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
Applicant's election with traverse of Group I, claims 1-9, 11-12, 14, and 16, in the reply filed on 06/29/2026 is acknowledged. The traversal is on the ground(s) that the art Augustin et al is no longer available as prior art because the inventors of the instant invention have provided a declaration establishing that Augustin et al is describing the inventor’s own work. This is not found persuasive because although Augustin et al is now not available as prior art, the special technical feature of an attenuated Salmonella cell comprising a mutation or deletion in one or more of the Salmonella genes encoding for cell surface proteins that induce IL-6 secretion is taught by Zhao et al (Vaccine, “Immunogenicity and protection efficacy of a Salmonella enterica serovar Typhimurium fnr, arcA and fliC mutant”, available online Dec. 17, 2020). Zhao et al teaches a Salmonella Typhimurium named SLT39 with mutations in fnr, arcA and fliC, of which fliC encodes for a cell surface protein that induces IL-6 secretion (abstract).
The requirement is still deemed proper and is therefore made FINAL.
Claims 17-20, 23, 26, and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/29/2026.
Status of the Claims
Claims 1-9, 11-12, 14, 16-20, 23, and 26-27 are currently pending.
Claim 9 is amended.
Claims 17-20, 23, 26, and 27 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 10, 13, 15, 21-22, 24-25, 28-37 are cancelled.
Claims 1-9, 11-12, 14, and 16 have been considered on the merits.
Claim Rejections - 35 USC § 102
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.
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 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al (Vaccine, “Immunogenicity and protection efficacy of a Salmonella enterica serovar Typhimurium fnr, arcA and fliC mutant”, available online Dec. 17, 2020).
With regards to claim 1, Zhao teaches an attenuated Salmonella cell comprising a mutation in one or more of the salmonella genes coding for cell surface proteins that induce IL-6 secretion, resulting in reduced or no expression of said one or more cell surface proteins (abstract).
Regarding claim 2, Zhao teaches that the Salmonella cell is S. Typhimurium (abstract).
Regarding claim 3, Zhao teaches wherein the one or more Salmonella genes codes for flagellin (abstract).
Regarding claim 4, Zhao teaches wherein the one or more Salmonella genes are fliC, related to flagellin (abstract).
Regarding claim 16, Zhao teaches a composition comprising a population of cells of claim 1 and a pharmaceutically acceptable carrier, PBS (pg. 590, col. 2, para 3).
Therefore, Zhao anticipates claims 1-4 and 16.
Claims 1-4 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frahm et al (American Society for Microbiology, 2015).
With regards to claim 1, Frahm teaches an attenuated Salmonella cell comprising a mutation/deletion in one or more of the Salmonella genes coding for cell surface proteins that induce IL-6, so as to result in reduced or no expression of said one or more cell surface proteins and optionally a decrease in expression of cell surface lipopolysaccharide protein (LPS) (abstract).
Regarding claim 2, Frahm teaches wherein the cell is a S. Typhimurium cell (abstract).
Regarding claim 3, Frahm teaches wherein the one or more Salmonella genes code for LPS (abstract).
Regarding claim 4, Frahm teaches wherein the one or more Salmonella gene are rfaL (abstract).
Regarding claim 16, Frahm teaches a composition comprising a population of cells of claim 1 and a pharmaceutically acceptable carrier, PBS, (pg. 10, col. 1, para 1).
Therefore, Frahm anticipates claims 1-4 and 16.
Claims 1-5, 11-12, and 16 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Thanos (WO 2021/097144 A2, published on 05/20/2021).
With regards to claim 1, Thanos teaches an attenuated Salmonella cell comprising a mutation/deletion in one or more of the Salmonella genes coding for cell surface proteins that induce IL-6, so as to result in reduced or no expression of said one or more cell surface proteins (pg. 5, last para) and optionally an increase in expression of one or more outer membrane proteases that inhibit complement activation (pg. 109, para 2) and/or decrease in expression of cell surface lipopolysaccharide protein (LPS) (pg. 77, last para).
Regarding claim 2, Thanos teaches wherein the cell is a S. Typhimurium cell (pg. 194, para 1-3).
Regarding claim 3, Thanos teaches wherein the one or more Salmonella genes code for flagellin (pg. 5, last para).
Regarding claim 4, Thanos teaches wherein the one or more Salmonella genes are FliC, fljB, and/or rfal (pg. 5, last para; and pg. 77, last para).
Regarding claim 5, Thanos teaches wherein the one or more outer membrane proteases is PgtE (pg. 109, para 2).
Regarding claim 11, Thanos teaches wherein the cell comprises one or more exogenous immunomodulator genes which express an exogenous immunomodulator protein (pg. 120, para 3).
Regarding claim 12, Thanos teaches wherein the immunomodulator genes express IL-12, IL-18, IL-15, CXCL9, CXCL10 (pg. 120, para 3), CTLA-4 antibodies (pg. 410, para 3), PD-L1 antibodies (pg. 22, para 2), and CD47 antibodies (pg. 409, para 1).
Regarding claim 16, Thanos teaches a population of cells of claim 1 and a pharmaceutically acceptable carrier (pg. 194, last para).
Therefore, Thanos anticipates claims 1-5, 11-12, and 16.
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 (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.
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 6 is rejected under 35 U.S.C. 103 as being unpatentable over Thanos (WO 2021/097144 A2, published on 05/20/2021), as applied to claims 1-5, 11-12, and 16 above, and in view of Liu et al (BMC Microbiology, 2020).
Regarding claim 6, the limitations of the independent claim 1 are taught above.
Thanos does not specifically teach the deletion of the enterobacterial common antigen locus (eca) as required by claim 6.
