTD) (paragraph [0073]). However, while Armstrong teaches embodiments in which these specific types of MLL mutations are absent, Armstrong does not explicitly reference embodiments in which all MLL mutations are absent – i.e. where MLL genes of the subject are wild-type. It would have been at least obvious, however, to apply the method of Armstrong to subjects having wild-type MLL genes, because it was known in the art that the three types of mutations excluded by Armstrong are the predominant MLL mutations observed in leukemia. See, for example, Cancer Genome.
Cancer Genome teaches a study of mutations and their frequency as found in adult acute myeloid leukemia (Abstract). Cancer Genome teaches that whole genome sequencing was performed on samples from 200 AML patients (pg. 2061, left column, first full paragraph), and mutations were identified by locus as well as categorized as by type (e.g. copy number alterations, single nucleotide variants and small insertions and deletions, rearrangements, etc. – pg. 2061, right column, first two full paragraphs). Cancer Genome raw data shows that 12 of the leukemic samples had a MLL copy number alteration (deletion or addition, not typically considered a leukemogenic driver), 5.5% had a MLL structural variant (e.g. fusion, the type of mutation excluded in the embodiment of Armstrong), and 1% had a MLL small mutation (point mutation or small insertion/deletion). Thus, over 80% of AML samples had no MLL mutation. In view of the embodiment of Armstrong that excludes structural variant mutations, and the teaching of Cancer Genome that the strong majority of adult AML samples have no MLL mutation, it would have been obvious to apply the method of Armstrong to leukemia subjects having no MLL mutation.
Claims 9-10 are obvious over Armstrong, Yokota, and Collins:
Claims 9-10 are rejected under 35 U.S.C. § 103 as being unpatentable over Armstrong, in view of Yokota, further in view of the non-patent publication, Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets, Oncogene, 35, pgs. 1090-1098 (2015) by Collins et al. (hereinafter, “Collins”).
Claim 9 recites the method of claim 3 wherein the subject exhibits an aberrant expression or activity of homeobox 9 (HOXA9) gene or HOXA9 protein, and claim 10 specifies that the aberrant expression is overexpression of HOXA9 protein.
Neither Armstrong nor Yokota expressly teaches administering the menin inhibitor to a subject that exhibits aberrant expression of HOXA9, but does teach that menin-MLL inhibition inhibits cell proliferation in NPM1mut AML cells most likely via alteration (in context, suppression) of Hox and Meis1 expression (paragraph [0124]). Furthermore, Collins teaches that HOXA9 is overexpressed in more than 50% of acute myeloid leukemias (pg. 1090, Introduction, second paragraph). As such, and with respect to claims 9 and 10, it would have been obvious to perform the method of claim 3 on a subject that exhibits overexpression of HOXA9 protein.
Claims 400-405 are obvious over Armstrong, Yokota, and Burrows:
Claims 400-405 are rejected under 35 U.S.C. § 103 as being unpatentable over Armstrong, in view of Yokota, further in view of International Patent Application Publication No. WO2018/175746 to Burrows et al. (hereinafter, “Burrows”).
Claims 400 and 403 recite the method of claim 3 wherein the menin inhibitor is a compound of Formula (I-B-1) [claim 400] or of Formula (VI-B) [claim 403]
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where the variable groups are as defined. Claims 401-402, depending from claim 400, recite the menin inhibitor as sub-genera and species of Formula (I-B-1), culminating in compound I-151; while claim 404 recites that the menin inhibitor is Compound VI-253, a species of Formula (VI-B).
Burrows teaches methods and compositions for treating hematological malignancies (Abstract), including menin inhibitors of a disclosed Formula (I-A) [paragraph [0009]] or a disclosed Formula (VI), [paragraph [0015]]. In particular, Burrows discloses a number of working examples of compounds useful as menin inhibitors for the treatment of hematological malignancies (paragraph [0151], including Compound I-151 (Table 1, pg. 121, bottom left), which is a menin inhibitor of instant claims 400-402, and Compound (VI-253) (paragraph [0157], pg. 201, last structure of Table 6) which is a menin inhibitor of instant claims 404-405. It would have been obvious to use Compounds I-151 and VI-253 of Burrows as menin inhibitors in the method of Armstrong/Yokota, because Burrows expressly teaches these compounds as useful menin inhibitors for the treatment of hematological malignancy. Of note, Cacatian also teaches Compound (VI-253), but does not teach Compound I-B-1).
Double Patenting – Modified in View of Amendment
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 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the first ’041 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21-22 of U.S. Patent No. 10,174,041 to Grembecka et al. (hereinafter, “the first ’041 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 1 of the first ’041 patent.
