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 .
Status of Claims
Claims 1-20 are pending. Claims 11-16 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made in the reply filed on 3/13/2026. Claims 1-10 and 17-20 will be examined on the merits.
Election/Restrictions
Applicant’s election of Group I, claims 1-10 and 17-20, in the reply filed on 03/13/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Priority
Provisional application 63/171,067 is acknowledged as disclosing the claimed invention and the effective filing date is 04/05/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 10/02/2023 has been considered. Signed copies are enclosed.
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.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-6, 17-18, and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claims recites a natural product (bacteria not significantly modified). This judicial exception is not integrated into a practical application because the claims are drawn to products, not methods of using, and thus recite only the modified bacteria. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the modified bacteria of claims 1-6 can occur naturally (as evidenced by Susskind & Botstein, 1978, (as evidenced by Sanderson & Ziegler, 1991, Methods in enzymology, 204, 248-264).
The following analysis is laid out in accordance with MPEP 2106:
Step 1: Is the claim directed to a process, machine, article of manufacture, or composition of matter?
Yes – the claims are directed to compositions of matter – namely, bacteria.
Step 2A: Is the claim directed to a law of nature, natural phenomenon, natural product, or an abstract idea?
2A prong 1: Does the claim recite an abstract idea, law of nature, or natural phenomenon (natural product)?
Yes – the claim recites a natural product, or bacteria. Claim 1 recites the genomes of the bacteria are modified to encode a holin protein and a lysozyme; however, bacteria in nature can encode these proteins. Claims 2-5 further specify the strain of bacteria as non-pathogenic Salmonella enterica (SE) serovar Typhimurium (S. Typhimurium). Claim 6 specifies that the holin protein is encoded by gene 13 and the lysozyme is encoded by gene 19 of Salmonella Typhimurium-specific bacteriophage P22.
Bacteriophage P22 is naturally occurring as well, and has long been known to naturally infect S. Typhimurium (Susskind and Botstein, 1978, page 385, right column). When P22 infects Salmonella, it integrates into the genome of the bacterium (Susskind et al., figure 5). The process of autolysis that results from expression of P22 gene 13 and gene 19 is also well established in the art (Susskind, “Lysogeny” starting page 396). Therefore, not only is infection with P22 a naturally occurring process, which results in a holin and a lysozyme modifying the genome of the bacterium, but it is also well understood, routine, and conventional in the art.
2A prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No. Claims 1-6 and 17, 18, and 20 do not recite any additional elements beyond the bacteria, and do not recite any methods or application of said bacteria.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
No. Claims 1-6 recite no additional elements beyond the bacteria. Claim 17 also does not recite any additional element to the claimed ‘vaccine formulation’ beyond the modified bacteria. Claim 18 recites both the modified bacteria and a sealable container in which the modified bacteria are held, and claim 20 recites an additional element of printed instructions. However, placing bacteria in a container and adding printed instructions are well understood, routine, and conventional in the art of bacterial storage and vaccine administration, as evidenced by Sanderson et al., 1991. Therefore, no additional elements amount to significantly more than the judicial exception.
Therefore, claims 1-6, 17, 18, and 20 are rejected under USC 101 as being drawn to the judicial exception of naturally occurring products.
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 1-7 and 17 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 7,871,604 B1, Curtiss, III et al., publication date 01/18/2011, (hereinafter Curtiss).
Claims 1-7 are drawn to Salmonella enterica (SE) serovar Typhimurium (S. Typhimurium) bacteria modified to include the holin protein is encoded by gene 13 and the lysozyme is encoded by gene 19 of Salmonella Typhimurium-specific bacteriophage P22 expressed under an endogenous bacterial promoter. Claim 17 is drawn to a vaccine formulation comprising the modified bacteria of claim 1.
Curtiss discloses an Environmentally Limited Viability System (ELVS) comprising a porin and a lysozyme under control of a bacterial promoter, which can be used for vaccines, especially avirulent Salmonella vaccines (abstract). Column 9, lines 41-45 disclose that the endolysins and holins of P22 can be used in this ELVS, and lines 49-51 disclose that genes 13 and 19 of P22 are preferred, anticipating claim 6. Column 9, line 62 discloses the genes may be on a chromosome, modifying the genomes of the bacteria. Column 12 discloses bacterial promoters that may control the expression of these lethal genes, anticipating claim 7. Column 17 discloses that the bacteria that host these genes include S. typhimurium, and column 18, line 67 recites that the most preferable host is avirulent Salmonella, anticipating claims 1-5. Column 22, section H lists vaccine compositions that comprise these live Salmonella bacteria, anticipating claim 17.
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.
Claims 1-10 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over US 7,871,604 B1, Curtiss, III et al., publication date 01/18/2011, (hereinafter Curtiss) in view of Xu et al., Infection and immunity 78.11(2010):4828-4838 (hereinafter Wu).
