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
This application is in response to the papers filed on June 17, 2026. Claims 1-6, 8, 17, 19, 21-25, 27, 34-36, 40-44 are currently pending as per Applicant’s amendment filed on June 17, 2026 of which claims 1, 5, 8, 17, 19, 21-25, 27, 34, and 40-43 have been amended, and claims 7, 9-16, 18, 20, 26, 28-33, 37-39 have been cancelled. No claims have been added.
Therefore, claims1-6, 8, 17, 19, 21-25, 27, 34-36, 40-44 are currently under examination to which the following grounds of rejection are applicable.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/US22/53183, filed on December 16, 2022. Applicant’s claim for the benefit of a prior-filed parent provisional application 63/290,649 filed on December 16, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is December 16, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on January 18, 2025, August 1, 2025, and July 1, 2026 were filed. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 25 is objected to because of the following informalities:
Claim 25 appears to recite two different groups consisting of microcin operons, and should be written in such a manner, e.g. group 1., and group 2., and line separated accordingly.
Claim 25 incorrectly uses a semicolon instead of a period at the end of the claim.
Appropriate corrections are required.
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 25 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 25 is indefinite in the recitation of “a first constitutive promoter” and “a second constitutive promoter” as it is unclear if these promoters are the same as the “constitutive promoter,” recited in claim 17, from which the claim depends, or rather different constitutive promoters. Claim 27 is similarly rejected as it is dependent on claim 25, and for not clarifying the indefinite issue set forth. . Clarification is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 23 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 23 does not further limit the scope of claim 17 from which it depends due to the claim stating the vector as being a plasmid. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 17, 19, 21-23, 25, 27, 34-36, and 40-44 are rejected under 35 U.S.C. 102(a)(1)(2) as being anticipated by Bucci et al. (WO 2020/227155 A1; of record IDS filed January 18, 2025).
Regarding claim 17, Bucci teaches a microcin operon comprising a set of microcin genes comprising one or more Microcin H47 (MccH47) genes and/or Microcin 147 (MccI47) genes (“In some embodiments, the vector can include a set of genes for a Class IIa microcin (e.g., MccH47, MccE492, MccM, MccG492, and MccI47).” p 15, line 14-26; Fig. 2), and a constitutive promoter, wherein the constitutive promoter allows for continual transcription and expression of at least one microcin gene (“The mchA can controlled by a constitutive promoter (e.g., J23119).” p 18, line 16-26; Fig. 2).
Regarding claims 1-4, Bucci teaches the E. coli is E. coli Nissle 1917 (EcN).comprising the self-retaining vector of claim 17 (p 19, 5-17).
Regarding claims 19 and 21, both dependent on claim 17, Bucci teaches wherein the set of MccH47 genes comprises one or more of mchA, mchB, mchC, mchD, mchE, mchF, mchX and mchI (Fig. 1 and 2; p 5, par 5; p 15).
Regarding claim 22, dependent on claim 17, Bucci teaches wherein the constitutive promoter is a J23119 promoter (“The mchA can controlled by a constitutive promoter (e.g., J23119).” (p 18, ln 18-19).
Regarding claim 23, dependent on claim 17, the rejection to claim 17 is applied herein as it makes clear Bucci teaches the vector as a plasmid.
Regarding claims 25 and 27, both dependent on claim 17, Bucci teaches the vector comprising the microcin operon comprising mciI, mciA, mchC, mchD, mchE, and mchF (p 2, par 2) or mchB. mchC, mchD, mchE, mchF mchX and mchI (p 16, par 3); wherein the controllable promoter is p23119, a constitutive promoter (p 3, ln 7; p 18, ln 25-26; claim 6), mchA, and a second constitutive promoter, wherein the second constitutive promoter allows for continual transcription and expression of the mchA (p 18, ln 18-19).
Regarding claim 34, dependent on claim 1, Bucci teaches method of treating intestinal dysbiosis or a bacterial infection, the method comprising: identifying a subject as having intestinal dysbiosis or a bacterial infection; and administering to the subject a therapeutically effective amount of a composition comprising the genetically engineered microorganism of claim 1 (p 22, line 4- p 23, line 26).
