DETAILED CORRESPONDENCE
Status of the Application
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 amendment to the claims, filed July 27, 2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s amendment to claim 1 does not comply with 37 CFR 1.121(c), which requires the claim listing to commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment (37 CFR 1.121(c)(1)) and also requires the text of any added subject matter to be shown by underlining the added text (37 CFR 1.121(c)(2)). Applicant’s attention is directed to MPEP 714.II.C regarding amendments to the claims.
Claims 1 and 2 are pending in the application.
Restriction/Election
Applicant's election with traverse of Group I, claims 1 and 2, drawn to the technical feature of an omega-transaminase mutant, omega-transaminase mutant, obtained by carrying out single-point mutation or multi-point combined mutation at positions 275, 115, and 97 of an amino acid sequence shown in SEQ ID NO: 2, and the species of mutation position 97 in the reply filed July 27, 2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Priority
This application is filed under 35 U.S.C. 371 as a national stage of international application PCT/CN2023/138290, filed December 13, 2023, which claims foreign priority under 35 U.S.C. 119(a-d) to Chinese application no. 202211623314.8, filed December 16, 2022.
A certified copy of the foreign priority document has been filed in this application on November 5, 2024. Should applicant desire to obtain the benefit of the filing date of the foreign priority application, a certified English translation of the application must be submitted. Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 5, 2024 has been considered by the examiner.
U.S. Patent Citation 1 has been lined through because the Patent Number 829,350 does not have an issue date of November 11, 2010. It appears applicant has entered the incorrect patent number.
Foreign Patent Documents 1 and 4-8 have been lined through because there is no copy of these references in the application file.
Specification/Informalities
The specification is objected to for disclosing sequences that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2), yet failing to comply with the requirements of 37 CFR 1.821 through 1.825; applicants’ attention is directed to the final rulemaking notice published at 55 FR 18230 (May 1, 1990), and 1114 OG 29 (May 15, 1990). See specification at paragraphs [0064], [0067], and [0078] to [0083].
To be in compliance, applicants should identify nucleotide sequences of at least 10 nucleotides and amino acid sequences of at least 4 amino acids in the specification by a proper sequence identifier, i.e., “SEQ ID NO:” (see MPEP 2422.01). If these sequences have not been listed in the computer readable form and paper copy of the sequence listing, applicant must provide an initial computer readable form (CRF) copy of the “Sequence Listing”, an initial paper copy of the “Sequence Listing”, as well as an amendment directing its entry into the specification, and a statement that the content of the paper and CRF copies are the same and, where applicable, include no new matter as required by 37 C.F.R. 1.821(e) or 1.821(f) or 1.821(g) or 1.821(b) or 1.825(d).
Claim Objections
Claim 2 is objected to in the recitation of “mutation” and in the interest of improving claim form and improving consistency with claim 1, it is suggested that all instances of the term “mutation” in claim 2 be replaced with “substitution.”
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) 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 this case, claim 2 repeats the substitutions recited in claim 1 and fails to further limit the omega-transaminase mutant of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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.
Claims 1 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (CN 112048485 A; cited on the attached Form PTO-892; hereafter “Chen-1”) in view of
Chen et al. (WO 2023/169184 A1; cited on the attached Form PTO-892; hereafter “Chen-2”),
Schultz et al. (Proteins Structure and Function, pp. 521-528, Plenum Press, New York, 1987; cited on the attached Form PTO-892; hereafter “Schultz”), and
Airaksinen et al. (Nucleic Acids Res. 26:576-581, 1998; cited on the attached Form PTO-892; hereafter “Airaksinen”).
Reference is made to a machine translation of Chen-1 (cited on the attached Form PTO-892; hereafter “translation”).
In the interest of clarity, it is noted that following rejection is directed to the non-elected species of mutation position 115. However, the non-elected species has yet to be searched and examined on the merits because the cited prior art was identified during a search and examination of the elected species of mutation position 97.
The claims are drawn to an omega-transaminase mutant, comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2, wherein the amino acid sequence comprises, relative to SEQ ID NO: 2, one or more amino acid substitutions selected from the group consisting of: (1) a substitution of glycine at position 275 with alanine (G275A); (2) a substitution of lysine at position 115 with methionine (K115M); and (3) a substitution of lysine at position 97 with arginine (K97R), wherein the positions are numbered with reference to SEQ ID NO: 2, and wherein the mutant has omega-transaminase activity (claim 1),
wherein the mutation is one or a combination of two or more of the following: (1) mutation of glycine at the position 275 to alanine; (2) mutation of lysine at the position 115 to methionine; and (3) mutation of lysine at the position 97 to arginine (claim 2).
Chen-1 is directed to an engineered transaminase polypeptide (translation at p. 1, top). Chen-1 teaches an improved engineered transaminase polypeptide derived from the wild-type Aspergillus fumigatus transaminase, the improved engineered transaminase polypeptide comprising the amino acid sequence of SEQ ID NO: 8 (translation at p. 1, middle-bottom). SEQ ID NO: 8 of Chen-1 is identical to instant SEQ ID NO: 2 (see attached Appendix for sequence alignment). Chen-1 teaches that SEQ ID NO: 8 has a substitution at position 115 (translation at p. 5, Table 2). Chen-1 teaches a desired improved property of the engineered transaminase polypeptide includes solvent stability (translation at p. 4, middle).
Chen-1 does not teach substituting position 115 with methionine.
Chen-2 is also directed to an engineered transaminase polypeptide (p. 1, top) derived from the wild-type Aspergillus fumigatus transaminase (p. 4, bottom; p. 20, bottom). Chen-2 teaches position 115 as a mutagenesis site predicted to be beneficial for stability in solvents (p. 22, Table 4). Chen-2 teaches subjecting the candidate mutagenesis site to saturation mutagenesis (p. 22, top).
