DETAILED ACTION
All objections and rejections stated in prior Office Actions are withdrawn unless restated below.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/18/2025 has been entered.
Claim Interpretation
“Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification - the greatest clarity is obtained when the specification serves as a glossary for the claim terms.” MPEP 2111.01.
“The only exceptions to giving the words in a claim their ordinary and customary meaning in the art are (1) when the applicant acts as their own lexicographer; and (2) when the applicant disavows or disclaims the full scope of a claim term in the specification. To act as their own lexicographer, the applicant must clearly set forth a special definition of a claim term in the specification that differs from the plain and ordinary meaning it would otherwise possess.” MPEP 2111.01.
Claim 1 recites a parent microorganism. The specification, page 5, provides: “As used herein, the term "microorganism producing L-tryptophan" refers to a microorganism naturally having an L-tryptophan producing ability or a microorganism obtained by imparting L-tryptophan producing ability to a parent strain having no L- tryptophan producing ability.”
An embodiment of the claims can be made by making multiple modifications to an original cell. By means of example: an original cell [Wingdings font/0xE0] an intermediate engineered cell with a first modification [Wingdings font/0xE0] an intermediate engineered cell with first and second modifications [Wingdings font/0xE0] an embodiment intermediate cell with first, second and third modification.
The ordinarily meaning of the term “parent cell” as recited would at leas include the original cell, which may be a naturally-occurring or wild-type cell not modified by the hand of man. A parent cell could also be interpreted under a plain meaning to further include any intermediately produced cells as indicated above.
However, the statement in page 5 of the specification of “a parent strain having no L- tryptophan producing ability” is further understood as applicant acting as their own lexicographer that a parent strain as recited in the claims is a specific reference to a strain having no L-tryptophan production ability. For this reasons, any C. glutamicum strain having enhanced prephenate dehydratase ability producing any non-zero amount of L-tryptophan has increased ability of producing L-tryptophan compared with a parent microorganism wherein the specification states that “a parent strain ha[s] no L- tryptophan producing ability.”
This Claim Interpretation section is incorporated by reference into all rejections appearing below.
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.
Claim(s) 1, 3-8 and 10-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ikeda et al. (Metabolic Engineering To Produce Tyrosine or Phenylalanine in a Tryptophan-Producing Corynebacterium glutamicum Strain, Appl. Environ. Microbiol. 58, 1992, 781-85) as evidenced by Hagino et al. (L-Tryptophan Production by Analog-resistant Mutants Derived from a Phenylalanine and Tyrosine Double Auxotroph of Corynebacterium glutamicum, Agr. Biol. Chem. 39, 1975, 343-49) and Katsumata et al. (Hyperproduction of Tryptophan in Corynebacterium glutamicum by Pathway Engineering, Bio/Technology 11, 1993, 921-25).
Ikeda, abstract, teaches:
The aromatic amino acids are synthesized via a common biosynthetic pathway. A tryptophan-producing mutant of Corynebacterium glutamicum was genetically engineered to produce tyrosine or phenylalanine in abundance. To achieve this, three biosynthetic genes encoding the first enzyme in the common pathway, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DS), and the branch-point enzymes chorismate mutase and prephenate dehydratase were individually cloned from regulatory mutants of C. glutamicum which have either of the corresponding enzymes desensitized to end product inhibition. These cloned genes were assembled one after another onto a multicopy vector of C. glutamicum to yield two recombinant plasmids. One plasmid, designated pKY1, contains the DS and chorismate mutase genes, and the other, designated pKF1, contains all three biosynthetic genes. The enzymes specified by both plasmids were simultaneously overexpressed approximately sevenfold relative to the chromosomally encoded enzymes in a C. glutamicum strain. When transformed with pKY1 or pKF1, tryptophan-producing C. glutamicum KY10865, with the ability to produce 18 g of tryptophan per liter, was altered to produce a large amount of tyrosine (26 g/liter) or phenylalanine (28 g/liter), respectively, because the accelerated carbon flow through the common pathway was redirected to tyrosine or phenylalanine.
Ikeda, page 781, right col., provides:
C. glutamicum KY10693 and KY10694, phenylalanine-producing mutants derived from strain 31-PAP-20-22 (7), were used as the DNA donors for cloning of the deregulated biosynthetic genes. The former has a phenylalanine-insensitive PD, and the latter has a DS and CM highly desensitized to synergistic feedback inhibition by phenylalanine and tyrosine. C. glutamicum KY10865, used as the host strain for production of the aromatic amino acids, is a tryptophan-producing mutant derived from strain Px-115-97 (8). This strain is a CM-deficient, phenylalanine and tyrosine double auxotroph whose DS is wild type and whose anthranilate synthase is partially desensitized to inhibition by tryptophan. Strains KLS4, KY9457, and KY9182 are lysozyme-sensitive, phenylalanine and tyrosine double auxotrophic (CM-deficient),and phenylalanine auxotrophic (PD-deficient) mutants, respectively, derived from C. glutamicum wild-type strain ATCC 13032.
