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/KR2022/007115 (05/18/2022)
and claims foreign priority to KOREA, REPUBLIC OF 10-2021-0064278 (05/18/2021)
and KOREA, REPUBLIC OF 10-2022-0060706 (05/18/2022).
Claim Rejections - 35 USC § 102
Claims 1, 2, 6-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jin et al. (WO2017007241, citations to machine translation).
Jin teaches treating colorectal cancer patients with a simultaneous inhibitor of PARP and tankyrase, specifically compound B which is the same as in instant claim 1 ([46]: “Compound B is 6-{4-[(5-oxo -1,2,3,4,5,6-hexahydrobenzo [h] [1,6 ] naphthyridin-8-yl)methyl ] piperazin-1-yl } nicotinonitrile”; [58]: “The present invention can maximize the effect of treating colorectal cancer by classifying patients having susceptibility to simultaneous inhibitor against PARP and tankyrase”). Jin teaches in vivo mouse experimental results where compound B reduced tumor size in a resistant tumor compared to olaparib ([207]-[[217] Examples 21-22; [239]-[243] Example 26, Fig. 20; [240]: “colorectal cancer patient-derived cells 11-CT-79558D (p53 WT LIG4 MT), 11-CT -80464B (p53 WT LIG4 MT) and 11CT-94575 (p53 WT LIG4 WT), 13 CT -78649B (p53 WT LIG4 WT)”).
Regarding amended claim 1, Jin teaches the same compound administered to an effective amount to a patient (mouse) with a p53 mutation, for example Fig. 19A shows a “KM12C (p53 mt/LIG4 mt)” demonstration with administration of Compound B. Regarding the amended language relating to PARP resistance, Jin teaches in Fig. 17A showing the same cancer “KM12C (p53 mt/LIG4 mt)” which is resistant to Olaparib, a PARP inhibitor.
Regarding claim 2, the LIG4 mutant tumor cells are HRD.
Regarding claim 6, the tumor cells do not have a BRCA mutation.
Regarding claims 7-8, the mutant tumor cells are olaparib resistant.
Response to Remarks - 35 USC § 102
Applicant amended the claims and argues that the prior art does not teach wherein the patient has a p53 mutation.
This argument is not persuasive because Jin does teach administration of the same compound in the same manner as claimed, for example Fig. 19A shows a “KM12C (p53 mt/LIG4 mt)” demonstration with administration of Compound B.
Applicant argues that RKO cell line is not PARP inhibitor resistant.
This argument is not persuasive because Jin teaches in Fig. 17A the same cancer “KM12C (p53 mt/LIG4 mt)” which is resistant to Olaparib, a PARP inhibitor.
Claim Rejections - 35 USC § 103
Claims 1-12, 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Jin et al. (WO2017007241, citations to machine translation) in view of Guo et al. (Cancer Management and Research 2021:13 3081–3100, published 08-Apr-2021), Lee et al. (US20180162834) and Cook et al. (BioDrugs (2019) 33:255–273).
Jin teaches as in the 35 USC 102 rejection of claims 1, 2, 6-8 above. One of ordinary skill in the art following the teaching of Jin would have recognized the importance of first determining a cancer’s sensitivity to a PARP inhibitor therapy in selection of the optimal therapeutic (Jin Abstract: “a method for determining sensitivity to a simultaneous inhibitor against poly ADP ribose polymerase (PARP)”, “treatment effect can be maximized by sorting patients having sensitivity to the simultaneous inhibitor against PARP and Tankyrase”) and in following the successful demonstrations with colorectal cancer, one of ordinary skill in the art would consider the same technique in other cancers where PARP inhibition is a known therapy.
Guo teaches target therapy for ovarian cancer based on mutation status of p53 (TP53 gene) and BRAC1/2 mutations which are the most frequent genetic alteration in certain ovarian cancers (Abstract; p. 3082). Guo teaches that the different mutations are associated with different responses to therapy (p. 3084: “mutations of P53 are associated with progression and prognosis of OC”; p. 3094-95), including PARP inhibitors (Table 2, Fig. 3).
Lee claims compound 89 (the same as Jin’s Compound B) (claim 10: “89) 6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile”) useful in treating cancers including tumors of ovarian cancer which has BRCA-1 and -2 mutation and PARP resistant cancer (claim 18: “treating diseases caused by PARP-1, tankyrase-1 or tankyrase-2 activity”; [0003]: “PARP inhibitors were reported to be useful for specific killing of tumors deficient in DNA double-strand repair factors such as BRCA-1 and BRCA-2, and thus have been developed as patient-specific anticancer agents against various types of cancers, including breast cancer, ovarian cancer”, “PARP can contribute to resistance that may occur in various types in cancer therapy”; claim 15;).
