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 .
Election/Restrictions
1. Applicant’s election without traverse of the invention of Group I (drawn to a recombinant yeast) and the species FAS2, M. hydrocarbonoclasticus (same as M. aquaeolei) and S. cerevisiae, SEQ ID NOs: 4 and 6, pQCR10 and pPRB1, a strain expressing all EEB1/EHT1/MGL2, and characteristics (a) and (b) of claim 32, in the reply filed on 12/15/2025 is acknowledged.
Claims 4, 5, 7, 8, 10, 11, 13, 15, 16, 18, 20, 21, 23, 25, 27, 29-31, 33-35, 38, 40-46, 48, 50-53, and 55-77 have been cancelled.
Claims 9, 12, 19, 24, 36, 37, 39, 47, 49, 79, and 80 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions and species, there being no allowable generic or linking claim.
Claims 1-3, 6, 9, 14, 17, 22, 26, 28, 32, 54, and 78 are under examination.
Claim Objections
1. Claim 3 is objected to because of the recitation “the enzyme having AAT activity comprises a sequence having at least 90% sequence identity to”. The term “comprising” in this case is not appropriate because the enzyme having AAT activity cannot comprise more than its amino acid sequence. Correction to “the amino acid sequence of the enzyme having AAT activity is at least 90% identical to” is suggested.
2. Claim 14 is objected to because of the recitation “the enzyme having FAS2 activity comprises a sequence having at least 90% sequence identity to”. Correction to “the amino acid sequence of the enzyme having FAS2 activity is at least 90% identical to” is suggested.
3. Claim 22 is objected to because of the recitation “an enzyme” in line 2. Correction to “the enzyme” is required.
4. Claim 78 is objected to because of the recitation “a promoter” in lines 2-3. Correction to “the promoter” is required.
Claim Rejections - 35 USC § 112(b)
5. 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.
6. Claims 1-3, 6, 17, 26, 28, and 54 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “enzyme having fatty acid synthase (FAS2) activity”. The enzymes having fatty acid synthase activity represent a genus, while the enzymes having FAS2 activity are a subgenus (see Kawaguchi, Comprehensive Natural Products Chemistry, 1999, Abstract). The embodiment within parenthesis may be set forth in another dependent claim; when stated in a single claim, the embodiment within parenthesis leads to confusion over the intended scope of the claim because it is not clear whether the claim is limited by the genus of enzymes having fatty acid synthase activity or the specific FAS2 subgenus recited within parenthesis. Claims 2, 3, 6, 26, 28, and 54 are rejected for being dependent from the rejected claim 1 and also for failing to further clarify the basis of the rejection.
Claim 17 is indefinite as being both incomplete, by its dependence on a cancelled claim; and for lack of antecedent basis for its limitation which is not present in the cancelled base claim. Amending claim 17 to refer to a claim which recites FAS2 would obviate this rejection.
Claim Rejections - 35 USC § 102
7. 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.
8. Claims 1, 14, 28, 32, 54, and 78 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (CN 110804561), as evidenced by Saccharomyces Genome Database. The English language translation of CN 110804561 is provided. The passages cited below which indicate the teachings of the CN 110804561 publication are based on its English translation.
Chen et al. teach a S. cerevisiae cell genetically modified to comprise a gene encoding strawberry AAT (SAAT, i.e., heterologous) and S. cerevisiae FAS2, both operably linked to promoters; the growth of the cell is not affected by the genetic modifications. The genetically engineered cell produces enhanced amounts of medium chain C6-C10 acyl ethyl esters such as ethyl caproate (or ethyl hexoanate), ethyl caprylate (or ethyl octanoate), and ethyl decanoate (or ethyl caprate) from C6-C10 acyl-CoA and ethanol; the medium chain C6-C10 acyl ethyl esters improve the flavor and quality of wine and liquor (claims 1, 14, 28, 32, and 78) (see Abstract; p. 1, second paragraph; p. 2; p. 6-7). As evidenced by the attached Saccharomyces Genome Database, S. cerevisiae comprises endogenous FAS2 (claim 32) (see summary paragraph and reference 11).
Chen et al. also teach using the genetically engineered S. cerevisiae cell producing the C6-C10 acyl ethyl esters in fermenting and brewing (see p. 6; claim 8), i.e., Chen et al. teach a fermentation composition comprising ethanol and the genetically engineered S. cerevisiae cell (claim 54).
Thus, Chen et al. teach every claim limitation and anticipate the claimed invention.
9. Claims 1, 14, 28, 32, 54, and 78 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Chen et al. (CN 110804561), as evidenced by Saccharomyces Genome Database.
Chen et al. teach a S. cerevisiae cell genetically modified to comprise a gene encoding strawberry AAT (SAAT, i.e., heterologous) and S. cerevisiae FAS2, both operably linked to promoters; the growth of the cell is not affected by the genetic modifications. The genetically engineered cell produces enhanced amounts of medium chain C6-C10 acyl ethyl esters such as ethyl caproate (or ethyl hexoanate), ethyl caprylate (or ethyl octanoate), and ethyl decanoate (or ethyl caprate) from C6-C10 acyl-CoA and ethanol; the medium chain C6-C10 acyl ethyl esters improve the flavor and quality of wine and liquor (claims 1, 14, 28, 32, and 78) (see Abstract; p. 1, second paragraph; p. 2; p. 6-7). As evidenced by the attached Saccharomyces Genome Database, S. cerevisiae comprises endogenous FAS2 (claim 32) (see summary paragraph and reference 11).
