DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 12/02/2025 in response to the Non-Final Rejection mailed on 06/03/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claim 76 is cancelled.
4. Claims 1-2, 12, 17, 30, 39-40, 47, 62-63, 66, 78, 91, 95, 97, 99, 104, and 110-114 are pending.
5. Claims 99 and 104 stand withdrawn pursuant to 37 CFR 1.142(b).
6. Applicant’s remarks and declaration filed on 12/02/2025 in response to the Non-Final Rejection mailed on 06/03/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Claim Rejections - 35 USC § 102
7. The rejection of claims 1, 40, 91, 95, 97, 110-111, and 113-114 under 35 U.S.C. 102(a)(1) as being anticipated by Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as evidenced by NCBI (Sacchoromyces cerevisiae Vin13, retrieved from NCBI on 05/30/2025; cited on PTO-892 mailed on 06/03/2025) is withdrawn in view of applicants’ persuasive remarks and declaration filed on 12/02/2025 that one of ordinary skill in the art would recognize that Vin13 is not considered to be a “brewing yeast”.
8. The rejection of claims 1, 76, 91, 95, 97, 110-111 and 113-114 under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) is withdrawn in view of applicants’ amendment to the claims to remove the flavor compound “ethyl caproate” and to cancel claim 76.
Claim Rejections - 35 USC § 103
9. The rejection of claims 1-2, 91, 95, and 110-114 under 35 U.S.C. 103 as being unpatentable over Adachi et al. (Journal of Fermentation and Bioengineering, 1998; cited on IDS filed on 09/04/2020) in view of Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as evidenced by NCBI (Sacchoromyces cerevisiae Vin13, retrieved from NCBI on 05/30/2025; cited on PTO-892 mailed on 06/03/2025) is withdrawn for the reasons set forth above regarding Lilly et al.
10. The rejection of claims 1, 12, 91, 95, 97, 110, 113, and 114 under 35 U.S.C. 103 as being unpatentable over Farhi et al. (Metabolic Engineering, 2011; cited on PTO-892 mailed 01/25/2024) in view of Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as evidenced by NCBI (Sacchoromyces cerevisiae Vin13, retrieved from NCBI on 05/30/2025; cited on PTO-892 mailed on 06/03/2025) is withdrawn for the reasons set forth above regarding Lilly et al.
11. The rejection of claims 1, 17, 91, 95, 97, 110, 113, and 114 under 35 U.S.C. 103 as being unpatentable over Gavira et al. (Metabolic Engineering, 2013; cited on PTO-892 mailed 01/25/2024) in view of Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as evidenced by NCBI (Sacchoromyces cerevisiae Vin13, retrieved from NCBI on 05/30/2025; cited on PTO-892 mailed on 06/03/2025) is withdrawn for the reasons set forth above regarding Lilly et al.
12. The rejection of claims 1, 47, 62, 91, 95, 97, 110-111 and 113-114 under 35 U.S.C. 103 as being unpatentable over Lee et al. (Microbial Cell Factories, 2016; cited on PTO-892 mailed 01/25/2024) in view of Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as evidenced by NCBI (Sacchoromyces cerevisiae Vin13, retrieved from NCBI on 05/30/2025; cited on PTO-892 mailed on 06/03/2025) is withdrawn for the reasons set forth above regarding Lilly et al.
13. The rejection of claims 1, 66, 91, 95, 97, and 110-114 under 35 U.S.C. 103 as being unpatentable over Wang et al. (J. Ind. Microbiol. Biotechnol., 2017, available online 10/21/2016; cited on PTO-892 mailed 01/25/2024) in view of Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as evidenced by NCBI (Sacchoromyces cerevisiae Vin13, retrieved from NCBI on 05/30/2025; cited on PTO-892 mailed on 06/03/2025) is withdrawn for the reasons set forth above regarding Lilly et al.
14. The rejection of claims 1, 30, 91, 95, 97, 110-111, and 113-114 under 35 U.S.C. 103 as being unpatentable over Strucko et al. (Metabolic Engineering Communications, 2015; cited on PTO-892 mailed 01/25/2024) in view of Yang et al. (PLoS One, 2013; cited on PTO-892 mailed 01/25/2024) and Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as evidenced by NCBI (Sacchoromyces cerevisiae Vin13, retrieved from NCBI on 05/30/2025; cited on PTO-892 mailed on 06/03/2025) is withdrawn for the reasons set forth above regarding Lilly et al.
