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
This application is a 371 of PCT/US2021/023452 03/22/2021, PCT/US2021/023452 has PRO 63/151,905 02/22/2021, PCT/US2021/023452 has PRO 63/024,761 05/14/2020, and PCT/US2021/023452 has PRO 62/993,135 03/23/2020
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/15/2022, 01/30/2024, and 03/22/2024 were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of each form 1449 is enclosed herewith.
Status of Claims
Claims 1-17 are currently pending and currently under examination. Claims 18-33 are cancelled and not under examination.
Allowable Subject Matter
Claims 14-15 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.
Claim Rejections - 35 USC § 102
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.
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Bauer (WO 2018/111707 Al).
Bauer teaches a derivative of formula I in the compound of 7-[[(lS)-1-[4-[(lR)-2-Cyclopropyl-l-(4-prop-2-enoylpiperazin-l-yl) ethyl] phenyl]ethyl]amino]-l-ethyl-4H-pyrimido[4,5-d] [l,3]oxazin-2-one (example 1, pg.. 39). The compound of example 1 is used in treating an IDH1 mutant cancer including the solid cancer cholangiocarcinoma, angioimmunoblastic T-cell lymphoma (AITL), myelodysplastic syndrome (MOS), acute myeloid leukemia (AML) (pg. 2, line 9 - pg. 3, line 29). Bauer also teaches inhibiting R132 mutations with the compound of formula I (pg. 60, lines 30-33) which anticipates applicants claims of treating an IDH1 cancer with a R132 mutation. Bauer’s compound in example 1 anticipates applicants formula in claim 1 where R1 is a CH2-cyclopropyl, R2 is a CH2CH3, and is the same compound as applicants compound in claim 6.
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Applicants compound Bauer’s compound of example 1
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Bauer (WO 2018/111707 Al).
The instant claims are directed to a method of treating a solid tumor cancer of cholangiocarcinoma, head and neck cancer, chondrosarcoma, hepatocellular carcinoma, melanoma, pancreatic cancer, astrocytoma, oligodendroglioma, glioma, glioblastoma, bladder carcinoma, colorectal cancer, lung cancer, or sinonasal undifferentiated carcinoma, cholangiocarcinoma, or hematologic malignancy of acute myeloid leukemia, comprising administering to a human cancer subject with an IDH1 R132 mutation and one or more secondary IDHl mutations, a therapeutically effective amount of a compound of the formula:
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Bauer et al. teach inhibiting an IDH1 mutant cancer with the compound of 7-[[(l S)-1-[ 4-[(lR)-2-Cyclopropyl-l-(4-prop-2-enoylpiperazin-lyl)ethyl]phenyl ]ethyl]amino]-l-ethyl-4H-pyrimido[4,5-d] [1,3]oxazin-2-one in example I (pg. 39, lines 4-7).
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Bauer also teaches a method of treating an IDH1 mutant cancer including angioimmunoblastic T-cell lymphoma (AITL), myelodysplastic syndrome (MOS), acute myeloid leukemia (AML), or cholangiocarcinoma, comprising administering an effective amount of formula I to a patient in need thereof (pg. 3, lines 22-29). Bauer does not teach the limitations of claims 7-13 with sufficient specificity to anticipate the claims.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art, prior to the effective filing date of the instant claims, to administer a compound of formula I to a human cancer subject following the teachings of Bauer to treat a solid tumor cancer of cholangiocarcinoma and the hematologic malignancy of acute myeloid leukemia (AML) because Bauer teaches an embodiment of formula 1 as 7-[[(l S)-1-[4-[(lR)-2-Cyclopropyl-l-(4-prop-2-enoylpiperazin-lyl)ethyl]phenyl]ethyl]amino]-l-ethyl-4H-pyrimido[4,5-d] [1,3]oxazin-2-one, for the treatment of acute myeloid leukemia (AML), and cholangiocarcinoma. See MPEP 2143 Examples of Basic Requirements of a Prima Facie Case of Obviousness.
A person of ordinary skill in the art would have been motivated to administer a derivative of formula I to a human subject with acute myeloid leukemia (AML) or cholangiocarcinoma following the teachings of Bauer because of the desirable effects inhibiting tumor cell growth and progression of cancer in a patient. From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success intreating acute myeloid leukemia (AML) or cholangiocarcinoma in a human subject to provide the instantly claimed method. Therefore, claims 7-13 are prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference.
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Bauer (WO 2018/111707 Al) in view of Kelly (US 2019/0350919 Al).
The instant claims are directed to a method of treating cancer, comprising administering to a human cancer subject with an IDHl R132 mutation and one or more secondary IDHl mutations of R119P, G131A, D279N, S280F, G289D or H315D, a therapeutically effective amount of a compound of the formula:
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.
