The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of Group I, claims 1-5, 7, 9-11, 13-16, 18-19, 22, to a microbiome in vivo, bacteriocin, in the reply filed on June 29, 2026, is acknowledged.
Claims 6, 8, 12, 17, 20-21, 23-25, 30-37 are canceled. Claims 26-29 have been withdrawn from further consideration by the examiner because they are drawn to non-elected inventions. 1-5, 7, 9-11, 13-16, 18-19, 22, to a microbiome in vivo, bacteriocin, are under consideration.
Priority: This application is a 371 of PCT/US2021/072262, filed November 5, 2021, which claims benefit to provisional application 63/112073, filed November 10, 2020.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code: see at least paragraph 0067 (of the application publication US 20230416797). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 9, 15-16, 19, 22 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 9 recites wherein the antimicrobial peptide is digested by the protease outside of the environment. Claim 9 is dependent on claim 1, which recites the antimicrobial peptide is in an environment and digesting the antimicrobial peptide with a protease. Therefore, the antimicrobial peptide appears to already be digested by the protease in the environment. Claim 9 is therefore confusing because it is not clear how the antimicrobial peptide is then digested by the protease outside of the environment. Further clarification and/or correction is requested.
Claim 15 recites wherein administering the antimicrobial peptide comprises the genetically engineered microbial organism expressing and secreting the antimicrobial peptide into the environment. It is not clear how a peptide further comprises a microbial organism. Further clarification and/or correction is requested.
Claim 16 is included in this rejection because it is dependent on claim 15 and fails to cure its defects.
Claim 19 recites wherein the antimicrobial peptide (of claim 1) is administered in a cocktail further comprising a first additional antimicrobial peptides different from the antimicrobial peptide. Claim 19 is dependent on claim 1, which already recites an antimicrobial peptide and would be considered a “first” antimicrobial peptide; therefore, it is confusing to recite additional antimicrobial peptides, in addition to the original antimicrobial peptide, as a “first” antimicrobial peptide. Further correction and/or clarification is requested.
Claim 22 is confusing in general because it is not clear whether the limitations recited in the wherein clauses are results to be achieved or are active steps that are to be carried out in the method of modulating the half-life of the antimicrobial peptide. Further, claim 22 recites the limitation "the food product" in the claim. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1-5, 9-10, 14, 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ebbensgaard et al. (2015 PLoS 10(12): e0144611, 18 pages; previously cited). Ebbensgaard et al. teach a method of assessing antimicrobial activity comprising adding an antimicrobial peptide into an assay and incubating the antimicrobial peptide with a protease for either 30 s, 2, 5, 15, or 30 min (at least p. 5, 8-10; instant claims 1, 3, 14). Therefore, Ebbensgaard et al. can be deemed to teach a method comprising administering an antimicrobial peptide to an environment, wherein the antimicrobial peptide remains active in the environment until a specified endpoint, digesting the antimicrobial peptide with a protease, thereby inactivating the antimicrobial peptide and modulating the half-life of the antimicrobial peptide (instant claims 1, 3, 14).
Regarding instant claim 2, Ebbensgaard et al. teach that there is an increasing awareness of antibiotic resistant bacteria (at least p. 2); therefore, the environment noted in the method of Ebbensgaard et al. above can be deemed to be an environment that is permissive for the growth of one or more microbial organisms capable of developing resistance to the antimicrobial peptide, wherein the method of Ebbensgaard et al. teaches the antimicrobial peptide is digested with a protease for either 30 s, 2, 5, 15, or 30 min (at least p. 5, 8-10), and therefore before any microbial organisms develop resistance to the antimicrobial peptide.
Regarding instant claim 4, since Ebbensgaard et al. teach an antimicrobial peptide comprising the same features as recited in the instant claim(s), it would follow that the antimicrobial peptide of Ebbensgaard et al. has the recited properties of inhibiting the growth or reproduction of an undesired microbial organism.
Regarding instant claim 5, as noted above, Ebbensgaard et al. teach the antimicrobial peptide is digested with a protease for either 30 s, 2, 5, 15, or 30 min (at least p. 5, 8-10), and therefore before any microbial organisms develop resistance to the antimicrobial peptide.
