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
Claims 27-46 are currently pending.
Claim 29-34 and 39-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/08/2025.
Claims 27-28, 35-38 and 45-46 are under consideration.
Rejections/Objections Withdrawn
All 35 USC 103 rejections have been withdrawn in view of Applicant’s successful disqualification of the Hanley reference (See: Remarks of 5/01/2026, p 2, ¶ 1-3)
New Rejections
Claim Rejections - 35 USC § 103
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 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.
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.
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) 27-28 and 37-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang, et al., Oncotarget (2014) 5(12):4392) in view of Chen (Chen, et al., Oxidative Medicine and Cellular Longevity (2016), Article ID: 1580967) and Morse (Morse, et al., Blood (2008) Vol 112, No. 3: 610)
Zhang teaches on the subject of NOX4 levels in NSCLC (Zhang, Abstract). Zhang teaches that NADPH oxidases (NOXs) are a family of seven enzymes, one of which being NOX4, whose primary function is to generate superoxide or hydrogen peroxide (same as reactive oxygen species/ROS) (Zhang, p 4392, ¶2). Zhang teaches that NOX4 is highly expressed in 82% of NSCLC samples (Zhang, p 4393, ¶ 4). Zhang also teaches that NSCLC patients having higher NOX4 expression had shorter overall survival (Zhang, p 4393, ¶ 5). Zhang also teaches that high expression of NOX4 in NSCLC promotes the aggressiveness of NSCLC both in vitro and in vivo (Zhang, p 4393, ¶ 5) and that inhibition of NOX4 with shRNA attenuates this effect (Zhang, Fig 3). Zhang also teaches that, in NSCLC, NOX4-derived ROSs directly affect numerous cellular signaling pathways (Zhang, p 4401, ¶ 2-4). Zhang also teaches that numerous specific NOX4 inhibitors have been developed for the treatment of NOX4 associated diseases, one of which being GKT137831, which has a high safety profile and was in clinical trials before the effective filing date of the instant application (Zhang, p 4393, ¶ 1).
Zhang does not teach a method of treating a subject suffering from a solid tumor that is NSCLC presenting resistance to an immunotherapy that is a cancer vaccine, said method comprising administration of GKT137831 in concert with the immunotherapy that is a cancer vaccine, wherein said administration is effective to treat said lung cancer presenting resistance to the cancer vaccine and wherein said administration restores sensitivity to the immunotherapeutic treatment that is a cancer vaccine.
Chen teaches on the immunosuppressive link between elevated ROS levels in the tumor microenvironment and its implications on T cell-based therapies (Chen, Abstract). Chen teaches that the NOX pathway is one of the main pathways by which ROS are generated (Chen, p 1, ¶ 1). Chen teaches that ROS produced by cancer cells and tumor-infiltrating leukocytes (such as myeloid-derived suppressor cells (MDSCs), tumor associated macrophages and regulatory T cells (Tregs)) is known to suppress immune functions (Chen, p 2, ¶ 2). Chen teaches that administration of ROS inhibitors has been demonstrated to completely abrogate the immunosuppressive effect that MDSCs have on T-cells (Chen p 3, ¶ 1). Chen also directly suggests the combination of T-cell based therapies in concert with ROS modulation as a strategy for rapid clinical treatment of cancers (Chen, p 6, ¶ 3).
Morse teaches on the subject of depletion of human Tregs specifically enhancing antigen-specific immune responses to cancer vaccines (Morse, Title). Morse teaches that depletion of Treg cells decreased Treg cell function and enhanced antigen-specific T cell responses to immunization with the cancer vaccine carcinoembryonic antigen (CEA) and directly suggests combining Treg cell depletion to enhance tumor antigen-specific immune responses to cancer vaccines (Morse, Abstract).