Chen et al. also teach using the genetically engineered S. cerevisiae cell producing the C6-C10 acyl ethyl esters in fermenting and brewing (see p. 6; claim 8), i.e., Chen et al. teach a fermentation composition comprising ethanol and the genetically engineered S. cerevisiae cell (claim 54).
Thus, Chen et al. teach every claim limitation and anticipate the claimed invention.
Claim Rejections - 35 USC § 103
10. 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 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.
11. Claims 1-3, 14, 22, 26, 28, 32, 54, and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. as evidenced by Saccharomyces Genome Database, in view of both Petronikolou et al. (ACS Catal., 2018, 8: 6334-6344) and Barney et al. (Appl. Environ. Microbiol., 2013, 79: 396-399).
The teachings of Chen et al. are applied as above for claims 1, 14, 28, 32, 54, and 78. Chen et al. do not teach the AAT set forth by SEQ ID NO: 4 (claims 2, 3, and 6). However, using the AAT set forth by SEQ ID NO: 4 is suggested by the prior art. For example, Chen et al. teach that SAAT lacks strong specificity (see p. 1, second paragraph). Furthermore, Petronikolou et al. teach Ma-WS/DGAT (an AAT from M. aquaeolei), which is used for the in vivo production of ethyl esters from medium-chain acyl-CoA and ethanol substrates (see Abstract; p. 6334, column 2). As evidenced by the attached sequence alignment, the amino acid sequence of Ma-WS/DGAT is 99.5% identical to the claimed SEQ ID NO: 4 (a Ma-WS/DGAT mutant comprising the A144F and A360I mutations). Petronikolou et al. teach that introducing the A144F mutation into Ma-WS/DGAT enhances its affinity for the medium chain C6-CoA (see p. 6340, paragraph bridging columns 1 and 2). Based on these teachings, one of skill in the art would have reasonably expected that the high affinity of the A144F mutant for the C6 acyl-CoA substrate would mediate efficient and increased ethyl caproate production. One of skill in the art would have found obvious to modify Chen et al. by replacing SAAT with the A144F Ma-WS/DGAT mutant, with the reasonable expectation that doing so would result in enhanced ethyl caproate production.
Furthermore, Barney et al. teach that introducing A360I mutation into Ma-WS/DGAT increases selectivity for shorter alcohol substrates (see p. 397, paragraph bridging columns 1 and 2; p. 398, column 2, first paragraph; paragraph bridging p.398 and 399). While Barney et al. do not specifically teach ethanol as the shorter alcohol substrate, Barney et al. teach that the modification improves binding of smaller substrates to the active site (p. 398, column 2, first paragraph). Based on these teachings, one of skill in the art would have reasonably expected that the modification would also improve the binding of ethanol. Further introducing the A360I mutation would have been obvious to one of skill in the art, with the reasonable expectation that doing so would increase selectivity for the ethanol substrate, and thus, would further improve the yield of medium chain ethyl esters. By doing so, one of skill in the art would have used the AAT set forth by the claimed SEQ ID NO: 4 (claims 2, 3, and 6).
With respect to claim 22, there is no evidence of record that specifically using the combination of pQCR10 and pPRB1 leads to unexpected results over the cited prior art.
With respect to claim 26, the applicant elected the species of a cell expressing endogenous EEB1, EHT1, and MGL2. Since the cited prior art does not teach deletion of these genes, one of skill in the art would have reasonably concluded that the genetically engineered S. cerevisiae cell expresses EEB1, EHT1, and MGL2. While the cited prior art does not teach deleting endogenous ATTs other than EEB1, EHT1, and MGL2, it is noted that there is no evidence of record indicating that doing so leads to unexpected results.
As per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Using the combination of pQCR10/pPRB1 or deleting endogenous ATTs (other than EEB1, EHT1) is not significant if it does not provide a novel feature.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
12. Claims 1, 14, 28, 32, 54, and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. as evidenced by Saccharomyces Genome Database, in view of Akada et al. (J. Biosci. Bioeng., 1999, 87: 43-48).
The teachings of Chen et al. are applied as above for claims 1, 14, 28, 32, 54, and 78. Chen et al. do not teach the FAS2 G1250S mutant (claims 14 and 17). Akada et al. teach that the FAS2 G1250S mutant produces high levels of ethyl caproate, a flavor component of sake (see p. 44, column 2, last paragraph; p. 47, column 2, first paragraph). One of skill in the art would have found obvious to modify Chen et al, by replacing the wild type FAS 2 with the FAS2 G1250S mutant, to achieve the predictable result of obtaining increased amounts of the flavor component ethyl caproate. By doing so, one of skill in the art would have used a FAS2 at least 90% identical to SEQ ID NO: 6 (claim 14, the specification discloses that SEQ ID NO: 6 is the sequence of the wild S. cerevisiae G1250S FAS 2 mutant, see p. 27) and also comprising a substitution at a position corresponding to position 1250 of SEQ ID NO: 5 (claim 17; the specification teaches that SEQ ID NO: 5 is the sequence of the wild type FAS 2 from S. cerevisiae WLP001; see p. 25).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
13. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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