15. The rejection of claim 39 under 35 U.S.C. 103 as being unpatentable over Strucko et al. (Metabolic Engineering Communications, 2015; cited on PTO-892 mailed 01/25/2024) in view of Yang et al. (PLoS One, 2013; cited on PTO-892 mailed 01/25/2024) and Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) as applied to claims 1, 30, 91, 95, 97, 110-111, and 113-114 above, and further in view of Gallage et al. (Nature Communication, 2014; cited on PTO-892 mailed on 01/25/2024) is withdrawn for the reasons set forth above regarding Lilly et al.
16. Claims 1, 40, 91, 95, 97, 110-111 and 113-114 are newly rejected under 35 U.S.C. 103 as being unpatentable over Lilly et al. (Applied and Environmental Microbiology, 2000; cited on PTO-892 mailed on 01/25/2024) in view of Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
17. With respect to claim 1, Lilly et al. teach the distinctive flavor of wine, brandy (distilled beverage) and other grape-derived alcoholic beverages is affected by many compounds, including esters like ethyl caproate and isoamyl acetate [see Abstract]. Lilly et al. further teach a recombinant wine yeast Saccharomyces cerevisiae Vin13 strain transformed with a heterologous nucleic acid encoding an alcohol acetyltransferase gene for production of the flavor compound isoamyl acetate [see Abstract; Table 1; p. 745, column 2; p. 746, column 2]. Given that Saccharomyces cerevisiae contains a natural ethanol production pathway, and given that Lilly et al. teach recombinant Saccharomyces cerevisiae that structurally meet the limitations of the claim, it is the examiner’s position that the strains of Saccharomyces cerevisiae taught by Lilly et al. would necessarily accumulate at least 5 g/L of ethanol during fermentation. Since the Office does not have the facilities for examining and comparing applicants’ yeast host cell with the yeast host cell of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the yeast host cell of the prior art does not possess the same material structural and functional characteristics of the claimed yeast host cell). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claims 40, Lilly et al. teach a recombinant wine yeast Saccharomyces cerevisiae Vin13 transformed with a nucleic acid encoding an alcohol acetyltransferase gene for the overexpression of said alcohol acetyl transferase enzyme for production of the flavor compound isoamyl acetate [see Abstract; Table 1; p. 745, column 2; p. 746, column 2].
With respect to claim 91, Lilly et al. teach the recombinant yeast host cell is Saccharomyces cerevisiae Vin13 [see Abstract; p. 745, column 2].
With respect to claim 95, Lilly et al. teach the fermenting agent comprising the recombinant yeast host cell and a rich medium supplemented with glucose (nutrient) [see p. 745, column 2].
With respect to claim 97, Lilly et al. teach a recombinant wine yeast Saccharomyces cerevisiae Vin13 transformed with a nucleic acid encoding an alcohol acetyltransferase gene for production of the flavor compound isoamyl acetate [see Abstract; Table 1; p. 745, column 2; p. 746, column 2] and a control yeast (non-genetically modified yeast) [see p. 745, column 2; p. 747, column 1].
With respect to claim 110, Lilly et al. teach the recombinant yeast host cell wherein the nucleic acid molecule is linked to a heterologous promoter [see p. 746, column 1].
With respect to claim 111, Lilly et al. teach the recombinant yeast host cell wherein the heterologous promoter is from the pgk1 gene [see p. 746, column 1].
With respect to claim 113, the recitation of "wherein the flavoured alcoholic beverage is a beer or a distilled spirit" limits the intended use of “for making a flavoured alcoholic beverage in the preamble of claim 1 merely recites the purpose of the yeast host cell and does not limit the body of the claims, while the active steps of "a recombinant yeast cell comrpsiing a heterologous nucleic acid that produces a flavour compound, a native ethanol production pathway and accumulates at least 5 g/L during fermentation" fully and intrinsically“ set forth all of the limitations of the claimed invention. See MPEP 2111.02.II. Nevertheless, Lilly et al. teach the production of isoamyl acetate for flavoring of wine and distillates [see Abstract].