Cook teaches successful treatment with PARP inhibitors in patients with BRCA germline and somatic mutations (p. 255: “women with BRCA1/2 mutations (either germline or somatic), maintenance PARP inhibitor therapy for those with recurrence has led to a nearly fourfold prolongation of progression-free survival”).
One of ordinary skill in the art following the teaching of Jin to determine PARP inhibitor sensitivity in optimization of cancer therapy, would have considered the teaching of Guo that the particular p53 and BRCA1/2 mutation would be a result effective variable to consider in ovarian cancer. One of ordinary skill in the art would have also considered Lee’s teaching of treating cancer including BRCA mutations with the same compound and further in view of Cook’s teaching of success with PARP inhibitors with respect to BRCA mutation status. One of ordinary skill in the art would have had a reasonable expectation of success in the combination because the prior art are in the same field of endeavor of cancer therapy using PARP inhibitors. Given the mechanism described in the prior art of PARP inhibition and the teaching of determining mutation status for therapy optimization, one of ordinary skill in the art would have considered utilizing the same class of inhibitor in treating the same cancer and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 3, Jin does not teach the cancer has BRCA 1/2 mutation, however, the combined teaching of the art reasonably suggested to one of ordinary skill in the art that the mutation status is important in optimization of the cancer therapy.
Regarding claims 4-5, Cook teaches successful treatment with PARP inhibitors in patients with BRCA germline and somatic mutations (p. 255: “women with BRCA1/2 mutations (either germline or somatic), maintenance PARP inhibitor therapy for those with recurrence has led to a nearly fourfold prolongation of progression-free survival”).
Regarding claim 6, Cook teaches successful treatment with PARP inhibitors without BRCA mutations (p. 255: “Those without BRCA1/2 mutations experience an approximately twofold increase in progression-free survival.”).
Regarding claim 9-10, Lee and Cook both teach PARP inhibition for treating ovarian cancer.
Regarding claim 11, Cook teaches PARP inhibition in treating metastatic ovarian cancer (p. 269: clinical trial in “Metastatic or recurrent endometrial or ovarian carcinosarcoma post first-line chemotherapy”).
Regarding claim 12, Lee teaches pharmaceutically acceptable salts of the compound, including citrate salt ([0228]; claim 1, Formula 1) which one of ordinary skill in the art would consider a routine substitution of a known equivalent and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 17-18, Guo teaches high-grade serous ovarian carcinoma (HGSOC) is the most commonly observed ovarian cancer and encompasses peritoneal OC (p. 3081, 3084-86).
Regarding claims 19-20, Guo teaches the targeted approached included PARPi resistant and/or refractory ovarian cancers (p. 3090).
Regarding claim 21, Guo teaches p53 mutation was associated with metastatic progression in HGSOC (p. 3084).
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues the Jin not only fails to disclose a p53 mutated patient, but also teaches away from doing so.
This argument is not persuasive because as detailed above, one of ordinary skill in the art following the combined teaching to treat ovarian cancer would have considered optimization of the therapy based on the particular p53 mutation status. In addition, Jin’s alleged teaching away would have been viewed by one of ordinary skill in the art as being a result for colorectal cancer and would not be expected to apply to all cancers including OC where the various mutations would result in different therapeutic responses.
Double Patenting
Claims 1-12, 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 9 of U.S. Patent No. 10464919 (sharing the same disclosure as Lee et al. (US20180162834)) in view of Jin et al. (WO2017007241, citations to machine translation) Guo et al. (Cancer Management and Research 2021:13 3081–3100, published 08-Apr-2021), and Cook et al. (BioDrugs (2019) 33:255–273). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims the same compound and as detailed in the 35 USC 103 rejection supra would render the instant claims obvious.
Claims 1-12, 17-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 24-33 of copending Application No. 18561962 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims the same compound with a disclosed utility of treating cancers in the same manner as in the instant claims. Thus, one of skill in the art construing the scope of the claims would consider the same utility thereby rendering the instant claims obvious
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks - Double Patenting
Applicant argues similar as with the 35 USC 103 rejection or that the rejection be held in abeyance.
These arguments are not persuasive for the same reasons as in the above 103 rejection and thus are maintained.
Conclusion
No claims allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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