DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 5-20 are pending in the instant application. Claims 14-20 have been withdrawn from further consideration as being drawn to a nonelected invention.
Claims 5-13 and SEQ ID NO:21 are under consideration in this Office Action.
The previous rejections of the claims under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph; 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph; have been withdrawn in view of the claim amendment and arguments filed 01/22/2026.
In view of the claim amendment and arguments filed 01/22/2026 the previous rejection of the claims under 35 U.S.C. 103 has been withdrawn in favor of the instant rejection of the claims under 35 U.S.C. 103.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd Paragraph
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 6-13 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 pre-AIA the applicant regards as the invention.
Claim 6 recites the phrase “modified glutamate dehydrogenase (GluDH) comprising substitutions at positions 173, 175 and 182 as compared to the initial GluDH thereof, wherein the initial GluDH has a sequence identity of at least 90% to SEQ ID NO:1 or SEQ ID NO:2” which renders the claim vague and indefinite since it is unclear if the modified glutamate dehydrogenase comprises the amino acid sequence of SEQ ID NO: 1 and has the recited amino acid substitutions. The specific amino acid sequence, structure, and SEQ ID NO is not known and not recited in the claims. Dependent claims 2-13 are also rejected because they do not correct the defect. For examination purposes the claims will not be limited to a specific SEQ ID NO amino acid sequence since the specific amino acid sequence, structure, and SEQ ID NO is not known and not recited in the claims.
Amending the claims to recite that the modified glutamate dehydrogenase comprises the amino acid sequence of SEQ ID NO: 1 and amino acid substitutions at positions 173, 175, 182; and the modified glutamate dehydrogenase has an increased activity for catalyzing the reaction of PPO and an amino donor to generate L-glufosinate as compared to wild type glutamate dehydrogenase would aid in overcoming the rejection.
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 of this title, 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 5-13 are rejected under 35 U.S.C. 103 as being unpatentable over Accession B1HV12 (29-APR-2008; reference of record) in view of US20200102546 (04/02/2020; PTO 892), Yin et al. ("Rational Molecular Engineering of Glutamate Dehydrogenases for Enhancing Asymmetric Reductive Amination of Bulky a-Keto Acids" Adv. Synth. Catal., Vol. 361. 28 December 2018 (2018-12-28). pp. 803-812; IDS filed 01/09/2023), Bornscheuer et al. (Curr Protoc Protein Sci. 2011 Nov;Chapter 26:Unit26.7; PTO 892), Yoshikuni et al. (Curr Opin Chem Biol. 2007 Apr;11(2):233-9; PTO 892)
The arguments filed 01/22/2026 have been considered but are not persuasive. According to MPEP 2111 claims must be given their broadest reasonable interpretation in light of the specification. The claims are broad, widely varying, and encompass any modified GluDH that is not limited to a specific amino acid sequence, amino acid structure, and any SEQ ID NO for reasons stated above.
Accession B1HV12 teaches the Lysinibacillus sphaericus glutamate dehydrogenase comprising an amino acid sequence that is 100% identical to SEQ ID NO: 2 (see attached record). The teachings of the reference differ from the claims in that the reference does not teach the claimed modified glutamate dehydrogenase
US20200102546 teaches a glutamate dehydrogenase (GluDH) mutants and their application in preparation of L-phosphinothricin where the glutamate dehydrogenase derived from Lysinibacillus which has amino acid sequences as shown in SEQ ID NOs: 7-8 and has an Al75G or V386A mutation compared with the original glutamate dehydrogenase. US20200102546 teaches by means of molecular engineering, mutating the specific alanine in glutamate dehydrogenase substrate-binding pocket into glycine and/or mutating the specific valine in glutamate dehydrogenase substrate-binding pocket into alanine, the present invention has obtained NADPH-specific glutamate dehydrogenase mutants with high enzyme activity in catalyzing the substrate 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid or its salt for L-phosphinothricin preparation or NADH-specific glutamate dehydrogenase mutants with catalytic activity toward PPO; this has significantly improved substrate conversion, increased the product concentration of the L-phosphinothricin preparation process. US20200102546 teaches a method for preparing L-phosphinothricin by means of using a genetically engineered strain expressing the GluDH mutant to catalyze PPO or a salt thereof. See entire publication and claims especially paragraphs [0009] - [0038], SEQ ID NOs: 7-8, Table 4, and claims 1-10.
