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 a 371 of PCT/US20/22031 filed on 3/11/2020 which claims benefit of 62/816,403 filed on 3/11/2019 and 62/930,796 filed on 11/5/2019.
The effective filing date of the current application is March 11, 2019.
The objection the specification is withdrawn in light of the 2/20/2026 amendment including the sequence listing size in bytes.
The previous rejection of claim 1 under 35 U.S.C. 102(a)(1) as being clearly anticipated by GenBank reference corresponding to accession number KYD28876 (GenBank 01) is withdrawn in light of the 2/20/2026 claim amendment limiting the mutation positions to W25, M85, F86, G155, A156, or I236. GenBank 01 does not teach a mutation at any of those 6 positions.
Claims 2-10, 17-18, 20-24, 26-29, 31-33, 35, 37-39, 41, 43 and 45 are cancelled.
Claims 1, 11-16, 19, 25, 30, 34, 36, 40, 42 and 44 are pending in the current application. Claims 19, 25, 30, 34, 36, 40, 42 and 44 are withdrawn.
Claims 1 and 11-16 are under examination.
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 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.
New rejection necessitated by amendment: Claims 1 and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Dong et al. (“AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora”, PNAS, 2000, Vol. 97, No.7, pp.3526-3531; previously cited) in view of Morohoshi et al. (“Complete genome sequence and characterization of the N-acylhomoserine lactone-degrading gene of the potato leaf-associated Solibacillus silvestris”, Journal of Bioscience and Bioengineering, 2012, Vol. 113, Issue 1, pp.20-25). The rejection of claims 1 and 11 is further evidenced by the GenBank reference corresponding to accession number WP_387814672, deposited in GenBank on January 30, 2025 and referred to as GenBank 03.
Regarding claims 1 and 11, the specification defines that as an example, for M21, the substitution is for any other amino acid; e.g. the substitution at position 21 can be to any amino acid other than methionine (specification p.19, lines 24-25). Thus, the mutation M85 is being interpreted to require the amino acid in position 85 to be substituted to any amino acid except methionine (M).
Dong teaches N-acylhomoserine lactones, known as autoinducers (AIs), are widely conserved signal molecules present in quorum-sensing systems of many Gram-negative bacteria (abstract). Dong teaches that a bacterial isolate, Bacillus sp. 240B1, is capable of enzymatic inactivation of Ais, and the gene aiiA for autoinducer inactivation from Bacillus sp. 240B1 has been cloned and shown to encode a protein of 250 amino acids (abstract). Dong further teaches that sequence alignment indicates that AiiA contains a “HXHXDH” zinc-binding motif that is conserved in several groups of metallohydrolases (relevant to a metallo-β-like lactonase (MLL)) (abstract). Dong teaches that expression of aiiA in transformed Erwinia carotovora strain SCG1 significantly reduces the release of autoinducers, decreases extracellular pectolytic enzyme activities, and attenuates the pathogenicity on potato, eggplant, Chinese cabbage, carrot, celery, cauliflower and tobacco, and autoinducer-inactivation represents a promising strategy for the prevention of diseases regulated by autoinducers (abstract).
Dong et al. does not teach one amino acid substitution mutation at a position functionally equivalent to M85, or that the MLL has at least 80% identity to SEQ ID NO:1.
However, Morohoshi teaches N-acylhomoserine lactones are used as quorum-sensing signal molecules by many gram-negative bacteria (abstract). Morohoshi teaches sequencing Solibacillus silvestris, which has AHL-degrading activity, and identifying a region that showed similarity to AiiA-like AHL lactonase from Bacillus cereus group (abstract). Morohoshi teaches the cloning and characterization of a novel AHL-lactonase gene from the chromosome of S. silvestris strains (p.20, 2nd column middle paragraph). Morohoshi teaches a conserved HXHXDH sequence that is a zinc-binding motif found in the metallo-β-lactamase superfamily and was found in amino acid sequences of SSIL_0083, which appears to encode AHL lactonase like AiiA (p.22, 2nd column, AiiA homologous gene is present in StLB046 genome).
