DETAILED ACTION
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 election of Group I (Invention I) in the reply filed on 05/19/2026 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 § 818.03(a)).
Claims 6-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The requirement is still deemed proper and is therefore made FINAL.
Claims 1-5 are under consideration in this Office Action.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd 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.
Claims 1-5 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 1 encompasses any carbonyl reductase mutant, wherein the mutation site of the carbonylreductase mutant comprises positions 88, 142, 190, and 193 of the amino acid sequence as shown in SEQ ID NO: 1. However the claim is vague and indefinite since it is unclear if the mutant comprises the amino acid sequence of SEQ ID NO: 1 and any mutations including substitution mutations. Dependent claims 2-5 are also rejected because they do not correct the defect. For examination purposes the claim will not be limited to a specific amino acid SEQ ID NO.
Claims 2 and 4 recite “preferably” which renders the claim vague and indefinite since it is uncertain if the claims are limited to the subject matter recited after “preferably”.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 1-5 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 claims are drawn to a broad and widely varying genus of any carbonyl reductase mutants having any mutations and of any amino acid sequence and structure wherein the mutation site of the carbonyl reductase mutant comprises positions 88, 142, 190, and 193 of the amino acid sequence as shown in SEQ ID NO: 1. According to MPEP 2163:
“For each claim drawn to a genus: The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…”
According to MPEP 2163.02:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; PTO 892) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; PTO 892) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a 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 entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). The reference teachings only provide guidance for searching and screening for the claimed carbonyl reductase mutant.
The specification as originally filed does not disclose a representative number of species encompassed by the claimed genus by actual reduction to practice. The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict which amino acid sequences and structures correlate with carbonyl reductase activity where the said carbonyl reductase mutant has higher enzymatic activity than wild-type carbonyl reductase.
Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants were in possession at the time the application was filed of the claimed genus of any carbonyl reductase mutants having any mutations and of any amino acid sequence and structure, wherein the mutation site of the carbonyl reductase mutant comprises positions 88, 142, 190, and 193 of the amino acid sequence as shown in the amino acid sequence of SEQ ID NO: 1.
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 of this title, 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 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Accession ADS18090 (16-DEC-2004; PTO 892) in view of Bornscheuer et al. (Curr Protoc Protein Sci. 2011 Nov;Chapter 26:Unit26.7; PTO 892), US20160040138 (2016-02-11; PTO 892).
Accession ADS18090 teaches the Exiguobacterium sp. carbonyl reductase having an amino acid sequence that is 100% identical to SEQ ID NO: 1 where said carbonyl reductase
has the ability to reduce a carbonyl group and synthesize optically active alcohol (see attached record and alignment).
The teachings of the reference differ from the claims in that the reference does not teach the claimed carbonyl reductase mutant.
Bornscheuer et al. teach protein engineering strategies to improve or change the properties of proteins, teach concepts for protein engineering using rational design including substitution and/or deletion of amino acids, directed evolution, and combinations of them where different strategies are presented for identifying the best mutagenesis method, how to identify desired variants by screening or selection, and examples for successful applications are shown which enable researchers to choose the most promising tools to solve their protein engineering challenges (see entire publication especially pages 26.7.1- 26.7.10 and Tables 26.7.1, 26.7.2, and 26.7.3).
US20160040138 teach altered carbonyl reductases having better reactivity in the presence of an organic solvent than the wild-type enzyme, from among a mutant enzyme library prepared by randomly mutating the wild-type enzyme gene; and methods for producing optically active alcohols useful as starting materials or intermediates for the synthesis of pharmaceuticals or agricultural chemicals (see entire publication and claims especially paragraphs [0010] - [0083]. US20160040138 teach the following in the claims:
1. A polypeptide having the following properties (a) to (c):
(a) the polypeptide comprises an amino acid sequence having at least 78% sequence identity to the amino acid sequence of SEQ ID NO:1 in the sequence listing;
(b) the polypeptide reduces 2-pentanone into 2-pentanol; and
(c) the polypeptide has higher reactivity to a carbonyl compound in the presence of an organic solvent and/or higher thermal stability than a carbonyl reductase comprising the amino acid sequence of SEQ ID NO:1 in the sequence listing.
2. The polypeptide according to claim 1,
wherein the organic solvent is dimethylformamide.
