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 .
Status of the Application
1. Claims 1-17 are pending and subject to examination on the merits. Claims 4-14 are 16-17 are withdrawn from consideration as being drawn to non-elected subject matter. Additionally, SEQ ID NO: 133 was elected. Claims 1-3 and 15 are currently under examination.
Priority
2. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China (CN202110684461.5) on 21 June 2021. It is noted, however, that applicant has not filed a certified copy of the CN202110684461.5 application as required by 37 CFR 1.55.
Acknowledgement is made of applicant’s claim for foreign priority based on an application filed in China (CN202110682123.8 on 20 June 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
3. Applicant’s election without traverse of Group I (Claims 1-3 and 15) and SEQ ID NO: 133 in the reply filed on 07 April 2026 is acknowledged.
Drawings
4. The drawings are objected to because Figs. 1 and 9 recite “IRED” without properly defining the abbreviation. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
5. The disclosure is objected to because of the following informalities: “Aeromonas veronii” should be italicized to “Aeromonas veronii” to conform with conventional scientific name nomenclature (paragraph 0014). “Escherichia coli BL21(DE3)” should be italicized to “Escherichia coli BL21(DE3) (paragraph 0045). “Escherichia coli BL21” should be italicized to “Escherichia coli BL21 (paragraph 0047). “Aeromonas veronii” should be italicized to “Aeromonas veronii” (paragraph 0069). “Escherichia coli BL21(DE3)” should be italicized to “Escherichia coli BL21(DE3) (paragraph 0069). “E. coli” should be italicized to “E. coli” (paragraph 0069, 0070). “Escherichia coli BL21(DE3)” should be italicized to “Escherichia coli BL21(DE3) (paragraph 0123).
Appropriate correction is required.
Claim Objections
6. Claim 3 objected to because of the following informalities: “one of amino acid sequences selecting from a group consisting of” should be amended to “one of the amino acid sequences selected from the group consisting of” to improve grammar. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
7. 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.
8. Claims 1-3 and 15 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.
9. Claim 1 recites “comprising a mutation in an amino acid sequence represented by SEQ ID NO: 1,” where the term “an” does not make it clear that the mutant consists of the full length of SEQ ID NO: 1 or a partial sequence of SEQ ID NO: 1. Claim 1 should be amended to recite “comprising a mutation in the amino acid sequence.” Claims 2-3 and 15 are included in the instant rejection, since they do not mitigate the issue.
10. Claim 1 recites “comprising a mutation in an amino acid sequence represented by SEQ ID NO: 1,” where the term “represented by” does not make it clear that the mutant consists of of SEQ ID NO: 1 or some other sequence. Claim 1 should be amended to recite “comprising a mutation in the amino acid sequence of SEQ ID NO: 1.” Claims 2-3 and 15 are included in the instant rejection, since they do not mitigate the issue.
11. Claim 15 recites the limitation "An imine reductase mutant" in line 1. To establish antecedent basis from claims 11 and previously 1, claim 15 should be amended to “The imine reductase mutant” to clearly delineate dependency, ensure no confusion, and to avoid introducing broader subject matter to the claim.
Claim Rejections - 35 USC § 103
12. 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.
13. 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.
14. Claims 1-2 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Zumbragel et al (Zumbragel et al., 2019, J. Org. Chem.—cited herein) and Aleku et al. (Aleku et al., 2016, ACSCatalysis—cited herein) as evidenced by Velikogne (Velikogne et al., 2018, ChemCatChem—cited herein). Claims 1-2, drawn to an imine reductase mutant, comprising an amino acid sequence represented by SEQ ID NO: 1, wherein, the mutation in the amino acid sequence comprises V171Y/N/A/S, A172V/F, Y230G/A/T or a combination thereof. Zumbragel et al. teaches the enantioselective biocatalytic reduction of 2H-1,4-Benzoxazines using imine reductases, where 2 of the imine reductases tested are Aeromonas veronii (Table S1 and Figure 1), specifically IRED28 and IRED29, where IRED29 had activity toward all of the 2H-1,4-benzoxazines tested, and IRED28 had activity against one of the tested 2H-1,4-benzoxazines (Figure 1), where SEQ ID NO: 1 is identified as Aeromonas veronii (See Supplemental file: 20260508_125735_us-18-389-868-1.rag; Result 1, Duplicate 4). Regarding claim 15, drawn to the production of the imine reductase mutant of claim 1 by culturing a cell to generate the imine reductase mutant, Zumbragel et al. teaches the expression of the IREDS in E. coli BL21(DE3).
Zumbragel et al. does not teach mutations at V171 (V171Y/N/A/S), A172V/F, or Y230G/A/T (claims 1-2). Aleku et al. teaches the Amycolaptopsis orientalis imine reductase with amino acid 171 naturally as an N and is mutated to an A to determine the contribution of the amino acid to the S-selectivity of the enzyme (abstract), where amino acid 171 is part the conserved regions of many different imine reductases start at or include the amino acid 171, as evidenced by Velikogne et al (Table 1).
Therefore, it 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 combine the teachings of Zumbragel et al. and Aleku et al. as evidenced by Velikogne et al. to mutate amino acid 171 of SEQ ID NO: 1 to an N or A to alter or determine the S- or R- stereoselectivity of the enzyme as taught by Aleku et al. One would be motivated to combine these teachings to arrive at the instant claims to alter amino acid 171 of SEQ ID NO: 1 to an N or an A because producing imine reductases that are capable of asymmetric synthesis of chiral amines is important to chemical industries, as these moieties feature in a large proportion of pharmaceuticals and agrochemicals as taught by Aleku et al (p. 3880, Introduction). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Zumbragel et al. and Aleku et al. as evidenced by Velikogne et al. to mutate amino acid 171 of SEQ ID NO: 1 to an N or A, since Aleku et al. teaches an N at amino acid 171 and the mutation thereof to A.
Conclusion
16. All claims are rejected; however, it is noted that no prior art was found on SEQ ID 133 (claim 3) which has mutations at amino acid positions V171A, A172N, Q202R, D213E. Claim 3 would be allowable if its dependency on claim 2 is deleted.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath 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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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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