DETAILED ACTION
Status of the Application
Claims 9-10 are pending.
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 amendments of claims 9-10 as submitted in a communication filed on 12/24/2025 is acknowledged.
As submitted in a communication filed on 11/10/2024, Applicant elected a transketolase gene that comprises SEQ ID NO: 83, a DAHP synthase gene that comprises SEQ ID NO: 84, an O-methyltransferase gene that comprises SEQ ID NO: 85, a carboxylic acid reductase gene that comprises SEQ ID NO: 47, a 4’-phosphopantetheinyl transferase gene that comprises SEQ ID NO: 87, a 5’-methyltetrahydropteroyltriglutamate homocysteine methyltransferase gene that comprises SEQ ID NO: 49, a S-adenosylmethionine synthase gene that comprises SEQ ID NO: 50, a homoserine O-acetyltransferase that comprises SEQ ID NO: 51 and an adenosylhomocysteinase gene that comprises SEQ ID NO: 52.
As previously indicated, upon search of the elected genes, it was found that the genes of SEQ ID NO: 47, SEQ ID NO: 85 and SEQ ID NO: 87 are free of the prior art of record. While claims 9-10 require combinations that comprise genes that were not elected, in view of the fact that each of the gene combinations of claims 9-10 comprise at least one of the genes of SEQ ID NO: 47, 85, and 87, the combinations that comprise the genes of SEQ ID NO: 47, 85 or 87 have been rejoined for examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Specification
The specification was objected to as introducing new matter in view of the submission of a new sequence listing with the response of 7/11/2025 without a statement in accordance with MPEP § 2414.03. Applicant has submitted a statement in the response of 12/24/2025 identifying the location of all additions, deletions, or replacements of sequence information relative to the replaced “Sequence Listing XML”; a statement that indicates the support for the additions, deletions, or replacements of the sequence information, with specific references to particular parts of the application as originally filed (specification, claims, drawings) for all amended sequence data in the replacement “Sequence Listing XML”; and a statement that the replacement “Sequence Listing XML” includes no new matter. Therefore, the previous objection to the specification as containing new matter is hereby withdrawn.
Claim Objections
Claim 9 is objected to due to the recitation of “…knocking out pcaHG…genes from Corynebacterium..”. To enhance clarity and to be consistent with commonly used claim language, the claim should be amended to recite “…knocking out the pcaHG…genes from Corynebacterium …”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 9-10 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 pre-AIA the applicant regards as the invention. New grounds of rejection are necessitated by amendment.
Claim 9 is indefinite in the recitation of “…glutamicum is obtained by knocking out pcaHG, van, vdh and fud genes from Corynebacterium glutamicum ATCC13032. ….wherein the genetically engineered bacterium overexpresses any one of combinations (a)-(d) based on the recombinant Corynebacterium glutamicum: (a) the transketolase gene is …; the 3-deoxy…synthase gene is…; the O-methyltransferase gene is…; the carboxylic acid reductase gene is …; the 4’-phosphopantetheinyl…gene is…; the 5-methyltetra….gene is..; the S-adenosyl….gene is….; the homoserine O-acetyltransferase gene is ….; the adenosylhomocysteinase gene is….; …” and “….wherein a sequence of the…gene is SEQ ID NO: X” for the following reasons.
It is unclear as to how one could obtain the recombinant C. glutamicum by knocking out genes from another cell, namely C. glutamicum ATCC13032. Applicant argues that the term “knockout” is well known in the art and provides a description of different techniques to knock out genes in a cell. Applicant’s arguments have been fully considered but not deemed persuasive. The issue is not whether one could knock out a gene in a C. glutamicum cell. The issue is how knocking out genes from C. glutamicum ATCC13032 is associated with the recombinant C. glutamicum of the preamble. The term as written simply states that the recombinant C. glutamicum is obtained by knocking out genes from a specific C. glutamicum strain but does not provide any indication of the relationship between the source of these genes being knocked out and the recombinant C. glutamicum of the preamble. If the intended limitation is “wherein the recombinant C. glutamicum is a variant of a C. glutamicum ATCC13032 cell obtained by knocking out the pcaHG….genes in said C. glutamicum ATCC13032 cell”, the claim should be amended accordingly.
It is reiterated herein that the term “fud gene” is unclear because there is no known gene in C. glutamicum which is called “fud”. Applicant argues that there is no fudA or fudB genes in C. glutamicum and that Tsuge et al. describes a fudC gene. Applicant states that the specification refers to “fud” as an NADP+ and Zn-dependent alcohol dehydrogenase. Applicant has presented an alignment in support of the argument that the fudC gene of Tsuge et al. and the fud gene of the present application are identical. Applicant states that the primers labeled fud-L and fud-R were used to remove the fud gene and that these primers align with the fudC gene. Applicant states that these primers were used for fud deletion and therefore, a fud deletion is a deletion of the fudC gene. Applicant’s arguments have been fully considered but not deemed persuasive. The BLAST alignment provided on page 14 of the response of 12/24/2025 of two sequences having 1062 nucleotides fails to provide the identity of the Query and the Subject. While one would infer that one of the sequences in the alignment is allegedly the nucleotide sequence of the fudC gene of Tsuge et al., it is unclear as to which is the other nucleotide sequence of the alignment. Applicant has not indicated which is the sequence identifier provided by Applicant’s specification associated with the BLAST alignment provided. Therefore, one cannot reasonably conclude that the fudC gene of Tsuge et al. is the same fud gene of the specification.
