11897927DETAILED 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 .
The response filed 1-29-2026 has been entered into the record.
Status of Claims
Claims 1-21 are pending.
Election/Restrictions
Applicant's election with traverse of Group I, species
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in the reply filed on 1-29-2026 is acknowledged. The traversal is on the ground(s) that separate subclassifications is not justification given search tools available to examiners. This is not found persuasive because the search of over 300 distinct species combined with different neoantigens, combined with different cytokines combined with different cancers is beyond millions of potential inventions. The art in this area is not just symbols it is different concepts. The search of different cancers, evaluation of treatment therapies is not coextensive and there is no unifying single embodiment either claimed or disclosed that provides for treatment of all cancer types. The search is not co-extensive for the different microorganisms, different neoantigens, different cancers etc. Each type of cancer requires a separate search that is not coextensive. The search burden is but a single criterion as the examination burden also is considered. Given the enormous search burden, the examination burden is beyond enormous to read and evaluate all the separate thousands of potential documents and evaluate each as it relates to the claims for all the relevant patent statues and provide a written office action on such. The evaluation under the patent statutes of each of thousands of potential inventions is not undue as asserted. In conclusion, the search and examination of thousands of inventions given the combinations provided in the specification and the claims is therefore found to be an enormous burden and Applicant’s arguments are not persuasive.
The requirement is still deemed proper and is therefore made FINAL.
Claims 3, 4 and 13-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species and invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 1-29-2026.
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.
Claim 7-9 are 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.
As to claim 7 and dependent claims 8 and 9, it is unclear how the language further limits an element of claim 2. Is the therapeutic protein in addition to the neoantigen ? If so, then the claims should state that the bacteria further comprise a modification to express a therapeutic protein. Clarification is requested.
Information Disclosure Statement
The information disclosure statements have been considered. Initialed copies are enclosed.
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)(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.
Claim(s) 1, 2, 6, 10, 11 and 12 are rejected under 35 U.S.C. 102(a)(2) as being clearly anticipated by Thanos et al (US 12,226,439, issue Feb 18, 2025 with priority to at least July 11, 2019).
Thanos et al provide for a method of treatment of cancer comprising administering an immunostimulatory bacterium, the immunostimulatory bacterium comprising a plasmid that encodes and anti-cancer therapeutic product wherein the therapeutic product is an immunostimulatory protein that confers or contributes to an anti-tumor immune response in the tumor microenvironment is a tumor antigen or tumor neoantigen (see column 381-185, see for example claims 1, 2, 9, claim 19; column 4, lines 55-60; column 20, first full paragraph). The cancer is selected from colon etc. (see claim 25). The bacterium is a Salmonella species, particular Salmonella typhimurium (see claims 27 and 28). The immunostimulatory bacterium can be a strain of a variety of bacteria at claim 33 and strains set forth in paragraphs bridging columns 11-12 which include VNP20009( see column 12, lines 27-38. The Salmonella bacteria of the invention have potent anti-tumor activity by increasing their ability to accumulate in or target tumors (see column 3, first paragraph). The strains can be modified to encode immunostimulatory and immunomodulatory proteins (column 12, lines 39-54). Administration can be by any suitable route including systemic, local, topical, parental including oral or rectal, intratumorally, intravenously, intramuscularly or subcutaneously (see column 19, line 54 to column 20, line 33). The second anti-cancer agent is a chemotherapeutic agent, radiotherapy or an anti-immune check point inhibitor such as anti-PD-1, anti PD-L1, anti-CTLA-4 antibody or other therapeutic cells. The combination therapy can also include anti-VEGR or anti-VEGFR or anti-VEGFR2 antibody, anti-IL-6 antibody, oncolytic virus therapy or a cancer vaccine. The bacteria can be administered in combination with a second-anti-cancer agent where the second agent is administered before, concomitantly, with, after or intermittently with the immunostimulatory bacteria (see paragraph bridging columns 44-45; column 20, lines 16-27). The cancers that can be treated include colon cancer, rectal cancer, colorectal cancer (see column 120, lines 9-16; column 121, lines 30-32). Thanos et al anticipate claims 1, 2, 6, 7, 10, 11 and 12.
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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Thanos et al (US 12,226,439, issue Feb 18, 2025 with priority to at least July 11, 2019) in view of Arrach et al (American Association for Cancer Research 70(6):2165-70, 2010; of record).
The teachings of Thanos et al are set forth supra. Thanos et al differ by not teaching Salmonella strain STM3120 modified to express a cancer neoantigen.
