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 .
Election/Restrictions
Applicant’s response the restriction/ election requirement is hereby acknowledged. Applicant’s election with traverse the invention of claims 40-63 is acknowledged, but is rendered moot since in the amended claim set from 11/8/2022 there is one group of claims. Applicant was further required to elect as species a single patient population defined by a single therapy received by the patient prior to treatment. Applicant elected medical castration, plus prednisolone, from claim 44, but failed to designate the claims, which read on the elected species. According to Applicant’s specification, “medical castration” is defined in the following paragraph.
“[0241] ADT uses surgery or medicines to lower the levels of androgens made in the testicles, to stop them from fueling prostate cancer cells. ADT includes, without being limited to, surgical castration or orchiectomy; and medical castration like luteinizing hormone-releasing hormone (LHRH) agonists, e.g., leuprolide, goserelin, triptorelin, histrelin; LHRH antagonists; abiraterone acetate; ketoconazole; anti-androgens like flutamide, bicalutamide, nilutamide, enzalutamide, apalutamide, darulotamide; or estrogens.”
Based on that definition from Applicant’s specification, and in the absence of Applicant’s designation, the Examiner determines that claim 40-50, 53, 54 and 58-63 read on the elected species.
The restriction/ election requirement is hereby MADE FINAL. Claims 40-50, 53, 54 and 58-63 are pending, and have been examined herewith to the extent of Applicant’s elected species.
Note to File on A Related Adjudicated Patent File Wrapper
While res judicata has not been invoked, because the instant claims are of a somewhat different scope, the Examiner notes that claims of a similar scope were already examined and rejected by a different examiner in patent application 15/950,707, were subsequently appealed to PTAB, which in turn affirmed the other examiner in 2023, and were then further affirmed on appeal by the Federal Circuit in 2024. Some related claims of the ‘707 application are noted for the record.
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The Examiner also notes in comparison some claims in the instant application.
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Claim Objections
Claim 40 is objected to because of the following informalities: “mCSPC” is abbreviated without having been spelled out beforehand in the claim, and where this is not a well-known and widely accepted abbreviation. Appropriate correction is required.
In the interest of contact prosecution, consistent with Applicant’s specification, the Examiner interprets the claim to be directed in relevant part to: “metastatic castration sensitive prostate cancer (mCSPC)”.
Claim Rejections - 35 USC § 112
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 49, 50, 58-60 and 63 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.
Claim 63 is directed to the method of claim 40, wherein said pharmaceutical formulation is a fixed-dose combination (FDC) as defined in any one of Tables 1-12. The claim is vague and ambiguous, because it is unclear what is being claimed, as there are many and different compositions in these tables, with additional inactive ingredients with no antecedent basis in claim 40. This makes the claims vague and indefinite, because it is unclear what the metes and bounds of the claim are. The MPEP recognizes that incorporation by reference into claims is exceptional and created a two-part test to determine whether to permit such incorporation: (i) “where there is no practical way to define the invention in words” and (ii) “where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.” MPEP § 2173.05(s). In the instant case, Applicant’s claim does not meet this requirement because there is certainly a practical way to define the invention in words.
Claims 58-60 recite nirapartib, but have no antecedent basis, because they depend from claim 40, which recites niraparib tosylate mononhydrate. What is even more confusing, is that the claim term use in the same claims is inconstant too, e.g. 58 and 59 recite both niraparib and niraparib tosylate mononhydrate. Claim 60 is further confusing, because it recites yet a third claim term “niraparib eq.”, and that too is unclear what it is. To the extent that there is description in the specification, it appears to be with the specification term “free base niraparib”. (See, e.g., p. 4, ll. 27-30).
Claims 49 and 50 are vague and indefinite and subject to many different interpretations. The specifically provides no definition for a claim term “next generation androgen signaling inhibition therapy”. To the extent that there is any reference to “generation” therapy in the specification, it refers to “first”, “second” and “third” generation and comes from the following paragraphs.
“[0026] As used herein, the term “first-generation anti-androgen” refers to an agent that exhibits antagonist activity against a wild-type AR polypeptide. However, first-generation anti-androgens differ from second-generation anti-androgens in that first-generation anti-androgens can potentially act as agonists in CRPC.
[0027] Exemplary first-generation anti-androgens include, but are not limited to, flutamide, nilutamide and bicalutamide.
[0028] As used herein, the term “second-generation anti-androgen” refers to an agent that exhibits full antagonist activity against a wild-type AR polypeptide. Second-generation anti-androgens differ from first-generation anti-androgens in that second-generation anti-androgens act as full antagonists in cells expressing elevated levels of AR, such as for example, in CRPC. Exemplary second-generation anti-androgens include 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N methylbenzamide (also known as ARN-509; CAS No. 956104-40-8); 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide (also known as MDV3100 or enzalutamide; CAS No: 915087-33-1) and RD162 (CAS No. 915087-27-3). In some embodiments, a second-generation anti-androgen binds to an AR polypeptide at or near the ligand binding site of the AR polypeptide.