It would be prima facie obvious to one of ordinary skill in the art to combine the GKT137831 NOX4 inhibitor taught by Zhang with the cancer vaccine administration coupled with Treg depletion for taught by Morse in view of the relationship between Treg immunosuppressive activity and NOX4 activity taught by the combined teachings of Chen and Zhang to form a method of treating a subject suffering from a solid tumor that is lung cancer presenting resistance to an immunotherapy that is a cancer vaccine, said method comprising administration of GKT137831 in concert with the immunotherapy that is a cancer vaccine, wherein said administration is effective to treat said lung cancer presenting resistance to the cancer vaccine and wherein said administration restores sensitivity to the immunotherapeutic treatment that is a cancer vaccine. One of ordinary skill in the art would be motivated to do this in order to better treat lung cancer. One of ordinary skill in the art would have a reasonable expectation of success administering GKT137831 in a method comprising administration of GKT137831 in concert with the immunotherapy that is a cancer vaccine, wherein said administration is effective to treat said lung cancer presenting resistance to the cancer vaccine and wherein said administration restores sensitivity to the immunotherapeutic treatment that is a cancer vaccine because: 1) Zhang teaches that administration of the NOX4 inhibitor GKT137831 had been established as a treatment for NOX4 associated diseases and was in clinical trials before the effective filing date of the instant application, 2) Morse teaches that reduction in Treg activity enhances T-cell-based, antigen-specific immune responses to cancer vaccines, 3) one of skill in the art would recognize that the combined teachings of Chen and Zhang provides a natural nexus between the teachings of Morse and the teachings of Zhang because Chen teaches that inhibition of NOX4-produced ROS attenuates the immunosuppressive effects that Tregs have on T-cell based responses while Zhang teaches that NOX4 is abundantly expressed and generates NOX4-derived ROSs in NSCLC, with said NOX4-generated ROSs affecting numerous biochemical signaling pathways in NSCLC, as the ROSs generated by NOX4 as taught by Zhang are the same as the ROSs generated by NOX2 taught by Chen (i.e., superoxides, peroxides, singlet oxgen, etc…), which are taught by Chen to possess immunosuppressive properties affecting T cell-based responses. As such, one of ordinary skill in the art would reasonably expect that a large portion of the immunosuppressive ROSs present in NSCLC are NOX4-derived ROSs and, as such, administration of the GKT137831 of Zhang would attenuate ROS-induced immunosuppression of T cells and, as such, would enhance the effect of T cell-based therapies, such as cancer vaccines.
Response to Arguments
Applicant’s arguments with respect to claim(s) 27-28 and 37-38 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim(s) 27-28, 35-38 and 45-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang, et al., Oncotarget (2014) 5(12):4392), Chen (Chen, et al., Oxidative Medicine and Cellular Longevity (2016) Article ID: 1580967) and Morse (Morse, et al., Blood (2008) Vol 112, No. 3: 610) as applied to claims 27-28, 35, 37-38 and 45 above and in further view of Woller (Woller, et al., Front. Oncol. (2014) Vol. 4; Article 188).
The combined teachings of Zhang, Chen and Morse are discussed above.
The combined teachings of Zhang, Chen and Morse do not teach that the specific cancer vaccine administered
Woller teaches on the subject of oncolytic virotherapy in cancer (Woller, Abstract). Woller teaches that antitumoral activation by oncolytic virus infection of tumor tissue comprises both immediate effects of innate immunity and also adaptive responses for long-lasting antitumoral activity (Woller, Abstract). Woller teaches that all oncolytic viruses, including HSVs and adenoviruses, have in common is the immunogenic nature of virus-induced cell-death, which comprises viral oncolysis of tumor cells, which involves viral oncolysis followed by release of tumor-associated antigens (TAAs)/neoepitopes followed by dendritic cell presentation of the TAAs/neoepitopes, which induces tumor-specific T-cell priming (Woller, p 3, ¶ 3- p 4, ¶ 1; Fig. 1). Woller also teaches that administration of an oncolytic Ad (adenovirus) combined with vectors encoding FLT3L and MIP-1alpha consistently produced results in a mouse lung cancer model wherein tumor-directed T-cells were significantly increased and improved immune responses were obtained (Woller, p 7, ¶ 2).
It would be prima facie obvious to one of ordinary skill in the art to choose the HSV oncolytic virus taught by Woller as the specific cancer vaccine administered in the combined method of Zhang, Chen and Morse. The net result of this combination would be a method of treating a subject suffering from a solid tumor that is lung cancer presenting resistance to an immunotherapy that is an oncolytic HSV cancer vaccine, said method comprising administration of GKT137831 in concert with the immunotherapy that is an oncolytic HSV cancer vaccine, wherein said administration is effective to treat said lung cancer presenting resistance to the cancer vaccine that is an oncolytic HSV cancer vaccine and wherein said administration restores sensitivity to the immunotherapeutic treatment that is an oncolytic HSV cancer vaccine. One of ordinary skill in the art would be motivated to do this in order to better treat lung cancer. One of ordinary skill in the art would have a reasonable expectation of success choosing the HSV oncolytic virus taught by Woller as the cancer vaccine administered in the combined method of Zhang, Chen and Morse because: 1) Woller teaches that Ab-based vaccines deliver consistent anti-tumor results in murine lung cancer models but Woller also teaches that all oncolytic viruses (including Abs and HSVs) act on cancer cells via the same mechanism and, as such, one of ordinary skill in the art would have a reasonable expectation of success that HSV-based vaccines similar to the Ab vaccines of Woller would also elicit an anti-lung cancer response and 2) Woller teaches that oncolytic virus vaccines induce cancer antigen-specific T cell responses and the combined method of Zhang, Chen and Morse enhances T cell responses via Treg attenuation via NOX4 inhibition and, as such, one of ordinary skill in the art would reasonably deduce that the T cell-based anti-cancer response taught by Woller would be enhanced by the GKT137831 administered in the combined method of Zhang, Chen and Morse.
Response to Arguments
Applicant’s arguments with respect to claim(s) 27-28, 35-38 and 45-46 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Claims 27-28, 35-38 and 45-46 are rejected.
No claims are allowed.
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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