DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1 and 4-13 are pending in the application.
Applicant’s amendment to the claims, filed April 13, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks and declaration under 37 CFR 1.132 (hereafter “Second Wei Declaration”) filed April 13, 2026 in response to the non-final rejection filed January 14, 2026 have been fully considered.
The text of those sections of Title 35, U.S. Code or judicially created doctrine not included in this action can be found in a prior Office action.
Restriction/Election
In response to a requirement for restriction/election mailed March 25, 2025, applicant elected with traverse Group I, pending claims 1 and 5-8, in the reply filed May 14, 2025. The requirement was deemed proper and made FINAL in the Office communication mailed June 5, 2025.
Claims 4 and 9-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claim Objections
Claim 8 is objected to in the recitation of “E. coli K12 (W3110)” and in the interest of improving claim form, it is suggested that the noted phrase be amended to remove the parentheses from “(W3110)” and recite “E. coli K12 W3110.”
Claim Rejections - 35 USC § 103
Claims 1 and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (US 2015/0072382 A1; cited on Form PTO-892 mailed June 5, 2025; hereafter “Schneider”) in view of “Start Codons” (University of Washington, obtained from https://depts.washington.edu/agro/genomes/students/stanstart.htm, 2004, 3 pages; cited on Form PTO-892 mailed September 16, 2025).
Claim 1 is drawn to a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO: 14;
claims 5 and 6 are drawn to a recombinant vector, comprising the nucleic acid molecule according to claim 1; and
claims 7 and 8 are drawn to a recombinant strain, comprising the nucleic acid molecule according to claim 1.
Regarding claim 1, Schneider teaches SEQ ID NO: 1, which is an E. coli spoT gene encoding ppGppase (pp. 17-20). SEQ ID NO: 1 of Schneider has two nucleotide differences relative to instant SEQ ID NO: 14 – the first nucleotide difference being that SEQ ID NO: 1 of Schneider has T at nucleotide position 1, while instant SEQ ID NO: 14 has A at nucleotide position 1, and the second nucleotide difference being that SEQ ID NO: 1 of Schneider has G at nucleotide position 520, while instant SEQ ID NO: 14 has T at nucleotide position 520 (see Appendix at pp. 9-11 of the Office action filed January 14, 2026 for sequence alignment).
Regarding the second nucleotide difference, Schneider teaches an amino acid mutation at position G174 (paragraphs [0016] and [0144]) and specifically teaches a G520T nucleotide mutation (paragraph [0281]), which, as shown by SEQ ID NO: 1 of Schneider, replaces the codon GGT encoding glycine at position 174 with the codon TGT, which encodes cysteine. One of ordinary skill in the art would have recognized that Schneider is teaching and/or suggesting a mutant spoT gene with a G520T nucleotide mutation, thus teaching and/or suggesting the second nucleotide difference.
Schneider does not teach and/or suggest the first nucleotide difference as described above.
“Start Codons” teaches (p. 1, second full paragraph) there are many varieties of codons that can be used as start codons in bacteria, including ATG and TTG. According to “Start Codons,” while ATG is the most common start codon, all of these will put a methionine amino acid in the first position of the protein. “Start Codons” teaches that it is important to note that most start codons are ATG (>90%).
In view of the combined teachings of Schneider and “Start Codons,” it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify a mutant spoT gene with a G520T nucleotide mutation as taught and/or suggested by Schneider (hereafter “Schneider’s mutant spoT gene” for brevity) by substituting T with A at nucleotide position 1. One of ordinary skill would have expected success and could have substituted T with A at nucleotide position 1 of Schneider’s mutant spoT gene because “Start Codons” taught either ATG or TTG can be used as a start codon in bacteria as each results in a methionine in the first position of the protein. One of ordinary skill would have found it obvious to make the substitution because, based on the relevant teachings of “Start Codons,” an ordinarily skilled artisan would have predicted that an ATG start codon in Schneider’s mutant spoT gene would result in a methionine in the first position of the protein. See MPEP 2143.I.B regarding a “simple substitution” obviousness rationale.
Regarding claim 5, Schneider teaches a vector comprising the nucleic acid molecule (paragraph [0183]).
Regarding claim 6, the recitation of “wherein the recombinant vector is constructed by…” is interpreted as a product-by-process limitation and does not structurally and/or functionally limit the recombinant vector.
