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 .
DETAILED ACTION
This office action is in reply to the application 18/729,657 filed 17 July 2024, 371 of PCT/US2023/061184 filed 24 January 2023, with PRO 63/384,554 filed 21 November 2022, PRO 63/375,601 filed 14 September 2022, and PRO 63/302,891 filed 25 January 2022. Claims 1-8, 17-18, 22-25, and 29-31 are amended. Claims 9-16, 19-21, 28, and 33-35 are canceled. Currently, claims 1-8, 17-18, 22-27, and 29-32 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 17 July 2024 was filed on the mailing date of the application on 17 July 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is 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 1-8, 29, and 31-32 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. 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.
A review of the rejected claim language indicates that this claim is drawn toward “a method of treating a solid tumor in a human patient…”. A description of the term “a method of treating or preventing a disease or disorder…” may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ Application/Control Number: 18/335,687 369, 372-73 (Fed. Cir. 1984).
In Applicant’s originally filed specification, 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine is identified as an inhibitor of USP1 and USP1 has been identified as a target in cancer therapy. Cancer is a broad class of heterogenous diseases for which there exists no general treatment or prevention. Hanahan et al. (The hallmarks of cancer, Cell 2000, 100, 1, 50-70) teaches that “there are more than 100 distinct types of cancer and subtypes of tumors can be found within specific organs (pg. 1). It is an incredibly broad field encompassing numerous possibilities that are differentiated by target, types and subtypes, patient populations, etiologies, co-morbidities, etc. teach that as a tumor progresses to a metastatic phenotype, the susceptibility to a particular treatment can differ, and as such, makes predicting the responsiveness to treatment difficult. Furthermore, K. B. Blackburn (Benign tumors: 5 common questions, Cancerwise Blog, 10 January 2022, mdanderson.org/cancerwise/what-are-benign-tumors-and-four-more-questions.h00-159536589.html) explains types of non-cancerous or benign solid tumors including adenomas, fibroids, lipomas, meningiomas, and nevi. As cancerous tumors are only a sub-genus of the overarching genus of solid tumor, one of skill in the art would not recognize from the disclosure that the Applicant was in possession of “a method of treating a solid tumor in a human patient” for all possible solid tumors as claimed.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 17-18, 22-27, and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 17-18, 22-25, and 30 recite the limitation "the cancer" in lines 1. There is insufficient antecedent basis for this limitation in the claim. The base claim only refers to solid tumors of which those derived from cancers are only a subset of the genus of solid tumors.
Dependent claims 26-27 are rejected for depending on a rejected claim and not resolving the ambiguity present in parent claim 25.
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 non-obviousness.
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 1-8, 17-18, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Compositions of substituted pyrazolopyrimidines and uses thereof, US 12,624,040 B2, 2026; filed 14 January 2021) in view of Beelen et al. (G1T38 superior dosage regimens, US 2020/0405721 A1, 2020).
Liu discloses solids or salts of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine, described as formula II (pg. 27, col. 1-2, lines 64-67, lines 1-14). Liu also discloses the application of compound, for the treatment of a USP1 protein mediated disorder… proliferative diseases including cancer (pg. 31, col. 9, lines 52-56), further specifying its application in instances where the cancer is a solid tumor (pg. 32, col. 11, line 60).
Liu does not, however, teach a dosage regimen between 75-2250 mg.
Beelen rectifies this deficiency by teaching that pharmaceutical compositions generally can be formulated for oral administration, containing any amount of active compound that achieve the desired result, giving an example of 0.1-99% by weight of the compound in a formulation (para. 0135). Optimization of the dosing regimen is refined as part of the research process as a person of ordinary skill in the art would necessarily be motivated to do as to obtain the desired clinical outcome or improved clinical outcome, whether it encompasses tumor inhibition or symptom management, regarding the amount, frequency, formulation, etc. Moreover, it is well-known that dosages may vary between patients due to parameters such as patient mass, co-morbidities, age, etc. The limitations of claim 1, in agreement with Beelen’s teachings, can be construed as a conclusion from the optimization process.
Therefore, in the instant case, there is a reasonable expectation of success that a therapeutically efficacious amount of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine, dosed in an appropriate manner, would result in growth arresting or diminishing of solid tumors.
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to be motivated to optimize dosing regimens of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine for the purposes of treating solid tumors as disclosed by Liu.
Regarding the limitations of claim 2, wherein about 1000 to 2250 mg of compound I or an amount of the salt, solvate, hydrate, or co-crystal thereof equivalent to about 1000 mg to about 2250 mg of the Compound I is administered, are met by case of obviousness presented in paragraphs 12-16.
