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
Applicants’ election without traverse of claims 1-6, 8, 10, 11, 13, 16-20 in the reply filed on 6/16/2026 is acknowledged.
Claims 21, 22, 25, 26, 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 without traverse in the reply filed on 6/16/2026.
Claims 1-6, 8, 10, 11, 13, 16-20 have been considered on the merits herein.
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, 8, 10,11,13,16-20 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.
Claims 1 and 18 are confusing in that claim 1 requires “administering” a nucleic acid to organisms of a microbial community in situ, while claim 18 requires the nucleic acid to be administered to an organism ex vivo, and then administering the community to a subject. The claims do not distinctly claim the invention. It is unclear how the nucleic acid is administered to an organism in situ and ex vivo of a community and then administering the community to a subject. Applicants example 1 teaches Bifidobacterium is confirmed to be a desired microorganism in the gut microbiome and a phage comprising a bacteriocin is administered to the Bifidobacterium species by ingestion, and thus a portion of the population of Bifidobacterium in the gut is modified to express bacteriocin by phage transduction. Ex. 2 teaches administering a plasmid encoding an antimicrobial peptide to S. cerevisiae, which is introduced into a fermenter, wherein a subpopulation of S. cerevisiae in the fermenter are transformed with a plasmid and then secrete the peptide into the fermentation stock. However, there is not administering of a community. Thus, it appears as if applicants’ invention is the ex vivo introduction of or genetic modification of an organism (which could be part of a community) with a nucleic acid encoding an antimicrobial peptide, and introducing said modified organism into a community, wherein the peptide is secreted; however, as currently claimed, the invention is unclear as presented in claims 18 and 19 (see below).
Claim 2 is confusing as a whole. It is not clear what applicants are intending to claim, for example, does the claim intend to mean that the amount of desired organisms which have the nucleic acid and grow does not change, or that they grow in equal amounts, or does the claim mean that desired microorganism of the community are not affected by the growth of the genetically modified organism growing the community?
Claim 4 recites the limitation "said secreting" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 19, it is not clear how the microbial community can be both a preserved healthy sample, while the subject suffers from dysbiosis. The claims do not clearly point out the connection between the community and the subject, for example, has the community been previously isolated from a subject prior to the subject suffering from dysbiosis?
For examination purposes, the claims are interpreted in light of the specification, i.e. the ex vivo introduction of or genetic modification of an organism (which could be part of a community) with a nucleic acid encoding an antimicrobial peptide and introducing said modified organism into a community wherein the organism grows and secretes the peptide.
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.
Claim(s) 1-6, 8, 10, 11, 13, 16, 17, 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gabant (WO2019/046577).
Gabant (WO2019046577) teaches methods for tuning populations of microbial organisms to reduce or eliminate undesired microorganisms. Such methods are useful in maintaining tissues comprising microorganisms and in industrial processes (0004). Gabant teaches methods of making bacteriocins comprising producing nucleic acids which encode antimicrobial peptides, i.e. bacteriocins, wherein microbial organisms are genetically modified to express the nucleic acid encoding the bacteriocin (0016, 0024, 0075, 0078, 0102, 0104, 0181). Gabant teaches that the bacteriocin is selected to target an undesired microorganism or population of undesired microorganisms in situ to balance a microbiome, i.e., a microbial community, of an animal, human, plant, or soil (0006, p. 3, 0007, p. 5, 0010, 0027, 0091, 0125) and can be administered to a microbiome orally or topically (0010, 0125).
Regarding claim 2, the bacteriocins are selected and produced by microorganisms to target undesired microbial cells while causing little to no neutralization of the desired microbial organism (0034, 0035).
Regarding claim 3, the microbial organism does not comprise a nucleic acid encoding an immunity modulator (0006, 0008, 0025, 0102, 0106, 0181).
Regarding claim 5, Gabant teaches that the bacteriocin secreted by the host cell neutralizes at least one cell other than the host cell, thus exerting cytotoxic or growth-inhibiting effect on a plurality of other microorganisms other than the bacteriocin secreting microorganism (0027, 0030, 0031, 0032). Gabant teaches that the method comprises screening the antimicrobial peptides/bacteriocins in situ for a desired effect, wherein the screening is for inhibiting growth or reproduction of a pathogenic microorganism in a microbiome of a subject (p. 8, 0011), i.e. an undesired microbial organism according to claims 4 and 5, and screening to enhance growth or reproduction of a non-pathogenic microorganisms of a microbiome (p. 9, 0011). Gabant teaches that a mixture of nucleic acids/bacteriocins can be added to the microbiome to target microbial cells of the population, which has a greater target towards a specific microbial organism (0026, 0100, 0114).
