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 .
Response to Amendment
The amendment filed 12/05/2025, in which claims 1, 21 and 27 were amended, claims 2-20 were previously canceled, is acknowledged and has been entered.
Claims 1, 21-30 are under examination on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 09/08/2025 after the Nonfinal Office Action mailed on 08/08/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
(Previous objection, withdrawn) Applicant’s amendments to the Specification submitted on 12/05/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed on 08/08/2025.
Claim Objections
(Previous objections, withdrawn as to claim 1). Applicant’s amendments to claim 1 have overcome previous objections to claim 1.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(Previous rejection, withdrawn as to claims 1, 21-30) Claims 1, 21-30 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
See claims 1, 21-30 as submitted on 12/05/2025.
Applicant’s amendment to claim 1 has overcome previous rejection to claims 1, 21-30.
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.
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.
(previous rejection, maintained as to claims 1, 21-27) Claims 1, 21-27 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., in view of Newman et al., and Gao et al. (prior art of record).
See claims 1, 21-27 as submitted on 12/05/2025.
Regarding claims 1 and 21, it is noted that all of the amendments were made to overcome the previous objections and rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/08/2025. No new limitations were introduced in the amendment filed on 03/03/2025. Accordingly, the rejection under 35 U.S.C. § 103 set forth in the previous Non-Final Office Action mailed on 08/08/2025 still applies to amended claims 1 and 21. As previously explained, Deng et al. teach a method of inducing an immune response in a subject diagnosed with a malignant solid tumor, wherein the solid tumor is an adenocarcinoma tumor, and wherein the subject had been challenged with a virus by injection, the method comprising injecting directly the adenocarcinoma tumor with a composition comprising a vaccine against said virus (Abstract, pages 18, 35, 36, 44, 45). It is noted that the step of selecting a subject is already taught by the method of Deng et al. because the method of Deng et al. requires that the patient be diagnosed with a malignant solid tumor, wherein the solid tumor is an adenocarcinoma tumor, and wherein the subject had been challenged with a virus by injection (Abstract, pages 18, 35, 36, 44, 45, Examples 4-6).
Newman et al. teach the use of preparations comprising multiple pathogens, including coxsackievirus, vaccinia virus, adenovirus, reovirus, Newcastle disease virus, measles virus, and others for use as oncolytic virus therapy of cancer (pages 1, 4), wherein for example, an intratumoral unadjuvanted viral vaccine can be used to convert immunologically inactive “cold” tumors to “hot,” to generate systemic responses, and to sensitize resistant tumors (pages 1, 4).
Neither Deng et al. nor Newman et al. explicitly teach wherein the virus is SARS-CoV-2.
However, Gao et al. teach a purified inactivated SARS-CoV-2 virus vaccine which induces an enhanced immune response comprising partial or complete protection against SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection (Abstract, page 2).
Further, it is noted that the scientific principle underlying the claim invention, which involves the use of intratumoral unadjuvanted viral vaccine to convert immunologically inactive “cold” tumors to “hot,” to generate systemic responses, and to sensitize resistant tumors to checkpoint blockade is well known in the art. For example, an intratumoral injection of an influenza vaccine has been used not only provide protection against influenza virus, but also reduce tumor growth by increasing antitumor CD8+ T cells and decreasing regulatory B cells within the tumor (See Deng et al., see Newman et al. 2020 [cited in Applicant’s IDS submitted on 02/07/2023]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the inactivated SARS-CoV-2 vaccine taught by Gao et al. into the method taught by Deng et al. and Newman et al. for the benefit of eliciting an enhanced immune response to target a tumor as well as partial or complete protection against SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the inactivated SARS-CoV-2 vaccine taught by Gao et al. into the method taught by Deng et al. and , Newman et al. given that the methods of administering inactivated vaccines and assessing immune responses are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claims 22-24, it is noted that no amendments were introduced to claims 22-24 in the amendment filed on 12/05/2025. As previously explained, the combined teachings of Deng et al., Newman et al. and Gao et al. described above teach the limitations of claim 21. As indicated above Gao et al. teach an inactivated SARS-CoV-2 vaccine comprising SARS-CoV-2 virions inactivated using β-propiolactone (page 1, Fig. 1C). Gao et al. further teach such SARS-CoV-1 virions contain viral SARS-CoV-2 genomic RNA of the CN2 strain encoding SARS-CoV-1 proteins and said virions are able to replicate normally in cells (capable of inducing the expression, as recited in claim 23) (page 1). Gao et al. further teach the viral SARS-CoV-2 genomic RNA encodes a SARS-CoV-2 spike protein comprising a receptor binding domain (RBD) which is properly expressed, as per cryo-electron microscopy analysis (page1).
