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 Group II, claims in the reply filed on 1/20/2026 is acknowledged.
Claims 1 - 4 and 8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 1/20/2026.
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.
Claim(s) 5-7 and 9-14 are rejected under 35 U.S.C. 103 as being unpatentable over Dai et al. (Sci Immunol, 2017, hereinafter, “Dai”), in view of Vlachostergios (Immuno-oncology and Technology, 2021, hereinafter, “Vlachostergios”) and Nagarsheth et al. (Cancer Res, 2016, hereinafter “Nagarsheth”).
Regarding claim 5, Dai teaches the use of heat inactivated, as well as UV inactivated, modified vaccinia virus Ankara (MVA) to alter the tumor immune-suppressive microenvironment that leads to antitumor activity (Abstract). Dai administered MVA along with immune checkpoint inhibitors, such as anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies, intratumorally to in murine melanoma models finding the MVA was effective of changing the tumoral from resistant to permissive of checkpoint blockade therapy (Figure 8). Along with turning ‘cold’ tumors to ‘hot’ tumors, Dai found the combination MVA and immune checkpoint inhibitor therapy to stop tumor growth (Figure 8). Dai also teaches the measurement of protein levels within tumor cells such as IRF3 (Supplementary figure 2E) and the measurement of RNA levels within tumor cells such as that of Ifna4 (Supplementary figure 1G).
The reference fails to teach the specific measurement of either protein levels or RNA levels of PRC2.
However, regarding claims 5 -7, Vlachostergios teaches that mutations of PRC2 are found in melanoma cancer (Figure 3). Furthermore, Nagarsheth teaches that PRC2 is known to suppress T-Cell trafficking in cancers, a hallmark of cold tumors (Abstract). Regarding claim 6, Dai teaches the use of RT-PCR to measure the RNA levels within tissue (Supplementary figure 1G, Methods: RNA isolation and quantitative real-time PCR). Regarding claim 7, Dai teaches the use of western blot to measure protein levels within tissue (Supplementary figure 2E, Methods: Western Blot Analysis). Together, measuring PRC2 levels with RT-PCR and western blots would function as a readout of the efficacy of MVA and immune checkpoint inhibitor therapy.
Regarding claim 9, Dai teaches the use of MVA to sensitize or in other words alter the tumor microenvironment to be more permissive to the activity of immune checkpoint inhibitors. Dai uses MVA in combination with immune check point inhibitors such as anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies to effectively treat melanoma tumors within subjects.
Regarding claim 10, Dai used both a heat inactivated and a UV inactivated MVA to sensitize and treat melanoma tumor models (Abstract).
Regarding claims 11 and 12, Dai used inactivated MVA in combination with anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies to sensitize and treat melanoma tumor models (Figure 8).
Regarding claims 13 and 14, Dai used a combination of inactivated MVA in combination of anti-PD-L1 antibody, delivered intratumorally, to eliminate tumors in 80% of subjects (Section: Intratumoral Heat-iMVA is superior to TLR agonist poly (I:C) in treating large established tumors alone and in combination with immune checkpoint blockade; ¶2).
Dai, Vlachostergios, and Nagarsheth are considered to be analogous to the claim invention because they are in the same field of treating PRC2 related cancer. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the method taught by Dai in the method taught by Vlachostergios because, as Nagarsheth teaches, PRC2 is known to suppress T-Cell trafficking in tumors, measuring the levels of PRC2 within tumors using western blots or RT-PCR would advantageously measure the effects of MVA and an immune checkpoint inhibitor administration by using PRC2 as a proxy of efficacy. While Dai does not teach the measurement of PRC2, it would have been obvious to measure PRC2 as it is a biomarker because it is well known that PRC2 mutations and activity can lead to cold tumors and that when MVA is administered with an immune checkpoint inhibitor cold tumors are sensitized and treated, such of those found in the murine melanoma models of Dai. One of ordinary skill in the art would have had a reasonable expectation of success of measuring PRC2 while administering MVA and an immune checkpoint inhibitor given that PRC2 is a well-known biomarker and the method of treating melanoma was well known, has been successfully demonstrated, and commonly used as evidence by the prior art.
Conclusion
NO CLAIMS ARE ALLOWED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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/DANYAL HASSAN ALAM/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672