However, Liu teaches about the effect of the deletion of the eca in attenuated Salmonella Typhimurium vaccines (abstract).
Regarding claim 6, Liu teaches the deletion of the whole eca operon (pg. 2, col. 2, para 2). Liu teaches that they found the deletion of the eca in attenuated S. Typhimurium did not effect growth, LPS production or motility of the bacterium but significantly affected the virulence when administered orally to mice (abstract).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the attenuated mutant Salmonella Typhimurium taught by Thanos with the deletion of the eca as a form of attenuation in Salmonella Typhimurium taught by Liu to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Liu teaches that they found the deletion of the eca in attenuated S. Typhimurium did not effect growth, LPS production or motility of the bacterium but significantly affected the virulence when administered orally to mice (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Thanos with Liu because both teach the necessary information to attenuate and mutate a Salmonella Typhimurium for the expressed use of bacteria-mediated vaccination/delivery.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Thanos (WO 2021/097144 A2, published on 05/20/2021), as applied to claims 1-5, 11-12, and 16 above, and in view of Noriega et al (US6190669B1).
Regarding claim 7, the limitations of the independent claim 1 are taught above.
Thanos does not specifically teach that the cell further comprises a deletion of the rpoS gene, deletion of the glmS and/or the addition of a viaB locus as required by claim 7.
However regarding claim 7, Noriega teaches about attenuated Salmonella mutants which are attenuated through constitutively expresses Vi antigen wherein the vipR promoter is replaced by a constitutive promoter to cause the constitutive expression of viaB (abstract and claim 1 of Noriega). Noriega teaches that that attenuated Salmonella mutant is used for the delivery of a vaccine against typhoid fever (claim 12 of Noriega).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the attenuated mutant Salmonella Typhimurium taught by Thanos with the addition of a viaB locus as a form of attenuation in Salmonella Typhimurium taught by Noriega to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Noriega teaches that the viaB locus attenuated Salmonella mutant is used for the delivery of a vaccine against typhoid fever (claim 12 of Noriega). One of ordinary skill in the art would have a reasonable expectation of success when combining Thanos with Noriega because both teach the necessary information to attenuate and mutate a Salmonella cell for the expressed use of bacteria-mediated vaccination/delivery.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Thanos (WO 2021/097144 A2, published on 05/20/2021), as applied to claims 1-5, 11-12, and 16 above, and in view of De Greve et al (US20110052635 A1).
Regarding claim 8, the limitations of the independent claim 1 are taught above.
Thanos does not specifically teach that the cell further comprises a deletion of one or more of fljA, rflP, flgKL and/or motAB as required by claim 8.
However, De Greve teaches the deletion of fljA and fljB as a way to attenuate Salmonella Typhimurium ([0135]). De Greve teaches that the attenuated strains of the invention are highly suitable for use in a live attenuated vaccine ([0040]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the attenuated mutant Salmonella Typhimurium taught by Thanos with the attenuated in Salmonella Typhimurium taught by De Greve to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because De Greve teaches that the attenuated strains of the invention are highly suitable for use in a live attenuated vaccine ([0040]). One of ordinary skill in the art would have a reasonable expectation of success when combining Thanos with De Greve because both teach the necessary information to attenuate and mutate a Salmonella cell for the expressed use of bacteria-mediated vaccination/delivery.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 9 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Thanos (WO 2021/097144 A2, published on 05/20/2021), as applied to claims 1-5, 11-12, and 16 above, and in view of Thanos (WO 2020/176809), referred to as Thanos 2 below.
Regarding claims 9 and 14, the limitations of the independent claim 1 are taught above.
Thanos does not specifically teach that the flhDP (also known as flhDC) promoter is replaced with a tumor-specific expression promoter as required by claim 9. Thanos does not specifically teach wherein the one or more exogenous immunomodulator genes are under the control of a tumor-specific expression promoter as required by claim 14.
However, Thanos 2 teaches an attenuated Salmonella for the use of tumor localization (abstract).
Regarding claim 9, Thanos 2 teaches that flhDC related gene expression partially protects mice from invasion and replication of S. Typhimurium, however modification to the immunostimulatory bacteria of the invention to mutate or knockout the genes encoding flhDC can enhance the anti-tumor immune response by focusing S. Typhimurium infection to non-epithelial cell, and by reducing cell death in immune cells (pg. 115, last two para).
Regarding claim 14, Thanos 2 teaches that the immunostimulatory proteins which the S. Typhimurium express are encoded under control of a promoter which can be a promoter selected for the environment of the tumor cell, tissue specific promoters, or for example the tumor-specific promoter CV706 (pg. 19, second to last para; pg. 169, last para spanning pg. 170).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the attenuated mutant Salmonella Typhimurium taught by Thanos with the attenuated in Salmonella Typhimurium including the knockout of flhDC and the tumor-specific promoters taught by Thanos 2 to arrive at the instant invention. One of ordinary skill in the art would be motivated to include the tumor-specific promoter within the flhDC to cause a deletion/loss-of-function mutation of flhDC Thanos 2 teaches that flhDC related gene expression partially protects mice from invasion and replication of S. Typhimurium, however modification to the immunostimulatory bacteria of the invention to mutate or knockout the genes encoding flhDC can enhance the anti-tumor immune response by focusing S. Typhimurium infection to non-epithelial cell, and by reducing cell death in immune cells (pg. 115, last two para). One of ordinary skill in the art would have a reasonable expectation of success when combining Thanos with Thanos 2 because both teach the necessary information to attenuate and mutate a Salmonella cell for the expressed use of bacteria-mediated vaccination/delivery.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
Prosecution Insights