Regarding claim 6, the antimicrobial peptide is synthetic (0016, 0027, 0075).
Regarding claims 8 and 13, the nucleic acid encodes two or more different antimicrobial peptides (0006, 0007, 0010, 0011, p.7, 0025, 0091, 0095, 0100, 0111).
Regarding claim 10, Gabant teaches administering the peptides to a tissue, microbiome, or wound and using a mixture of peptides to target against a microbial infection (p. 9, 0011, p. 11, 0012, p. 15, 0024, 0170-0173, 0175) and teach that a mixture of antimicrobial peptides/bacteriocins are screened in situ for a desired effect, including inhibiting the growth or reproduction of pathogenic microbial organisms of a microbiome, specifically for inhibiting MRSA, an antibiotic resistant infection (0170, 0171).
Regarding claim 11, the reference teaches using a phage or plasmid as vectors to “administer” the nucleic acid to the microbial organism (0075, 0076).
Regarding claims 16 and 17, the microbial community is a microbiome selected from the gastrointestinal tract, skin, mammary gland, placenta, biofluid, seminal fluid, uterus, vagina, ovarian follicle, lung, saliva, oral cavity, mucosa, conjunctiva, biliary tract, and soil (p. 8, 0011, 0026, 0170).
Regarding claim 20, the microbial community is an industrial culture (0026).
Thus, the reference anticipates the claimed subject matter.
Claim(s) 1, 3, 6, 8, 11, 13, 16, 17 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Kaznessis et al. (WO2020/139852, IDS).
WO’852 teaches a method of producing a secreted antimicrobial peptide comprising “administering” a nucleic acid to a desired microorganism by genetically engineering bacteria to express an antimicrobial peptide (AMP), i.e. a genetically engineered probiotic. The reference teaches a combination of genetically engineered probiotics which express different peptides and using a mixture of said genetically engineered probiotics which express different peptides in a composition to eliminate pathogenic microbes in a microenvironment. The composition is for administration to an animal to treat gastrointestinal tract pathogens (p. 4, lines 5-p. 5, lines 1-2, 29-p. 7, lines 1-8, 24-p. 8, lines 1-4). The probiotic microorganisms are modified using synthetic methods to express and deliver AMP’s including bacteriocins in the GI tract of animals, where the probiotics colonize and secrete the peptide (p. 16, lines 8-17, p. 24, lines 20-22).
The GI tract is contaminated with pathogens, and the AMP is used to reduce and eliminate pathogen of the GI tract (p. 7, lines 20- p. 9, lines 1-4, for example, p. 14, lines 8-10,
Regarding claim 6, the peptide is exogenous to the genetically modified microbial organism (p. 7, lines 27-32, p. 10, lines 15-20, for example).
Regarding claim 8, the reference teaches administering a composition which comprises a combination of genetically engineered probiotics which each contain varying antimicrobial peptides (p. 1, lines 22-28, p. 13, lines 4-8).
Regarding claim 11, the reference teaches the use of vectors including phages to “administer” the nucleic acid to the microorganism (p. 6, lines 28-34, p. 10, lines 8-14, p. 27, Table 6, for example).
Regarding claim 13, the administering includes the administration of different antimicrobial peptides (p. 1, lines 22-28, p. 4, whole page, p. 13, lines 4-8).
Regarding claims 16 and 17, the microbial community is a microbiome, and the microbiome is the GI tract.
Thus, the reference anticipates the claimed subject matter.
Claim(s) 1, 2, 3, 6, 8, 11, 13, 16, 17 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Kearney et al. (WO2021/034879).
WO’879 teaches a method of producing a secreted antimicrobial peptide (AMP) in the gut, i.e. a microbial community. The reference teaches a probiotic bacterium which is made to express a nucleic acid encoding an antimicrobial peptide to target undesired microorganisms in the gut microbiome, specifically the peptide targets the undesired microorganism H. pylori and the peptide is administered orally using an ingestible probiotic which does not disrupt the balance of the gut microbiota (abstract, 0006, 0031, 0032, 0038, 0039). The reference teaches the dysbiosis of the gut microbiome results in an imbalance of a person’s normal protective microflora and can be caused by ingestion of pathogenic bacteria and antibiotic-mediated depletion of the microbiome (0002, 0003). To solve the problem of dysbiosis, the reference teaches the use of a guide-AMP hybrid gene in a probiotic bacterium administered to the gut microbiome, which targets an undesired microorganism and leaving the commensal bacteria undisturbed (0035). The reference teaches that other bacteria can also be treated using the AMP secreting probiotic bacteria (0035, 0056, 0057).
Regarding claim 2, the antimicrobial peptides are selected and produced by microorganisms to target undesired microbial cells while causing little to no disturbance of the other members of the microbial community (0009, 0030, 0033).
