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 .
Election/Restrictions
Applicant’s election without traverse of invention II in the reply filed on 5/30/25 is acknowledged.
Claims 1-6, 8, 10 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/30/2025.
Claims 14-16, 18-22, 31-34 and 36-38 are examined on the merits.
Response to Amendment
The declaration under 37 CFR 1.132 filed 1/9/26 is insufficient to overcome the rejection of claims 14-16, 18-22, 31-34 and 36-38 based upon 35 USC 103a as set forth in the last Office action because: see response below.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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.
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.
(Prior Rejection Maintained) Claim(s) 14-16, 18-22, 31-34 and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Falb et al. (US PGPub 2019/0160115) and Clark et al. (Clin Cancer Res, 2019, Vol. 25, No. 7) and Sturm et al. (Journal of Translational Medicine, 2012, Vol. 10, No. 9).
Falb et al. teach the use of oncolytic viruses in combination with other cancer related therapeutics for treating a cancer. One example of an oncolytic virus is oncolytic recombinant vaccinia virus (rVACV), which is discussed in Stritzker et al. [see paragraph 791] rVACV is a vaccinia virus derived from Lister strain of vaccinia virus. Another example of a virus is vaccinia virus that has been modified by manipulating the thymidine kinase protein to be not expressed while the vaccinia virus can be engineered to express a GM-CSF cytokine. [see paragraph 223] Falb et al. also teach that genetically engineered oncolytic viruses can comprise a gene encoding an inhibitor of a checkpoint inhibitor, such as an inhibitor of PD-1. [see paragraphs 235 and 247] It is also taught that doses may be administered at day or weekly intervals or that more than one dosage can be administered each day. [see paragraph 1075]
However, Falb et al. fail to teach that a palbociclib at a concentration of 10mg/kg/day to 90 mg/kd/day is to be administered and the vaccinia virus is to be administered at a 1X10^5 to 1x10^10 pfu at a rate of 7 to 30 days.
Clark et al. teach the co-administration of Palbociclib with Paclitaxel for treating cancer. The dosing of the medications was days 2-6, 9-13 and 16-20 and 28. [see right column of page 2073] The dosing of the Palbociclib was 50, 75, 100 and 125 mg per dose. [see right column page 2073]
Strum et al. teach the administration of vaccinia virus with mitomycin C and dosage of vaccinia virus was 5X10^6, which expressed hyper-IL-6. [see page 2, right hand column] This composition was tested for level of anti-cancer properties.
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Falb et al. in order to co-administer Palbociclib at the claimed interval. One would have been motivated to do so, given the suggestion by Falb et al. that the vaccinia viruses can be administered with additional anti-cancer compounds. There would have been a reasonable expectation of success, given the knowledge that Palbociclib and Paclitaxel were administered to a subject with cancer, as taught by Clark et al., and also given the knowledge that vaccinia viruses with anticancer substances can be co-administered, as taught by Strum et al. MPEP § 2144.05 (II) (A) states, “…Optimization Within Prior Art Conditions or Through Routine Experimentation…“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to dis-cover the optimum or workable ranges by routine experimentation…”. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to arguments:
Applicant’s arguments have been fully considered, however, they are not persuasive:
Applicants contend that co-administration of vaccinia virus and palbociclib produced a synergistic anticancer effect across many cancer cell lines, compared to administering other of these components alone. Applicants also point to examples 19 and 20 of the instant specification to establish that co-administration of a vaccinia virus with an anti-cancer agent is not predictable since example 19 revealed that lenalidomide with oncolytic vaccinia virus did not exhibit a reduction in tumor size, but administration of lenalidomide, hydroxyurea and vaccinia virus did (see figure 25). In comparison, example 20, which tested a different vaccinia virus compared to example 19, involved co-administration of palbociclib with WOTS-418 and this combination exhibited an greater decrease in tumor size compared to vaccinia virus by itself.
Applicants also provide information in a declaration that revealed synergistic anticancer effect against cancer cell lines A549, HT-29, SW620 and SK-MEL-5 (Experiment 2). In these in vitro experiments, a Western Reserve Vaccinia virus with an inactivated Thymidine Kinase gene was administered with Palbociclib or the virus and Palbociclib were administered separately. Applicants tested cell viability and observed a significant decrease in cell viability after 3 days when both virus and palbociclib were administered. However, effect on tumor size or any other indicator of treating a cancer in an individual having cancer was not tested in this declaration.
With regard to experiment 1 of the declaration, the treatment schedule provided in Figure A is not commensurate in scope with the claimed method of treatment since a vaccinia virus and palbociclib are administered together, but only once (claim 14) or a granulopoiesis inhibitor is administered after a vaccinia virus (claim 32). While claim 18 provides additional treatments of a granulopoiesis inhibitor, the vaccinia virus is not commensurate in scope with the virus tested by applicant. With regard to Figure B from the declaration, the tumor size reduction from virus administration, palbociclib administration and then administration of virus and palbociclib would appear to be additive and not synergistic, particularly when considering the standard deviation values.
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Therefore, the declaration is insufficient to overcome this rejection.
Lastly, the combined teachings of Falb et al., Clark et al. and Sturm et al. fail to teach or suggest that co-administration of a vaccinia virus lacking a thymidine kinase gene with palbociclib.
Applicants appear to be focused more on amended claim 14 and not claim 32, which does not require that palbociclib be administered or that any drug be co-administered with a vaccinia virus.
In response, whether co-administration of vaccinia virus and palbociclib produced a synergistic anticancer effect against tumors in vivo, compared to administering other of these components alone were not tested by applicant. Moreover, the vaccinia viruses employed in examples 19 and 20 of the specification were different. In example 19, WR TK- is a western reserve vaccinia virus that lacks a functional thymidine kinase gene and in example 20 vaccinia virus (WOTS-418) is a mutated western reserve vaccinia virus that expresses a mutated herpes simplex virus thymidine kinase gene in place of the endogenous thymidine kinase gene. Also tested in example 20 was WOTS-418 with hydroxyurea, which exhibited a reduction in tumor size similar to WOTS-418 + palbociclib. Therefore, the combination of an oncolytic vaccinia virus and an anti-cancer agent is effective with more than just palbociclib. Furthermore, the pharmaceuticals of lenalidomide and palbociclib are distinct products which act on cancerous cells in a different manner and the claimed unexpected results appear to not be commensurate in scope with the claimed method. For example, the claimed method of at least claims 14 and 32 do not recite a cancer that has been tested by applicants and the treatment regimen tested by applicants (see example 20 of instant specification) does not involve the co-administration of vaccinia virus with palbociclib.
With regard to the combined teachings of Falb et al., Clark et al. and Sturm et al., Falb et al. teach the use of oncolytic viruses (rVACV) in combination with other cancer related therapeutics for treating a cancer and that check point inhibitors can also be expressed by such a a virus and the teachings of Clark et al. and Strum et al. provide additional guidance as to anti-cancer therapies (palbociclib and paclitaxel) and successful use of vaccinia virus with an anticancer drug (mitomycin C), respectively. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
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 BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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