Regarding instant claim 9, Ebbensgaard et al. teach that after incubating the antimicrobial peptide and protease for the specified time, the temperature is raised to 90º C (p. 5). Therefore, Ebbensgaard et al. can be deemed to teach a new environment and that the antimicrobial peptide is digested by the protease outside of the environment.
Regarding instant claim 10, Ebbensgaard et al. teach the protease and antimicrobial peptide are on a plate (at least p. 5); therefore, Ebbensgaard et al. can be deemed to teach that the protease is disposed on a substrate (plate).
Regarding instant claim 22, Ebbensgaard et al. teach antimicrobial peptides that are trypsin sensitive and that the protease is trypsin (at least p. 5, 8-9). Since it is not clear whether all the limitations recited in the wherein clauses are results to be achieved or are active steps that are to be carried out in the method of modulating the half-life of the antimicrobial peptide, the wherein clauses reciting limitations regarding food spoilage are interpreted as properties of the antimicrobial peptide. Since Ebbensgaard et al. teach an antimicrobial peptide comprising the same features as recited in the instant claim(s), it would follow that the antimicrobial peptide that is sensitive to trypsin inhibits the growth or reproduction of microbial organisms that cause food spoilage.
Claims 1-5, 9-10, 14, 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ayres et al. (US 5635484, IDS 06.29.26). Ayres et al. teach a peptide, produced by propionibacteria, having a molecular weight of between 300-1200 daltons and is inhibitory to gram-negative bacteria; the peptide can be produced by purification of a propionibacteria metabolite mixture, by chemical synthesis, or by a host transformed with a recombinant vector, is useful in treating bacterial infections (at least abstract). Ayres et al. teach that newly discovered bacteriocins have application in development of preservation systems for food, in improving their own production by microorganisms, and in medicine (at least col. 1 lines 16-20). Ayres et al. teach samples of the propionibacteria metabolite mixture are treated with various proteases, where the action of protease (papaya), chymotrypsin, pepsin, eliminated the microbial activity (at least col. 10 lines 33-67; instant claims 1, 3, 14). Therefore, Ayres et al. can be deemed to teach a method comprising administering an antimicrobial peptide to an environment, wherein the antimicrobial peptide remains active in the environment until a specified endpoint, digesting the antimicrobial peptide with a protease, thereby inactivating the antimicrobial peptide and modulating the half-life of the antimicrobial peptide (instant claims 1, 3, 14).
Regarding instant claim 2, Ayres et al. teach that many microorganisms which spoil food or cause infections are resistant to agents currently in use (at least col. 1 lines 25-30); therefore, the environment noted in the method of Ayres et al. above can be deemed to be an environment that is permissive for the growth of one or more microbial organisms capable of developing resistance to the antimicrobial peptide, wherein the method of Ayres et al. teaches the antimicrobial peptide is digested with a protease after a time of standard incubation (at least col. 10 lines 33-67), and therefore before any microbial organisms develop resistance to the antimicrobial peptide.
Regarding instant claim 4, since Ayres et al. teach an antimicrobial peptide comprising the same features as recited in the instant claim(s), it would follow that the antimicrobial peptide of Ayres et al. has the recited properties of inhibiting the growth or reproduction of an undesired microbial organism.
Regarding instant claim 5, as noted above, Ayres et al. teach the antimicrobial peptide is digested with a protease after a time of standard incubation (at least col. 10 lines 33-67), and therefore before any microbial organisms develop resistance to the antimicrobial peptide.
Regarding instant claim 9, Ayres et al. teach that after incubating the antimicrobial peptide and protease for a time of standard incubation, the temperature is raised and the pH is adjusted (at least col. 10 lines 33-67). Therefore, Ayres et al. can be deemed to teach a new environment and that the antimicrobial peptide is digested by the protease outside of the environment.
Regarding instant claim 10, Ayres et al. teach the protease and antimicrobial peptide are in an assay and therefore are on a surface (at least col. 10 lines 33-67). Therefore, Ayres et al. can be deemed to teach that the protease is disposed on a substrate (surface).
Regarding instant claim 18, Ayres et al. teach the propionibacteria metabolite mixture comprises a bacteriocin (at least col. 4 lines 10-26, col. 5 examples 5-6).
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.
