DETAILED ACTION
The examiner of this application in the PTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Sharon Wen, Group Art Unit 1641, Technology Center 1600.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-18 are pending.
Election/Restrictions
Applicant's election with traverse of Group I and species CEA-specific CAR and checkpoint inhibitor in the reply filed on 05/18/2026 is acknowledged. The traversal is on the ground(s) that a search for the pharmaceutical composition will likely encompass search results for the methods of treating. This is not found persuasive because for reasons stated in the Restriction Requirement.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Upon further consideration, the Restriction between Groups II-III has been withdrawn.
The requirement is still deemed proper and is therefore made FINAL.
Claims 5-12 and 16-17 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1-4, 13-15 and 18 are under examination.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 13-15 and 18 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Fernandez Santidrian et al. (US 20200140824 A1; see entire document).
Fernandez Santidrian teaches a pharmaceutical composition comprising a carrier cell associated with an oncolytic virus (e.g., paragraph 0006). The reference teaches that the carrier cell may comprise an immune cell, including genetically modified T cells and CAR-T cells directed against tumor-associated antigens (paragraphs 0188). The reference further teaches that suitable oncolytic viruses include parvovirus H-1 (H-1PV) (paragraphs 0294). Importantly, the reference teaches that the disclosed pharmaceutical compositions may comprise any of the disclosed carrier cells together with any of the disclosed oncolytic viruses (paragraph 0014). Accordingly, the reference teaches a pharmaceutical composition comprising H-1PV and CAR-T cells directed to a tumor antigen. Furthermore, Fernandez Santidrian taught checkpoint inhibitor (paragraph 0014) and kits (paragraph 0113).
It is noted that claims 13-15 and 18 recite intended uses of the pharmaceutical composition, the kit or the oncolytic virus, i.e., for administration via intratumoral or intravenous route; for treating an individual having cancer; and for use in a method of increasing TH1 type cytokines. However, such intended uses are not given patentable weight.
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.
Claims 1-4, 13-15 are rejected under 35 U.S.C. §103 as being unpatentable over Rosewell Shaw et al. (Frontiers in Immunology 2018 Vol 9 Article 2103) in view of Marchini et al. (Frontiers in Immunology 2019 Vol 10 Article 1848), Jiang et al. (WO 2018/205344 A1), and further in view of Zhong (US 2020/0338128 A1) as applied to claim 14.
Rosewell Shaw et al. teach combining oncolytic viruses with adoptive T-cell immunotherapy, including chimeric antigen receptor (CAR)-T-cell therapy, for the treatment of solid tumors (see entire document, in particular, see, e.g., Abstract). Rosewell Shaw teaches that CAR-T-cell therapy has demonstrated limited efficacy in solid tumors due to poor trafficking, limited persistence, and the immunosuppressive tumor microenvironment. The reference further teaches that oncolytic viruses stimulate systemic antitumor immunity and remodel the tumor microenvironment, and expressly teaches that oncolytic viruses and CAR-T-cell therapies can be combined to overcome the inherent limitations of each therapy and improve antitumor efficacy (pages 2-4). Rosewell Shaw further teaches that oncolytic viruses convert immunologically “cold” tumors into inflamed tumors by promoting inflammatory cytokines and chemokines, recruiting antigen-presenting cells, enhancing T-cell activation and trafficking, and improving CAR-T-cell infiltration and persistence within tumors.
Rosewell Shaw does not expressly teach that the oncolytic virus is parvovirus H-1 (H-1PV).
