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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/17/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Status
Claims 10 has been amended by the amendment dated 12/17/2025, No claims were deleted or newly added. Accordingly, claims 1-18 remain pending in the application and are under current examination.
Priority & Response to Arguments
Applicant’s claim under 35 U.S.C. §§ 119(e) and/or 120, 121, or 365(c) for benefit of the filing date of earlier filed applications is acknowledged.
As indicated in the previous non-final office action date 06/18/2025, , the claims do not properly benefit under §§ 119 and/or 120 by the earlier filing dates of the priority documents claimed, since the claims fail to find support for e.g. for the limitations non-small cell lung carcinoma, docetaxel and pembrolizumab in the disclosures of Provisional applications 62/255259 and 62/115468. To receive benefit of the earlier filing date under §§ 119 and/or 120, the later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application); the disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. § 112(a). M.P.E.P. § 201.11.
Applicant disagrees and argues that the provisional applications identify PD-1 antibodies and lung cancer and incorporate disclosures by reference to previous patent documents. Applicant’s arguments have been fully considered but are not found persuasive. The Provisional applications fail to provide support for NSCLC, pembrolizumab, the combination of docetaxel or platinum based chemotherapy with plinabulin. The provisional applicationss do not provide support for platinum based chemotherapy or docetaxel, alone or in combination. The earliest provisional, ‘429 does not provide support for treatment cycles, and fails to disclose 14 or 21 day cycles (or any cycles). The ‘259 application specifically incorporates by reference several US Patents but none of these Patents are for pembrolizumab. The patents are directed to nivolumab and BMS936559. The US patents for pembrolizumab are US8354509 and 8900587, neither of which are incorporated by reference. Applicant points to US 8168757 asserting that other patents state the amino acid sequence of pembrolizumab and method of using are disclosed in 8168757. However the remarks do not point to any sequence in ‘757 that is pembrolizumab and only reference another patent that states this. Specifically, applicant asserts that US8217149 states amino acid sequence of pembrolizumab and method of using are disclosed in US Patent 8168757. The examiner finds no support for this statement in US8217149 or any mention of pembrolizumab. Additionally, support for lung cancer (para 52 of ‘468 application) fails to specifically incorporate NSCLC by reference in any US Patents. The argument that one would know that it includes NSCLC and the patent US 8008449 teaches the antibodies are used to treat NSCLC is not sufficient to incorporate NSCLC into the provisional for support. Additionally, Applicant has failed to find support for doxetaxel. Finally, there is no support in the ‘259 or ‘468 application for treatment cycles including 14 and 21 days.
Accordingly, the effective filing date of instant claims is deemed the filing date of the international application (PCT/US2016/017602), namely February 11, 2016.
Response to Arguments re: Claim Rejections Under 35 USC § 103
Applicant’s arguments on pages 5-6 of the response filed 12/7/2025 have been fully considered, but are not found persuasive. Regarding the allegation that the references lack a suggestion of potentiating immune checkpoint inhibition, it should be noted that it is the active steps recited in the instant claimed method that are critical. Once the administration of the combinations has been addressed by the cited prior art, the resulting inhibition would necessarily be present. Regarding the Declaration under 37 CFR §1.132 by Dr. Steven Lin that plinabulin could enhance immune checkpoint inhibitor therapy, it would have been obvious to combine plinabulin with docetaxel, and PD1 with docetaxel for enhanced effects. There was no demonstration of unpredictability, and as indicated in Dr. Lin’s declaration, plinabulin was indicated as safe in human clinical studies, PD1 inhibitors were safe and effective immunotherapies to treat NSCLC and docetaxel and platinum-based agents were deemed safe and effective for treating NSCLC (para 10) and thus no undue experimentation is required to implement the combination therapy. Moreover, Examples 3 and 7 and Fig 4A-4C demonstrate that Plinabulin, PD1 ab and CTLA4 ab had better tumor inhibitor effect than treatment with Plinabulin and PD1 Ab and better inhibitor effect than Plinabulin alone. However, there is no experiment or Declaration addressing plinabulin with docetaxel. Thus, the results are not commensurate in scope with the instant claims. Accordingly, the rejection is maintained.
Maintained 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.
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.
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.
Claim(s) 1-8 and 10-18 stand rejected under 35 U.S.C. 103 as being unpatentable over Rajan and Gulley, (Transl. Lung Cancer Res., 2014; 3(6): 403-405 (Rajan), in view of Millward et al. Invest. New Drugs, 2012; 30: 1065-73 (Millward), and further in view of Johnson et al. (Curr. Treat. Options in Ocology, 2014; 15:658-669).