Regarding claim 35, dependent on claim 34, Bucci teaches wherein the subject is a human and the composition is administered by endoscopy, enteroscopy, colonoscopy, a nasoduodenal catheter, enema, or by oral administration (p 23, line 21-26).
Regarding claim 36, dependent on claim 35, Bucci wherein the composition is orally administered, optionally in a capsule. (p 23, line 21-26).
Regarding claim 40, dependent on claim 34, Bucci teaches wherein the subject has a bacterial infection that is a gram-negative bacterial infection (Bucci claim 12).
Regarding claim 41, dependent on claim 40, Bucci teaches wherein the bacterial infection is carbapenem-resistant Enterobacteriaceae infection, E. coli infection, Salmonella infection, and/or Shigella infection (Bucci claim 13).
Regarding claim 42, dependent on claim 41, Bucci teaches wherein the carbapenem-resistant Enterobacteriaceae infection is a Klebsiella pneumoniae infection (p 6, par 3; p 32, par 2).
Regarding claim 43, dependent on claim 1, the rejection to claim 34 is applied herein as it teaches a method of reducing a risk of a bacterial infection by identifying a subject as having a risk of a bacterial infection; and administering to the subject a composition comprising the genetically engineered microorganism.
Regarding claim 44, dependent on claim 43, Bucci teaches wherein the subject is being administered one or more antibiotics (p 4, par 3).
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 5-6, 8, 17, 23, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Bucci et al. (WO 2020/227155 A1) as applied to claims 1, 17, and 23 above, and further in view of Kan et al. (ACS synthetic biology 10.1 (2020): 94-106; of record IDS filed January 18, 2025).
The teachings of Bucci are discussed supra.
Regarding claims 5 and 6, Bucci does not teach wherein the self-retaining vector comprises one or more genetic modifications of a native vector of the microorganism, and more specifically wherein the modification comprises a deletion of the native vector and the introduced self-retaining, genetically modified vector.
Kan teaches the method of removing the native plasmids of E. coli Nissle [EcN], e.g. pMUT1 and pMUT2, which may act as vectors for recombinant DNA, via CRISPR-Cas9 while transfecting these cells with modified pMUT vectors (“Our work developed a simple method to remove the native pMUT plasmids, and generated reliable pMUT plasmid vectors capable of secreting a functional curli material within the mouse gut without plasmid loss. Furthermore, our pMUT-based plasmid vectors simplified in vivo experiments by forgoing the need for antibiotics for plasmid maintenance or inducers for gene expression through temperature sensitive circuits.” (p 102, col 1; Fig 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to modify the E. coli Nissle strain that comprises the claimed self-retaining vector as taught by Bucci with the same plasmids and related methods taught by Kan, due to the there being a reasonable expectation of success in the deletion of the native plasmids while introducing modified plasmid vectors. There is clear motivation in doing so based on the deletion of the native vectors would reduce the risk of expressing recombinant DNA from such vectors, and furthermore to improve expression from the introduced modified vectors that control microcin expression.
Regarding claim 8, Kan teaches the introduced modified pMUT plasmids do not require antibiotic selection as described in the rejection above.
Regarding claim 24, dependent on claim 23, Bucci teaches the vector as plasmid vectors, but does not teach these vectors as being pMUT1 or pMUT2 plasmid vectors (p 28, par 2).
Kan teaches the transfection of EcN cells with modified pMUT1 and pMUT2 vectors as described in the rejection to claims 5& 6, wherein the native vectors were removed with Cas9 (p 96, col 2; abstract).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to modify the E. coli Nissle strain that comprises the claimed self-retaining vector as taught by Bucci with the same plasmids and related methods taught by Kan, due to the there being a reasonable expectation of success in the deletion of the native plasmids while introducing modified plasmid vectors. There is clear motivation in doing so based on the deletion of the native vectors would reduce the risk of expressing recombinant DNA from such vectors, and furthermore to improve expression from the introduced modified vectors that control microcin expression.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634
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