Yin et al. ("Rational Molecular Engineering of Glutamate Dehydrogenases for Enhancing Asymmetric Reductive Amination of Bulky a-Keto Acids" Adv. Synth. Catal., Vol. 361. 28 December 2018 (2018-12-28). pp. 803-812; IDS filed 01/09/2023) teach a glutamate dehydrogenase (GluDH) mutant, which has an Al 75G or V386A mutation compared with the original GluDH derived from Lysinibacillus. Yin et al. teach the mutant shows a polycrystalline structure formed by means of compounding the reported GluDH derived from Corynebacterium glutamicum with NADP+ and a-KG. Yin et al. teach that by means of rationally designing the GluDH derived from Pseudomonas putida (NCBI accession no.: NP 742836.1) by homology modeling and conducting a site directed mutation on amino acids Lys93, Ala167, Thr196, Arg208, Vla378 and Ser381 at the substrate binding pocket of the GluDH, a class of NADPH- or NADH-dependent GluDH mutants with high enzyme activity in catalyzing the substrate 2-oxo-4-(hydroxymethylphosphinoyl) butyric acid (PPO) or a salt thereof for L-phosphinothricin preparation are obtained by means of screening, so that the enzymatic activity, the catalytic activity to PPO, the substrate conversion rate and the concentration of the product L-phosphinothricin are significantly improved and the ee value is greater than 99%. Yin et al. further teach a method for preparing L-phosphinothricin by means of using a genetically engineered strain expressing the GluDH mutant to catalyze PPO or a salt thereof. The mutation method is also applicable to constructing mutants in other PPOs (see abstract, page 804, right-hand column, paragraph 2 to page 806, left-hand column, paragraph 1, page 809, right-hand column, paragraph 2 to page 810, right-hand column, paragraph 1, Tables 1-4, and Figure S13).
Bornscheuer et al. teach protein engineering strategies to improve or change the properties of proteins, teach concepts for protein engineering using rational design including substitution and/or deletion of amino acids, directed evolution, and combinations of them where different strategies are presented for identifying the best mutagenesis method, how to identify desired variants by screening or selection, and examples for successful applications are shown which enable researchers to choose the most promising tools to solve their protein engineering challenges (see entire publication especially pages 26.7.1- 26.7.10 and Tables 26.7.1, 26.7.2, and 26.7.3).
Yoshikuni et al. teach protein engineering methodology to redesign enzyme function which was developed on the basis of the theories of divergent molecular evolution: (i) enzymes with more active and specialized functions have evolved from ones with promiscuous functions; (ii) this process is driven by small numbers of amino acid substitutions (plasticity); and (iii) the effects of double or multiple mutations are often additive (quasi-additive assumption). Yoshikuni et al. teach the impact of multiple mutations can be calculated by first determining the effects of a mutation at a single position and subsequently summing these effects using the quasi-additive assumption where the shape of the fitness landscape of a particular enzyme function can be estimated, and the combinations of mutations predicted to yield global optima for desired functions can then be selected and introduced into the enzymes. Yoshikuni et al. teach that the methodology has been demonstrated to be very powerful to redesign enzyme function. See entire publication and abstract especially pages 234-7 and Fig. 2.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by using the protein engineering strategies of US20200102546, Yin et al., Bornscheuer et al., Yoshikuni et al. on the glutamate dehydrogenase of Accession B1HV12 to make the claimed modified glutamate dehydrogenase recited in the claims. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a modified glutamate dehydrogenase that can be used to produce products including L-glufosinate or can be used for further studies to search, screen, and isolate modified glutamate dehydrogenase having improved properties compared to the wild-type glutamate dehydrogenase including increased activity. One of ordinary skill in the art before the effective filing date of the claimed invention would have a reasonable expectation of success in view of the reference teachings showing modification of glutamate dehydrogenase. Hence, the claimed invention as a whole is prima facie obvious.
Amending the claim 5 to recite that the modified glutamate dehydrogenase comprises the amino acid sequence of SEQ ID NO: 21 and has an increased activity for catalyzing the reaction of PPO and an amino donor to generate L-glufosinate as compared to wild type glutamatewould aid in overcoming the rejection. Further, amending the claims 6-13 to recite that the modified glutamate dehydrogenase comprises the amino acid sequence of SEQ ID NO: 1 and amino acid substitutions at positions 173, 175, 182; and the modified glutamate dehydrogenase has an increased activity for catalyzing the reaction of PPO and an amino donor to generate L-glufosinate as compared to wild type glutamate dehydrogenase would aid in overcoming the rejection.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 5-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of Serial No. 18725181. Applicant’s request filed 01/22/2026 to table the rejection has been considered. However, until terminal disclaimer is filed the claims are rejected for reasons stated below.
Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. The claims and/or specification of the copending application teach the claimed modified glutamate dehydrogenase (GluDH) comprising the amino acid sequence of SEQ ID NO: 21; and the claimed modified GluDH comprising the recited substitutions at the recited positions. Thus, the teachings anticipate the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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 extension fee 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 date of this final action.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652