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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/14/2025 has been entered.
Election/Restrictions
Applicant’s election of Group I (i.e., drawn to a method of converting a trichothecene comprising a 3-oco-group into a trichothecene comprising a 3-hydroxy group, claims14, 19-26, 28, 30, 35-38 and newly added claims 39-40) and SEQ ID NO: 3 (the polypeptide sequence of Group I) in the reply filed on 11/13/2024 is acknowledged. The election was made with traverse, which was previously addressed and made final.
Amendments Received
Amendments to the claims were received and entered on 11/14/2025.
Status of Claims
Claims 14, 19-26, 28, 30, and 35-40 are currently pending and under consideration.
Priority
The present application claims status as a 371 (National Stage) of PCT/EP2020/074056 filed on August 28, 2020 and claims priority to foreign application EP19194632.6 filed on August 30, 2019. Acknowledgment is made of applicant’s claim for foreign priority and papers submitted under 35 U.S.C. 119(a)-(d). The present application and all claims are being examined with an effective filing date of August 30, 2019.
Withdrawn Objections
In view of Applicant’s amendments, objection to claim 19 is hereby withdrawn.
Withdrawn Rejections
In view of Applicant’s cancellation of claims 31-34, all rejections of claims 31-34 are now moot and are hereby withdrawn.
In view of Applicant’s amendments, requiring a polypeptide having at least 90% sequence identity to any one of SEQ ID NOs: 1-14, rejections of claims 14, 20-25, 30, and 35-38 under 35 USC § 103 over Hassan et al., Carere et al., and A0A0F5LPU3 are hereby withdrawn.
In view of Applicant’s amendments, requiring a polypeptide having at least 90% sequence identity to any one of SEQ ID NOs: 1-14, rejections of claims 19 and 26 under 35 USC § 103 over Hassan et al., Carere et al., and A0A0F5LPU3, further in view of Ito et al., are hereby withdrawn.
Specification-Objection/Sequence Compliance
Applicants’ are advised that the application is not in compliance with 37 CFR §§ 1.821-1.825. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR §§ 1.821-1.825. Specifically, applicants’ are required to comply with the sequence rules by inserting the sequence identification numbers of all sequences within the claims and/or specification. For example, pg. 15-20 of specification recites many sequences (e.g., S-P-L-X5-G-G-X6-L-X7-G-K in para 0082), but applicants’ fail to provide the SEQ ID NO: (sequence identifiers) to all the sequences recited in the specification; i.e., nucleotides 10 (ten) or more and amino acids 4 (four) or more. Sequences must be referred to by their sequence identifiers, see particularly 37 CFR 1.821(d). If the sequences appearing in the specification do not have SEQ ID NO: assigned to them, then an amendment to the sequence listing will be required as well. There must not be any new matter submitted, therefore it is important to be careful to include only the sequences that are already disclosed in the current specification. Failure to correct the deficiency will be held a non-responsive to this Office action.
Required response – Applicant must provide:
• a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Sequence Rules: The nucleic acid sequences presented requires having a sequence identifier. In order to comply with the sequence rules Applicants must identify the sequence by providing SEQ ID NO:, and where required provide a new version of the sequence listing and disk. Applicant must submit a CRF copy and paper copy of the Sequence Listing, a statement that the content of the paper and computer readable copies are the same and where applicable include no new matter as required by 37 C.F.R. j 1.821(e) or 1.821(9 or 1.821(g) or 1 .825(d), as well as an amendment directing its entry into the specification. Note: If the nucleic acid sequences are already part of the sequence listing and the CRF, Applicants may amend the specification by providing the appropriate SEQ ID NO: or provide the SEQ ID NO, to the legend of the figure(s). Applicant's cooperation is requested in correcting other unidentified sequences of which applicant may become aware of in the specification.
Claim Objections
Claims 21-24 are objected to for failing to properly recite amino acid sequence identifiers, as required under 37 CFR §§ 1.821-1.825.
Appropriate correction is required.
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 14, 20-25, 28, 30, and 35-40 are rejected under 35 U.S.C. 103 as being unpatentable over Carere et al. (The Identification of DepB: An Enzyme Responsible for the Final Detoxification Step in the Deoxynivalenol Epimerization Pathway in Devosia mutans 17-2-E-8, 2018, Front. Microbiol. 9:1573, cited in the IDS), Hassan et al. (The enzymatic epimerization of deoxynivalenol by Devosia mutans proceeds through the formation of 3-keto-DON intermediate, 2017, Scientific Reports 7: 6929, cited in the IDS), and A0A085FJY9 (UniProt Database, 2019, cited in the IDS).