Claims 1-5, 9-11,13-14, 18-19, 22 are rejected under 35 U.S.C. 103 as being unpatentable over Hols et al. (2019 Trends in Microbiology 27(8): 690-702, IDS 06.29.26). Hols et al. disclose the beneficial aspects of bacteriocins compared with classical antibiotics and emphasize their use in cocktails to curb the emergence of new resistance (at least p. 690). Hols et al. disclose that due to their peptide backbone, bacteriocins can be sensitized to proteases compared with chemically-based antibiotics; thus, they would display a lower biological half-life in nature and organic environments (at least p. 692). Hols et al. disclose that this is considered as an asset to dampen the emergence of resistance, since low remnant and sublethal concentrations of toxins are mutagenic and favor the progressive acclimation of an initial clonal population (at least p. 692). Therefore, Hols et al. can reasonably be deemed to disclose a system comprising a bacteriocin (an antimicrobial peptide) in an environment comprising a protease, where the half-life of the bacteriocin is modulated at a time point.
Hols et al. further disclose that bacteriocins can be used to curb the emergence of new resistance (p. 690) and due to their properties, including narrow spectrum, low environmental remanence, modular nature, can be utilized in various environments, including food preservation, human health, and counteracting the misbalance of microbial populations in the human microbiome (at least p. 692-694, 699).
Since Hols et al. disclose that bacteriocins displaying a lower biological half-life in the presence of proteases in nature and organic environments is considered as an asset to dampen the emergence of resistance, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at a method comprising administering a bacteriocin (an antimicrobial peptide) to an environment, wherein the antimicrobial peptide remains active in the environment until a specified endpoint, digesting the antimicrobial peptide with a protease, thereby inactivating the antimicrobial peptide and modulating the half-life of the antimicrobial peptide (instant claims 1, 3, 14, 18).
Regarding instant claim 2, Hols et al. disclose the beneficial aspects of bacteriocins include their use in cocktails to curb the emergence of new resistance (at least p. 690); therefore, the environment disclosed in the method suggested in Hols et al. above can be deemed to be an environment that is permissive for the growth of one or more microbial organisms capable of developing resistance to the bacteriocin, wherein the method suggested in Hols et al. discloses the bacteriocin is digested with a protease after a time point (at least p. 692), and therefore before any microbial organisms develop resistance to the antimicrobial peptide.
Regarding instant claim 4, since Hols et al. disclose a bacteriocin (an antimicrobial peptide) comprising the same features as recited in the instant claim(s), it would follow that the bacteriocin of Hols et al. has the recited properties of inhibiting the growth or reproduction of an undesired microbial organism.
Regarding instant claim 5, as noted above, Hols et al. disclose the bacteriocin is digested with a protease after a time in the environment and is considered as an asset to dampen the emergence of resistance (at least p. 692), and therefore before any microbial organisms develop resistance to the antimicrobial peptide.
Regarding instant claim 9, Hols et al. disclose various environments that bacteriocins can be utilized in or incorporated in (p. 692-693), in nature and organic environments with protease. Therefore, Hols et al. can be deemed to disclose a second (or new) environment and that the bacteriocin is digested by the protease outside of the environment.
Regarding instant claim 10, Hols et al. disclose various environments that bacteriocins can be utilized in or incorporated in (p. 692-693), in nature and organic environments with protease. Therefore, it would be obvious to one of ordinary skill that the protease is in contact with a surface and further in contact with the bacteriocin.
Regarding instant claims 11, 13-14, as noted, Hols et al. disclose that bacteriocins can be used to curb the emergence of new resistance (p. 690) and can be utilized in various environments, including food preservation, human health, and counteracting the misbalance of microbial populations in the human microbiome (at least p. 692-694, 699). Therefore, it would be obvious that the bacteriocin can be administered to an environment comprising a microbiome in vivo.
Regarding instant claim 19, Hol et al. disclose bacteriocins alone or in rational combinations (cocktails) might be exploited to externally and locally cure multi-drug resistant infections or microbial disorders (at least p. 690, 699). Therefore, it would be obvious that the bacteriocin can be administered in a cocktail comprising additional different bacteriocins where the additional different bacteriocins are not sensitive to the same protease.
Regarding instant claim 22, as noted, Hols et al. disclose that bacteriocins can be used to curb the emergence of new resistance (p. 690) and can be utilized in counteracting the misbalance of microbial populations in the human microbiome (at least p. 692-694, 699). Therefore, it would be obvious that the bacteriocin can be administered to an environment comprising a microbiome in vivo, where enzymes present in the microbiome in vivo environment reasonably comprises a trypsin. Since it is not clear whether all the limitations recited in the wherein clauses are results to be achieved or are active steps that are to be carried out in the method of modulating the half-life of the antimicrobial peptide, the wherein clauses reciting limitations regarding food spoilage are interpreted as properties of the antimicrobial peptide.
