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
Claim status
Claims 1-10, 12-17 are currently pending. Claim 1 has been amended currently. Claim 11 is canceled. Claims 8-9, 16-17 are withdrawn. Claims 1-7, 10, 12-15 will be examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement (IDS)
The IDS submission is in compliance with the provisions of 37 CFR 1.97.
Election/Restrictions
Applicant’s election with traverse of Group I (claims 1-7, 10, 12-15) in reply filed on April 21, 2026 is acknowledged. Claims 8-9, 16-17 have been withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to nonelected invention, there being no allowance or linking claim.
Applicant’s arguments in reply filed on April 21, 2026 have been considered but are not persuasive.
Applicant argues at pg. 4 that the claimed invention is technically distinct from the combination of the cited references because it does not disclose "an activity of a protein comprising a sequence having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 1 is weakened compared to an intrinsic activity of the microorganism" as set forth in the present claims Applicants arguments are not persuasive because Ma teaches C. glutamicum ATCC 13032 and gene, Cgl2690 (also known as cg2977; cgR_2591; cg2591), which is 98% identical to SEQ ID NO: 2. The SEQ ID NO: 2 encodes a protein that is 97% identical to SEQ ID NO: 1. The gene, cgl2690 has 3 SNP Missense variants and an indel in frame deletion 613_624del Glu205_Pro208del.
It is noted that the SEQ ID NO: 1 lacks the N-terminus sequence of 17 amino acid residues present in the protein encoded by gene, cgl2690 of Ma. Thus, the SEQ ID NO: 2 lacks 51 nucleotides (which corresponds to 17 amino acid residues) present in the gene cgl2690 of Ma. The SEQ ID NO: 2 is within the sequence of gene, cgl2690 of Ma. See Figure below.
Further, both claim 1 and the specification explicitly teach that “a microorganism, in which an activity of a protein comprising a sequence having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 1 is weakened compared to an intrinsic activity of the microorganism”. See page 1, paragraph [6]. The specification also teaches that “It is apparent that a protein having an amino acid sequence in which some sequences are deleted, modified, substituted, conservatively substituted or added is also included within the scope of the present disclosure as long as the amino acid sequence has such homology or identity and exhibits efficacy corresponding to the protein including the amino acid sequence of SEQ ID NO: 1”. See page 3, paragraph [16].
Since Ma teaches cgl2690 gene, which encodes a protein comprising a sequence having 97% (at least 85% identical) sequence identity to SEQ ID NO:1, the protein encoded by the cgl2690 gene of Ma is weakened compared to an intrinsic activity of the microorganism.
Therefore, there is no special technical features and the restriction is maintained. Claims 1-7, 10, 12-15 will be examined on the merits in this office action.
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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 1-4, 7, 10, 12-13, 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ma (Published 2018; hereafter Ma; PTO-892).
As claim 1, 1-5, 7, 10, 12-13, 15, Ma teaches a comparative genomic analysis was performed to explore the core genome, structural variations, and gene mutations referring to an industrial L-leucine-producing strain, C. glutamicum CP, and the widely used C. glutamicum ATCC 13032”. See abstract.
Ma also teaches comparative genomic analyses, SNP and Indel identification between L-Valine-producing strain and C. glutamicum ATCC 13032, mutation, genomic position, gene, influence, N.T. change and A.A change.
Ma teaches C. glutamicum ATCC 13032, and the gene, Cgl2690 (also known as cg2977; cgR_2591; cg2591). Ma teaches that gene Cgl2690 has 3 SNP Missense variants; Genome position 2863711, T (13032 strain) to C (C. glutamicum XV strain); 712 A>G (N.T); Thr238Ala (A. A); Genomic position 2863803, A (13032 strain) to T (C. glutamicum XV strain); 260 T>A (N.T); Val207Glu (A.A); Genome position 2863833; A (13032 strain) to G (C. glutamicum XV strain); 590 T>C (N.T); Met197Thr (A.A). Also, Cgl2690 has an indel in frame deletion: 613_624del Glu205_Pro208del; See Supplementary table 8.
*SEQ ID NO: 2 encodes SEQ ID NO: 1.
It is noted that the Cgl2690 (also known as Ncgl2977, cgR_2591; cg2977) gene in C. glutamicum strain R encodes a 2,5-diketo-D-gluconic acid reductase (dkgA), which is 97% identical to SEQ ID NO:1. The SEQ ID NO: 2 encodes the SEQ ID NO: 1. See Figures below. The protein encoded by cgl2690 comprises the SEQ ID NO: 1. See Figure below.