Regarding claim 3, the reference does not teach the microbial organism to comprise a nucleic acid encoding an immunity modulator.
Regarding claim 6, the antimicrobial peptide is exogenous and synthetic (0084-0086).
Regarding claim 11, the reference teaches using a phage or plasmid as vectors to “administer” the nucleic acid to the microbial organism (0072, 0074).
Regarding claims 8, 13, the reference teaches administering different nucleic acids expressing different AMP’s, i.e., plectasin and eurocin (0057, 0059, 0071, for example).
Regarding claims 16 and 17, the microbial community is a microbiome selected from the gastrointestinal tract and skin (Ex. 5, 6 and entire teachings of document).
Thus, the reference anticipates the claimed subject matter.
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(s) 4, 5, 10, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kaznessis et al. (WO2020/139852) as applied to claims 1, 3, 6, 8, 11, 13, 16, 17 above, and further in view of Gabant (WO2019/046577).
While Kaznessis teaches treating a known undesired microbial organism with the antimicrobial peptide which kills the undesired microbial organism, it would be well within the purview of the skilled artisan to use antimicrobial peptides of Kaznessis to treat unknown organisms as the reference teaches using different probiotic microorganisms expressing different AMP’s to target different pathogens. The reference teaches that different pathogens are found throughout different parts of the GI tract, and using a mixture would cover different pathogens and they teach that AMP’s are less specific and can target a large diversity of different bacteria.
Further, Gabant teaches that methods of using genetically modified bacteria AMP’s are used to screen the antimicrobial peptides/bacteriocins in situ for a desired effect, wherein the screening is for inhibiting growth or reproduction of a pathogenic microorganism in a microbiome of a subject.
Therefore, one would have a reasonable expectation of successfully making genetically modified bacteria which could target different bacteria, including one which may be unknown (or suspected) to be present in the community.
Regarding claim 10, while Kaznessis (WO’852) discusses the emergence of antibiotic resistance pathogens which is a growing problem, they do not teach specifically targeting an antibiotic-resistant infection. The reference teaches using a combination of peptides which can help reduce the development of resistance of the pathogen to any one AMP and allows for more effective control of pathogen in the GI tract (p. 26, lines 1-12).
Further, Gabant teaches that AMP’s can be used in a microbiome environment to specifically target antibiotic-resistant infections. Therefore, it would have been before the effective filing date of the claimed invention, to use and make a combination of AMP’s which specifically target antibiotic-resistant infections in view of the combined teachings of the prior art references.
Regarding claim 20, while WO852 does not teach the microbial community to be an industrial community, it would have been obvious is light of the teachings of Gabant who teach that AMP’s can be made and used in industrial culture communities, and thus one of ordinary skill in the art would have had a reasonable expectation of successfully making and using the appropriate AMP’s which target undesired microorganisms present in industrial communities, given the combined teachings of the prior art references.
Claim(s) 4, 5, 10, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kearney et al. (WO2021/034879) as applied to claims 1, 2, 3, 6, 11, 13, 16, 17 above, and further in view of Gabant (WO2019/046577).
While Kearney teaches treating a known undesired microbial organism with the antimicrobial peptide which kills the undesired microbial organism, it would be well within the purview of the skilled artisan to use antimicrobial peptides of Kearney to treat unknown organisms as the reference teaches that the antimicrobial peptide kills other bacteria (0075), which were not the targeted bacteria per se.
Further, Gabant teaches that methods of using genetically modified bacteria AMP’s are used to screen the antimicrobial peptides/bacteriocins in situ for a desired effect, wherein the screening is for inhibiting growth or reproduction of a pathogenic microorganism in a microbiome of a subject.
Therefore, one would have a reasonable expectation of successfully making genetically modified bacteria which could target different bacteria, including one which may be unknown (or suspected) to be present in the community.
Regarding claim 10, while Kearney teaches that increases in antibiotic resistant H. pylori are now being seen, the reference does not specifically teach that the specific H. pylori treated is antibiotic resistant.
Gabant teaches that AMP’s can be used in a microbiome environment to specifically target antibiotic-resistant infections. Therefore, it would have been before the effective filing date of the claimed invention, to use and make a combination of AMP’s which specifically target antibiotic-resistant infections in view of the combined teachings of the prior art references.
Regarding claim 20, while WO852 does not teach the microbial community to be an industrial community, it would have been obvious is light of the teachings of Gabant who teach that AMP’s can be made and used in industrial culture communities, and thus one of ordinary skill in the art would have had a reasonable expectation of successfully making and using the appropriate AMP’s which target undesired microorganisms present in industrial communities, given the combined teachings of the prior art references.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/ Supervisory Patent Examiner, Art Unit 1651
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