Regarding claim 25, it is noted that no amendments were introduced to claim 25 in the amendment filed on 12/05/2025. As previously explained, Deng et al. teach a method comprising injecting directly an adenocarcinoma tumor with a dose of a composition comprising a vaccine against a virus, wherein such does is capable of inducing an immune response. (Abstract, pages 18, 35, 36, 44, 45).
Regarding claim 26, it is noted that no amendments were introduced to claim 26 in the amendment filed on 12/05/2025. As previously explained, Gao et al. teach doses of a SARS-CoV-2 vaccine comprising three immunizations of either 3 micrograms (for a total of 9 micrograms), or 6 micrograms (for a total of 18 micrograms). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
Regarding claim 27, it is noted that amended claim 27 recites “ductal adenocarcinoma” however no new limitations were introduced to the claim in the amendment filed on 12/05/205. As indicated previously, Deng et al. teach a method comprising injecting directly an adenocarcinoma tumor, wherein the adenocarcinoma tumor is a colon carcinoma (pages 17-18).
Accordingly, claims 1, 21-27 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
(previous rejection, maintained as to claim 28) Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., Newman et al. and Gao et al. as applied to claims 1, 21-27 above, further in view of Kalat et al. (prior art of record).
See claim 28 as submitted on 12/05/2025.
Regarding claim 28, it is noted that no amendments were introduced to claim 28 in the amendment filed on 12/05/2025. As previously explained, Deng et al., Newman et al. and Gao et al. in combination teach the method of claim 21. Neither Deng et al. nor Newman et al., nor Gao et al. explicitly teach wherein the tumor has previously been subjected to electroporation.
However, Kalat et al. teach a method of performing electroporation-enhanced vaccination (electrovaccination). Kalat et al. further teach the use of electroporation to tumor cells promotes high numbers of T cells recognizing the specific epitopes, where the T cells display a high degree of antigen-specific reactivity and against cancer cells thereby delaying tumor growth (Abstract, page 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the teachings of Kalat et al. about electroporation into the method taught by Deng et al., Newman et al. and Gao et al. for the benefit eliciting an enhanced immune response comprising high numbers of T cells thereby promoting delayed tumor growth. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the electroporation taught by Kalat et al. into the method taught by Deng et al., Newman et al. and Gao et al. given that the methods of administering in vivo electroporation to solid tumors are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, claim 28 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
(previous rejection, maintained as to claims 29-30) Claims 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., Newman et al. and Gao et al. as applied to claims 1, 21-27 above, further in view of Diop-Frimpong (prior art of record).
See claims 29-30 as submitted on 12/05/2025.
Regarding claims 29-30, it is noted that no amendments were introduced to claims 29-30 in the amendment filed on 12/05/2025. As previously explained, Deng et al., Newman et al. and Gao et al. in combination teach the method of claim 21. Deng et al. further teaches the use of combination therapy, wherein other drugs are administered to the subject with an adenocarcinoma tumor (page 24).
Neither Deng et al. nor Newman et al., nor Gao et al. explicitly teach losartan for combination therapy in a method of inducing an immune response comprising injecting a solid tumor with a virus vaccine.
