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 .
Applicant’s cancellation of claims 33-41, amendment of claim 32, in the paper of 3/13/2026, is acknowledged. Claims 32, 42-51 are still at issue and are present for examination.
Election/Restrictions
Applicant's election without traverse of the invention of Group 1, claims 32, to a recombinant microorganism for high production of carnosine, in the paper of 3/13/2026, is acknowledged. Applicant's election without traverse of the species of the beta-alanine pathway, in the paper of 3/13/2026, is acknowledged.
Claims 42-51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Applicants filing of information disclosure statements on 11/10/2023 and 7/17/2025 are acknowledged and have been considered.
Claim Objections
Claim 32 is objected to because of the following informalities:
Claim 11 recites “phosphoribosyltransferase(HisG)”, which should be “phosphoribosyltransferase (HisG)”.
Appropriate correction and/or comment is required.
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.
Claim 32 is 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.
Claim 32 is indefinite in the recitation “high production of carnosine” in that “high” is a relative term and the recitation is unclear absent reference or teaching of what “high production of carnosine” is.
Claim 32 is further indefinite in the recitation “wherein a pentose phosphate pathway is enhanced” in that the reference to “a pentose phosphate pathway” suggests that there are multiple pentose phosphate pathways. Further the reference to “a pentose phosphate pathway” is inconsistent with the later recitation in the claim which recites “the pentose phosphate pathway is enhanced by” which raises the question of antecedent basis.
Claim 32 is further indefinite in multiple recitations “a nucleotide sequence represented by SEQ ID NO:” in it is unclear as to applicants intent in “represented by”. Is it applicants intent that the recited “nucleotide sequence” comprises the recited “SEQ ID NO:” or is it merely represented by as in encoding a protein with similar function (i.e. phosphoribosyltransferase, pyrophosphokinase, aspartate 1-decarboxylase, or carnosine synthase activity).
Appropriate correction and/or comment is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim(s) 32 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim(s) 32 is directed to all possible recombinant microorganisms for high production of carnosine, wherein a pentose phosphate pathway is enhanced; and a mammal-derived carnosine synthase 1 (Cams1) gene is introduced, wherein the pentose phosphate pathway is enhanced by replacement of a promoter of an operon-type gene with a highly expressing synthetic promoter H36 and the replacement of an initiation codon of a glucose-6-phosphate isomerase (pgi) gene from ATG to GTG, the recombinant microorganism has an L-histidine biosynthetic pathway enhanced by the overexpression of a ATP phosphoribosyltransferase(HisG) gene consisting of a nucleotide sequence represented by SEQ ID NO: 13 and the overexpression of a GTP pyrophosphokinase (Rel) gene consisting of a nucleotide sequence represented by SEQ ID NO: 14, the recombinant microorganism has a beta-alanine biosynthetic pathway enhanced by the overexpression of an aspartate 1-decarboxylase (PanD) gene consisting of a nucleotide sequence represented by SEQ ID NO: 19, the Carns1 gene consists of a nucleotide sequence represented by SEQ ID NO: 22, and the recombinant microorganism is derived from Corvnebacterium glutamicum (see also above rejection under 112(b)). The specification, however, only provides the representative species of that recombinant microorganism, wherein a pentose phosphate pathway is enhanced; and a mammal-derived carnosine synthase 1 (Cams1) gene is introduced, wherein the pentose phosphate pathway is enhanced by replacement of a promoter of an operon-type gene encoding the pentose phosphate pathway enzymes with a synthetic promoter H36 and the replacement of the initiation codon of a glucose-6-phosphate isomerase (pgi) gene from ATG to GTG, the recombinant microorganism has an L-histidine biosynthetic pathway enhanced by the overexpression of a ATP phosphoribosyltransferase (HisG) gene consisting of a nucleotide sequence comprising SEQ ID NO: 13 and the overexpression of a GTP pyrophosphokinase (Rel) gene consisting of a nucleotide sequence comprising SEQ ID NO: 14, the recombinant microorganism has a beta-alanine biosynthetic pathway enhanced by the overexpression of an aspartate 1-decarboxylase (PanD) gene consisting of a nucleotide sequence comprising SEQ ID NO: 19, the Carns1 gene consists of a nucleotide sequence comprising SEQ ID NO: 22, and the recombinant microorganism is derived from Corvnebacterium glutamicum, encompassed by these claims. There is no disclosure of any particular structure to function/activity relationship in the disclosed species. The specification also fails to describe additional representative species of these microorganism and the nucleotide sequences by any identifying structural characteristics or properties, for which no predictability of structure is apparent.
Regarding the level of skill and knowledge in the art of amino acid (and nucleotide) mutation, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with amino acid (and encoding nucleotide) mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
Given this lack of additional representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Closest Prior Art
US 2017/0211105 teaches the biosynthetic production of carnosine and beta-alanine, including a modified microorganism for production of carnosine and beta-alanine comprising at least one heterologous enzyme selected from the group consisting of aspartate decarboxylase, carnosine synthase, and PanD autocleavage accelerator,
Schwenter et al. (Biotechnology for Biofuels, Vol 12, pp 1-21, 2019) teach that the pentose phosphate pathway is enhanced to increase histidine production, a precursor of carnosine.
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
5/13/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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