Wherein the human subject had been previously treated with ivosidenib (Tibsovo, AG-120) an IDH1 inhibitor other than applicants compound.
Bauer et al. teach inhibiting an IDH1 mutant cancer with the compound of formula I (pg. 2, lines 9-17). Bauer also discloses that the compounds of their invention “demonstrate that the exemplified and tested compounds inhibit mutant IDHl activity against IDH1/R132H and IDH1/R132C” (pg. 60 lines 30-31). Bauer also teaches a method of treating an IDH1 mutant cancer including angioimmunoblastic T-cell lymphoma (AITL), myelodysplastic syndrome (MOS), acute myeloid leukemia (AML), or cholangiocarcinoma, comprising administering an effective amount of formula I to a patient in need thereof (pg. 3, lines 22-29). Bauer discloses “The exact dosage required to treat a patient and the length of treatment time will be determined by a physician in view of the stage and severity of the disease as well as the specific needs and response of the individual patient. Although expressed as dosage on a per day basis, the dosing administration may be adjusted to provide a more optimal therapeutic benefit to a patient and to manage or ameliorate any drug related toxicities” (pg. 5, lines 7-12). Bauer also teaches that a compound of formula I may be administered after one or more other therapeutic agents (pg. 6, lines 4-6)
However, Bauer et al. fail to teach the specific IDH1 inhibitor of ivosidenib as a therapeutic agent administered to a human subject prior to administering the compound of formula I.
Kelly et al. teach the compound of AG-120 (applicants ivosidenib) is useful for the treatment of IDH1 cancers on table 1 [0005]. Kelly also discloses the cancer has a IDH1 mutation (mIDH1) [0002]. Kelly discloses the IDH1 mutations are R132 mutations [0004].
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art, prior to the effective filing date of the instant claims, to administer a compound of formula I to a human cancer subject as taught by Bauer after administering ivosidenib to inhibit an IDH1 R132 mutated cancer as taught by Kelly because both disclosed treating the same types of IDH1 cancers (cholangiocarcinoma, chondrosarcoma, AML, and MDS) and Bauer teaches a compound of Formula I may be administered either simultaneously with, or before, or after, one or more other therapeutic agents where clearly ivosidenib is taught as a therapeutic agent by Kelly.
Prior to the filing of the instant application, a person of ordinary skill in the art would have been motivated to administer a compound of formula I to a human cancer subject after administering ivosidenib because Kelly identified ivosidenib as having desirable effects as a IDH1 cancer therapeutic in table 1 and Bauer taught the compound of formula I also had inhibitory effects against an IDH1 R132 mutated cancer. Furthermore, Bauer also disclosed that a compound of formula I could be used after administering other therapeutic agents. A person of ordinary skill in the art would have recognized the potential cumulative effects of combining two compounds beneficial in inhibiting an IDH1 R132 mutated cancer into a sequential therapy to manage or ameliorate any drug related toxicities in treating a human subject with cancer. Using the disclosures of Bauer and Kelly, a person of ordinary skill would have had a reasonable expectation of success in treating an IDH1 R132 mutated cancer to arrive at the instant claims.
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 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-16, and 18 of copending Application No. 17/912,341 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because a person having ordinary skill in the art following the teachings of claims 1, 8-16, and 18 of copending application No. 17/912,341 would have found it prima facie obvious to provide a method of treating cancer, comprising administering a compound of claim 1 of the instant application to a human cancer subject having an IDHl R132 mutation and one or more secondary IDHl mutations, thereby arriving at the instantly claimed subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, and 11-14 of copending Application No. 18/565,484 in view of Bauer (WO 2018/111707 Al). Bauer both teaches the same compound disclosed in the instant and reference application and makes clear that the compound of formula I is suitable for inhibiting mutant IDH1 and IDH2 as taught by applicant. Therefore, a person having ordinary skill in the art following the claims of 1-9, and 11-14 in copending application No. 18/565,484 would have found it prima facie obvious to provide a method of treating cancer, comprising administering a compound of claim 1 of the instant application to a human cancer subject having an IDHl R132 mutation and one or more secondary IDHl mutations, thereby arriving at the instantly claimed subject matter.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 7-9, 11-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-6 and 12-15 of copending Application No. 17/202,867 in view of Bauer (WO 2018/111707 Al). Bauer both teaches the same compound disclosed in the instant and reference application and makes clear that the compound of formula I is suitable for inhibiting mutant IDH1 and IDH2 as taught by applicant. Therefore, a person having ordinary skill in the art following the claims of 5-6 and 12-15 in copending application No. 17/202,867 would have found it prima facie obvious to provide a method of treating cancer, comprising administering a compound of claim 1 of the instant application to a human cancer subject having IDHl and IDH2 mutations, thereby arriving at the instantly claimed subject matter.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-13 and 16-17 are rejected. Claims 14-15 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623