While it is agreed that the fudC gene is a known gene in C. glutamicum, there is absolutely no indication in the prior art, the specification or the reference by Tsuge et al. that the term “fud” is an abbreviation for “fudC”. The Examiner acknowledges the primers disclosed and their location in the fudC gene of Tsuge et al. However, it is noted that the issue is whether the term “fud gene” conveys to one of skill in the art a particular structure and/or function such that one of skill in the art could recognize which gene is being referred to. As previously indicated, there is no fud gene disclosed in the prior art. It is also noted that the specification refers to the term “fud” as being associated with an NADP+ dependent alcohol dehydrogenase and not to a furfural detoxification dehydrogenase, which is the protein associated with the term “fudC” described by Tsuge et al. If the specification discloses the nucleotide sequence of the “fud gene” in the sequence listing as originally filed, the term “fud gene” could be replaced with “gene comprising SEQ ID NO: X”. If the intended gene is one that is amplifiable by the primers of SEQ ID NO: 35 and SEQ ID NO: 36, the term “fud gene” could be replaced with “gene amplified by the primers of SEQ ID NO: 35 and SEQ ID NO: 36”.
The term “….wherein a sequence of the…gene is SEQ ID NO: X” is unclear because one cannot determine if the gene is required to comprise SEQ ID NO: X or if the gene can, but is not required to, comprise SEQ ID NO: X. Please note that the claim recites “a sequence of the…gene is SEQ ID NO: X”, thus implying a genus of sequences for the gene where one of the sequences is SEQ ID NO: X. If the intended gene is one that comprises SEQ ID NO: X, the term should be amended to recite “wherein the sequence … is SEQ ID NO: X”.
The term “wherein the genetically engineered bacterium overexpresses any one of combinations (a)-(d) based on the recombinant Corynebacterium glutamicum” is unclear and confusing because (a) the term “overexpresses” is a relative term and the claim fails to provide the basis for comparison so that one could determine “overexpression” (e.g., overexpresses compared to what?), and (b) one cannot determine the meaning of the term “based on the recombinant Corynebacterium glutamicum ….” and how it further limits the claim. In addition, it is unclear as to which combinations are being referred to and how one could overexpress combinations (i.e., combinations of what?). Please note that (a)-(d) as recited appear to be definitions for a series of genes but there is no statement indicating that these definitions are somehow a combination.
If the intended limitation is “wherein the recombinant C. glutamicum expresses any one of the combinations of genes selected from (a) an E. coli tktA gene; an E. coli K12 3-deoxy-7-phosphoheptulonate synthase gene having the sequence of SEQ ID NO: 45; a Rattus norvegicus O-methyltransferase gene having the sequence of SEQ ID NO: 46; a Nocardia iowensis carboxylic acid reductase gene having the sequence of SEQ ID NO: 47, a Mycobacterium marinum 4’-phosphopantetheinyl transferase gene having the sequence of SEQ ID NO: 48, a C. glutamicum 5-methyltetrahydroteroyltriglutamate-homocysteine methyltransferase gene having the sequence of SEQ ID NO: 49……; and a C. glutamicum adenosylhomocysteinase gene having the sequence of SEQ ID NO: 52; (b) a C. glutamicum transketolase gene having the sequence of SEQ ID NO: 83, a C. glutamicum 3-deoxy-7-phosphoheptulonate synthase gene having the sequence of SEQ ID NO: 84……(c) a S. cerevisiae S288C tkl1 gene; a S. cerevisiae S288C aro4 gene, a Homo sapiens O-methyltransferase gene having the sequence of SEQ ID NO: 105….and (d) an E. coli K12 tktA gene; an E. coli K12 3-deoxy-7-phosphoheptulonate synthase gene having the sequence of SEQ ID NO: 45;…. and a C. glutamicum adenosylhomocysteinase gene having the sequence of SEQ ID NO: 52”, the claim should be amended accordingly. For examination purposes, it will be assumed that the claim recites the language indicated above with regard to the combinations. Correction is required.
Claim 10 is indefinite in the recitation of “fud genes…..fud genes with a combination of genes selected from any one of the combinations (a), (b), (c) and (d)” for the following reasons. It is reiterated herein that the term “fud gene” is unclear because there is no known gene in C. glutamicum which is called “fud”. See also extensive discussion above as to the reasons why this term is found indefinite. In addition, there is no antecedent basis for the combinations (a), (b), (c) and (d). Please note that claim 10 as amended is now an independent claim. It is suggested the claim be amended to recite the combinations that are recited in claim 9. The Examiner will interpret the claim to recite the combinations of genes as interpreted above with regard to claim 9. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(d) or Fourth Paragraph (pre-AIA )
Claim 10 was rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In view of the amendment of claim 10 which is now an independent claim, this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 9-10 were 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 and enablement requirements.
In view of the amendments to the claims and in view of the interpretation given to the claims as set forth above, these rejections are hereby withdrawn.
Conclusion
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
Applicant is advised that any Internet email communication by the Examiner has to be authorized by Applicant in written form. See MPEP § 502.03 (II). Without a written authorization by Applicant in place, the USPTO will not respond via Internet email to any Internet correspondence which contains information subject to the confidentiality requirement as set forth in 35 U.S.C. 122. Sample written authorization language can be found in MPEP § 502.03 (II). An Authorization for Internet Communications in a Patent Application or Request to Withdraw Authorization for Internet Communications form (SB/439) can be found at https://www.uspto.gov/patent/forms/ forms-patent-applications-filed-or-after-september-16-2012, which can be electronically filed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
January 29, 2026