Regarding claims 14, 20 and 38, Carere et al. teaches a two-step enzymatic epimerization pathway for detoxification of deoxynivalenol (DON), wherein DON is first oxidized to 3-keto-DON and subsequently reduced to 3-epi-DON. It is noted that DON and 3-epi-DON are trichothecenes comprising a 3-hydroxy group, and 3-keto-DON is a trichothecene comprising a 3-oxo-group (Specification, pg. 2, para 005-007). Carere et al. specifically discloses identification of DepB as the enzyme responsible for the reduction of 3-keto-DON to 3-epi-DON, confirmed by disappearance of 3-keto-DON and appearance of 3-epi-DON following incubation with purified DepB, as verified by HPLC and LC-MS/MS (“Identification of DepB,” pg. 4, right column). Carere et al. further teaches DepB is characterized as an NADPH-dependent dehydrogenase belonging to the aldo-keto reductase (AKR) family, with conserved catalytic motifs and residues characteristic of AKR enzymes (pg. 6, right column). Furthermore, comparative genomic analysis demonstrates that coding sequences in the DepB genomic region are largely conserved across 19 Devosia strains, including Devosia sp. LC5, indicating the presence of closely related DepB homologs within the genus (pg. 4, left column). Additionally, Carere et al. teaches that DepB activity is influenced by reaction parameters, including pH, temperature, enzyme handling, and cofactor availability, demonstrating that enzyme performance and product formation are condition-dependent (“Buffer, pH, and Cofactor Specificity,” pg. 4, left column; “Thermostability and Effect of Lyophilization,” pg. 5, left column and Fig. 3-7). Accordingly, Carere et al. teaches a method of converting a trichothecene comprising a 3-oxo group (i.e., 3-keto-DON) to a trichothecene comprising a 3-hydroxy group that comprises 3-epi-DON, as recited in claim 14, carried out by a defined enzyme (DepB) of a known family (AKR), whose structure, cofactor dependence, and sensitivity to reaction conditions are established. However, Carere et al. does not explicitly describe polypeptides defined by sequence identity to instant SEQ ID NOs: 1-14.
A0A085FJY9 discloses a polypeptide annotated as a putative oxidoreductase/aldo-keto reductase from Devosia sp. LC5, having 100% sequence identity to instant SEQ ID NO: 2 and 93.5% sequence identity to SEQ ID NO: 3 (see sequence alignments below). Many of the disclosed species taught are similar to that taught by Carere et al.
Hassan et al. demonstrates that multiple Devosia species are capable of reducing 3-keto-DON to 3-epi-DON, confirming that the reductions step identified by Carere et al. is not unique to D. mutans but occurs across the genus. Accordingly, a person of ordinary skill in the art would have reasonably expected predictable results. Furthermore, Hassan et al. confirms that the reaction environment effects product formation by demonstrating variable DON transformation in D. mutans depending on growth media composition (Fig. 4).