Claims 1-5, 9-11,13-14, 15-16, 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Hols et al. (2019 Trends in Microbiology 27(8): 690-702, IDS 06.29.26) in view of Gabant I (US 20190191709; IDS 06.29.26). The teachings of Hols et al. over at least instant claims 1-5, 9-11,13-14, 18-19 are noted above.
As noted above, Hols et al. disclose that bacteriocins displaying a lower biological half-life in the presence of proteases in nature and organic environments is considered an asset to dampen the emergence of resistance and that it would have been obvious to administer a bacteriocin to an environment, wherein the bacteriocin remains active in the environment until a time point and digesting the bacteriocin with a protease to inactivate the bacteriocin and modulate the half-life of the bacteriocin.
Gabant I discloses that it is useful to regulate the growth of microbial cells (at least abstract, paragraphs 0004-0005). Gabant I discloses providing microorganisms engineered to produce bacteriocins to control the growth of microbial cells (at least abstract, 0006-0012).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate an engineered microbial cell comprising nucleic acid molecules encoding bacteriocin of Gabant I in the method suggested in Hols et al. of administering a bacteriocin to an environment, wherein the bacteriocin remains active in the environment until a time point and digesting the bacteriocin with a protease (instant claim 15). The motivation to do so is given by the prior art Gabant I, which disclose microbial cells engineered to produce bacteriocins have the same purpose for regulating and/or controlling growth of microbial cells as bacteriocins disclosed in Hols et al. One of ordinary skill would have a reasonable expectation of success because the art discloses that the bacteriocins produced by the engineered microorganisms also control growth of microbial cells.
Regarding instant claim 16, Gabant I discloses that in some instances, gene activity is decreased; conceptually, gene activity can be decreased by including among others, inactivating a polypeptide (by a polypeptide-specific protease) (at least paragraph 0060). Hols et al. have disclosed that bacteriocins displaying a lower biological half-life in the presence of proteases in nature and organic environments are considered as an asset to dampen the emergence of resistance (p. 692). It would have been obvious to one of ordinary skill in the art that the engineered microbial cell comprising nucleic acid molecules encoding bacteriocin of Gabant I can be further engineered to comprise nucleic acid molecules encoding a protease that cleaves the bacteriocin because Hols et al. disclose bacteriocins displaying a lower biological half-life in the presence of proteases is considered an asset to dampen the emergence of resistance. One of ordinary skill would have a reasonable expectation of success because techniques to engineer microorganisms to produce target polypeptides, including bacteriocins and proteases, were known in the prior art.
Claims 1-5, 7, 9-11,13-14, 15-16, 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Hols et al. (2019 Trends in Microbiology 27(8): 690-702, IDS 06.29.26) in view of Gabant I (US 20190191709; IDS 06.29.26) and Gabant II (WO 2019046577, cited as US 2020263221 on IDS 06.29.26). The teachings of Hols et al. and Gabant I over at least instant claims 1-5, 9-11,13-14, 15-16, 18-19 are noted above.
Regarding instant claim 7, Gabant II also discloses tuning populations of microbial organisms, for example to reduce or eliminate undesired microbial organisms, including producing gene products (bacteriocins) for the control of growth of microorganisms (at least paragraphs 0004, 0005). Gabant II discloses that in some embodiments, an auxiliary protein, such as a protein with anti-protease activity (for example a serpentin) can accompany the bacteriocin (at least paragraph 0130). It is noted that the “serpentin” disclosed in Gabant II is a misspelling of the protease inhibitor serpin. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further include an auxiliary protein such as a serpin protease inhibitor as suggested in Gabant II dependent on the bacteriocin administered and result to be achieved in the method of Hols et al. in view of Gabant I comprising administering a bacteriocin to an environment, wherein the bacteriocin remains active in the environment until a time point and digesting the bacteriocin with a protease. One of ordinary skill would have a reasonable expectation of success because the art discloses that auxiliary proteins, including protease inhibitors, can be incorporated with the bacteriocins to affect activity.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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