Regarding claim 7, Schneider teaches a cell overexpressing the variant nucleic acid (paragraph [0016]). Schneider does not teach or suggest “wherein the host strain is used for the production of L-threonine.” However, this limitation is interpreted as merely reciting the purpose or an intended use and does not structurally and/or functionally any aspect of the claimed recombinant strain. Schneider also does not teach or suggest “produces L-threonine with a higher concentration as compared with an unmutated wild-type strain.” However, according to MPEP 2112.01, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent, and since the structure of the mutant spoT gene as taught and/or suggested by Schneider with a T1A nucleotide mutation is encompassed by claim 7, it is presumed that it produces L-threonine with a higher concentration as compared with an unmutated wild-type strain.
Regarding claim 8, Schneider teaches the cell is E. coli strain W3110 (paragraph [0206]).
Therefore, the invention of claims 1 and 5-8 would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Applicant’s remarks and the Second Wei Declaration contend that while Schneider teaches a non-engineered E. coli strain with three mutations at nucleotide positions 252, 520, and 1585 of the spoT gene, Schneider does not teach a spoT gene with a G520T mutation that does not also have mutations at nucleotide positions 252 and 1585 relative to the wild-type spoT gene. Applicant’s remarks and the Second Wei Declaration further contend there is no report of a lab scientist making a spoT gene with only a G520T mutation relative to the wild-type spoT gene and given that Schneider teaches only a triple mutant, the effects of a single G520T mutation without also having mutations at nucleotide positions 252 and 1585 would have been unpredictable to one of ordinary skill in the art. Applicant’s remarks and the Second Wei Declaration further contend that applicant was aware of the triple mutant of Schneider and argued against it in other jurisdictions.
Applicant’s arguments and Second Wei Declaration have been fully considered and are not found persuasive. There is nothing in Schneider or other prior art of record that teaches and/or suggests a requirement for all three mutations at nucleotide positions 252, 520, and 1585 of the spoT gene. Rather, Schneider teaches “…having at least one of the following modifications…” (paragraphs [0016] and [0144]) and one of ordinary skill in the art would have recognized that Schneider is teaching and/or suggesting the embodiment of a singular amino acid mutation at Gly174 with the corresponding nucleotide mutation G520T. In this case, it appears applicant is requiring an explicit teaching and absolute predictability of the claimed invention. However, the instant rejection is an obviousness rejection and according to MPEP 2143.02.II, obviousness does not require absolute predictability, only some degree of predictability is required. In view of the teachings of Schneider, one would have recognized that Schneider is teaching and/or suggesting a spoT gene with a G520T mutation that does not also have mutations at nucleotide positions 252 and 1585 relative to the wild-type spoT gene and in view of the combined teachings of Schneider and “Start Codons” would have had at least some degree of predictability to modify the mutant spoT gene as taught and/or suggested by Schneider with a T1A nucleotide mutation.
Applicant’s remarks and the Second Wei Declaration further contend that when start codon TTG is replaced with ATG, the strain demonstrates superior efficacy in enhancing L-threonine fermentation yields
Applicant’s arguments and Second Wei Declaration have been fully considered and are not found persuasive. According to the Second Wei Declaration, applicant’s results were achieved using an E. coli comprising the spoT gene of SEQ ID NO: 14, however, with the exception of claim 8, the claims do not require an E. coli comprising the spoT gene of SEQ ID NO: 14 and thus, applicant’s results are not commensurate in scope with the claimed invention (see MPEP 716.02(d)). Also, differences between the claimed invention and the prior art may be expected to result in some differences in properties (see MPEP 716.02) yet applicant fails to explain why the 5% increase in L-threonine fermentation yield for ATG start codon (see item 8 of the Second Wei Declaration) is really unexpected (see MPEP 716.02(b).I).
For these reasons, it is the examiner’s position that the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
Status of the claims:
Claims 1 and 4-13 are pending.
Claims 4 and 9-13 are withdrawn.
Claims 1 and 5-8 are rejected.
No claim is in condition for allowance.
THIS ACTION IS MADE FINAL. 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 DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MANJUNATH N RAO can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/David Steadman/Primary Examiner, Art Unit 1656
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