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 .
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.
Current Status of 17/790,038
This Office Action is responsive to the arguments and amendments received 8 April 2026.
Claims 9-11 and 15-24 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed applications PCT/CN2020/142257 (filed 31 December 2020) and CN 201911417368.7 (filed 31 December 2019) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The Examiner acknowledges Applicant’s submission of a translation of CN 201911417368.7 (filed 31 December 2019). The Examiner determines the priority date of the instant claims, for the purposes of this action, to be 31 December 2019.
Response to Amendments
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein.
Response to Arguments
Applicant's arguments received 8 April 2026 have been fully considered.
Applicant argues that XIN does not teach the combination of a PARP inhibitor and a PD-1/L1 inhibitor, nor does JIANG. Applicant argues that combining two drugs may not produce an efficacious effect, and instead my lead to a reduction in efficacy. Applicant argues that their newly submitted MONK reference shows a clinical trial of the co-administration of a PARP inhibitor (rucaparib) with a PD-1 inhibitor (nivolumab), which reduces the progression-free survival by 25% compared to the monotherapy.
Applicant’s argument, that combining two drugs known to treat the same condition will have entirely unknown effects and may result in a reduced efficacy, does not to take away from the general understanding in the pharmaceutical literature that combining multiple drugs, with different interaction mechanisms, is often beneficial (Introduction section, Koo, O. “Manufacturing Process Considerations for Fixed-Dose Combination Drug Products” American Pharmaceutical Review, 1 April 2010). Applicant’s argument also does not remove the teaching of BOBILEV, that combining a PD-1 inhibitor with a PARP inhibitor is specifically useful for the treatment of breast cancer. One of ordinary skill in the art, knowing that two drugs are useful for the same condition, would immediately find it obvious that they could be given as a combination to treat said condition, unless there was a significant teaching in the art that they could not be combined. As stated within In re Kerkhoven (citation in the 35 USC 103 rejections below), it is prima facie obvious to combine two compositions, which are known in the art to perform the same function, into a third composition that performs the same function.
Turning to the MONK reference presented by Applicant: The conclusions section of MONK states that the combination therein “did not add to” progression free survival benefit observed when administering the mono therapy. Additionally, it states that the safety profile of the combination was “consistent with previously reported studies and their individually known safety profiles”. It appears that the authors of MONK found the combination therapy to simply not be beneficial over the monotherapy.
The declaration provided by HUANG has been reviewed by the Examiner. HUANG argues that PARP inhibitor-PD1 inhibitor combinations can fail to possess enhanced antitumor efficacy over a monotherapy. HUANG specifically points out two mefuparib-containing combinations that yielded tumor growth inhibition rates “comparable to or about 12% lower than that of the single-agent PARP inhibitor”, mefuparib. Overall, the data of HUANG show that three PARP inhibitor-PD1 inhibitor combinations were tested in a xenograft model; one combination performed better than mefuparib alone, one combination performed about equally well, and one combination performed worse.
Taken together, the data and arguments provided by Applicant are not persuasive. The natural inclination for one of ordinary skill in the art, knowing that two drugs are beneficial for the same condition, is to combine them, as discussed above. Applicant is arguing that there would not be a reasonable expectation of success, and has provided data for four total PARP inhibitor-PD1 inhibitor combinations. One of the combinations appears to have performed poorly compared to the monotherapy, two were about equal to the monotherapy, and one was superior. It is the opinion of the Examiner that one of ordinary skill in the art, reading that toripalimab and mefuparib are separately useful for the treatment of breast cancer (as taught by JIANG and XIN below), would not have been concerned enough by the results of MONK and the failed results of the instant declaration as to not test the combination of mefuparib and toripalimab. This is especially clear in view of the fact that BOBILEV teaches that a PARP inhibitor-PD1 inhibitor is beneficial for the treatment of the same cancer type.
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.
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 nonobviousness.
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 9, 17, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over:
XIN (CN 102627620 A, Publication Date 8 August 2012, Machine Translation of claims provided by Examiner)
and in view of:
JIANG (Jiang, Ze Fei “A Study of First-line JS001 and Nab-paclitaxel Versus Palcelbo and Nab-Paclitaxel in Participants With Advanced Recurrent or Metastatic TNBC” ClinicalTrials.gov, NCT03777579, 6 August 2019)
as evidenced by:
XU (Xu, Ruihua “The Study to Evaluate Toripalimab (JS001) in Patients With Advanced GC, ESCC, NPC, HNSCC” ClinicalTrials.gov, NCT02915432, 22 October 2019).