Reference (8) of Ikeda is Hagino. Hagino, abstract explain that strain Px-115-97 That is, strain KLS4 in a non-wild-type phenylalanine and tyrosine double auxotrophic mutant C. glutamicum derived from wild-type strain ATCC 13032. Hagino, abstract and Fig. 4, evidences that strain Px-115-97 is produced from strain KY9456, which is explained by Ikeda to be derived from C. glutamicum wild-type strain ATCC 13032. Hagino, abstract, describes strain KY9456 (a non-wild-type auxotrophic strain) produces “only a trace amount of L-tryptophan (150 µg/ml).” Katsumata, Table 1, evidences that C. glutamicum ATCC13032 does not accumulate tryptophan or at least not a significant amount of tryptophan.
Table 3 of Ikeda demonstrates C. glutamicum KY10865 strain expressing pKF1 plasmid including expression of a PD gene producing 0.5 g/L of tryptophan. 0.5 g/L of tryptophan is greater than a zero or trace amount of tryptophan produced by wildtype ATCC 13032 strain from which the strains described in Ikeda are derived. In reference to the Claim Interpretation section above, since wildtype strain ATCC 13032 is both 1) the progenitor of all strains shown in Table 3 of Hagino, and 2) a strain that does not produce L-tryptophan, wildtype strain ATCC 13032 meets the requirements of “a parent microorganism” as recited in claim 1.
That is, although culture conditions vary between Ikeda, Hagino and Katsumata, at least Katsumata evidences that wildtype ATCC 13032 does not accumulate significant amounts of tryptophan as to provide a basis in fact and/or technical reasoning to reasonably support a determination that the amount of 0.5 g/L of tryptophan production reported in Table 3 of Ikeda is a greater or increased amount of tryptophan that would be produced by wild-type strain ATCC 13032, a parent microorganism, cultured under the same conditions. Ikeda, page 82, left col., discloses amino acid production on TP1 medium containing 60 g/l of glucose and 20 g/l corn step liquor. Katsumata, page 924, right col., also describes “test tube production” of amino acids as reported in Table 1 that is also performed with TP1 medium apparently having the same or similar composition.
For this reason, Ikeda discloses the features of at least claims 1, 3-5 and 8 wherein expression of the plasmid pKF1 having a PD gene is “an increase in copy number of a gene encoding the prephenate dehydratase.” The cultures described in Table 3 of Ikeda are compositions as recited in claim Regarding claims 6 and 10-12, Table 3 and page 782, left col. (Cultivations for production of amino acids) of Ikeda described producing L-tryptophan by culturing a microorganism having increased ability to produce L-tryptophan and enhanced PD activity compared to wildtype microorganism ATCC 13032 (i.e. a parent microorganism as recited in claim 1). Regarding claim 7, Ikeda, page 782, right col., describes “The aromatic amino acids were analyzed by high-performance liquid chromatography,” which is considered to be within the broadest reasonable interpretation of recovering the L-tryptophan from a culture medium or microorganism.
Regarding claims 2 and 9, Fig. 2 indicates that PD gene was obtained from “KY10693 chromosomal DNA fragment containing the PD gene.” Ikeda, abstract, states that strain KY10693 is produced from strain 31-PAP-20-22 as described by Hagino 2d (reference (7) of Ikeda. Hagino 2d describes that strain 31-PAP-20-22 is produced by NTG treatment of C. glutamicum ATCC 13032.
Uniprot P10341 evidences that prephenate dehydratase as produced and encoded by a gene of C. glutamicum ATCC 13032 is over 99% identical to recited SEQ ID NO: 2 (one amino acid residue mismatch). As such, the evidence of record supports that the pKF1 plasmid described by Ikeda includes a PD gene encoding an amino acid sequence with greater than 90% identity to SEQ ID NO: 2 even if NTG treatment may induce additional substitutions (90% identity allows for 20 of 201 amino acid residues of SEQ ID NO: 2 to vary). It is further noted that reference (4) of Ikeda is Follettie, wherein Uniprot P10341 describes that the prephenate dehydrogenase gene as described by Follettie is described therein. “Follettie and Sinskey (4) reported the cloning of the C. glutamicum PD gene and showed that the gene was unable to complement CM-deficient mutants of C. glutamicum.” Ikeda, page 785, left col.
