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 .
Support for the amendments is within the instant application specification.
Applicants’ amendment to the claims filed on 9/18/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-8, 10-21 are pending.
Claim 9 is cancelled.
Priority
Acknowledgement is made of this national stage entry of PCT/CN2022/143106 of Non-
provisional Application No. 18/833,597, filed on 12/29/2022, which claims foreign priority under 35
U.S.C. 119(a)-(d) to Chinese Patent Application No. CN202210107366.3, filing date 1/28/2022. The
certified copy has been filed in the present application on 7/26/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/26/2024, 4/21/2026, 6/15/2026, 9/18/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Election/Restrictions
Applicant’s election with traverse of Group II, claims 4-8, 19-21 in the reply filed on 9/18/2026 is acknowledged. Applicant contends that the common special technical feature "the 20-30 bp segment upstream of the start codon of the gene encoding phosphoenolpyruvate carboxylase in the Corynebacterium species is replaced with a strong promoter" is neither disclosed nor suggested by O'Regan, which the Examiner cites in support of the restriction requirement. Applicant contends that the function of the 20 to 30 bp segment upstream of the ppc in a Corynebacterium species is unknown, and it is unexpected that replacing this segment with a strong promoter may increase the expression of the ppc gene. O'Regan neither discloses nor implies the feature of "replacing the 20-30 bp segment upstream of the start codon of the genomic gene encoding phosphoenolpyruvate carboxylase in the Corynebacterium species with a strong promoter."
The argument is not persuasive. Examiner contends that Applicant is not claiming a function of the promoter being placed 20-30bp upstream of a gene encoding phosphoenolpyruvate carboxylase. Examiner contends that Applicant is merely claiming the structure of the promoter being placed 20-30bp upstream of a gene encoding phosphoenolpyruvate carboxylase. Based on claim language, one of ordinary skill in the art would reasonably conclude that the function of said construct is the production of ‘phosphoenolpyruvate carboxylase.’ Any function beyond that is not envisioned within the claimed limitations. Furthermore, Applicant’s own admission envisions said structure with the following teaching from Applicant’s remarks of ‘O'Regan also hypothesizes that the ppc promoter in the Corynebacterium species is located 10 and 35 bp upstream of the ppc ORF, followed by an SD sequence (ribosome binding site) (see Fig. 2 and its legend of O'Regan).’
Claims 1-3, 10-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 4-8, 19-21 are pending and examined on the merits.
Claim 9 is cancelled.
Claim Rejections - 35 USC § 112
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 4-8, 19-21 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 4 (5-8, 19-21 dependent thereof) recites the limitation ‘the 20-30 bp segment upstream of the start codon’ in lines 1-2.’ There is insufficient internal antecedent basis for this limitation in the claim. It is recommended that Applicant amend the claim to recite ‘ a 20-30 bp segment upstream of the start codon’ in lines 1-2.’ Appropriate correction is suggested.
Regarding claim 6 (claim 7 dependent thereof) the term "enhanced’ renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear which enhancement(s) Applicant is referencing among the infinite number of ‘enhancements.’ Appropriate correction is suggested.
Regarding claim 6 (claim 7 dependent thereof), the term "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. The metes and bounds of the claims are not clear. See MPEP § 2173.05(c)(I).
Regarding claim 6 (claim 7 dependent thereof), the phrase ‘wherein the enzyme activity of any one or more of the following enzymes (1) to (7) in the recombinant microorganism is enhanced and/or the feedback inhibition thereof is deregulated: (1) aspartate kinase; (2) aspartate semialdehyde dehydrogenase; (3) homoserine dehydrogenase; (4) threonine synthase; (5) homoserine kinase; (6) aspartate aminotransferase; and (7) threonine export protein; preferably, the threonine export protein is one derived from Escherichia coli’ renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear if the claim encompasses the claimed enzyme of claim 4, upon which claim 6 depends, or difference enzymes. It is recommended that Applicant amend the claim to add ‘further comprising’ claim language.
Claim 19 (20 dependent thereof) recites the limitation ‘the 27 bp segment upstream of the initiation codon’ in lines 1-2.’ There is insufficient antecedent basis for this limitation. Appropriate correction is suggested.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 4-8, 19, 21 are rejected under 35 U.S.C. 103 as being unpatentable over Nakagawa et al (EP 1108790A2, Date Published: 20.06.2001.
Claims 4-8, 19, 21 are drawn to a recombinant microorganism, wherein, the 20-30 bp segment upstream of the start codon of a gene encoding phosphoenolpyruvate carboxylase in the recombinant microorganism is replaced with a strong promoter.