Concerning the limitations of claim 3, wherein about 1000 mg of the Compound I or an amount of the salt, solvate, hydrate, or co-crystal thereof equivalent to about 1000 mg of the Compound I is administered, are met by the case of obviousness presented in paragraphs 12-16.
With respect to the limitations of claim 4, wherein about 75 mg to about 1000 mg of the Compound I or an amount of the salt, solvate, hydrate, or co-crystal thereof equivalent to about 75 mg to about 1000 mg of the Compound I is administered, are met by the case of obviousness presented in paragraphs 12-16.
With regards to the limitations of claim 5, wherein about 100 mg of the Compound I or an amount of the salt, solvate, hydrate, or co-crystal thereof equivalent to about 100 mg of the Compound I is administered, are met by the case of obviousness presented in paragraphs 12-16.
With concern to the limitations of claim 6, wherein the Compound I or the salt, solvate, hydrate, or co-crystal thereof is administered about once daily, are met by the case of obviousness presented in paragraphs 12-16.
Regarding the limitations of claim 7, wherein the Compound I or the salt, solvate, hydrate, or co-crystal thereof is administered as a divided dose over the course of a day, are met by the case of obviousness presented in paragraphs 12-16.
Concerning the limitations of claim 8, wherein the Compound I or the salt, solvate, hydrate, or co-crystal thereof is administered orally, are met by the case of obviousness presented in paragraphs 12-16.
With respect to the limitations of claim 17, wherein the cancer has a mutation in BRCA1, are met as Liu discloses the use of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine in treating cancers with a BRCA1 mutant (pg. 32, col. 11, lines 23-25).
With regards to the limitations of claim 18, wherein the cancer has a mutation in BRCA2, are met as Liu discloses the use of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine in treating cancers with a BRCA2 mutant (pg. 32, col. 11, lines 28-29).
With concern to the limitations of claim 22, wherein the cancer is selected from the group consisting of a DNA damage repair pathway deficient cancer, a homologous-recombination deficient cancer, a cancer comprising cancer cells with a mutation in a gene encoding p53, and a cancer comprising cancer cells with a loss of function mutation in a gene encoding p53, are met as Liu discloses the use of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine in treating cancers with DNA damage repair pathway deficient cancer (pg. 31, col. 10, lines 4-5), in treating cancers with a mutation in a gene encoding p53 (pg. 31, col. 10, lines 8-9), in treating cancers with a loss of function mutation in a gene encoding p53 (pg. 31, col. 10, lines 12-13), or treating homologous-recombination deficient cancers (pg. 32, col. 11, lines 10-11).
Regarding the limitations of claim 23, wherein the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer (NSCLC), colon cancer, bladder cancer, osteosarcoma, ovarian cancer, skin cancer, and breast cancer, are met as Liu discloses the use of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine in treating cancers including lung cancer, NSCLC, colon cancer, bladder cancer, osteosarcoma, skin cancer, ovarian cancer, or breast cancer (pg. 31, col. 10, lines 25-44).
Concerning the limitations of claim 24, wherein the cancer comprises cancer cells with elevated levels of RAD 18 protein and/or RAD 18 mRNA, are met as Liu discloses the use of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine in treating cancers with elevated levels of RAD 18 or elevated levels of RAD 18 mRNA (pg. 31, col. 10, lines 44-58).
Allowable Subject Matter
Claims 25-27 and 29-32 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.
Reasons for Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: the use of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine in treating patients with cancers with: 1) elevated levels of RAD51 protein and/or RAD51 mRNA, 2) where the patient has previously received treatment with a PARP inhibitor, 3) where the cancer is resistant or refractory to PARP inhibition, 4) administered as a co-crystal with a pharmaceutically acceptable salt, 5) and where that salt is gentisic acid, is not covered in the prior art in a 100% embodiment. The closest is Liu et al. (Compositions of substituted pyrazolopyrimidines and uses thereof, US 12,624,040 B2, 2026; filed 14 January 2021) who discloses the use of 6-(4-cyclopropyl-6-methoxypyrimidin-5-y1)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl) benzyl)-1H-pyrazolo[3,4-d]pyrimidine in treating patients with several cancers and cancers with elevated levels of RAD 18.
Summary
Claim 1 is rejected under 35 U.S.C. 112(a). Claims 17-25 and 30 are rejected under 35 U.S.C. 112(b). Claims 1-8, 17-18 and 22-24 are rejected under 35 U.S.C. 103. Claims 25-27 and 29-32 are objected to being dependent on a rejected base claim.
Conclusion
Claims 1-8, 17-18, 22-24, and 30 are rejected. Claims 25-27, 29, and 31-32 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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