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 5 December 2025.
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. 103 rejections to the claims, present in the previous office action, are maintained herein, but altered as necessitated by Applicant’s amendments.
Response to Arguments
Applicant argues that the combination of two drugs does not necessarily produce a “positive efficacious effect – in fact, it may lead to a reduction in efficacy”. Applicant points out that combination therapies “still undergo trials separate from monotherapy trials”. Applicant argues that Example 1 of the instant specification shows that treatment with Mefuparib + Tuoyi (toripalimab) in a mouse model produces an increased tumor inhibition percentage (60 %) relative to each monotherapy (54 % and 29 % respectively). Applicant argues that BOBILEV does not suggest the use of mefuparib or toripalimab. Applicant argues that XIN does not disclose the administration of a PARP inhibitor and a PD-1 inhibitor or the combination of mefuparib and toripalimab.
Applicant’s first 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). 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.
Applicant’s comment that combination therapies must undergo separate clinical trials is not relevant in this context, as the requirements to prove a therapy are safe and effective are different from the laws and regulations that govern obviousness.
The Examiner agrees that 60 % tumor inhibition value within instant Example 1 is better than the 54 % and 29 % tumor inhibition values reported for each monotherapy. It is not clear to the Examiner that this, seemingly small change, would have been unexpected to one of ordinary skill in the art. Applicant may choose to submit an affidavit or declaration to better explain why these data would have been unexpected to one of ordinary skill in the art (see MPEP 716 and 37 CFR 1.132).
The Examiner does not rely upon BOBILEV or XIN to teach the combination of mefuparib or toripalimab. See the Examiner’s arguments for the combination of these compounds above and below. The Examiner no longer relies upon NAKHJAVANI for any teachings.
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 9-11 and 15-24 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in making this determination include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number for a prima facie case are discussed below.
The methods of “preventing” a tumor within instant claims 9-11 and 15-24 are not properly enabled by the instant claims and specification. One of ordinary skill in the art, reading the instant claims and specification, would not know what patient population could be prevented from developing a tumor by the claimed method. COOPER (Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Development and Causes of Cancer. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9963/) teaches that cancer can be induced by at least radiation, UV radiation, chemicals, viruses, and smoking. COOPER also teaches that “it is overly simplistic to speak of single causes of most cancers” (causes of cancer section). Should one of ordinary skill in the art apply the claimed method of administering oncolytic drugs for the prevention of a tumor to: all smokers, anyone living in an area with high UV radiation, or all humans? The instant application does not make this clear. While the instant application describes the types of cancer that can be treated with the instantly claimed methods, there is insufficient description of who would be at risk for a tumor and could be prevented from developing a tumor. This represents an insufficient amount of direction provided by the instant application. Additionally, due to the low level of predictability in the chemical arts, one of ordinary skill in the art would not know which risk factors for cancer would be mitigated through the administration of the instantly claimed compounds. The Examiner determines that claims 9-11 and 15-24 are not properly enabled. Applicant may choose to amend the instant claims to remove “prevention” of a tumor.
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.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625