The C. glutamicum ATCC 13032 of Ma has a polynucleotide sequence (Cgl2690) 98% identical to SEQ ID NO: 2. See figure below. Also, SEQ ID NO: 2 is 100% identical to polynucleotide sequences present in the genome of C. glutamicum strain XV (accession CP018175.1), which is a L-leucine-producing strain and C. glutamicum strain CP (accession CP012194.1), which is a L-Valine strain taught by Ma. See Figure below.
In addition, a 100% sequence homology was also found in the genome of C. glutamicum strain TCCC11822 (CP 020033.1), which is a high producer L-glutamate industrial strain.
See Figure below.
Regarding the limitation in claim 1, "compared to an intrinsic activity of the microorganism”, the reference teaches all structural features from the claim, so it is presumed to be capable of the claimed intended use. Because the C. glutamicum ATCC 13032 of Ma has a protein with 85% identity (97% total) to SEQ ID NO: 1, the protein activity is necessarily weakened when compared to the intrinsic activity of the microorganism, C. glutamicum strain XV, C. glutamicum strain CP of Ma. Also, a 100% sequence homology was also found in the genome of C. glutamicum strain TCCC11822 (CP 020033.1), which is a L-glutamate high producer industrial strain. See MPEP 2112.01: "Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433." See also MPEP 2111.02: "To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997)".
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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.
Claims 6, 14 is rejected under 35 U.S.C. 103 as being unpatentable over Ma (Published 2018; hereafter Ma; PTO-892) as applied to claims 1-5, 7, 10, 12-13, 15 above, in view of Pompejus et al. (US Pat. 6962989; hereafter Pompejus; PTO-892) as evidenced by Light et al. (EP0305608-A1; hereafter Light; PTO-892).
Ma teaches the limitations of claims 1-5, 7, 10, 12-13, 15 as fully discussed above and incorporated herein.
However, Ma does not explicitly teach an expression control sequence for a gene encoding the protein is not an intrinsic sequence of the microorganism as claims 6, 14.
Pompejus teaches Corynebacterium glutamicum genes encoding novel proteins and *SEQ ID NO: 2282, which is pertinent to claims 6, 14. See for example, Column 1; see also column 77-78; Table 1 for *SEQ ID NO: 2282.
*SEQ ID NO: 2282 is 97.6% identical to SEQ ID NO: 1. See figure below.
Pompejus teaches novel bacterial nucleic acid molecules which have a variety of uses. These uses include the identification of microorganisms which can be used to produce fine chemicals (MCP), the modulation of fine chemical production in C. glutamicum or related bacteria, the typing or identification of C. glutamicum or related bacteria, as reference points for mapping the C. glutamicum genome, and as markers for transformation, which is pertinent to claims 6, 14. See for example, column 1; lines 24-44.
Pompejus teaches recombinant microorganisms can be produced which contain selected systems which allow for regulated expression of the introduced gene. For example, inclusion of an MCP gene on a vector placing it under control of the lac operon permits expression of the MCP gene in the presence of IPTG. Such regulatory systems are well known in the art, which is pertinent to claims 6, 14. See for example, column 27; lines 63-67; column 28; lines 1-2.
Pompejus teaches that to achieve sufficient intracellular concentrations of the anti-sense molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong prokaryotic, viral, or eukaryotic promoter, which is pertinent to claims 6, 14. See for example, column 23; lines 31-67.
Pompejus teaches “an endogenous MCP gene in a host cell is disrupted (e.g., by homologous recombination or other genetic means known in the art) such that expression of its protein product does not occur. An endogenous or introduced MCP gene in a host cell has been altered by one or more-point mutations, deletions, or inversions, but still encodes a functional MCP protein. One or more of the regulatory regions (e.g., a promoter, repressor, or inducer) of an MCP gene in a microorganism has been altered (e.g., by deletion, truncation, inversion, or point mutation) such that the expression of the MCP gene is modulated. One of ordinary skill in the art will appreciate that host cells containing more than one of the described MCP gene and protein modifications may be readily produced using the methods of the invention, and are meant to be included in the present invention”, which is pertinent to claims 6, 14.
Pompejus teaches Glutamate is most commonly used as a flavor additive (mono-Sodium glutamate, MSG) and Glutamate is synthesized by the reductive amination of α-ketoglutarate, an intermediate in the citric acid cycle, which is pertinent to claims 6, 14. See for examples, column 7; lines 53-67; column 8; lines 14-16.
The cgl2690 (also known as Ncgl2977, cgR_2591; cg2977) gene in C. glutamicum strain R encodes a 2,5-diketo-D-gluconic acid reductase (dkgA), which is 97% identical to SEQ ID NO:1. The SEQ ID NO: 2 encodes the SEQ ID NO: 1, which is pertinent to claims 6, 14. See Figures below.
