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 .
Priority
This application, represent a National Stage entry of the PCT/US20/59752, filed on 11/09/2020, and which claimed ultimate priority to the provisional Application 62/932,499, with a filing date of 11/07/2019. Thus, the effective filing date of the Application is recognized as 11/07/2019.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Election/Restrictions
Applicant's election with traverse of Group IV (claims 33, 35-37, 40, 42, 43, 47, 49, and 51) in the reply filed on 12/12/2025 is acknowledged. The traversal is on the ground that Group IV and non-elected Group I, relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they contain the same or corresponding special technical features. The special technical features of non-elected Group I include Ad5.F35 which are present and required in the methods set forth in elected Group IV.
This is found persuasive and the claims of Group I and Group IV, will be examined together, in view of the fact that the claims that were considered in Groups II and III were canceled. Claims 1, 3, 5, 8,9, 33, 35-37, 40, 42, 43, 47, 49, and 51 are pending and are examined.
The requirement is still deemed proper and is therefore made FINAL.
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 1 is rejected under 35 U.S.C. 103 as being unpatentable over NCT01972737 (Thomas Jefferson University- Phase I Study of AdS-hGCC (Human Guanylyl Cyclase C)-PADRE in Stage I/II Colon Cancer, 10/30/2013) in view of Yang et al. (A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy. Cancer biology & therapy, 18, 833-840, 2017).
The claim is drawn to a recombinant Ad5.F35 adenovirus comprising:
a) an adenoviral Ad5.F35 vector which is replication defective and further comprising:
b) a gene expression cassette comprising:
i) a heterologous promoter operatively linked to,
ii) a nucleic acid encoding a soluble human GUCY2C domain fused in frame to,
iii) a nucleic acid encoding a universal CD4+ helper epitope.
The purpose of NCT01972737 is to determine the safety, tolerability and ability to stimulate hGCC-specific antibody and killer T cell immune responses of an Ad5-hGCC-PADRE vaccine in stage I and stage II Caucasian and African American colon cancer patients. The biological used is Ad5-hGCC-PADRE vaccine.
The reference is silent about the use of a Ad5/F35 adenovirus variant.
Yang et al. teach that Conditionally replicating adenoviruses (CRAds), which not only kill cancer cells, but also serve as vectors to express therapeutic genes, are a novel and effective method to treat cancer. However, most adenoviruses are Ad5, which infect cells through the coxsackie and adenovirus receptor (CAR). The transduction efficacy of Ad5 is restricted because of the absent or low expression of CAR on several cancer cells. Ad serotype 35 has a different tropism pattern to Ad5. Ad35 attaches to cells via a non-CAR receptor, CD46, which is expressed widely on most tumor cells. Thus, chimeric adenoviral vectors consisting of the knob and shaft of Ad35 combined with Ad5 have been constructed. The chimeric fiber adenoviral vectors can transduce CAR-positive and CAR-negative cell lines (abstract). The chimeric adenovirus Ad5/F35 has a better safety profile than Ad5 and considering the characteristics of Ad5/F35-based vectors, it is believed that these vectors represent a better therapeutic approach to treat cancer (conclusion section).
It would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have modified that teachings in the NCT01972737 and use AD5.F35 adenoviruses to treat cancer with a reasonable expectation of success, since the benefits of using the modified adenovirus are clearly indicated by Yang et al.
Claims 33, 43, 47, 49 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over NCT01972737 (Thomas Jefferson University- Phase I Study of AdS-hGCC (Human Guanylyl Cyclase C)-PADRE in Stage I/II Colon Cancer, 10/30/2013) in view of Yang et al. (A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy. Cancer biology & therapy, 18, 833-840, 2017) and in further view of
Snook A. (Metastatic colorectal cancer immunotherapy with GUCY2C-expressing
Listeria monocytogenes. Project report [online]. September 2018 [retrieved 01/12/2026] Retrieved from the Internet: [URL: https://apps.dtic.mil/sti/citations/AD1062516]).
The claims are drawn to a method of treating a human patient diagnosed with cancer, wherein cells of said cancer express GUCY2C, the method comprising the steps of
a) administering to the patient an effective amount of an injectable pharmaceutical composition comprising:
i) a replication defective recombinant Ad5.F35 adenovirus comprising:
an adenoviral Ad5.F35 vector further comprising:
a gene expression cassette comprising:
a heterologous promoter operatively linked to,
a nucleic acid encoding a soluble human GUCY2C domain
fused in frame to,
a nucleic acid encoding a universal CD4+ helper epitope;
and
b) subsequently administering to the patient an effective amount of an injectable
pharmaceutical composition comprising:
i) a recombinant Listeria monocytogenes comprising:
a gene expression cassette comprising
a heterologous promoter operatively linked to
a nucleic acid encoding a soluble human GUCY2C domain.
The recombinant Listeria monocytogenes comprises a nucleic acid encoding a soluble human GUCY2C domain fused to a Listeria monocytogenes protein ActA. The cancer expressing GUCY2C is esophageal, gastric, pancreatic, or colorectal and may be metastatic.
The purpose of NCT01972737 is to determine the safety, tolerability and ability to stimulate hGCC-specific antibody and killer T cell immune responses of an Ad5-hGCC-PADRE vaccine in stage I and stage II Caucasian and African American colon cancer patients. The study will be the first step in translating GCC into a vaccine for the secondary prevention of metastases in African American and Caucasian colorectal cancer patients. The biological used is Ad5-hGCC-PADRE vaccine.
Yang et al. indicated the benefits of using Ad5.F35 adenovirus instead of Ad5 adenovirus.
The two references do not teach about the use of a recombinant Listeria monocytogenes comprising: a gene expression cassette comprising a heterologous promoter operatively linked to a nucleic acid encoding a soluble human GUCY2C domain (which may be fused with to a Listeria monocytogenes protein ActA).
Snook A. discloses the ability of a new vaccine to treat colorectal cancer in animal models. The vaccine uses attenuated Listeria monocytogenes to deliver GUCY2C, a colorectal cancer antigen to “antigen-presenting cells” (APCs) to induce GUCY2C-specific T cell responses against GUCY2C which may find and eliminate colorectal cancer. The project tests novel recombinant Listeria monocytogenes vaccines produced in our laboratory in mouse models of colorectal cancer to determine their activity, efficacy, and safety. If successful, the results of these studies could be applied to patients with metastatic colorectal cancer, a disease that is typically fatal.
The reference disclosed administering to a mouse an effective amount of a pharmaceutical composition (figure 7) comprising i) a recombinant Listeria monocytogenes (p. 2) comprising: a gene expression cassette comprising a promoter operatively linked to a nucleic acid encoding a soluble GUCY2C domain fused in frame to a nucleic acid encoding a universal CD4+ helper epitope (comprising a LLO promoter operatively linked to a nucleic acid encoding a soluble GUCY2C domain fused at its C-terminus (in frame) to a nucleic acid encoding S1 (a universal CD4+ helper epitope ) (p. 6; figures 1, 2) wherein amino acid residues 54-384 include a soluble domain of GUCY2C.
It would have been obvious to one of ordinary skill in the art at the time of the invention was filed to modify the disclosure of NCT01972737, modified by the teachings of Yang et al., to include a recombinant Listeria monocytogenes comprising: a gene expression cassette comprising a heterologous promoter operatively linked to a nucleic acid encoding a soluble GUCY2C domain fused in frame to a nucleic acid encoding a universal CD4+ helper epitope, as disclosed by Snook A, in order to provide a superior method for inducing potent antitumor immunity.
Allowable Subject Matter
Claims 3, 5, 8, 9, 35-37, 40, 42 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647