3. The polypeptide according to claim 1,
wherein the polypeptide comprises an amino acid substitution, relative to the amino acid sequence of SEQ ID NO:1 in the sequence listing, at one or more positions selected from the group consisting of positions 2, 22, 25, 39, 42, 45, 51, 56, 71, 87, 90, 102, 109, 124, 135, 138, 155, 159, 175, 177, 183, 190, 195, 212, 220, 226, 228, 236, 238, 250, 254, 257, 259, 265, 267, 270, 279, 298, 300, 301, and 331.
4. The polypeptide according to claim 3,
wherein the amino acid substitution is one or more of the following amino acid substitutions relative to the amino acid sequence of SEQ ID NO:1 in the sequence listing:
substitutions at position 2 with isoleucine, at position 22 with arginine, at position 25 with phenylalanine, at position 39 with arginine, at position 42 with arginine, at position 45 with aspartic acid, at position 51 with alanine, at position 56 with lysine, at position 71 with asparagine or arginine, at position 87 with isoleucine, at position 90 with glycine, at position 102 with isoleucine, at position 109 with glycine, at position 124 with leucine, at position 135 with alanine, at position 138 with asparagine, at position 155 with leucine or arginine, at position 159 with phenylalanine, at position 175 with aspartic acid, at position 177 with phenylalanine, at position 183 with threonine, at position 190 with serine, at position 195 with leucine, at position 212 with phenylalanine, threonine, or tyrosine, at position 220 with valine, at position 226 with glycine, at position 228 with valine, at position 236 with asparagine, at position 238 with isoleucine, at position 250 with proline, at position 254 with asparagine, at position 257 with serine, at position 259 with glutamic acid, at position 265 with lysine, at position 267 with proline, at position 270 with methionine, at position 279 with arginine, at position 298 with proline, at position 300 with aspartic acid, at position 301 with cysteine, and at position 331 with phenylalanine.
5. The polypeptide according to claim 4,
wherein the amino acid substitution is one or more of the following amino acid substitutions relative to the amino acid sequence of SEQ ID NO:1 in the sequence listing:
substitutions at position 2 with isoleucine, at position 45 with aspartic acid, at position 71 with asparagine or arginine, at position 102 with isoleucine, at position 124 with leucine, at position 175 with aspartic acid, at position 177 with phenylalanine, at position 183 with threonine, at position 195 with leucine, at position 220 with valine, at position 226 with glycine, at position 236 with asparagine, at position 238 with isoleucine, at position 257 with serine, at position 259 with glutamic acid, at position 265 with lysine, at position 267 with proline, at position 270 with methionine, at position 300 with aspartic acid, and at position 301 with cysteine, and
the polypeptide has better stability to the organic solvent than the carbonyl reductase comprising the amino acid sequence of SEQ ID NO:1 in the sequence listing.
6. The polypeptide according to claim 5,
wherein the amino acid substitution is selected from the following amino acid substitutions (1) to (35) relative to the amino acid sequence of SEQ ID NO:1 in the sequence listing:
(1) an amino acid substitution at position 71 with asparagine and at position 195 with leucine;
(2) an amino acid substitution at position 71 with arginine and at position 259 with glutamic acid;
(3) an amino acid substitution at position 71 with arginine and at position 270 with methionine;
(4) an amino acid substitution at position 71 with arginine and at position 300 with aspartic acid;
(5) an amino acid substitution at position 102 with isoleucine and at position 270 with methionine;
(6) an amino acid substitution at position 177 with phenylalanine and at position 220 with valine;
(7) an amino acid substitution at position 226 with glycine and at position 270 with methionine;
(8) an amino acid substitution at position 257 with serine and at position 259 with glutamic acid;
(9) an amino acid substitution at position 257 with serine and at position 270 with methionine;
(10) an amino acid substitution at position 259 with glutamic acid and at position 270 with methionine;
(11) an amino acid substitution at position 259 with glutamic acid and at position 300 with aspartic acid;
(12) an amino acid substitution at position 267 with proline and at position 270 with methionine;
(13) an amino acid substitution at position 270 with methionine and at position 300 with aspartic acid;
(14) an amino acid substitution at position 2 with isoleucine, at position 259 with glutamic acid, and at position 270 with methionine;
(15) an amino acid substitution at position 45 with aspartic acid, at position 175 with aspartic acid, and at position 183 with threonine;
(16) an amino acid substitution at position 102 with isoleucine, at position 226 with glycine, and at position 267 with proline;
(17) an amino acid substitution at position 124 with leucine, at position 259 with glutamic acid, and at position 270 with methionine;