Marchini et al. teach that H-1PV is an oncolytic parvovirus under clinical development that selectively infects and kills tumor cells while exhibiting intrinsic oncotropism and tumor selectivity (see entire document). Marchini further teaches that H-1PV and other oncolytic viruses convert immunologically “cold” tumors into inflamed tumors through induction of immunogenic cell death, release of tumor-associated antigens (TAAs), pathogen-associated molecular patterns (PAMPs), and danger-associated molecular patterns (DAMPs), activation of dendritic cells, stimulation of innate and adaptive immune responses, promotion of Th1 immune responses, induction of pro-inflammatory cytokines, and enhancement of T-cell priming and infiltration (see page 5, ONCOLYTIC VIRUSES AS TOOLS TO HEAT UP TUMORS) Figure 1 further illustrates that intravenous administration of H-1PV results in release of pro-inflammatory cytokines, recruitment of dendritic cells, expansion and infiltration of T cells, conversion of macrophages toward an M1 phenotype, and immune conversion of the tumor microenvironment.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to substitute the H-1PV taught by Marchini for the generic oncolytic virus taught by Rosewell Shaw because Marchini teaches that H-1PV possesses the very immune-modulating properties identified by Rosewell Shaw as desirable for enhancing CAR-T-cell therapy, including induction of inflammatory cytokines, activation of dendritic cells, promotion of Th1 immune responses, recruitment and infiltration of T cells, and conversion of immunologically “cold” tumors into inflamed tumors. A person of ordinary skill in the art would therefore have reasonably expected H-1PV to function as one of the oncolytic viruses contemplated by Rosewell Shaw for combination with CAR-T-cell therapy.
Rosewell Shaw further does not expressly teach that the CAR-T cells are specific for the elected species carcinoembryonic antigen (CEA).
Jiang et al. teach genetically modified T cells expressing a chimeric antigen receptor specific for CEA and pharmaceutical compositions comprising such CEA-specific CAR-T cells for treating CEA-positive cancers (see Summary of the invention). It would have been obvious to employ the known CEA-specific CAR-T cells taught by Jiang et al. in the combination therapy of Rosewell Shaw because CEA was a well-known tumor-associated antigen and Jiang teaches that CEA-directed CAR-T cells effectively target CEA-expressing malignancies. Therefore, claims 2 and 3 would have been obvious.
Claim 4 further recites one or more additional therapeutic agents, the elected species being a checkpoint inhibitor. Rosewell Shaw teaches that checkpoint blockade complements both oncolytic virotherapy and CAR-T-cell therapy by reducing T-cell exhaustion and enhancing antitumor immune responses, and further describes combining oncolytic viruses with checkpoint inhibitors to improve therapeutic efficacy. fimmu-09-02103.pdf Accordingly, it would have been obvious to further include a checkpoint inhibitor in the combination therapy to further improve CAR-T-cell function within the tumor microenvironment (page 4 Ovs and Checkpoint Blockade).
Claim 13 recites that the oncolytic virus and/or the CAR immune cells are administered by intratumoral or intravenous administration. Because claim 13 depends from a pharmaceutical composition claim, the recited route of administration merely states an intended use of the claimed pharmaceutical composition and does not impart any structural distinction to the claimed composition. Accordingly, this limitation is not accorded patentable weight, and claim 13 falls with claim 1. Furthermore, it is noted that Rosewell Shaw taught intratumoral administration of oncolytic viruses (see, e.g., page 4 last paragraph).
Claim 14 recites a kit comprising a first container comprising the oncolytic virus, a second container comprising the CAR immune cells, and a package insert containing instructions for treating cancer. Zhong teaches therapeutic kits comprising CAR-T-cell products packaged in separate containers together with package instructions (paragraphs 0188-0192). It would have been obvious to package the H-1PV composition and the CAR-T-cell composition in separate containers with instructions for administration because separate storage of viral products and living cell products preserves product stability and facilitates clinical administration.
Claim 15 depends from claim 14 and recites intended use for the kit, i.e., for the treatment of selected cancers. Such intended use is not given patentable weight for similar reasons noted above.
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Rosewell Shaw, Marchini, and Jiang, and further the conventional kit teachings of Zhong for claims 14-15, with a reasonable expectation of success. Rosewell Shaw teaches the overall concept of combining an oncolytic virus with CAR-T-cell therapy to improve treatment of solid tumors, Marchini identifies H-1PV as a known oncolytic virus possessing the immune-converting properties identified by Rosewell Shaw as desirable for such combination therapy, and Jiang teaches the elected CEA-specific CAR-T cells. The proposed combination merely substitutes one known oncolytic virus for another known oncolytic virus suitable for the same purpose and employs a known CAR-T-cell species according to its established function to obtain the predictable result of enhancing CAR-T-cell-mediated antitumor activity through immune conversion of the tumor microenvironment.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention as evidenced by the reference, especially in the absence of evidence to the contrary.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON X WEN whose telephone number is (571)270-3064. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHARON X WEN/Primary Examiner, Art Unit 1641
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