The reference of Schultz teaches that in order to thoroughly study the role of a residue in a polypeptide, substitution with all 19 possible amino acids (site saturation) is necessary (p. 521, first full paragraph).
The reference of Airaksinen teaches saturation mutagenesis is intended to replace a given codon with any amino acid in order to gain several different amino acid substitutions by the same effort and to obtain information about the nature of acceptable substitutive amino acids (p. 576, column 1, bottom).
In view of the combined teachings of Chen-1, Chen-2, Schultz, and Airaksinen, it would have been obvious to one of ordinary skill in the art before the effective filing date to perform saturation mutagenesis at position 115 of the engineered transaminase polypeptide of Chen-1, which would have replaced the amino acid at position 115 with all 19 other common amino acids including methionine. One would have been motivated to do so because Chen-1 taught an engineered transaminase polypeptide and suggests improving the property of solvent stability, Chen-2 taught position 115 as a mutagenesis site predicted to be beneficial for solvent stability and taught subjecting the candidate mutagenesis site to saturation mutagenesis, Schultz taught that in order to study the role of an important residue in a polypeptide, substitution with all 19 possible amino acids (site saturation) is necessary, and Airaksinen teaches replacing a single codon with the 19 other amino acids by a single mutagenesis process to obtain information about the nature of acceptable substitutive amino acids. One would have had a reasonable expectation of success to perform saturation mutagenesis at position 115 of the engineered transaminase polypeptide of Chen-1 because Chen-2 taught subjecting position 115 to saturation mutagenesis and each of Schultz and Airaksinen taught a protocol for saturation mutagenesis.
Therefore, claims 1 and 2 would have been obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
Status of the claims:
Claims 1 and 2 are pending.
Claims 1 and 2 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MANJUNATH N 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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/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX
ID BIU38513 standard; protein; 323 AA.
XX
AC BIU38513;
XX
DT 18-FEB-2021 (first entry)
XX
DE Mutant Aspergillus fumigatus transaminase polypeptide, SEQ ID 8.
XX
KW enzyme engineering; enzyme production; mutein; sitagliptin; transaminase.
XX
OS Aspergillus fumigatus.
OS Synthetic.
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CC PN CN112048485-A.
XX
CC PD 08-DEC-2020.
XX
CC PF 07-JUN-2019; 2019CN-10493876.
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PR 07-JUN-2019; 2019CN-10493876.
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CC PA (NING-) NINGBO MEISAI BIOLOGICAL ENG CO LTD.
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CC PI Chen H, Luo X, Cai B, Shang C, Sun L, Bocola M, Hu D, Wang Z;
CC PI Yu J;
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DR WPI; 2020-C4911P/005.
DR N-PSDB; BIU38512.
XX
CC PT New engineered aminotransferase polypeptide having ability to convert in
CC PT presence of amino donor, (2,4,5-trifluorophenyl)butan-1-one derivative
CC PT into sitagliptin intermediates, has specific amino acid sequence.
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CC PS Claim 5; SEQ ID NO 8; 37pp; Chinese.
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CC The present invention relates to a novel engineered transaminase
CC polypeptide useful for converting (2,4,5-trifluorophenyl) butan-1-one
CC derivative into sitagliptin intermediates. The invention further
CC provides: a polynucleotide encoding the novel polypeptide; an expression
CC vector comprising the polynucleotide; a host cell comprising the
CC expression vector; a method for preparing the transaminase polypeptide;
CC and a transaminase catalyst chosen from the culture, obtained from the
CC host cell or culture medium containing the transaminase polypeptide. The
CC present sequence represents a mutant transaminase comprising
CC V60G/I61F/S62H/F113M/E115K/V148L/T187I/L190M/S214P/A275G. Note: This
CC sequence is a mutant of the parent sequence shown in SEQ ID NO: 2 (see
CC BIU38507).
XX
SQ Sequence 323 AA;
Query Match 100.0%; Score 1707; Length 323;
Best Local Similarity 100.0%;
Matches 323; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MATMDKVFAGYYARQKLLERSDNPFSKGIAYVEGKFVLPSEARIPLLDEGFMGSDLTYDG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MATMDKVFAGYYARQKLLERSDNPFSKGIAYVEGKFVLPSEARIPLLDEGFMGSDLTYDG 60
Qy 61 FHVWDGRFFRLDDHLQRLLESCDKMRLKFPLALSSVKKILVEMVAKSGIRDAMGKIIVTR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FHVWDGRFFRLDDHLQRLLESCDKMRLKFPLALSSVKKILVEMVAKSGIRDAMGKIIVTR 120
Qy 121 GLTGVQGSKPEDLYNNNIYLLVLPYIWLMAPEKQRHGGSAIITRTVRRTPPGAFDPTIKN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GLTGVQGSKPEDLYNNNIYLLVLPYIWLMAPEKQRHGGSAIITRTVRRTPPGAFDPTIKN 180
Qy 181 LQWGDLIRGMFEAKDRGATYPFLTDGDTHLTEGPGFNIVLVKNGILYTPDRGVLEGITRK 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LQWGDLIRGMFEAKDRGATYPFLTDGDTHLTEGPGFNIVLVKNGILYTPDRGVLEGITRK 240
Qy 241 SVIEVARANSIDVRLEVVPVETAYHADEIFMCTTGGGIMPITLLDGKPVNDGQVGPITKK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SVIEVARANSIDVRLEVVPVETAYHADEIFMCTTGGGIMPITLLDGKPVNDGQVGPITKK 300
Qy 301 IWDGYWEMHYNAAYSFPVDYGSD 323
|||||||||||||||||||||||
Db 301 IWDGYWEMHYNAAYSFPVDYGSD 323
Prosecution Insights