Arrach et al teach Salmonella STM3120 mutant strains that have tumor homing ability and provide for reduction in tumor size after intragastric, intertumoral or intravenous injection in a murine model BALB/c mice bearing syngeneic orthotopic 4T1 breast tumors (see page 2169, column 2, last paragraph). Arrach et al teach that the STM3120 mutant was able to survive in tumors (see page 2169, column 1 second paragraph). Arrach et al also teach that mutants that retain tumor-targeting while being poor colonizers of normal tissue are candidates for deliver of cancer therapeutics.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing the invention was made to substitute the Salmonella STM3120 strain (parent background 14028) of Arrach et al for the Salmonella strain of Thanos et al in the method of treatment of cancer using expressed cancer antigens and/or neoantigens because Thanos et al teach that tumor targeting Salmonella are suitable for expressing cancer antigens and/or cancer neoantigens for the purpose of administration for treating cancer and Arrach et al teach mutants that retain tumor-targeting while being poor colonizers of normal tissue are candidates for deliver of cancer therapeutics.
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Thanos et al (US 12,226,439, issue Feb 18, 2025 with priority to at least July 11, 2019) in view of Loeffler et al (PNAS, 104(31):12879-12883, 2007; of record; of record).
The teachings of Thanos et al are set forth supra. Thanos et al differ by not teaching expressing a neoantigen in addition to a cytokine for treatment of cancer, however Thanos et al teach the strains can be modified to encode immunostimulatory and immunomodulatory proteins (column 12, lines 39-54).
Loeffler et al teach that an attenuated Salmonella typhimurium strain engineered to produce human cytokine LIGHT inhibits tumor growth. Loeffler et al teach that the non-virulent bacteria can be exploited as targeting vehicles for local generation of therapeutic proteins in tumors (see abstract). Loeffler et al teach that BALB/c mice bearing subcutaneous CT-26 colon carcinomas were injected intravenous with Salmonella transformed with LIGHT. Marked reduction of tumor growth was observed in mice treated with LIGHT-expressing Salmonella compared with control bacteria (see page 12880, column 1). In addition, LIGHT-expressing bacteria suppressed metastatic tumor growth compared with control-treated animals and untransformed Salmonella and that containing empty plasmid were not significantly different from PBS. Similar activity was also obtained using FasL or IL-18.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to further modify the Salmonella cancer antigen or cancer neoantigen expressing Salmonella strains of Thanos et al by further expressing the LIGHT cytokine because Loeffler et al teach that LIGHT-expressing Salmonella provide for inhibition of tumor growth and suppression of metastatic tumor growth and administer the neoantigen and LIGHT expressing Salmonella as a method of treating cancer including colon or colorectal cancer because both Thanos et al and Loeffler et al teach that the addition of therapeutic proteins a neoantigen and a cytokine LIGHT provide for therapeutic tumor treatment. Inasmuch as, both therapeutic proteins were taught as useful for treatment of colon/colorectal cancer the combination the expression of both therapeutic proteins in a single Salmonella bacterium is prima facie obvious.
Claims 1, 2, 6, 10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Thanos et al (US 12,226,439, issue Feb 18, 2025 with priority to at least July 11, 2019) in view of Petit et al (US 11,897,927 issued 2-13-24 with priority to November 30, 2017).
The teachings of Thanos et al are set forth supra. Thanos et al differ by not teaching the K-RAS neoantigen comprising resides p5-12 G12D for colorectal tumor targeting.
Petit et al teach methods for treatment of cancer including colon and colorectal cancer having tumor associated antigens or one or more recurrent mutations by administering a recombinant fusion polypeptide, a nucleic acid encoding a recombinant fusion polypeptide a recombination bacterial or Listeria strain comprising the nucleic acid or an immunogenic composition (see column 31, lines 38- column 32 end; column 120, lines 44-67; column 123, lines 40-45). The compounds can be administered in combination with one or more additional compounds (see column 128, lines 47 to column 129, line 13). Each antigenic peptide may be unique or administering one or more tumor associated antigens. Petit et al teach fusion protein comprising KRAS G12D having SEQ ID NO:489 which is a recurrent cancer mutations (see column 193, lines 30-50 and Table 7). Other KRAS cancer mutations are found at column 44, lines 27-60). Mutations found associated with colorectal cancer are delineated in Table 108 (column 296, lines 34-50) and include KRAS G12D. KRAS G12D 21-mer provided for significant decreases in in CT27 tumor volume in naïve and treated mice with treated with Lm KRAS-G12d-21-mer (see figures 1 and 34 and description thereof in specification).
It would have been prima facie obvious to one having ordinary sill in the art at the time the invention was filed to express KRAS G12D 21-mer of SEQ iDNO:489 of Petit et al as the colorectal neoantigen in the tumor-homing Salmonella strain as set forth in Thanos et al for the administration to and treatment of colorectal cancer because Petit et al identify the KRAS G12D 21-mer of SEQ ID NO:489 as having therapeutic anti-tumor activity in colon/colorectal cancer and Thanos et al teach that neoantigens expressed in Salmonella strains and administered are effective therapeutics for the treatment of cancer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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