Claim 1 of the first ’041 patent recites a method of treating a menin-mediated disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of a compound of Formula II-A, which is a menin inhibitor. Claims 21 and 22 of the first ’041 patent recite that the disease is one of several types of leukemia, such as AML or a leukemia having a Partial Tandem Duplication of MLL. This is therefore encompassed by the method of instant claim 3, except that the claim 1 of the first ’041 patent does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claims 1 and 21-22 of the first ’041 patent, in view of Armstrong and Yokota. Armstrong and the other secondary references are applied to claims 10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the ’639 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of U.S. Patent No. 10,752,639 to Wu et al. (hereinafter, “the ’639 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 14 of the ’639 patent.
Claim 14 of the ’639 patent recites a method of treating a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition having a compound of Formula I-E, which is a menin inhibitor. Claim 14 of the ’639 patent further recites that the disease can be a leukemia. This is therefore encompassed by the method of instant claim 3, except that the claim 1 of the ’639 patent does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claim 14 of the ’639 patent, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the second ’041 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 11,555,041 to Wu et al. (hereinafter, “the second ’041 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 1 of the second ’041 patent. Claim 10 of the second ’041 patent is substantially identical to claim 14 of the ’639 patent (albeit with a slightly more generic structure of menin inhibitor), and the instant claims are obvious variations of the former for the same reason that they are obvious variations of the latter.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the ’248 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of U.S. Patent No. 11,542,248 to Li et al. (hereinafter, “the ’248 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 14 of the ’248 patent.
Claim 14 of the ’248 patent recites a method of treating a disease or condition associated with MLL fusion proteins, comprising administering to a subject a therapeutically effective amount of a compound of Formula VIII, which is a menin inhibitor. Claim 14 of the ’248 patent further recites that the disease can be a leukemia. This is therefore encompassed by the method of instant claim 3, except that the claim 1 of the ’248 patent does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claim 14 of the ’248 patent, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the ’898 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,673,898 to Wu et al. (hereinafter, “the ’898 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 1 of the ’898 patent.
Claim 1 of the ’898 patent recites a method of treating a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of a compound of Formula VIII, which is a menin inhibitor. Claim 1 of the ’898 patent further recites that the disease can be a leukemia. This is therefore encompassed by the method of instant claim 3, except that the claim 1 of the ’898 patent does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claim 1 of the ’898 patent, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the ’184 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-27 of U.S. Patent No. 12,410,184 to Bakale et al. (hereinafter, “the ’184 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claims 25-27 of the ’184 patent.
Claim 25 of the ’184 patent recites a method of treating a disease or condition characterized by the interaction of menin with MLL in a subject, comprising administering to the subject a therapeutically effective amount of a crystalline Form 1 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1-(2-(4-(methylsulfonyl)piperazin-1-yl)propyl)-1H-indole-2-carbonitrile, which is a menin inhibitor. Claims 26-27 of the ’184 patent further recite that the disease can be a leukemia, such as AML. This is therefore encompassed by the method of instant claim 3, except that the claims 25-27 of the ’184 patent do not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claims 25-27 of the ’184 patent, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the ’627 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,944,627 to Burrows et al. (hereinafter, “the ’627 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claims 1, 7, and 10-13 of the ’627 patent.
Claim 1 of the ’627 patent recites, inter alia, a method of treating acute myeloid leukemia, comprising administering a menin inhibitor of Formula (I-B-1). This is therefore encompassed by the method of instant claim 3, except that the claims 1, 7, and 10-13 of the ’627 patent do not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. Furthermore, claims 18-20 of the ’627 patent recite methods using the compounds of instant claim 400-402. As discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claims 1, 7, and 10-13 of the ’627 patent, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the ’251 patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 17, and 19 of U.S. Patent No. 11,649,251 to Wu et al. (hereinafter, “the ’251 patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claims 6, 17, and 19 of the ’251 patent.
Claim 6 of the ’251 patent recites a method of treating hematological cancer in a subject having at least one of several mutations, comprising administering to the subject a compound of Formula (I), which is a menin inhibitor. Claims 17 and 19 differ in that they specify narrower selections of menin inhibitors. These methods are therefore encompassed by the method of instant claim 3, except that the claims 6, 17, and 19 of the ’251 patent do not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claims 6, 17, and 19 of the ’251 patent, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Claims 3-10, 13-15, and 400-405 are rejected for nonstatutory double patenting over the ’687 reissue patent, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 20 of reissued U.S. Patent No. RE49,687 to Grembecka et al. (hereinafter, “the ’687 reissue patent”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 20 of the ’687 reissue patent.