Claims 1-7 are drawn to Salmonella enterica (SE) serovar Typhimurium (S. Typhimurium) bacteria modified to include the holin protein is encoded by gene 13 and the lysozyme is encoded by gene 19 of Salmonella Typhimurium-specific bacteriophage P22 expressed under an endogenous bacterial promoter. Claim 17 is drawn to a vaccine formulation comprising the modified bacteria of claim 1.
Curtiss discloses an Environmentally Limited Viability System (ELVS) comprising a porin and a lysozyme under control of a bacterial promoter, which can be used for vaccines, especially avirulent Salmonella vaccines (abstract). Column 9, lines 41-45 disclose that the endolysins and holins of P22 can be used in this ELVS, and lines 49-51 disclose that genes 13 and 19 of P22 are preferred, anticipating claim 6. Column 9, line 62 discloses the genes may be on a chromosome, modifying the genomes of the bacteria. Column 12 discloses bacterial promoters that may control the expression of these lethal genes, anticipating claim 7. Column 17 discloses that the bacteria that host these genes include S. typhimurium, and column 18, line 67 recites that the most preferable host is avirulent Salmonella, anticipating claims 1-5. Column 22, section H lists vaccine compositions that comprise these live Salmonella bacteria, anticipating claim 17.
Curtiss does not fully disclose the limitations of claims 8-10, which recite that the endogenous bacterial promoter is an sseA promoter, that the holin and lysozyme are introduced into the chromosome downstream of said sseA promoter, and that sseA promoted expression of the holin and lysozyme proteins result in intracellular lysis. While Curtiss does disclose the integration of the holin and lysozyme into the chromosome and that the expression of the holin and the lysozyme results in intracellular autolysis (column 9, lines 45-56 and 62), as well as the use of many bacterial promoters (columns 11-13), Curtiss does not explicitly disclose the sseA promoter. However, promoter selection is well understood, routine and conventional in the art, as evidenced by Zhou et al. (2017), World Journal of Microbiology and Biotechnology, 33(2), 23 (abstract, whole document).
Xu et al. teach that, as of publication in 2010, the various regulatory systems in Salmonella are well characterized and allow the construction of strains for efficient in vivo expression of heterologous proteins (pg 4828, left column). Xu goes on to disclose that promoters regulated as part of Salmonella pathogenicity island 2 (SPI2) are induced when the Salmonella are intracellular, and control key virulence determinants (pg 4828, right column). Xu discloses the expression of heterologous proteins under the control of the sseA promoter (PsseA) in order to generate increased expression levels under conditions when virulence elements would be expressed (i.e., upon intracellular invasion) (pg 4829, left column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to combine the ELVS of Curtiss, preferably expressing the P22 genes 13 and 19 in S. Typhimurium on the chromosome under the control of an advantageous promoter with the sseA promoter of Xu, thereby arriving at the claimed invention. One would have motivation to do so, so that the levels of autolysis would increase if the bacteria became pathogenic, thereby killing the bacteria if they were to cause an infection; i.e. entering a non-permissive environment (Xu pg 4829, left column, and Curtiss, column 9, lines 18-20). One would have reasonable expectation of success as Xu shows that expression of heterologous proteins under PsseA increases under intracellular conditions (page 4830, right column, and Figures 1, 3). Therefore, the combination of Curtiss and Xu renders the current invention obvious as of the effective filing date.
Claims 1-10 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Curtiss and Xu as applied to claims 1-10 and 17 above, and further in view of US 2008/0220022 A1, Le Gros et al., publication date 9/11/2008.
Neither Curtiss nor Xu disclose the packaging of the bacteria into a kit, as in instant claim 18, either in a lyophilized or cryopreserved state, as in instant claim 19, or with additional printed matter, as in claim 20. Le Gros et al. discloses Salmonella vaccines comprising live, attenuated bacteria, for administration to avian animals (abstract), in a kit containing lyophilized bacteria (paragraph [0095]), sealed vials (containers), and printed instructions for administration (paragraph [0088], claim 17). It would be obvious to one of ordinary skill in the art to combine the modified bacteria of Curtiss and Xu with the manner of packaging disclosed by Le Gros in order to distribute the bacteria. One would be motivated to do so as a storage method is needed for distribution, and Le Gros provides a manner of packaging wherein the kit is operatively assembled to perform vaccine administration (claim 17). One would have a reasonable expectation of success, as the kit of Le Gros also comprises live Salmonella bacteria, indicating this is a proper method of storing the modified bacteria of Curtiss. Therefore, the combination of Curtiss in view of Xu and further in view of Le Gros renders obvious instant claims 1-10 and 17-20.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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