However, Diop-Frimpong et al. teach a method of administering losartan to a subject with a solid tumor, for example an adenocarcinoma tumor, for the benefit of inhibiting collagen I production by carcinoma-associated fibroblasts and improving the distribution and therapeutic efficacy of intratumorally injected virus preparations (Abstract, page 1). Diop-Frimpong et al. further teach daily doses of 20-60 mg/Kg over a period of 2 weeks prior to the injection (page 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the teachings of Diop-Frimpong et al. about the use of losartan into the method taught by Deng et al., Newman et al. and Gao et al. for the benefit inhibiting collagen I production by carcinoma-associated fibroblasts and improving the distribution and therapeutic efficacy of intratumorally injected virus preparations. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
One of ordinary skill in the art would have had reasonable expectation of success in incorporating losartan as taught by Diop-Frimpong et al. into the method taught by Deng et al., Newman et al., and Gao et al. given that the methods of administering losartan to patients with solid tumors are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, claims 29-30 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 12/05/2025 have been fully considered but they are not persuasive.
Applicant contends on page 7 of the Remarks submitted on 12/05/2025:
Neither Deng nor Newman discloses or suggests the use of a vaccine against SARS-CoV- 2 to promote an antitumor immune response in a subject that has an adenocarcinoma tumor at a site that is accessible to injection and wherein said subject has previously been exposed to the virus by infection or vaccination. Although Gao discloses a purified inactivated SARS-CoV-2 virus vaccine that induces an enhanced immune response as noted by the Examiner, this reference neither discloses nor suggests use of any viral vaccine to treat adenocarcinoma by intratumoral injection as recited in present claim 1.
In response:
Applicant's arguments against the references individually are not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As explained above and previously, Gao et al. were cited for teaching a purified inactivated SARS-CoV-2 virus vaccine, not Deng et al. nor Newman et al. Further, it is noted that the instant rejection is in view of instant claim language. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It is noted that the instant claims merely recite “a method for promoting an antitumor immune response” and not a “viral vaccine to treat adenocarcinoma.” As described above in detail the cited prior art teaches such method.
Applicant contends on page 7 of the Remarks submitted on 12/05/2025:
It cannot be extrapolated based on Gao, which discloses an inactivated SARS-CoV-2 vaccine, that incorporation of this vaccine into the methods of Deng et al. and Newman et al. would result in an antitumor immune response in a subject that has an adenocarcinoma tumor with a reasonable expectation of success… in view of the unpredictability of vaccines, such a result with an influenza virus does not provide the skilled person with a reasonable expectation of success that a SARS-CoV-2 virus vaccine would have any effect on generating an antitumor immune response. None of the other cited references remedies the deficiencies in the teachings of Deng, Newman and Gao. Applicant respectfully submits that the modifications required to be made to the prior art of record to arrive at the claimed invention are so substantive that it would change the principle of operation of the prior art and make the prior art unsuitable for its purpose.
In response:
The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the cited prior art provides clear teachings, suggestions and motivations to arrive at the claimed inventions. Specifically, the cited prior art teaches extensive studies of the use of viral vaccines to convert immunologically inactive “cold” tumors to “hot,” to generate systemic responses, and to sensitize resistant tumors (see Newman et al.). For example, as explained above and previously, Newman et al. teach the use of preparations comprising many pathogens, including coxsackievirus, vaccinia virus, adenovirus, reovirus, Newcastle disease virus, measles virus, and others for this application (Newman, pages 1, 4). Deng et al. teach the use of an inactivated vaccine against vaccinia Ankara virus in a method of inducing an immune response in a subject diagnosed with an adenocarcinoma tumor (See Deng et al. Abstract). Further, an intratumoral injection of an influenza vaccine has been used not only provide protection against influenza virus, but also reduce tumor growth by increasing antitumor CD8+ T cells and decreasing regulatory B cells within the tumor (See Deng et al., see Newman et al. 2020 [cited in Applicant’s IDS submitted on 02/07/2023]). The scientific principle underlying the claim invention, which involves the use of intratumoral unadjuvanted viral vaccine to convert immunologically inactive “cold” tumors to “hot,” to generate systemic responses, and to sensitize resistant tumors to checkpoint blockade was well known in the art and effectively tested with many viral vaccines before the effective filing date (see Newman et al. 2020). Accordingly, it is herein maintained that one of ordinary skill in the art would have been motivated and had a reasonable expectation of success to apply the known purified inactivated SARS-CoV-2 virus vaccine of Gao et al. to the method of Deng et al. and Newman et al. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Conclusion
No claims are 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 MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672