Claim 20 of the ’687 reissue patent recites, inter alia, a method of treating a hematological malignancy or Ewing's sarcoma (ES) in a subject who does not exhibit a mutation in nucleophosmin (NPM1) gene, the method comprising administering to the subject a menin inhibitor. This is nearly, but not quite, identical in scope to instant claim 3. This is therefore encompassed by the method of instant claim 3, except that claim 20 of the ’687 reissue patent does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claim 20 of the ’687 reissue patent, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Provisional Rejections for Nonstatutory Double Patenting:
Claims 3-10, 13-15, and 400-405 are provisionally rejected for nonstatutory double patenting over the ’538 application, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 24 of copending Application No. 18/827,538 to Tao et al. (hereinafter, “the ’538 application”), corresponding to U.S. Patent Application Publication No. 2025/0099469 in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 24 of the ’538 application.
Claim 24 of the ’538 application recites, inter alia, a method of treating a disease in a subject, the method comprising administering to the subject a pharmaceutical composition having a crystalline form of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1-(2-(4-(methylsulfonyl)piperazin-1-yl)propyl)-1H-indole-2-carbonitrile, which is a menin inhibitor. Claim 24 further recites that the disease can be leukemia. This is therefore encompassed by the method of instant claim 3, except that claim 24 of the ’538 application does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claim 24 of the ’538 application, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
This is a provisional nonstatutory double patenting rejection.
Claims 3-10, 13-15, and 400-405 are provisionally rejected for nonstatutory double patenting over the ’563 application, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/844,077 to McCloskey et al. (hereinafter, “the ’563 application”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. The ’563 application corresponds to U.S. Patent Application Publication No. 2025/0152591. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 1 of the ’563 application.
Claim 1 of the ’563 application recites, inter alia, a method for treating a hematological malignancy in a subject in need thereof comprising administering to the subject a menin inhibitor and a cellular efflux transporter inhibitor, optionally selected from a P-glycoprotein (P-gp) inhibitor and a breast cancer resistance protein (BCRP) inhibitor. This is therefore encompassed by the method of instant claim 3, except that claim 1 of the ’563 application does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claim 1 of the ’563 application, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Furthermore, the method of claim 1 of the ’563 application is an obvious variation of the method of the instant claims, because it would be obvious to combine the menin inhibitor of the instant claims with a P-gp inhibitor, because the latter were known in the art to be useful in the treatment of leukemia, as taught for example by the non-patent publication, Growth inhibition, cytokinesis failure and apoptosis of multidrug-resistant leukemia cells after treatment with P-glycoprotein inhibitory agents, Leukemia, 13, pgs. 768-778 (1999) by Lehne et al.
This is a provisional nonstatutory double patenting rejection.
Claims 3-10, 13-15, and 400-405 are provisionally rejected for nonstatutory double patenting over the ’077 application, Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows:
Claims 3-10, 13-15, and 400-405 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/844,077 to He et al. (hereinafter, “the ’077 application”), in view of Armstrong, Yokota, Cacatian, Cancer Genome, Collins, and Burrows. The ’077 application corresponds to U.S. Patent Application Publication No. 2025/0186445. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variations of claim 1 of the ’077 application.
Claim 1 of the ’077 application recites, inter alia, a method for treating a hematological malignancy in a subject in need thereof comprising administering to the subject a menin inhibitor and an immuno-oncology agent. This is therefore encompassed by the method of instant claim 3, except that claim 1 of the ’077 application does not require the absence of a NPM1 or MLL-r mutation or the presence of a RUNX1 or SETD2 mutation. However, as discussed above, Armstrong teaches methods of treating leukemias by administration of a menin inhibitor, where leukemias with a MLL-r mutation are expressly excluded in some embodiments and Yokota teaches AML or ALL with RUNX1 mutations is a significant subset of AML or ALL as a whole. As such, instant claim 3 is obvious over claim 1 of the ’077 application, in view of Armstrong. Armstrong and the other secondary references are applied to claims 4-10, 13-15, and 400-405 as discussed above in the description of the rejections under 35 U.S.C. § 103.
Furthermore, the method of claim 1 of the ’077 application is an obvious variation of the method of the instant claims, because it would be obvious to combine the menin inhibitor of the instant claims with an immuno-oncology agent, because the latter were known in the art to be useful in the treatment of leukemia, as taught for example by the non-patent publication, PD-1/PD-L1 inhibitors in haematological malignancies: update 2017, Immunology, 152, pgs.357-371 (2017) by Jelinek et al.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claim 406 is 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
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 extension fee 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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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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