Light teaches a protein having 2,5-diketogluconic acid (2,5-DKG) reductase activity is produced by recombinant host cells. This can be used to convert 2,5-DKG stereoselectively into 2-keto-L-gluonic acid (2-KLG) which is a useful intermediate in the production of ascorbic acid (vitamin C), which is pertinent to claim 6, 14. See for example, page 2; lines 4-8.
Light teaches Corynebacterium, genetic sequence encoding such enzymes, modifications of the sequence which do not interfere with, and may, in fact, improve the performance of this enzyme are also available to those knowledgeable in the art. Such modifications and altered sequences are included in the definition of 2,5-DKG reductase as used in this specification. In short, the term 2,5-DKG reductase has a functional definition and refers to any enzyme which catalyzes the conversion of 2,5-DKG to 2-KLG”, which is pertinent to claims 6, 14. See for example, page 4, lines 38-50.
Light teaches conversion of 2,5-DKG into 20KLG, and that the reaction is a reduction, a source of reducing equivalents is required; the enzyme is specific for NADPH, and this at least a catalytic amount of the coenzyme must be present and the reduced form constantly regenerated during the process. Sources of electrons for the reduction of the coenzyme may be provided by any reduced substrate in contact with an enzyme for its oxidation, such as, glucose/glucose dehydrogenase; formate/formate dehydrogenase; or glutamate/glutamate dehydrogenase, which is pertinent to claims 6, 14. See for example, page 6; lines 20-30.
Light teaches the solution in a typical conversion will contain an approximately equimolar amount of glucose, formate, glutamate or dissolved hydrogen to the 2,5-DKG concentration and the solid support will contain sufficient reducing catalyst to recycle continuously the NADP formed by the desired conversion to 2-KLG, which is pertinent to claims 6, 14. See for example, page 6; lines 44-49.
Light teaches cloning and expression of 2,5-DKG reductase, which is pertinent to claims 6, 14. See for example, page 6; line 52.
Light teaches “Further, access to the genetic machinery to produce such an enzyme is of convenience making improvements in carrying out this process since this machinery may be manipulated and localized to achieve production of the enzyme at a site most convenient for the conversion of 2,5-DKG. Most important among such loci is a site within the same organism which is capable or effecting the production of 2,5-DRK. Thus, a single organism would be able to use its own machinery to manufacture the 2,5-DKG, and then convert this endogenous 2,5-DKG in situ into the desired product, using the 2,5-DKG reductase gene and appropriate control sequences to produce the catalyst”, which is pertinent to claims 6, 14. See for example, page 2; lines 30-40.
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It would have been obvious to one of ordinary skill in the art to modify the teachings of Ma and Pompejus to have an expression control sequence that is not intrinsic of Corynebacterium for a gene encoding a recombinant protein of SEQ ID NO: 1 (or its variants), which is a 2,5-diketo-D-gluconic acid reductase (2,5 DKG) in a L-glutamate producer strain of Corynebacterium glutamicum. Since 2,5-DKG is specific for NADPH, which is a valuable and high-cost cofactor used for production of L-glutamate and its recycling method utilizes L-glutamate as sacrificial substrate for glutamate dehydrogenases, It would be obvious to use an enzymatic method for recycling of NADPH by altering expression and/or activity of 2,5-DKG in a L-glutamate producer strain, such as Corynebacterium as evidenced by Light, thereby arriving at the invention of claims 6, 14. It would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Also, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, the prior art teaches a product that only differs from the claimed invention by the substitution of a single component (i.e. heterologous or synthetic regulatory sequences for protein expression); the substituted elements (i.e. homologous/intrinsic regulatory sequences) were already known and known to function in an industrial L-glutamate producer, Corynebacterium glutamicum strain , therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of recognize genes sequences from the genome of Corynebacterium strains disclosed as being useful for L-glutamic acid production with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results), particularly because Ma and Pompejus teaches that C. glutamicum strains comprise the SEQ ID NO: 1, 2 or its variants, and Pompejus specially teaches the benefits of making alterations in SEQ ID NO: 1, 2, including modifications on its expression levels for production of valuable chemicals, such as L-glutamic acid in C. glutamicum producer strain used by industry, it would be obvious and beneficial to fine-tuning the expression levels of SEQ ID NO: 2, and/or incorporate the mutations found in homologous/heterologous sequence genes already described in the art to improve the enzyme activity of a 2,5-diketo-D-gluconic acid reductase (2,5 DKG) for the recycling of NADPH, and avoid the use of the high-cost valuable substrate, L-glutamate as evidenced by Light. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRICILA HAUK TEODORO whose telephone number is (571)272-2784. The examiner can normally be reached M-F 6:15AM-3:00PM.
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/PRICILA NMN HAUK TEODORO/Examiner, Art Unit 1645
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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