[0029] As used herein, the term “third-generation anti-androgen” refers to an agent that exhibits full antagonist activity against a wild-type AR polypeptide and against mutant forms of the AR polypeptide, with mutations arising in the ligand binding domain (LBD) of the AR polypeptide as set forth below. Third-generation anti-androgens retain the differentiation from first-generation anti-androgens in that third-generation anti-androgens act as full antagonists in cells expressing elevated levels of AR, such as for example, in CRPC.”
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, 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.
Claims 40-50, 53, 54 and 58-63 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018191141 A1 to Yu et al. (“Yu”), and further in view of Zejula (niraparib) capsules, for oral use, FDA Reference ID: 4600207, initial US. Approval: 2017, revised 04/ 2020 (“FDA label for niraparib”).
Claim interpretation
The Examiner restates her interpretation of Applicant’s claims from the 35 USC 103 rejection above.
Rejection
Yu discloses a method for treating a prostate cancer comprising administering to a patient a therapeutically effective amount of niraparib, a therapeutically effective amount of abiraterone acetate, and a therapeutically effective amount of prednisone (claim 1). The prostate cancer is hormone-sensitive or castration-resistant prostate cancer (claim 2). The prostate cancer may be metastatic ([0033]). Niraparib and abiraterone acetate are administered to the patient in a single composition, or in separate compositions (claims 3-4, [0035]). The route of administration may be oral (tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs) ([0043]). The dosing, either free dose or fixed dose are taught in paragraphs, to include specific dose of the drugs of Applicant’s claim 60. [0035]-[0040].
The patient might have been previously treated with anti-androgens (i.e. medical castration per Applicant’s specification at para [0241]), to include for the pre-treatment times of Applicant’s claims 45-48. ([0034]). “Additionally or alternatively, the patient may have undergone at least one line of androgen receptor-targeted therapy prior to administering a first dose of the niraparib, abiraterone acetate, and prednisone. The period of time between the end of the other treatment and the administration of niraparib, abiraterone acetate, and prednisone in accordance with the present invention may be years, months, weeks, days, a single day, or less than 24 hours.” There is no indication in Yu that the patient should have undergone prior therapy with an next generation androgen signaling inhibitor therapy, per Applicant’s claims 49 and 50.
Yu further provides motivation to specifically test for deleterious germline or somatic HRR gene mutations in prostate cancer as a part of the treatment, such as claimed by Applicant. It discloses that niraparib is a PARP inhibitor, and that the PARP inhibitor olaparib was recently investigated in a Phase 2 study to assess efficacy and safety in patients with mCRPC post-chemotherapy and AR-targeted agents, and that genetic sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes, including, but not limited to BRCA-1/2, ATM, Fanconi anemia genes, and CHEK2 in tumor samples. ([0004]-[0006]).
Even though the reference dose not specifically indicate the niraparib as tosylate monohydrate, this was the pharmaceutical form used in therapy, as exemplified by the FDA label for niraparib. (p. 16).
Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to combine the teachings of Yu and the FDA label for niraparib in order to practice Applicant’s claimed method with a reasonable expectation of success. The skilled artisan would have been motivated to do so guided by the desire to optimize the niraparib drug form with one, which has already gone through clinical testing.
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 40-50, 53, 54 and 58-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/429,778 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they disclose overlapping subject matter.
The claims of the instant application are directed to a method for the treatment of mCSPC in a male human patient, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, plus prednisone. (claim 40). Claim 60 recites specific doses of the drugs. Claim 42 pertains to applying the method to patients who are biomarker positive for at least one biomarker selected from BRCA-1 or BRCA-2.
The claims of the co-pending application are directed to a method for treating a prostate cancer comprising administering to a patient in need thereof a daily dose of about 30 to about 400 mg/day of niraparib administered once per day and a daily dose of about 500 to about 1500 mg/day of abiraterone acetate administered once per day, wherein the patient is biomarker positive for at least one biomarker selected from BRCA-1 or BRCA-2. (claim 1).
This discloses an overlapping indication, compounds, dose ranges and biomarkers. Further to the extent that some claims of the co-pending application are directed to mCRPC, it is noted that it is obvious in the art to try compounds with therapeutical utility in both resistant and sensitive prostate cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 40-50, 53, 54 and 58-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-17 and 19-33 of copending Application No. 18/799,339 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they disclose overlapping subject matter.
The claims of the instant application are directed to a method for the treatment of mCSPC in a male human patient, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, plus prednisone. (claim 40). Claim 60 recites specific doses of the drugs. Claim 42 pertains to applying the method to patients who are biomarker positive for at least one biomarker selected from BRCA-1 or BRCA-2.
The claims of the co-pending application are directed to a method for managing metastatic castration-resistant prostate cancer (mCRPC) comprising administering to a patient in need thereof a daily dose of about 30 to about 400 mg/day of niraparib administered once per day and a daily dose of about 500 to about 1500 mg/day of abiraterone acetate administered once per day, wherein the patient mCRPC is biomarker positive for at least one biomarker selected from BRCA-1 and BRCA-2. (claim 1).
This discloses an overlapping indication, compounds, dose ranges and biomarkers. Further to the extent that some claims of the co-pending application are directed to mCRPC, it is noted that it is obvious in the art to try compounds with therapeutical utility in both resistant and sensitive prostate cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SVETLANA M IVANOVA/ Primary Examiner, Art Unit 1627