JIANG teaches that JS001, being an anti-PD-1 antibody, was administered in combination with nab-paclitaxel to treat metastatic triple-negative breast cancer (TNBC) patients. While not stated within JIANG, XU provides evidence that JS001 is synonymous with toripalimab (title and detailed description). JIANG specifically teaches the administration of 240 mg of JS001 (toripalimab) via intravenous infusion (IV) on day 1 of every 21-day cycle (Arms and Interventions section). JIANG does not teach mefuparib (the instantly claimed compound of formula A).
XIN teaches the instantly claimed compound of formula A as the third compound shown in claim 4 therein (copied below), along with pharmaceutically acceptable salts thereof. This compound is identical to the instantly claimed formula A. XIN teaches that this compound is useful as a PARP inhibitor (claim 6). XIN also teaches that this compound is useful to treat breast cancer (claims 9 and 10).
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It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to combine the method of treating breast cancer using toripalimab (taught by JIANG) with the method of treating breast cancer through the administration of the compound of XIN copied above, for the purpose of increasing the anti-cancer efficacy of the drug cocktail of JIANG. One of ordinary skill in the art would have expected success with this combination, because JIANG teaches toripalimab to treat the same disease taught to be treated by the compound of XIN.
This is an example of combining equivalent therapeutic agents known to be useful for the same purpose. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
Claims 9-11 and 15-24 are rejected under 35 U.S.C. 103 as being unpatentable over:
XIN (CN 102627620 A, Publication Date 8 August 2012, Machine Translation of claims provided by Examiner)
and in view of:
JIANG (Jiang, Ze Fei “A Study of First-line JS001 and Nab-paclitaxel Versus Palcelbo and Nab-Paclitaxel in Participants With Advanced Recurrent or Metastatic TNBC” ClinicalTrials.gov, NCT03777579, 6 August 2019)
and in view of:
BOBILEV (WO 2018/208968 A1, International Publication Date 15 November 2018)
as evidenced by:
XU (Xu, Ruihua “The Study to Evaluate Toripalimab (JS001) in Patients With Advanced GC, ESCC, NPC, HNSCC” ClinicalTrials.gov, NCT02915432, 22 October 2019).
Teachings of XIN and JIANG, and the evidence provided by XU, are described within the 35 USC 103 rejections above. XIN and JIANG do not have specific teachings about the dosage of the mefuparib (the compound of instant formula A) to be administered for the treatment of breast cancer, or the timing of this administration.
BOBILEV teaches a method of treating cancer through the administration of “a therapy that inhibits programmed death-1 protein PD-1” and “a therapy that inhibits poly [ADP-ribose] polymerase (PARP)” (claim 1). BOBILEV teaches that this method of treatment can be used to treat a breast cancer (claims 1 and 4). BOBILEV teaches that the PD-1 inhibitor can be camrelizumab or atezolizumab (paragraph [140]). Taken together, BOBILEV teaches a method of treating breast cancer comprising the administration of a PD-1 inhibitor and a PARP inhibitor. The combination of mefuparib (taught to be a PARP inhibitor by XIN) and toripalimab (taught to be an anti-PD-1 antibody by JIANG), which is rendered obvious by XIN and JIANG, overlaps with the method of BOBILEV with the exception of the specific PARP inhibitor and specific anti-PD-1 antibody chosen.
Because XIN lacks specific teachings about dosing of the compounds therein, the artisan would have looked to similar methods in the literature to fill in the dosing details and arrive at a complete method that could be carried out. It would have been obvious, to one of ordinary skill in the art, before the filing date of the instant application, to combine the PARP inhibitor dosing teachings from BOBILEV with the method of treating breast cancer through administering toripalimab and the compound of XIN (rendered obvious by XIN and JIANG). The artisan would have expected success in this combination, because BOBILEV teaches the combination of a PARP inhibitor and an anti-PD-1 antibody, and the method rendered obvious by XIN and JIANG contains these same classes of compounds.
Regarding claims 10-11, 15-16, and 18-23: JIANG teaches specifically the administration of 240 mg of JS001 (toripalimab, an anti-PD-1 antibody) via intravenous infusion (IV) on day 1 of every 21-day cycle (arms and interventions section). Paragraph [0192] of BOBILEV teaches that the PD-1 inhibitor is administered through injection, and paragraph [0200] of BOBILEV teaches that the exemplary PARP inhibitor therein is administered once daily, orally at a dosage of 200 mg. BOBILEV teaches that an exemplary PD-1 inhibitor was administered every 21 days at a dosage of 200 mg (paragraphs [0202]-[0203]). BOBILEV teaches that “administration” of the compositions therein includes intravenous administration (paragraph [0066]), and this equally applies to the PARP inhibitors and PD-1 inhibitors therein.
Conclusion
No claims are currently allowable.
THIS ACTION IS MADE FINAL. 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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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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