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 .
DETAILED ACTION
Claim status
Claims 1-6, 8-9, 11-14, 16-19, and 21-24 are pending
Claims 16-19 and 21 are withdrawn
Claims 1-6, 8-9, 11-14, 22-24 are under examination
Election/Restrictions
Applicant’s election of the following invention in the reply filed on 6/08/2026 is acknowledged.
Although Applicant generically argues they do not agree with the Examiner’s characterization of Tonetti, 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 § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-6, 8-9, 11-14, 22-24, drawn to compositions comprising a S. typhimurium, pharmaceutical compositions thereof, and kits thereof
Claims 16-19 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/12/2024 and 6/08/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that 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.
Objection to Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code ([0109, 0177]). Applicant is required to amend or delete the embedded hyperlink and/or other form of browser-executable code. For example, “www” can be replaced with “world wide web” as the URL code, and “http” can be replaced with ‘hypertext transfer protocol”. See MPEP § 608.01.
Claim Objections
Claims 1, 8-9, and 12 are objected to because of the following informalities: standard botanical and scientific naming conventions dictate that Latin genus and species names should be written in italics. See MPEP § 1605.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 2 is rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling. The disclosure does not enable one of ordinary skill in the art to practice the invention without a sequence listing, which is/are critical or essential to the practice of the invention but not included in the claim(s). See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Although citing a GenBank database accession number does not trigger a formal electronic sequence listing requirement unless the actual nucleotide or amino acid sequence residues are explicitly disclosed in the text or drawings of the application; however, in instant case Claim 2 requires the use of polynucleotides found in Table 1 of the specification in order to make the S. Typhimurium bacterium expressing the exogenous collagenase.
Relying solely on a GenBank accession number, Gene ID number, and/or SEQ ID NO from another patent document to incorporate "essential material" (such as a sequence required to satisfy 35 U.S.C. 112 for enablement) is generally restricted or disallowed by the USPTO if the sequence is missing from the application text. Because GenBank, Uniprot, MGI, etc., are a non-patent public databases, they do not qualify as acceptable sources for essential material. Furthermore, under the MPEP, Applicant cannot replace the submission of a required sequence listing file by incorporating sequence data from another patent or prior application by reference.
Claim Rejections - 35 USC § 112(b)
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 2 is 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.
Claim 2 recites the limitation that the agent is from “Table 1”. A claim may be rendered indefinite by reference to a figure or table (see MPEP 2173.05(s)).
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
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.
Claims 1, 5-6, 8-9, 11-14 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Manuel et al., (US 2022/0193149, filed 5/15/2020, published 6/23/2022).
With respect to claim 1, Manuel teaches an engineered Salmonella Typhimuium bacterium comprising an exogenous collagenase encoding polynucleotide, wherein the engineered S. Typhimurium strain is VNP2009 ([0019-0021], Figs. 11-13, see also Claims 1-5, and 11-16 of Manuel).
In regard to claims 5 and 6, Manuel teaches the polynucleotide is present on a plasmid and is operably linked to a regulatory element ([0019], Fig. 11, see also Claims 12-16 of Manuel).
In regard to claims 8, 9 and 12, Manuel demonstrates the VNP2009-CTNase is capable of degrading a collagen matrix compared to a non-induced control ([0020], Fig. 12), and penetrate a tumor to a greater extent (i.e., about 4-fold) compared to a non-induced control ([0021], Fig. 13). It also must be noted that instant claims refer to the intended uses of the claimed composition, and a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.
In regard to claim 11, Manuel teaches the engineered bacterium is further combined an active agent such as saline [0068]. Note that Applicant’s specification defines “active agent” refers to a substance, compound, or molecule, which is biologically active or otherwise, induces a biological or physiological effect on a subject to which it is administered.
In regard to claims 13 and 14, Manuel teaches the engineered bacterium is in a pharmaceutical composition with a secondary active agent such as saline [0068-0069]
Accordingly, Manuel anticipates instant claims.
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 of this title, 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.
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 2 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Manuel et al., (US 2022/0193149, filed 5/15/2020, published 6/23/2022)
As discussed previously, Manuel teaches an engineered S. Typhimurium bacterium expressing an exogenous collagenase.
However, although Manuel teaches the enzyme can be from humans [0076], they do not provide a preferred embodiment of a human collagenase gene (which are MMPs).
Nevertheless, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to produce an engineered S. Typhimurium bacterium expressing an exogenous human collagenase gene because each of the individual elements of the instant claims are independently presented by Manuel as embodiments and are taught that they can be combined in various embodiments; therefore a combination of all the elements into a single embodiment would be apparent to an artisan skilled in GMO therapy in light of the Supreme Court’s KSR decision (see MPEP 2143 Exemplary Rationale (A)). Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of filing of the invention. Each of the elements (VNP0009, human collagenases gene, transfection methods and formulations) are taught by Manuel and further they are taught in various combinations and are shown to be used in a method for preparing genetically engineered bacterium. It would have been therefore predictably obvious to use a combination of these elements in said composition.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Manuel et al., (US 2022/0193149, filed 5/15/2020, published 6/23/2022), in view of Salamone et al., (Microorganisms, 2019, 7:387).
As discussed previously, Manuel teaches an engineered S. Typhimurium bacterium expressing an exogenous collagenase.
However, although Manuel teaches the enzyme can be from other bacteria [0076], they are silent to a MMP collagenase from a prtV homologue or orthologue thereof.
Salamone reviews Vibro collagenases for biomedical applications (Abstract, Introduction. With respect to homologues and orthologues of prtV, Salamone teaches several homologues and orthologues of collagenases from V. parahaemolyticus (p. 2, Introduction, pgs. 8-9, Results 3.3, see Fig. 4).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the engineered S. Typhimurium bacterium comprising an exogenous collagenase as taught by Manuel and choose an homologues or orthologues of the prtV collagenase as taught by Salamone with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Salamone because Vibrios produce some of the most promising bacterial collagenases that are used routinely for biomedical and pharmaceutical uses (Abstract, p. 2, Introduction).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Manuel et al., (US 2022/0193149, filed 5/15/2020, published 6/23/2022), in view of Thanos et al., (US 2020/0270613, see IDS filed 1/12/2024).
As discussed previously, Manuel teaches an engineered S. Typhimurium bacterium expressing an exogenous collagenase.
However, although Manuel teaches the engineered S. Typhimurium bacterium is in a pharmaceutical composition to be used clinically to treat a variety of cancers, including pancreatic, breast, prostate, skin, lung, and abdominal tumors [0068-0069, 0083-0088, they are silent to a kit with instructions for doing so.
With respect to claims 22-24, Thanos teaches a variety of engineered S. Typhimurium bacterium for treating diseases such as can, such as those that expresses an enzyme for degrading the extracellular matrix [0634]. Specifically Thanos teaches a kit and instructions for use for administration [0325].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the engineered S. Typhimurium bacterium comprising an exogenous collagenase as taught by Manuel and combine the engineered bacterium into a kit with written instructions for administration as taught by Thanos with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for purposes of convenience and economy. Furthermore, nonfunctional printed matter (i.e., instructions) do not distinguish a claimed product from an otherwise identical prior art product, unless there exists a new and unobvious functional relationship between the printed matter and the substrate (MPEP § 2112.01, III).
Hence, the claimed invention as a whole was prima facie obvious 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 ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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