With respect to the limitation “wherein 3-epi-DON is produced in an amount great than DON at a ratio of at least 25:1 or greater, the claimed ratio represents a degree of conversion of a known reaction, rather than a qualitatively different reaction or enzyme function. As taught by Carere et al., DepB-mediated reduction is influenced by reaction parameters such as pH (Fig. 3), temperature (Fig. 6), and cofactor availability (Fig. 4), demonstrating that the extent of conversion and product formation are condition-dependent. Hassan et al. further demonstrates that different Devosia enzyme systems performing the same reduction reaction yield different relative proportions of 3-epi-DON and DON under identical conditions (“Transformations of DON and 3-keto-DON by different Devosia species”, pg. 9 and Fig. 6), and that even when the same Devosia system (e.g. D. mutans) is employed, relative proportions of product vary depending on media composition (Fig. 4). Therefore, optimization of such result-effective variables to increase the proportion of 3-epi-DON relative to DON constitutes routine experimentation that would have been obvious to a person of ordinary skill in the art.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, the teachings of Carere et al., that DepB is an NADPH-dependent dehydrogenase belonging to the AKR family with conserved motifs and disclosure of DepB homologs among 19 different Devosia strains, and the teachings of Hassan et al., confirming that at least 6 different Devosia strains are capable of transforming DON to 3-epi-DON, would have led said practitioner to substitute/incorporate a known AKR from one of the disclosed Devosia species into the reaction of Carere et al. Given that Hassan et al. demonstrate a successful method of transforming DON to 3-epi-DON in 6 different Devosia species and given the comparative genomic analysis of 19 different Devosia species showing that coding sequences in the DepB genomic region are largely conserved across all species , said practitioner would have been motivated to substitute DepB with a known AKR from one of the 19 identified species, such as A0A085FJY9, an AKR from Devosia sp. LC5(having 100% seq id to SEQ 4/3) , and expect predictable results. A person of ordinary skill in the art would further be motivated to optimize reaction conditions, according to Carere et al., including optimizing temperature, pH and cofactor availability, as well as media composition, as taught by Hassan et al., in order to achieve greater transformation of DON to 3-epi-DON. There is a reasonable expectation of success because Carere et al. teaches that the coding sequence in DepB is largely conserved in Devosia sp. LC5 and establishes that DepB-mediated reduction is sensitive to reaction parameters, while Hassan et al. demonstrates that DON transformation occurs across the genus and establishes system-dependent variability. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 21, the polypeptide disclosed in A0A085FJY9 comprises a sequence of VHEWDGMTP, beginning at amino acid position 125, wherein, according to claim 21, X1 is not M; X2 is not A; X3 is not A; and X4 is not V.
Regarding claim 22, the polypeptide disclosed in A0A085FJY9 comprises a sequence of SPLAGGLLSG, beginning at amino acid position 211, wherein, according to claim 22, X5 is A, V, L, G or I; X6 is L, I, V, M, A, Y, F, Norleucin, or W; and X7 is S or T.
Regarding claim 23, the polypeptide disclosed in A0A085FJY9 comprises a sequence of SPLAGGLLSG, beginning at amino acid position 211, wherein, according to claim 23, X5 is A; X6 is L; and X7 is S.
Regarding claim 24, the polypeptide disclosed in A0A085FJY9 comprises a sequence of LGRSGLKVSS, beginning at amino acid position 6, wherein, according to claim 24, X8 is G, R, K, Q, N, A, V, L, I, S, T, E, or D; X9 is not M or G; X10 is not E; X11 is not S; X12is not Y; X13 is not G or A; X14 is not P; X15 is R, K, Q, N, P, A, Y, W, F, T, S, or H; and X16 is not N.
Regarding claim 25, the polypeptide disclosed in A0A085FJY9 comprises a sequence having several amino acid substitutions, compared to instant SEQ ID NO: 3, such as R12K.
Regarding claim 28, Carere et al. teaches a process for investigating 6 potential candidates responsible for the transformation of 3-keto-DON to 3-epi DON, wherein “the genes were then codon optimized for synthesis in E. coli, synthesized and cloned into pET28A by Genscript” and “were inserted to pET28a using NdeI and BamHI restriction sites to produce proteins with N-terminal polyhistidine tags. Each construct was transformed separately into E. coli BL21; a single colony was selected for protein expression”. Carere et al. further teaches “E. coli BL21 containing each synthesized construct (see above) was propagated at 37°C in 500 ml of LB medium supplemented with 34 mg l-1 kanamycin while shaking at 175 rpm. When the cultures reached an optical density of approximately 0.7, 150 μM of isopropyl β-d-1-thiogalactopyranoside (IPTG) was added to initiate protein expression. The cultures were incubated overnight at 18°C and harvested by centrifugation at 8,000 × g for 10 min and frozen at -20°C. Each pellet was thawed and resuspended in 5 ml of 50 mM Tris, pH 8.0, 150 mM NaCl. The cells were then lysed by sonication…”. Samples were tested for enzymatic activity, identified and purified (pg. 3, “Expression and Purification of Recombinant Proteins”).
Therefore, it would be obvious for a person of ordinary skill in the art to employ/apply techniques for recombinant protein expression that are well known in the art, and expressly taught by Carere et al., to evaluate a DepB like aldo-keto reductase from another Devosia species, such as the polypeptide disclosed in A0A085FJY9, and expect predictable results. Given Carere et al.’s demonstration that multiple candidates can be cloned, expressed, purified and tested using routine methods, there is a reasonable expectation of success when substituting A0A085FJY9 into the same experimental framework of Carere et al. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 30 and 39-40, as indicated above, the polypeptide disclosed in A0A085FJY9 has 100% sequence identity to instant SEQ ID NO: 2 and 93.5% sequence identity to instant SEQ ID NO: 3, which is at least 91% sequence identity as recited in claim 30, at least 93% sequence identity as recited in claim 39, and at least 95% sequence identity (to SEQ ID NO: 2) as recited in claim 40.