Claim 1-18 are directed to methods of treating non-small cell lung cancer (NSCLC), by administering combinations of Plinalbumin, PD-1 inhibitor, and/or docetaxel or a platinum-based agent via two or more treatment cycles.
Rajan describes the immunotherapeutic response rates to NSCLC by targeting PD-1 or PD-L1 (first two columns, p. 403). Rajan cites a phase I clinical study of nivolumab in patients with NSCLC, summarized in Table 1 (limitation of instant claim 5). The Table also compares the response rates of nivolumab to treatment with antineoplastic agent docetaxel. Rajan additionally discloses a similar Phase 3 study of nivolumab and docetaxel (left column, p. 405). Rajan further describes clinical trials in which NSCLC patients heavily pretreated with docetaxel and other approved drugs show that they benefit from nivolumab with higher response rates (left column, p. 404; limitation of claim 16). The foregoing evinces the use of PD-1 inhibitor nivolumab together with the antineoplastic agent docetaxel for treating NSCLC. Rajan is silent on co-administration of plinabulin with docetaxel, but the deficiency is cured by Millward.
Millward describes a phase I study of the vascular disrupting agent plinabulin combined with docetaxel on days 1 and only plinabulin on day 8, in 21 day cycles, with combination of both agents showing antitumor activity (Summary and right column, p. 1067; limitation of claim 13). A total of 6, 8 and 55 cycles were delivered to cancer patients, including those with NSCLC (Table 1, p. 1068; right column, p. 1070; limitation of instant claim 2). The results showed that patients with NSCLC had a 25% response rate compared to 5-10% reported with docetaxel alone (right column, p. 1071). Millward does not disclose co-adminstration of PD-1 inhibitor with their combination therapy using plinabulin together with docetaxel. But the deficiency is cured by Johnson.
Johnson describes the role of immune checkpoint inhibitors anti-PD-1 and PD-L1 in treatment of NSCLC, in combination with existing agents (Opinion statement, p. 658). Johnson describes the administration of monoclonal antibody to PD-1, pembrilizumab to patients with NSCLC, at every 2 weeks or every 3 weeks (p. 664; limitation of instant claims 3-6, 8, 9, 14, 17 and 19, for administering on Day 1 of each treatment cycle, that is 14-day or 21-day). Johnson further describes clinical trials to evaluate pembrolizumab in combination with chemotherapy or ipilimumab and comparison with platinum-based chemotherapy (p. 665), which Johnson describes as the standard treatment for advanced NSCLC (left column, p. 659). Johnson further describes results from platinum doublet chemotherapy in combination with nivolumab (last column, p. 663), and concurrent treatment of NSCLC patients with carboplatin with a separate monoclonal antibody (second bullet, p. 660, limitation of claims 7 and 12). In conclusion, Johnson states that these studies show the feasibility of combining anti PD-1/PD-L1 agents with other clinically active therapies for NSCLC (p. 667).
The prior art references of Rajan, Millward and Johnson and each directed to treatment of NSCLC with various combination of anti PD-1/PD-L1 monoclonal antibodies and chemotherapeutic agents (plinabulin or docetaxel or platinum-based agents). It would have been prima facie obvious to a person of ordinary skill in the art, to combine their respective teachings and to deliver the the anti-neoplastic agents in combination, in 14 or 21 day regimens, as instantly claimed, with a reasonable expectation of success, at the time of the instant invention. A person of ordinary skill in the art would have been motivated to deliver the therapeutic agents in combination, because such was expressly taught by the cited references and would result in more effective treatment of NSCLC. It should be noted that the combining of the chemotherapeutic agents in various combinations amounts to combining prior art elements according to known methods, to yield predictable results. Applicants should note that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. KSR International Co. v. Teleflex Inc., 550 U.S.-, 82USPQ2d 1385 (2007).
Prior Art Made of Record
An abstract by Lloyd et al. was presented one month prior to the EFD of the instant Application teaches the enhanced effect plinabulin with PD1 and PDL1 antibodies. The abstract was printed July 28, 2016 but was presented January 7-10, 2016.
Conclusion
No claims allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Fereydoun G Sajjadi whose telephone number is (571)272-3311. The examiner can normally be reached Monday-Thursday 6:00-4:00 PM EST Fridays 6:00-10:00 AM EST.
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/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699