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 .
Claim Status
Claims 1-17 are pending.
Applicant’s election without traverse of the invention of group I directed to a programmable bacterium and Applicant’s election of the species of lac // isopropyl-b-D-thiogalactopyranoside (IPTG) in the reply filed on 30 April, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of lac//IPTG has been treated as an election without traverse (MPEP § 818.01(a)). Claims 7-8, and 13-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Therefore, claims 1-6, and 9-12 are pending and under examination in the present Official Action.
Priority
The present application is a CON of International Application No. PCT/US2022/028977, filed 12 May, 2022, which claims priority to United States Provisional Application Nos. 63/187,556, and 63/228,343, filed 12 May, 2021, and 02 August, 2021 respectively. Acknowledgment is made of applicant’s claim for priority.
The earliest possible priority for the instant application is 12 May, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 31 January, 2024, and 23 July, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 20 May, 2024 are accepted by the Examiner.
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.
Claims 1-6, and 9-12 are 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 1 recites the limitation "the nanoencapsulation" in the third line of the claim. There is insufficient antecedent basis for this limitation in the claim. In addition, claim 1 recites “can be programmed or controlled” in the third line of the claim. This phrase is indefinite because it refers to a latent ability, and it is unknown whether the ability is expressed or observed in the invention. Consequently, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claims 2-6, and 9-12 are further rejected for their dependency on a rejected base claim.
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.
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 1-6, and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over WO2017/123676, published 20 July, 2017, hereinafter “Falb”, Of record on the IDS submitted 31 January, 2024 in view of Li et al. Advanced Materials 30.51 (2018): 1803925, hereinafter “Li”, Of record on the IDS submitted 31 January, 2024, McNulty et al. Molecular microbiology 59.3 (2006): 907-922, hereinafter “McNulty”, Of record on the IDS submitted 31 January, 2024, and Zhang et al. Metabolic Engineering 14.5 (2012): 521-527, hereinafter “Zhang”.
Falb teaches recombinant bacterial cells engineered with genetic circuitry to allow metabolic pathways to be turned on or off (Falb, Abstract). The bacterial cells are engineered to express enzymes for the treatment of diseases associated with amino acid metabolism including cancers (Falb, abstract). The bacteria are engineered to express therapeutic genes under control of exogenous inducible promoters (Falb, [072]-[074]; page 389, [0284]). Falb also suggests to further genetically engineer the bacteria of their invention to enhance or improve survivability (Falb, [085]).
Falb does not teach to put a gene which regulates capsular polysaccharide nanoencapsulation under control of an inducible promoter within the engineered bacteria.
Li teaches to nanoencapsulate therapeutic bacteria in alginate to protect them from antibiotics to allow for co-administration of antibiotics (Li, Abstract). Li teaches that one would want to facilitate coadministration of therapeutic bacteria with antibiotics to overcome antimicrobial resistance (Li, page 1, second paragraph). Li teaches that the coadministration of probiotics and antibiotics through encapsulation offers a promising therapeutic route for overcoming antimicrobial resistance (Li, page 4, last paragraph). Thus, a person having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to nanoencapsulate therapeutic bacteria to facilitate antibiotic coadministration and to overcome antimicrobial resistance.
Neither Falb, nor Li teach genes responsible for nanoencapsulation of bacteria under control of an inducible promoter.
McNulty teaches that the expression of a polysaccharide capsule is a common feature of many bacteria (McNulty, "Introduction"). McNulty also teaches that E. Coli expresses four proteins, KfiA-D that are responsible for the biosynthesis of K5 polysaccharide and six other proteins, KpsC, D, E, M, S, and T that are responsible for the transport of K5 polysaccharide to the cell surface (McNulty, “Introduction”).
In addition, Zhang teaches four genes, KfiA, KfiB, KfiC, and KfiD under control of inducible promoters in plasmids to modulate expression of heparosan which is K5 capsular polysaccharide (Zhang, Abstract). Zhang teaches the transformation of E. coli with the inducible KfiA-D plasmids and the induction of K5 capsular polysaccharide production (Zhang, “2.1.” subheading). Thus, a person having ordinary skill in the art before the effective filing date of the claimed invention knew from McNulty and Zhang that K5 polysaccharide encapsulation is an alternative to traditional encapsulation of bacteria and that plasmids for the inducible control of KfiA-D already existed for the modulation of K5 capsular polysaccharide production in E. coli.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have added one of the inducible KfiA-D gene plasmids of Zhang to the therapeutic bacteria of Falb and to have arrived at the invention claimed in instant claim 1 with predictable results because they could have done so according to the known methods of Zhang to produce bacteria that predictably produce capsular polysaccharide upon induction. Further, they would have been motivated by the teachings of Li to nanoencapsulate the therapeutic bacteria of Falb to facilitate the co-administration of antibiotics and overcome antimicrobial resistance. There would have been a reasonable expectation of success in nanoencapsulating the bacteria of Falb insofar as Falb suggests to further modify the cells to increase survivability and a person having ordinary skill in the art would have reasonably expected nanoencapsulated bacteria to have increased survivability upon co-administration of antibiotics as taught by Li.
Regarding claim 2, the bacteria of Falb is E. coli.
Regarding claim 3, Falb teaches to use Nissle 1917 E. coli (Falb, [083]).
Regarding claims 4 and 5, Zhang teaches plasmids comprising inducible KfiA-D genes.
Regarding claim 6, the inducible promoter of Zhang is lac and the inducer is IPTG (Zhang, “2.1.” subheading).
Regarding claim 9, the strains of Falb further comprise a plasmid comprising the therapeutic gene, PAL (phenylalanine ammonia-lyase) (Falb, page 390, [0290]).
Regarding claim 10, the combination therapeutic bacteria of Falb and Zhang would have a therapeutic agent under control of an inducible promoter with the gene that regulates capsular polysaccharide nanoencapsulation under control of another inducible promoter (Falb, [0759], Table 8, page 389, [0284]; Zhang, “2.1.” subheading).
Regarding claim 11, Falb teaches that the same or different inducible promoters can be used to drive multiple exogenous genes within the same therapeutic bacteria and teaches that the therapeutic genes can be under the control of a tetracycline or an arabinose inducible promoter as opposed to an IPTG inducible promoter (Falb, page 17, [035]; page 22, [056]).
Regarding claim 12, Falb specifically teaches pharmaceutical compositions comprising the recombinant bacterial cells wherein the pharmaceutical compositions comprise an excipient or a carrier or a diluent (Falb, page 34, [040]; page 53, [087]; page 58, [075]-[076]).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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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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/BRENDAN THOMAS TINSLEY/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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