Regarding claims 35-36, while neither Hassan et al. nor Carere et al. explicitly disclose values for the specific activity of the enzymes responsible for the reduction of 3-keto-DON to 3-epi-DON, the combined teachings of Hassan et al. and Carere et al., in particular the pH and temperature dependent results disclosed by Carere et al., suggest that reaction conditions play a significant role in determining the specific activity of the enzyme. The specific activities claimed are clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal pH and/temperature and/or other reaction conditions needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to modify any one or more reaction condition(s), such as those taught in Carere et al., for increasing or decreasing the specific activity of the enzyme responsible for the reduction of 3-keto-DON to 3-epi-DON in the results observed in any of the Devosia species that demonstrated the ability to complete the conversion of 3-keto-DON to 3-epi-DON, including Devosia sp. LC5, to achieve higher activity and the production of a greater ration of 3-epi-DON to DON, with a reasonable expectation of success. (see MPEP 2144.05 II., “Routine Optimization”).
Regarding claim 37, as described above, Carere et al. demonstrates the activity of DepB on 3-keto-DON under various reaction conditions, including various pH and temperatures. For example, when investigating the pH dependency of DepB, reactions contained 50 mM of three component buffer at various pH-values (pH 4-10), 100µg ml−1 3-keto-DON, 400µM NADPH, and 4.7µg DepB (see Fig. 3). Likewise, the effect of heat treatment and temperature on the activity of DepB was investigated at various temperatures. For example, when investigating the effect of heat treatment, each reaction contained 100µg ml−1 3-keto-DON, 400µM NADPH, 5µg DepB in 50 mM of Tris pH 7.5, wherein relative activity was recorded between 4°C and 60°C (see Fig. 5).
Thus, claims 14, 20-25, 28, 30, and 35-40 are rejected under 35 U.S.C. 103 as being unpatentable over Carere et al., Hassan et al. and A0A085FJY9.
Claims 19 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Carere et al., Hassan et al., and A0A085FJY9 as applied to claim 14 above, and further in view of Ito et al. (A novel actinomycete derived from wheat heads degrades deoxynivalenol in the grain of wheat and barley affected by Fusarium head blight. 2012, Appl Microbiol Biotechnol 96, pg. 1059–1070, cited in a previous office action).
The combined teachings of Carere et al., Hassan et al. and A0A085FJY9 as they apply to claim 14, have already been discussed above. Briefly, Carere et al. and Hassan et al. teaches that the epimerization of the mycotoxin DON to non-toxic 3-epi-DON occurs in two steps, using two separate enzymes, with 3-keto-DON as an intermediate. Hassan et al. further demonstrates that multiple different Devosia species successfully convert 3-keto DON to 3-epi DON. Carere et al. specifically identifies DepB from D. mutans as an NADPH dependent aldo-keto reductase responsible for the reduction of 3-keto-DON to 3-epi-DON, and further teaches that DepB homologs are conserved across multiple Devosia species. A0A085FJY9 discloses a DepB-like aldo-keto reductase from Devosia sp. LC5, one of the species also taught by Carere et al. Neither Hassan, Carere or A0A085FJY9 teach wherein the polypeptide or enzyme responsible for the conversion from 3-keto DON to 3-epi DON (i.e., the reductase) are added to an agrarian composition with a carrier, wherein said agrarian composition comprises a plant or plant parts and the trichothecene comprising the 3-oxo group (e.g., 3- keto DON).
Ito et al. teaches a DON-utilizing actinomycete, Marmoricola sp. strain MIM116, from wheat heads through a novel isolation procedure including an in situ plant enrichment step, wherein the strain had background degradation activity, and the activity was enhanced twofold by the consumption of DON. Ito et al. further teaches the utilization of “Tween 80 as a spreading agent of strain MIM116 because it promoted DON degradation and the growth of strain MIM116 in the presence of DON”. Ito et al. reports “the inoculation of MIM116 cell suspension plus 0.01% Tween 80 into 1,000 harvested kernels of wheat and barley resulted in a DON decrease from approximately 3 mg kg−1 to less than 1 mg kg−1 of dry kernels” (Abstract).
