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
1. This application is a 371 of This application is a 371 of PCT/IB2022/052536 03/21/2022. PCT/IB2022/052536 is a CON of 63/317,368 03/07/2022, PCT/IB2022/052536 has PRO 63/282,163 11/22/2021, PCT/IB2022/052536 has PRO 63/165,723 03/24/2021.
Claims 1-20 are pending.
Response to Restriction Election
2. Applicant’s election of the species of anti-androgen, enzalutamide, and further anticancer agent, leuprolide, in the reply filed on May 11, 2026 is acknowledged. The election was made without traverse. According to applicants’ representative claims 1-20 read on the elected species.
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.
3. Claims 18 – 19 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 18 describes an anti-cancer agent as an androgen deprivation therapy. A therapy is not an agent while there are androgen deprivation therapies that use certain agents this is not what is claimed. There are specific therapies that involve agents listed in claim 19 including various classes of luteinizing hormone releasing agents as well as gonadotropin ligands, however bilateral orchiectomy is also listed and is a surgical technique and cannot be classified as an agent.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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.
4. Claim(s) 1, 3-4, 6-16, 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Agarwal, N. “Clinical and safety outcomes of TALAPRO – 2: a two-part phase 3 study of talazoparib (TALA) in combination with enzalutamide (ENZA) in metastatic castration resistant prostate cancer (mCRPC).” Journal of clinical oncology 2019, 37, 5076. Agarwal describes the administration of talazoparib with enzalutamide, the elected species of antiandrogen, for the treatment of metastatic castration sensitive prostate cancer using the dosages in the instant claim 9, 0.5 mg of talazoparib and 160 mg of Enza, and that the frequency of once daily. The subjects have been identified as inherently having the DNA damage repair gene mutations as shown by the evidentiary reference Ratta1. These are the mutations in claim 3 according to line 7 the patients had no prior systemic treatment for mCRPC making them treatment naïve as per claim 4. The treatment was effective as shown by the declining prostate-specific antigen as compared to control.
5. Claim(s) 1-8, 12-18, 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boshoff WO 2020/095184. Boshoff on page 48 at claim 12 to claims 17 and claim 20 to 23, teaches the method of the instant claims where a PARP inhibitor, specifically described in claim 22 as talazoparib and the tosylate salt in claim 23, is given with antiandrogen therapy enzalutamide in claim 17, the genotype of the patient is described in claims 20 to 21 having DDR defects as determined by the foundation medicines foundation 1 essay which includes the mutations in the instant claims. According to page 44 “Patients will be considered DDR defect positive if they carry a known or likely deleterious/pathogenic defect in one of the following 35 DDR genes: ATM; ATR; ATRX; BRCA1; BRCA2; BRIP1; CDK12; CHEK1; CHEK2; ERCC4; FANCA; FANCC; FANCG; FANCL; MLH1; MRE11A; MSH2; MSH6; MUTYH; NBN;PALB2; PARP1; PARP2; PARP3; PMS2; POLD1; POLE; RAD51; RAD51 B; RAD51 C; RAD51 D; RAD52; RAD54L; XRCC2; XRCC3. Presence of such a defect must have been stablished via a tissue based next generation sequencing…” Claim 12 has additional agents, however these are not excluded from claim 1 because of the comprising language and the claimed agents appear before in the therapy, in addition these are also listed as potential therapeutics in claim 17-18. The dosages of talazoparib are listed on page 34 lines 10 and 12.
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.
6. Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, N. “Clinical and safety outcomes of TALAPRO – 2: a two-part phase 3 study of talazoparib (TALA) in combination with enzalutamide (ENZA) in metastatic castration resistant prostate cancer (mCRPC).” Journal of clinical oncology 2019, 37, 5076 as applied to claim(s) 1, 3-4, 6-16, 20 above and in further view of Ratta. As discussed above the claims are anticipated however no mention of the biopsy in claim 2 is specifically given. According to Ratta on page 557 col. 2, the trial of Agarwal involved genotyping the tumors:
TALAPRO-2 is an ongoing phase-III trial testing talazoparib in combination with enzalutamide compared with enzalutamide alone as a frontline therapy for patients with asymptomatic or mildly symptomatic mCRPC (NCT03395197). This study is structured in two parts: part 1 is an open-label, non-randomized, safety, and PK run-in study designed to confirm the starting dose of talazoparib in combination with enzalutamide through assessment of target safety events and PK. Part 2 is a randomized, doubleblind, placebo-controlled, multinational study comparing talazoparib plus enzalutamide vs placebo plus enzalutamide in patients with mCRPC. This trial pre-stratified patients in two cohorts of mCRPC: DDR-mutated and DDR wild type.
Page 550 describes the typical process which involves genetic analysis of biopsy tumor, “Robinson et al. in their study identified DDR genes in 23% of the 150 prostate cancers biopsies analyzed [7]. BRCA2 was altered in 13% of samples followed by ATM (7.3%), MSH2 (2%) and BRCA1, FANCA, MLH1, RAD51B, and RAD51C (0.3%). This study has shown for the first time that there are germline mutations in DDR genes, which are known to be linked to increased cancer risk, which were present in metastatic prostate cancer with a higher prevalence. Eight percent of the DDR mutations identified in the samples were in the germline.” There is no way that the genotyping could take place without taking a biopsy or other sample so it could be argued that this was an inherent feature of the trial also. Either way taking a biopsy is obvious. Other techniques including blood sampling can also reveal tumor characteristics.
7. Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, as applied to claim(s) 1, 3-4, 6-16, 20 above and in further view of Boshoff WO 2020/095184. As discussed above the claims are anticipated however no mention of the tosylate in claim 5 is specifically given. Boshoff on page 48 at claim 12 to claims 17 and claim 20 to 23, teaches the method of the instant claims where a PARP inhibitor, specifically described in claim 22 as talazoparib and the tosylate salt thereof in claim 23, is given with antiandrogen therapy enzalutamide in claim 17. Since the tosylate salt was known for the same treatment. It would be obvious to give this salt form in the method of Agarwal.
8. Claim(s) 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boshoff WO 2020/095184 as applied to claim(s) 1-8, 12-18, 20 above and further view of Agarwal. Boshoff does not describe the dosage limitations of enzalutamide in claims 9 to 11. Agarwal describes the administration of talazoparib with enzalutamide, the elected species of antiandrogen, for the treatment of metastatic castration sensitive prostate cancer using the dosages in the instant claim 9, 0.5 mg of talazoparib and 160 mg of Enza, and that the frequency of once daily. It will be obvious to give the appropriate dose of enzalutamide in the method of Boshoff since this is the known dose in coadministration.
9. Claim(s) 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim(s) 1, 3-4, 6-16, 20 above and in further view of Hoda, “Androgen deprivation therapy with Leuprolide acetate for treatment of advanced prostate cancer.” Expert Opinion on Pharmacotherapy, 18:1, 105-113. As discussed above Agarwal teaches the claimed method of administering as talazoparib with antiandrogen therapy enzalutamide. Agarwal does not teach additional add-on therapies such as androgen deprivation therapy as in the elected species of leuprolide. However this is a known standard of care for prostate cancer patients as disclosed in Hoda on page 107 “To date, leuprolide acetate (LA) is the most commonly prescribed depot LHRH agonist (Box 1), having been used for the treatment of PCa for more than 20 years and still counting [30].” On page 110 Hoda discusses the combination of leuprolide with enzalutamide “In consequence, backbone ADT with leuprolide or other LHRH agonists are still recommended when endocrine treatments with enzalutamide or abiraterone are initiated [74]. In addition, the guidelines of the European Urological Assosciation [sic] (EAU) suggest that treatment with LHRH-agonists/antagonists should be continued in CRPC patients receiving chemotherapy [2]. The results of several long-term studies, analyzing the combination of leuprolide with abiraterone, enzalutamide, or taxanes will be available in the next years [75,76].” Combining drugs known for the same purpose, treating prostate cancer, is obvious. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (MPEP § 2144.06). This is especially true in oncology where drugs are constantly combined. In this case leuprolide had already been combined with enzalutamide which had been combined with talazoparib. For these reasons combining leuprolide with the known treatment of Agarwal is prima facie obvious.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
10. Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 19/117,616. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the co-pending is drawn to talazoparib and the elected species of enzalutamide as antiandrogen for treating the same metastatic castration resistant prostate cancer patients. Additional claims like claim 4 and 5 are drawn the combination agents including those in claims 17, 18 and 19. The additional limitations regarding cycle be to C8 inhibitor and various other drugs are encompassed by additional agent and as well as the comprising language. The doses in claim 16 and 14 are the same.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
11. Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8-9, 12-39 of copending Application No. 19/139,753. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the co-pending is drawn to talazoparib and the elected species of enzalutamide as antiandrogen for treating the same metastatic castration resistant prostate cancer patients. The limitation regarding HRR gene mutation while semantically different includes the same mutations in instant claim 3 which are also listed in the co-pending claim 4. Additional claims like claim 8-9 are drawn the combination agents including those in claims 17, 18 and 19. The doses in claim 16 and 14 are the same. The limitations regarding survival and the company claims are simply the outcome of practicing the instantly claim method which is the same. If steps are the same results are the same.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID K O'DELL whose telephone number is (571)272-9071. The examiner can normally be reached on Monday - Friday 9:30 - 7:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached on 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID K O'DELL/Primary Examiner, Art Unit 1621
1 Raffaele Ratta “PARP inhibitors as a new therapeutic option in metastatic prostate cancer: a systematic review” Prostate Cancer and Prostatic Diseases volume 23, pages 549–560 Published: 04 May 2020. “Robinson et al. in their study identified DDR genes in 23% of the 150 prostate cancers biopsies analyzed [7]. BRCA2 was altered in 13% of samples followed by ATM (7.3%), MSH2 (2%) and BRCA1, FANCA, MLH1, RAD51B, and RAD51C (0.3%). This study has shown for the first time that there are germline mutations in DDR genes, which are known to be linked to increased cancer risk, which were present in metastatic prostate cancer with a higher prevalence. Eight percent of the DDR mutations identified in the samples were in the germline.” [page 550, col 2] According to Ratta the study of Agarwal, “pre-stratified patients in two cohorts of mCRPC: DDR-mutated and DDR wild type.”
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