As evidenced by GenBank 03, the sequence identified by Morohoshi corresponds to a AhlS family quorum-quenching N-acyl homoserine lactonase that is 282 amino acids in length comprising at least one amino acid substitution mutation at one position functionally equivalent to M85. In the GenBank03 sequence, amino acid serine (S) replaces the methionine (M) present at position 85 of instant SEQ ID NO:1. The protein sequence of GenBank 03 has 80.14% identity to instant SEQ ID NO:1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Dong to replace the gene aiiA from Bacillus sp.240B1 taught by Dong with the AHL lactonase taught by Morohoshi to arrive at the claimed invention. Each of Dong and Morohoshi teach lactonase enzymes having at least one amino acid substitution mutation in their sequence. One of ordinary skill in the art would reasonably expect that replacing one known metallohydrolase with another would predictably result in an enzyme that inactivates acylhomoserine lactone signals, because Dong teaches that metallohydrolases contain a conserved HXHXDH zinc-binding motif that contributes to enzyme activity, and that expression of the AiiA attenuated pathogenicity of Erwinia carotovora. One of ordinary skill in the art would have found it beneficial to use an enzyme that to reduce autoinducer activation as a strategy to prevent disease whose virulence is regulated by autoinducers.
Regarding claim 12, Dong teaches the actively growing bacteria were centrifuged for 1 min at 3,000 x g and resuspended in LB liquid medium (relevant to further comprising a pharmaceutically acceptable carrier) (p.3527, 2nd column – 1st paragraph). Dong further teaches that 4 µl of bacterial suspension was added to a cut surface or wound site, and inoculated plant tissues were incubated in a petri dish at 28°C for 48h (p.3527, 2nd column – 1st paragraph).
Regarding claim 13, the limitation wherein the composition is formulated for topical administration “to an animal” is being interpreted as an intended use of the composition for an animal, however the intended use does not confer any further structural limitations to the composition. If the prior art structure is capable of performing the intended use, then it meets the claim. Note: MPEP 2111.02 and MPEP 2145. Here, the composition is clearly formulated for topical administration as established in the discussion of claim 12 above.
Dong further teaches that 4 µl of bacterial suspension was added to a cut surface or wound site, and inoculated plant tissues were incubated in a petri dish at 28°C for 48h (relevant to wherein the composition is formulated for topical formulation) (p.3527, 2nd column – 1st paragraph).
Regarding claim 14, Dong teaches that the E7-R3 plasmid carrying the aiiA gene in the cosmid vector pLAFR3 was transferred into E. carotovora strain SCG1 (relevant to a composition comprising one or more of the MLL of claim 1) (p.3527, 1st column last paragraph). Dong teaches the actively growing bacteria were centrifuged for 1 min at 3,000 x g and resuspended in LB liquid medium (p.3527, 2nd column – 1st paragraph). Dong further teaches that 4 µl of bacterial suspension was added to a cut surface or wound site, and inoculated plant tissues were incubated in a petri dish at 28°C for 48h (relevant to wherein the composition is formulated for administration to a plant) (p.3527, 2nd column – 1st paragraph). Dong teaches Chinese cabbage, cauliflower and tobacco plants were inoculated with E. carotovora strains and incubated at 28°C for 3-7 days (relevant to foliar administration to a plant) (p.3527, 2nd column – 1st paragraph).
Regarding claim 15, “for use as a coating” is being interpreted as an intended use. While the recitation of different formulations indicate additional ingredients would be included in the composition, none of them require an additional ingredient that distinguishes the instantly claimed composition from that taught in the prior art. Note: MPEP 2111.02 and MPEP 2145.
Dong teaches that 4 µl of bacterial suspension was added to a cut surface or wound site, and inoculated plant tissues were incubated in a petri dish at 28°C for 48h (relevant to the composition is formulated for use as a coating) (p.3527, 2nd column – 1st paragraph).
Regarding claim 16, the term “article” is not limited by any definition in the specification. Thus, the term article is being interpreted to include any “thing” having the composition, including plants and plant tissues.