(18) an amino acid substitution at position 177 with phenylalanine, at position 259 with glutamic acid, and at position 270 with methionine;
(19) an amino acid substitution at position 220 with valine, at position 259 with glutamic acid, and at position 270 with methionine;
(20) an amino acid substitution at position 236 with asparagine, at position 259 with glutamic acid, and at position 270 with methionine;
(21) an amino acid substitution at position 238 with isoleucine, at position 259 with glutamic acid, and at position 270 with methionine;
(22) an amino acid substitution at position 257 with serine, at position 259 with glutamic acid, and at position 270 with methionine;
(23) an amino acid substitution at position 257 with serine, at position 259 with glutamic acid, and at position 300 with aspartic acid;
(24) an amino acid substitution at position 259 with glutamic acid, at position 265 with lysine, and at position 270 with methionine;
(25) an amino acid substitution at position 259 with glutamic acid, at position 270 with methionine, and at position 300 with aspartic acid;
(26) an amino acid substitution at position 259 with glutamic acid, at position 270 with methionine, and at position 301 with cysteine;
(27) an amino acid substitution at position 2 with isoleucine and at position 238 with isoleucine;
(28) an amino acid substitution at position 71 with asparagine and at position 195 with leucine;
(29) an amino acid substitution at position 109 with glycine and at position 331 with phenylalanine;
(30) an amino acid substitution at position 124 with leucine and at position 236 with asparagine;
(31) an amino acid substitution at position 159 with phenylalanine and at position 259 with glutamic acid;
(32) an amino acid substitution at position 42 with arginine, at position 155 with arginine, and at position 279 with arginine;
(33) an amino acid substitution at position 45 with aspartic acid, at position 175 with aspartic acid, and at position 183 with threonine;
(34) an amino acid substitution at position 155 with leucine, at position 250 with proline, and at position 298 with proline; and
(35) an amino acid substitution at position 56 with lysine, at position 138 with asparagine, at position 190 with serine, and at position 254 with asparagine.
7. The polypeptide according to claim 4,
wherein the amino acid substitution is one or more of the following amino acid substitutions:
substitutions at position 22 with arginine, at position 39 with arginine, at position 51 with alanine, at position 87 with isoleucine, at position 90 with glycine, at position 259 with glutamic acid, and at position 270 with methionine, and
the polypeptide has better resistance to reaction inhibition by the organic solvent than the carbonyl reductase comprising the amino acid sequence of SEQ ID NO:1 in the sequence listing.
8. The polypeptide according to claim 7,
wherein the amino acid substitution is one or more of the following amino acid substitutions (1) to (7) relative to the amino acid sequence of SEQ ID NO:1 in the sequence listing:
(1) an amino acid substitution at position 22 with arginine;
(2) an amino acid substitution at position 22 with arginine and at position 87 with isoleucine;
(3) an amino acid substitution at position 39 with arginine;
(4) an amino acid substitution at position 39 with arginine and at position 51 with alanine;
(5) an amino acid substitution at position 51 with alanine;
(6) an amino acid substitution at position 87 with isoleucine; and
(7) an amino acid substitution at position 90 with glycine.
15. A method for producing an alcohol compound, comprising
allowing the polypeptide according to claim 1 and/or a treated product thereof to act on a carbonyl compound.
16. The method according to claim 15,
wherein the carbonyl compound is an unsymmetrical ketone, and the alcohol compound is an optically active alcohol.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by using the protein engineering teachings of Bornscheuer et al. on the Exiguobacterium sp. carbonyl reductase of Accession ADS18090 teaches the Exiguobacterium sp. carbonyl reductase to make the claimed carbonyl reductase mutant comprising the amino acid sequence of SEQ ID NO: 1 and the amino acid mutations recited in each of all the claims. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a carbonyl reductase that can be used in methods for producing optically active alcohols useful as starting materials or intermediates for the synthesis of pharmaceuticals or agricultural chemicals as taught by US20160040138. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because modifying carbonyl reductase s are known in the art as shown by the above reference teachings especially the teachings of US20160040138. Hence, the claimed invention as a whole is prima facie obvious.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christian L Fronda whose telephone number is (571)272 0929. The examiner can normally be reached Monday-Thursday and alternate Fridays between 9:00AM-5:00PM.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652
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