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, given the teachings of Ito et al. above, and given that DON epimerization is a 2 step process, as taught by Carere et al. and Hassan et al., with 3-keto DON being an intermediate that requires a separate enzyme, such as the one disclosed in A0A085FJY9, for the conversion to the non-toxic trichothecene 3-epi DON, it would be obvious for a person of ordinary skill in the art to use a liquid such as Tween 80 as a spreading agent, or carrier, for the polypeptide disclosed in A0A085FJY9, an aldo-keto reductase that is capable of converting 3-keto Don to 3-epi-DON, in view of Carere et al.’s teachings. Said practitioner would be motivated to do so for the benefit of being able to facilitate the inoculation and treatment of infected crops commonly affected by the mycotoxin DON. There is a reasonable expectation of success because Ito et al. demonstrates the successful inoculation of harvested infected kernels of wheat and barley, using Tween 80 as a spreading agent for a DON degrading bacteria, and demonstrates the successful widespread degradation of DON as a result. Therefore, said practitioner would have readily predicted that the combination of teachings would successfully result in a method of converting a trichothecene comprising a 3-oxo group into a trichothecene comprising a 3-hydroxy group, by contacting a polypeptide according to claim 14 with a carrier to an agrarian composition comprising the trichothecene with the 3-oxo group. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Thus, claims 19 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Carere et al., Hassan et al., and A0A085FJY9 as applied to claim 14 above, and further in view of Ito et al.
Sequence alignment between A0A085FJY9 and instant SEQ ID NO: 2
A0A085FJY9_9HYPH
ID A0A085FJY9_9HYPH Unreviewed; 353 AA.
AC A0A085FJY9;
DT 29-OCT-2014, integrated into UniProtKB/TrEMBL.
DT 29-OCT-2014, sequence version 1.
DT 24-JAN-2024, entry version 26.
DE SubName: Full=Putative oxidoreductase, aldo/keto reductase family {ECO:0000313|EMBL:KFC71784.1};
DE EC=1.1.1.- {ECO:0000313|EMBL:KFC71784.1};
GN ORFNames=FF80_00401 {ECO:0000313|EMBL:KFC71784.1};
OS Devosia sp. LC5.
OC Bacteria; Pseudomonadota; Alphaproteobacteria; Hyphomicrobiales;
OC Devosiaceae; Devosia.
OX NCBI_TaxID=1502724 {ECO:0000313|EMBL:KFC71784.1, ECO:0000313|Proteomes:UP000028638};
RN [1] {ECO:0000313|EMBL:KFC71784.1, ECO:0000313|Proteomes:UP000028638}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LC5 {ECO:0000313|EMBL:KFC71784.1,
RC ECO:0000313|Proteomes:UP000028638};
RA Gan H.M., Gan H.Y., Barton H.A., Savka M.A.;
RT "Genome sequence of acyl-homoserine lactone-producing cave bacterial
RT isolate.";
RL Submitted (JUN-2014) to the EMBL/GenBank/DDBJ databases.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:KFC71784.1}.
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DR EMBL; JNNO01000002; KFC71784.1; -; Genomic_DNA.
DR RefSeq; WP_035097162.1; NZ_JNNO01000002.1.
DR AlphaFoldDB; A0A085FJY9; -.
DR STRING; 1502724.FF80_00401; -.
DR PATRIC; fig|1502724.3.peg.400; -.
DR eggNOG; COG0667; Bacteria.
DR OrthoDB; 8394608at2; -.
DR Proteomes; UP000028638; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR CDD; cd19091; AKR_PsAKR; 1.
DR Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR PANTHER; PTHR43364:SF4; NAD(P)-LINKED OXIDOREDUCTASE SUPERFAMILY PROTEIN; 1.
DR PANTHER; PTHR43364; NADH-SPECIFIC METHYLGLYOXAL REDUCTASE-RELATED; 1.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1.
PE 4: Predicted;
KW Oxidoreductase {ECO:0000313|EMBL:KFC71784.1};
KW Reference proteome {ECO:0000313|Proteomes:UP000028638}.