Dong teaches that 4 µl of bacterial suspension was added to a cut surface or wound site, and inoculated plant tissues were incubated in a petri dish at 28°C for 48h (relevant to an article comprising the composition) (p.3527, 2nd column – 1st paragraph).
This results in an article (i.e. plant tissues) comprising the composition.
Response to Arguments
Applicant argues that Dong and GenBank 01 fail to disclose or suggest at least one amino acid substitution mutation at one or more positions functionally equivalent to W25, M85, F86, G155, A156 or I236 in SEQ ID NO:1 (See Remarks dated 2/20/2026, p.8, 3rd paragraph). Applicant argues that regarding claim 11, GenBank 02 also fails to teach or suggest at least one amino acid substitution mutation at one or more positions functionally equivalent to W25, M85, F86, G155, A156 or I236 in SEQ ID NO:1, and therefore fails to cure the deficiencies of Dong and GenBank01 (See Remarks dated 2/20/2026, p.8, paragraph 5).
Applicant argues that claim 13 ultimately depends from claim 1, and therefore includes the subject matter of claim 1, and as stated above, Dong does not disclose a metallo-β-lacatamase-like lactone (MLL) comprising at least one amino acid substitution mutation at one or more positions functionally equivalent to W25, M85, F86, G155, A156 or I236 in SEQ ID NO:1 (See Remarks dated 2/20/2026, p.9, paragraph 2). Applicant argues that GenBank 01 and Kaplan fail to teach or suggest a metallo-β-lacatamase-like lactone (MLL) comprising at least one amino acid substitution mutation at one or more positions functionally equivalent to W25, M85, F86, G155, A156 or I236 in SEQ ID NO:1, and therefore fail to cure the deficiencies of Dong and GenBank01 (See Remarks dated 2/20/2026, p.9, paragraph 3).
Applicant argues that claims 15-16 ultimately depend from claim 1, which recites a metallo-β-lacatamase-like lactone (MLL) comprising at least one amino acid substitution mutation at one or more positions functionally equivalent to W25, M85, F86, G155, A156 or I236 in SEQ ID NO:1, and Dong does not disclose a metallo-β-lacatamase-like lactone (MLL) comprising at least one amino acid substitution mutation at one or more positions functionally equivalent to W25, M85, F86, G155, A156 or I236 in SEQ ID NO:1 (See Remarks dated 2/20/2026 p.10 paragraph 2). Applicant further argues that GenBank 01 and Chaignon fail to disclose a metallo-β-lacatamase-like lactone (MLL) comprising at least one amino acid substitution mutation at one or more positions functionally equivalent to W25, M85, F86, G155, A156 or I236 in SEQ ID NO:1, and therefore do not cure the deficiencies of Dong (See Remarks dated 2/20/2026, p.10, paragraph 3).
Applicant's arguments filed February 20, 2026 have been fully considered but they are not persuasive. As discussed above, Dong teaches an N-acylhomoserine lactone autoinducer. Morohoshi teaches an N-acylhomoserine lactone-degrading gene of the potato leaf-associated Solibacillus silvestris, whose sequence contains a mutation at a position M85 in reference to instant SEQ ID NO:1 and has 80.14% homology to instant SEQ ID NO:1. Thus, Dong in view of Morohoshi a metallo-β-lactamase-like lactonase comprising at least one amino acid substitution mutation at M85 and having at least 80% identity to SEQ ID NO:1. Regarding claim 13, one of ordinary skill in the art would have found it obvious to have taken the composition taught by Dong and Morohoshi and applied it to the skin of a pig taught by Kaplan, because both Dong and Kaplan teach applying a composition to interfere with pathogenic bacterial species. Regarding claims 15-16, one of ordinary skill in the art would have found it obvious to modify the composition of Dong and Morohoshi to formulate the composition for use as a cleaning solution taught by Chaignon, because Chaignon teaches having a biofilm degrading agent in a solution for washing-draining would improve the efficiency of the procedure and avoid having to remove the implant.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEEPA MISHRA whose telephone number is (571) 272-6464. The examiner can normally be reached Monday - Friday 9:30am - 3:30pm EST.
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/DEEPA MISHRA/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657