Prosecution Insights
Last updated: April 19, 2026
Application No. 18/696,968

NOVEL ACETOHYDROXY ACID SYNTHASE MUTANT AND L-ISOLEUCINE PRODUCTION METHOD USING SAME

Non-Final OA §102§112
Filed
Mar 28, 2024
Examiner
SAIDHA, TEKCHAND
Art Unit
1652
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Cj Cheiljedang Corporation
OA Round
1 (Non-Final)
83%
Grant Probability
Favorable
1-2
OA Rounds
2y 6m
To Grant
97%
With Interview

Examiner Intelligence

Grants 83% — above average
83%
Career Allow Rate
865 granted / 1044 resolved
+22.9% vs TC avg
Moderate +14% lift
Without
With
+13.9%
Interview Lift
resolved cases with interview
Typical timeline
2y 6m
Avg Prosecution
25 currently pending
Career history
1069
Total Applications
across all art units

Statute-Specific Performance

§101
3.4%
-36.6% vs TC avg
§103
14.4%
-25.6% vs TC avg
§102
19.9%
-20.1% vs TC avg
§112
37.0%
-3.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1044 resolved cases

Office Action

§102 §112
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 . DETAILED ACTION 1. Preliminary amendment and claims 1-12 filed 3/28/24 are present and under consideration in this Office Action. 2. Priority Receipt is acknowledged of papers (foreign priority filed 9/29/21) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file. 3. 35 U.S.C. § 112, first paragraph (Written Description) Claims 1-12 are 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. The claimed invention is directed to the following genus claims. 1. (Original) An acetohydroxy acid synthase (AHAS) variant, wherein an amino acid corresponding to position 42 and an amino acid corresponding to position 47 in an amino acid sequence of SEQ ID NO: 1 are each substituted with another amino acid. 2. (Original) The variant of claim 1, wherein the amino acid corresponding to position 42 is substituted with valine. 3. (Original) The variant of claim 1, wherein the amino acid corresponding to position 47 is substituted with leucine. 4. (Original) The variant of claim 1, wherein the amino acid corresponding to position 42 is alanine. 5. (Original) The variant of claim 1, wherein the amino acid corresponding to position 47 is histidine. 6. (Currently Amended) A polynucleotide encoding the variant of claim[[s]] 1. 7. (Currently Amended) A strain of the genus Corynebacterium, comprising the variant of any one of claim[[s]] 1 to 5; or a polynucleotide encoding the variant. 8. (Original) The strain of claim 7, wherein the strain has an increased L-isoleucine producing ability, as compared to a strain of the genus Corynebacterium including a wild-type acetohydroxy acid synthase having an amino acid sequence of SEQ ID NO: 1 or a polynucleotide encoding the same. 9. (Original) The strain of claim 7, wherein the strain is Corynebacterium glutamicum. 10. (Currently Amended) A method of producing L-isoleucine, the method comprising the step of culturing, in a medium, a strain of the genus Corynebacterium including the variant of claim[[s]] 1; or a polynucleotide encoding the variant. 11. (Currently Amended) A composition for producing L-isoleucine, the composition comprising the variant of claim[[s]] 1, a polynucleotide encoding the variant, a vector including the polynucleotide, a strain of the genus Corynebacterium including the polynucleotide of the present disclosure; a culture medium thereof; or a combination of two or more thereof. 12. (Currently Amended) Use of the variant of any one of claim[[s]] 1; a polynucleotide encoding the variant; or a strain of the genus Corynebacterium including the variant or the polynucleotide encoding the variant in the production of L-isoleucine. The claimed invention encompasses a genus of acetohydroxy acid synthase (AHAS) variants, polynucleotide encoding the variants and compositions comprising the variants/polynucleotides with no limit to the extent to the homology, as an amino acid sequence of SEQ ID NO: 1 could be interpreted to mean a fraction of the sequence and therefore not adequately described. The instant specification describes “An acetohydroxy acid synthase (AHAS) variant, wherein an amino acid sequence at least 95% identical to the sequence of SEQ ID NO: 1 and wherein position 42 and position 47 in the amino acid sequence of SEQ ID NO: 1 are each substituted with another amino acid, and wherein the variant has acetohydroxy acid synthase activity. The polynucleotide encoding such a variant or composition comprising the variant are also described. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated: "To fulfill the written description requirement, a patent specification must describe aninvention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what isclaimed."). Thus, an applicant complies with the written description requirement "bydescribing the invention, with all its claimed limitations, not that which makes it obvious,"and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966."Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398. Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents" of the University of California v. Eli Lilly & Co. the court stated: "A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents" of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398. The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case is discussed below. Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art. Moreover, Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir.1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993). Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed. 4. Claim Rejections - 35 USC § 112 (second paragraph) 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 12 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 pre-AIA the applicant regards as the invention. Claim 12 recites - Use of the variant of claim 1; a polynucleotide encoding the variant; or a strain of the genus Corynebacterium including the variant or the polynucleotide encoding the variant in the production of L-isoleucine. The claim is unclear regarding the ‘use’ of variant. Changing the claim to a method …….for the production of l-isoleucine…will overcome this rejection. Claims 7-9 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. Claim 7 recites - (Currently Amended) A strain of the genus Corynebacterium, comprising the variant of any one of claim[[s]] 1 to 5; or a polynucleotide encoding the variant. The claim is in the recitation – “any one of claim[[s]] 1 to 5” is confusing and grammatically incorrect. Limiting the dependency to claim 1 will overcome this rejection. Claims 8 & 9 are included in the rejection for failing to correct the defect present in the base claim(s). 5. 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim(s) 1-12 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by US Patent 10,316,297. 1. An acetohydroxy acid synthase variant, wherein the 137.sup.th amino acid from the N-terminus of an amino acid sequence of SEQ ID NO: 3, leucine (L), is substituted with an amino acid other than leucine, and thereby releasing the feedback inhibition to L-valine. 2. The acetohydroxy acid synthase variant of claim 1, wherein the variant has the amino acid sequence of SEQ ID NO: 4. As shown by the sequence alignment between Applicants’ SEQ ID NO: 1 and US patent SEQ ID NO: 3 – presented below – there is a natural variant at positions A42V & H47L. Therefore anticipates claims 1-5. Also in column 2 – lines 28-34, Acetohydroxy acid synthase catalyzes decarboyxlation of pyruvate and a condensation reaction with another pyruvate molecule to produce acetolactate, which is a precursor of valine, or catalyzes decarboyxlation of pyruvate and a condensation reaction with 2-ketobutyrate to produce acetohydroxybutyrate, which is a precursor of isoleucine, will therefore produce isoleucine and reads on claim 10. The encoding DNA is also taught in the sequence of SEQ ID NO: 5. SEQ ID Nos. 3-5 are all from Corynebacterium glutamicum. The variants and the encoding DNA in buffered solution comprise the claimed composition (claim 11), or the DNA & variants of claims 6-9 & 12. PNG media_image1.png 837 782 media_image1.png Greyscale 6. Claim(s) 1-6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2016021932 A1. As shown by the sequence alignment between Applicants’ SEQ ID NO: 1 and WO 2016021932 A1 SEQ ID NO: 4 – presented below – the variant positions A42V & H47L are shown as per the sequence alignment. The encoding DNA is also disclosed. Therefore WO 2016021932 A1 anticipates claims 1-6. PNG media_image2.png 852 961 media_image2.png Greyscale PNG media_image3.png 752 966 media_image3.png Greyscale 7. No claim is allowed. 8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /TEKCHAND SAIDHA/ Primary Examiner, Art Unit 1652 Recombinant Enzymes, Hoteling Telephone: (571) 272-0940 Fax: (571) 273-0940
Read full office action

Prosecution Timeline

Mar 28, 2024
Application Filed
Feb 25, 2026
Non-Final Rejection — §102, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
83%
Grant Probability
97%
With Interview (+13.9%)
2y 6m
Median Time to Grant
Low
PTA Risk
Based on 1044 resolved cases by this examiner. Grant probability derived from career allow rate.

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