FT DOMAIN 16..315
FT /note="NADP-dependent oxidoreductase"
FT /evidence="ECO:0000259|Pfam:PF00248"
SQ SEQUENCE 353 AA; 38815 MW; EDE50A8F3F6A0480 CRC64;
Query Match 100.0%; Score 1836; Length 353;
Best Local Similarity 100.0%;
Matches 353; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDYRYLGRSGLKVSSLTMGTMTFGGSEKVGHTPQAEATRQIDLCLDHGINLLDTANVYNA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDYRYLGRSGLKVSSLTMGTMTFGGSEKVGHTPQAEATRQIDLCLDHGINLLDTANVYNA 60
Qy 61 GVSEEMIGVALAENGRRQKALVATKVRFRMGDGPNEVGLSRHHIVAQAEASLKRLKTDVI 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GVSEEMIGVALAENGRRQKALVATKVRFRMGDGPNEVGLSRHHIVAQAEASLKRLKTDVI 120
Qy 121 DLYQVHEWDGMTPIEETMEALDTLVRQGKVRYIGCSNYSGWHIMKALAAADKNHGQRFIS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DLYQVHEWDGMTPIEETMEALDTLVRQGKVRYIGCSNYSGWHIMKALAAADKNHGQRFIS 180
Qy 181 QQIHYTLHSREAEYELVPISQDQGLGILIWSPLAGGLLSGKYRRDGGPESGRHVGGSREP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QQIHYTLHSREAEYELVPISQDQGLGILIWSPLAGGLLSGKYRRDGGPESGRHVGGSREP 240
Qy 241 PVPDWGKLYDIVEVIVAIA EARGVSGAQVALAWALGRPGVTSVIIGGRSEAQFKDNLAAA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PVPDWGKLYDIVEVIVAIA EARGVSGAQVALAWALGRPGVTSVIIGGRSEAQFKDNLAAA 300
Qy 301 DLKLTPEERQKLDAVSQPPLLYPYWHQSFTAQDRLSRIDLDLIGPYAEEFKRG 353
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DLKLTPEERQKLDAVSQPPLLYPYWHQSFTAQDRLSRIDLDLIGPYAEEFKRG 353
Sequence alignment between A0A085FJY9 and instant SEQ ID NO: 3
A0A085FJY9_9HYPH
ID A0A085FJY9_9HYPH Unreviewed; 353 AA.
AC A0A085FJY9;
DT 29-OCT-2014, integrated into UniProtKB/TrEMBL.
DT 29-OCT-2014, sequence version 1.
DT 24-JAN-2024, entry version 26.
DE SubName: Full=Putative oxidoreductase, aldo/keto reductase family {ECO:0000313|EMBL:KFC71784.1};
DE EC=1.1.1.- {ECO:0000313|EMBL:KFC71784.1};
GN ORFNames=FF80_00401 {ECO:0000313|EMBL:KFC71784.1};
OS Devosia sp. LC5.
OC Bacteria; Pseudomonadota; Alphaproteobacteria; Hyphomicrobiales;
OC Devosiaceae; Devosia.
OX NCBI_TaxID=1502724 {ECO:0000313|EMBL:KFC71784.1, ECO:0000313|Proteomes:UP000028638};
RN [1] {ECO:0000313|EMBL:KFC71784.1, ECO:0000313|Proteomes:UP000028638}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LC5 {ECO:0000313|EMBL:KFC71784.1,
RC ECO:0000313|Proteomes:UP000028638};
RA Gan H.M., Gan H.Y., Barton H.A., Savka M.A.;
RT "Genome sequence of acyl-homoserine lactone-producing cave bacterial
RT isolate.";
RL Submitted (JUN-2014) to the EMBL/GenBank/DDBJ databases.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:KFC71784.1}.
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DR EMBL; JNNO01000002; KFC71784.1; -; Genomic_DNA.
DR RefSeq; WP_035097162.1; NZ_JNNO01000002.1.
DR AlphaFoldDB; A0A085FJY9; -.
DR STRING; 1502724.FF80_00401; -.
DR PATRIC; fig|1502724.3.peg.400; -.
DR eggNOG; COG0667; Bacteria.
DR OrthoDB; 8394608at2; -.
DR Proteomes; UP000028638; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR CDD; cd19091; AKR_PsAKR; 1.
DR Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR PANTHER; PTHR43364:SF4; NAD(P)-LINKED OXIDOREDUCTASE SUPERFAMILY PROTEIN; 1.
DR PANTHER; PTHR43364; NADH-SPECIFIC METHYLGLYOXAL REDUCTASE-RELATED; 1.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1.
PE 4: Predicted;
KW Oxidoreductase {ECO:0000313|EMBL:KFC71784.1};
KW Reference proteome {ECO:0000313|Proteomes:UP000028638}.