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.
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.
Claim(s) 1-12 (all pending claims) is/are rejected under 35 U.S.C. 103 as being unpatentable over Ikeda et al. (Metabolic Engineering To Produce Tyrosine or Phenylalanine in a Tryptophan-Producing Corynebacterium glutamicum Strain, Appl. Environ. Microbiol. 58, 1992, 781-85) as evidenced by Hagino et al. (L-Tryptophan Production by Analog-resistant Mutants Derived from a Phenylalanine and Tyrosine Double Auxotroph of Corynebacterium glutamicum, Agr. Biol. Chem. 39, 1975, 343-49) and Katsumata et al. (Hyperproduction of Tryptophan in Corynebacterium glutamicum by Pathway Engineering, Bio/Technology 11, 1993, 921-25) as applied to claims 1, 3-8 and 10-12 above, and further in view of Hagino et al. (L-Phenylalanine Production by Analog-resistant Mutants of Corynebacterium glutamicum, Agr. Biol. Chem. 38, 1974, 157-61) (Hagino 2d), Uniprot, Accession No. P10341, 2014, www.uniprot.org, and Follettie et al. (Molecular Cloning and Nucleotide Sequence of the Corynebacterium glutamicum pheA Gene, J. Bacteriol. 167, 1986, 695-702).
Regarding claims 2 and 9, Fig. 2 of Ikeda indicates that PD gene was obtained from “KY10693 chromosomal DNA fragment containing the PD gene.” Ikeda, abstract, states that strain KY10693 is produced from strain 31-PAP-20-22 as described by Hagino 2d (reference (7) of Ikeda). Hagino 2d (abstract) describes that strain 31-PAP-20-22 is produced by NTG treatment of C. glutamicum ATCC 13032.
Uniprot P10341 evidences that prephenate dehydratase as produced and encoded by a gene of C. glutamicum ATCC 13032 is over 99% identical to recited SEQ ID NO: 2 (one amino acid residue mismatch). It is further noted that reference (4) of Ikeda is Follettie, wherein Uniprot P10341 describes that the prephenate dehydrogenase gene as described by Follettie is described therein. “Follettie and Sinskey (4) reported the cloning of the C. glutamicum PD gene and showed that the gene was unable to complement CM-deficient mutants of C. glutamicum.” Ikeda, page 785, left col.
The above suggests that the prephenate dehydrogenase expressed from plasmid pKF1 of Ikeda has an amino acid sequence with at least 90% identity to SEQ ID NO: 2. Regardless, the description of Ikeda that PD gene was obtained from “KY10693 chromosomal DNA fragment containing the PD gene” directly suggests that prephenate dehydrogenases from the parent strain of KY10693, which is C. glutamicum ATCC13032 having a prephenate amino acid sequence as taught by Uniprot P10341 and Follettie, as an appropriate prephenate dehydrogenase to express in embodiments of Ikeda. Stated in other words, Ikeda teaches that a C. glutamicum prephenate dehydrogenase is expressed from plasmid pKF1 wherein Ikeda directly references Follettie as teaching such a prephenate dehydrogenase from C. glutamicum.
Response to arguments
Applicant argues:
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The specification (see claim interpretation section above) defines a parent strain as “a parent strain ha[s] no L- tryptophan producing ability.” Specification, page 5. Table 3 of Ikeda shows strain KY10865 as production 6.8 g/L of tryptophan, which is not consistent with “a parent strain ha[s] no L- tryptophan producing ability.” As such, applicant’s arguments that KY10865 is a “parent strain” as recited in the claims are not accepted.
Since the specification, page 5, provides “a parent strain ha[s] no L- tryptophan producing ability,” the broadest reasonable interpretation of “a parent strain” in view of the specification cannot be limited to a microorganism otherwise structurally identical to an embodiment microorganism of claim 1 except for increased activity of prephenate dehydratase. As discussed in the body of the rejection, Ikeda discusses references wherein the parent strain from which strain KY10865 is produced are described (i.e. Hagino and Katsumata), which is C. glutamicum wild-type strain ATCC 13032 that is also expressly identified in Ikeda. However, Ikeda does not provide tryptophan production for ATCC 13032 , which is set forth to be zero tryptophan production in Katsumata. Regardless, the specification, claim 5, defines a parent strain as “a parent strain ha[s] no L- tryptophan producing ability.” As such, any microorganism producing any amount of L-tryptophan satisfies the claim feature of “increased ability of producing L-tryptophan compared with a parent microorganism” that produces no L-tryptophan.
Conclusion
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652