With respect to claims 4-5, 8, 19, 21, Nakagawa teaches a recombinant bacterium encoding the instant application SEQ ID NO: 1 (appendix A) derived from Corynebacterium glutamicum (para 0004, 0010, 0017) under the control of an expression modulating fragment (EMF) as a high-expression promoter located upstream of the target gene (instant application SEQ ID NO: 1, appendix A) (para 0091, 0095). It is the Examiner’s position that a high expression promoter is the same as a strong promoter since a strong promoter intrinsically drives high levels of gene expression. Said promoter is usually positioned between two genes. Although the references of Nakagawa does not explicitly teach the limitations of claim 4 (the 20-30 bp segment upstream of the start codon of a gene encoding phosphoenolpyruvate carboxylase in the recombinant microorganism is replaced with a strong promoter) and claim 19 (he 27 bp segment upstream of the initiation codon of a gene encoding phosphoenolpyruvate carboxylase in the recombinant microorganism is replaced with a strong promoter), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the location of the ‘strong promoter’ depending on the particular application. It would be routine for one to arrive at the location within the nucleotide sequence to place the ‘strong promoter’ relative to the target sequence for the application they intend on using the construct. Therefore, the above invention would have been prima facie obvious.
With respect to claims 6-7, Nakagawa teaches the lysine-productivity of Corynebacterium glutamicum was improved by replacing the base at the 932-position of aspartokinase gene lysC of the Corynebacterium glutamicum ATCC 13032 genome with cytosine to thereby replace threonine at the 311-position by isoleucine, which indicates that this mutation is an effective mutation contributing to the production of lysine (para 0138).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Nakagawa et al (EP 1108790A2, Date Published: 20.06.2001) {herein Nakagawa} in view of Ma et al (2018, Micro Cell Fact, Examiner cited) {herein Ma}.
Claim 20 is drawn to the recombinant microorganism of claim 19, wherein the strong promoter is Ptuf.
With respect to claim 20, Ma teaches a strong constitutive promoter, tuf, that enables the constitutive expression of the target gene and are not affected by transcriptional regulators in Corynebacterium glutamicum (page 2, column 1, para 1).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to apply the teachings of Nakagawa et al of a recombinant microorganism encoding the instant application SEQ ID NO: 1 (appendix A) derived from Corynebacterium glutamicum (para 0004, 0010, 0017) under the control of an expression modulating fragment (EMF) as a high-expression promoter located upstream of the target gene (instant application SEQ ID NO: 1, appendix A) (para 0091, 0095) or combine the teachings of Ma because Ma teaches a strong constitutive promoter, tuf, that enables the constitutive expression of the target gene and are not affected by transcriptional regulators in Corynebacterium glutamicum (page 2, column 1, para 1).
One of ordinary skill in the art would be motivated to either use the teachings of Nakagawa et al by itself of combine the teachings Ma because Ma provides Nakagawa the motivation to substitute the EMF taught by Nakagawa for Ptuf taught by Ma as Ma teaches the tuf promoter functions independently of native transcriptional repressors, offering highly predictable, steady-state transcription without complex cloning designs (page 2, column 1, para 1). Whereas EMF is regulated by transcriptional repressors which may have a negative impact on the synthesis of the target gene. One of ordinary skill in the art knowing the benefit of strong promoters based on the teachings of Nakagawa and Ma would have a reasonable expectation of success to substitute the EMF promoter for the tuf promoter because one of ordinary skill in the art would expect Ptuf to ensure high, uninterrupted enzyme synthesis throughout both exponential growth and stationary phases (Ma: page 2, column 1, para 1) thereby resulting in a large amount of enzyme production.
One of skill in the art would have a reasonable expectation of success to make and use the claimed strong promoter Ptuf because Nakagawa provides the basic recombinant microorganism and its uses and methods of making. While Ma provides the teaching of a strong constitutive promoter, tuf, that enables the constitutive expression of the target gene and are not affected by transcriptional regulators in Corynebacterium glutamicum (page 2, column 1, para 1). Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
Status of the Claims
Claims 1-3, 10-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 4-8, 19-21 are pending.
Claim 9 is cancelled.
Claims 4-8, 19-21 are rejected.
No claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 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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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Instant Application SEQ ID NO: 1 vs Nakagawa et al SEQ ID NO: 6970 (STIC search .rag result #1)
Query Match 100.0%; Score 4671; Length 919;
Best Local Similarity 100.0%;
Matches 919; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MTDFLRDDIRFLGQILGEVIAEQEGQEVYELVEQARLTSFDIAKGNAEMDSLVQVFDGIT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTDFLRDDIRFLGQILGEVIAEQEGQEVYELVEQARLTSFDIAKGNAEMDSLVQVFDGIT 60
Qy 61 PAKATPIARAFSHFALLANLAEDLYDEELREQALDAGDTPPDSTLDATWLKLNEGNVGAE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PAKATPIARAFSHFALLANLAEDLYDEELREQALDAGDTPPDSTLDATWLKLNEGNVGAE 120
Qy 121 AVADVLRNAEVAPVLTAHPTETRRRTVFDAQKWITTHMRERHALQSAEPTARTQSKLDEI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AVADVLRNAEVAPVLTAHPTETRRRTVFDAQKWITTHMRERHALQSAEPTARTQSKLDEI 180
Qy 181 EKNIRRRITILWQTALIRVARPRIEDEIEVGLRYYKLSLLEEIPRINRDVAVELRERFGE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 EKNIRRRITILWQTALIRVARPRIEDEIEVGLRYYKLSLLEEIPRINRDVAVELRERFGE 240
Qy 241 GVPLKPVVKPGSWIGGDHDGNPYVTAETVEYSTHRAAETVLKYYARQLHSLEHELSLSDR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GVPLKPVVKPGSWIGGDHDGNPYVTAETVEYSTHRAAETVLKYYARQLHSLEHELSLSDR 300
Qy 301 MNKVTPQLLALADAGHNDVPSRVDEPYRRAVHGVRGRILATTAELIGEDAVEGVWFKVFT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 MNKVTPQLLALADAGHNDVPSRVDEPYRRAVHGVRGRILATTAELIGEDAVEGVWFKVFT 360
Qy 361 PYASPEEFLNDALTIDHSLRESKDVLIADDRLSVLISAIESFGFNLYALDLRQNSESYED 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 PYASPEEFLNDALTIDHSLRESKDVLIADDRLSVLISAIESFGFNLYALDLRQNSESYED 420
Qy 421 VLTELFERAQVTANYRELSEAEKLEVLLKELRSPRPLIPHGSDEYSEVTDRELGIFRTAS 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 VLTELFERAQVTANYRELSEAEKLEVLLKELRSPRPLIPHGSDEYSEVTDRELGIFRTAS 480
Qy 481 EAVKKFGPRMVPHCIISMASSVTDVLEPMVLLKEFGLIAANGDNPRGTVDVIPLFETIED 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 EAVKKFGPRMVPHCIISMASSVTDVLEPMVLLKEFGLIAANGDNPRGTVDVIPLFETIED 540
Qy 541 LQAGAGILDELWKIDLYRNYLLQRDNVQEVMLGYSDSNKDGGYFSANWALYDAELQLVEL 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LQAGAGILDELWKIDLYRNYLLQRDNVQEVMLGYSDSNKDGGYFSANWALYDAELQLVEL 600
Qy 601 CRSAGVKLRLFHGRGGTVGRGGGPSYDAILAQPRGAVQGSVRITEQGEIISAKYGNPETA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CRSAGVKLRLFHGRGGTVGRGGGPSYDAILAQPRGAVQGSVRITEQGEIISAKYGNPETA 660
Qy 661 RRNLEALVSATLEASLLDVSELTDHQRAYDIMSEISELSLKKYASLVHEDQGFIDYFTQS 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RRNLEALVSATLEASLLDVSELTDHQRAYDIMSEISELSLKKYASLVHEDQGFIDYFTQS 720
Qy 721 TPLQEIGSLNIGSRPSSRKQTSSVEDLRAIPWVLSWSQSRVMLPGWFGVGTALEQWIGEG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 TPLQEIGSLNIGSRPSSRKQTSSVEDLRAIPWVLSWSQSRVMLPGWFGVGTALEQWIGEG 780
Qy 781 EQATQRIAELQTLNESWPFFTSVLDNMAQVMSKAELRLAKLYADLIPDTEVAERVYSVIR 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 EQATQRIAELQTLNESWPFFTSVLDNMAQVMSKAELRLAKLYADLIPDTEVAERVYSVIR 840
Qy 841 EEYFLTKKMFCVITGSDDLLDDNPLLARSVQRRYPYLLPLNVIQVEMMRRYRKGDQSEQV 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 EEYFLTKKMFCVITGSDDLLDDNPLLARSVQRRYPYLLPLNVIQVEMMRRYRKGDQSEQV 900
Qy 901 SRNIQLTMNGLSTALRNSG 919
|||||||||||||||||||
Db 901 SRNIQLTMNGLSTALRNSG 919