FT DOMAIN 16..315
FT /note="NADP-dependent oxidoreductase"
FT /evidence="ECO:0000259|Pfam:PF00248"
SQ SEQUENCE 353 AA; 38815 MW; EDE50A8F3F6A0480 CRC64;
Query Match 94.4%; Score 1736; Length 353;
Best Local Similarity 93.5%;
Matches 330; Conservative 12; Mismatches 11; Indels 0; Gaps 0;
Qy 1 MDYRYLGRSGLRVSTLTMGTMTFGGSEKVGHTPQAEATRQIDLCLDHGINLLDTANVYNA 60
|||||||||||:||:|||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDYRYLGRSGLKVSSLTMGTMTFGGSEKVGHTPQAEATRQIDLCLDHGINLLDTANVYNA 60
Qy 61 GVSEEMIGVALAENGRRQKALIATKVRFRMGDGPNEVGLSRHHIIAQAEASLKRLKTDVI 120
|||||||||||||||||||||:||||||||||||||||||||||:|||||||||||||||
Db 61 GVSEEMIGVALAENGRRQKALVATKVRFRMGDGPNEVGLSRHHIVAQAEASLKRLKTDVI 120
Qy 121 DLYQVHEWDGMTPIEETMEALDTLVKQGKVRYIGCSNYSGWHIMKALAAADKSHGQRFIS 180
|||||||||||||||||||||||||:||||||||||||||||||||||||||:|||||||
Db 121 DLYQVHEWDGMTPIEETMEALDTLVRQGKVRYIGCSNYSGWHIMKALAAADKNHGQRFIS 180
Qy 181 QQIHYTLHSREAEYELVPISQDQGLGILIWSPLAGGLLSGKYRRDGGPESGRHVGGSREP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QQIHYTLHSREAEYELVPISQDQGLGILIWSPLAGGLLSGKYRRDGGPESGRHVGGSREP 240
Qy 241 PVPDWDKLYDIVDVIVAIA EERGVSGAQVALAWALGRPGVTSVIIGGRSEAQFKDNLAAA 300
||||| ||||||:||||||| |||||||||||||||||||||||||||||||||||||||
Db 241 PVPDWGKLYDIVEVIVAIA EARGVSGAQVALAWALGRPGVTSVIIGGRSEAQFKDNLAAA 300
Qy 301 DLKLSDEERQKLDAVSRPPLLYPYWHQTFTANDRLGPADQDLLSTYVEDFKRG 353
||||: ||||||||||:||||||||||:||| ||| | ||: | |:||||
Db 301 DLKLTPEERQKLDAVSQPPLLYPYWHQSFTAQDRLSRIDLDLIGPYAEEFKRG 353
Response to Arguments for Rejections under 35 USC § 103
In the response filed on 11/14/2025, Applicant argues that the prior art of Hassan et al., Carere et al. and A0A0F5LPU3 fails to teach or suggest a polypeptide having at least 90% sequence identity to SEQ ID NOs: 1-14, that the cited art does not disclose production of 3-epi-DON in an amount greater than DON at a ratio of at least 25:1 and that Carere et al. identifies functional activity only in Devosia mutans without demonstrating that enzymes from other Devosia strains would perform the same reaction with high efficiency. Applicant further argues that the cited art does not provide motivation or a reasonable expectation of success to substitute enzymes from other Devosia species, and that variability in product distribution among strain demonstrates unpredictability. Applicant’s arguments have been fully considered and are persuasive with respect to sequence identity, which previously relied upon A0A0F5LPU3 to teach sequence identities having at least 75% sequence identity. Therefore, the prior art rejections based on A0A0F5LPU3 have accordingly been withdrawn.
As set forth in the rejections above, the rejections have been modified to address the recited 90% or greater sequence identity, which is disclosed by A0A085FJY9; to further clarify that the claimed 25:1 ratio represents optimization of a known enzymatic reaction which would have been obvious to a person of ordinary skill in the art through routine optimization of reaction parameters; and to address enzyme identity and strain scope.
Conclusion
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAGHMEH NINA MOAZZAMI whose telephone number is (703)756-4770. The examiner can normally be reached Monday-Friday, 9:00-5:00.
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/NAGHMEH NINA MOAZZAMI/ Examiner, Art Unit 1652
/RICHARD G HUTSON/ Primary Examiner, Art Unit 1652