Regarding claim 114, it is acknowledged that Lilly et al. does not explicitly teach “wherein the majority of the carbohydrates in of the fermentation medium comprise maltose and maltotriose”; however, these limitations recite the process by which the recombinant yeast host cell is obtained. As stated above, the limitations, “is obtained from a brewing or distilling yeast parental cell”, are “product-by-process” limitations. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
However, Lilly et al. does not teach wherein the yeast is a brewing or distilling yeast.
Chen et al. is in the same field of Lilly et al. and teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor [see Abstract]. Chen et al. teach a recombinant yeast host cell of Saccharomyces cerevisiae comprising a heterologous nucleic acid encoding a acetyl-CoA carboxylase, fatty acid synthase 1, and fatty acid synthase 2 for the production of ethyl caproate [see Abstract; p. 1262, column 2; Table 1]. Chen et al. teach that the yeast strain ais a Chinese liquor yeast S. cerevisiae [see Abstract; p. 1262, column 2; Table 1, and given that one of ordinary skill in the art associates liquor as a distilled product, the liquor yeast of Chen et al. can reasonably be interpreted as a distilling yeast.
Stewart et al. teach that the objectives of brewer’s and distiller’s wort fermentations are to consistently metabolize wort constituents into ethanol and other fermentation products [see p. 202, column 2]. Stewart et al. teach that the use of manipulated yeast strain will become commonplace through genetic modifications for the expression of various heterologous proteins [see p. 202 bridging to p. 203]. Stewart et al. teach several yeast strains useful in the brewing and distilling of alcoholic spirits [see Table 1].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Lilly et al., Chen et al. and Stewart et al. to include a brewing and distilling yeast strain for the host cell of Lilly to produce isoamyl acetate because Lilly et al. teach the production of isoamyl acetate by a genetically modified wine yeast strain and teach that isoamyl acetate distinctive flavor of wine, brandy (distilled beverage) and other grape-derived alcoholic beverages. Chen et al. teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor and teach the production of ethyl ester flavor compounds with a genetically modified distilling yeast. Stewart et al. teach several yeast strains that are useful in the brewing and distilling field. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Lilly et al., Chen et al. and Stewart et al. because Chen et al. acknowledges flavor compounds in distilling yeast can be produced by genetically modifying distilling yeast and Stewart acknowledges several yeast strains useful in the brewing and distilling field. It would require simple substitution for one of ordinary skill in the art depending on the desired spirit and flavor to be made to choose an appropriate yeast strain for genetic modification based on the teachings of Stewart. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
18. Claims 1-2, 91, 95, and 110-114 are newly rejected under under 35 U.S.C. 103 as being unpatentable over Adachi et al. (Journal of Fermentation and Bioengineering, 1998; cited on IDS filed on 09/04/2020) in view of Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
19. With respect to claim 1, Adachi et al. teach a recombinant Saccharomyces cerevisiae comprising a heterologous gene encoding a lactate dehydrogenase and expression of said lactate dehydrogenase, has a native ethanol production pathway; and accumulates up to 10 g/L ethanol and lactate [see Abstract; Figures 4 and 5]. Adachi et al. further teach that acidification during alcoholic fermentation using yeast is sometimes desirable for brewing and cider making [see p. 284, column 2].
With respect to claim 2, Adachi et al. teach the recombinant yest host cell wherein the flavor compound comprises lactate [see Abstract; Figures 4 and 5].
With respect to claim 91, Adachi et al. teach wherein the recombinant yeast host cell is Saccharomyces cerevisiae [see Abstract; Figures 4 and 5].
With respect to claim 95, Adachi et al. teach a fermenting agent comprising the recombinant yeast host cell and a culture comprising glucose and/or galactose (interpreted as nutrient) [see Abstract; Figures 4 and 5; p. 285, column 1].
With respect to claim 110, Adachi et al. teach the recombinant yeast host cell, wherein the heterologous nucleic molecule is operatively associated with a heterologous promoter [see Abstract; p. 285, column 2].
With respect to claims 111-112, Adachi et al. teach the recombinant yeast host cell, wherein the heterologous promoter is the adh1 promoter [see Abstract; p. 285, column 2].
With respect to claim 113, it is acknowledged that Adachi et al. does not explicitly teach wherein the flavoured alcoholic beverage is a beer or a distilled spirit; however, the recitation of "wherein the flavoured alcoholic beverage is a beer or a distilled spirit" limits the intended use of “for making a flavoured alcoholic beverage in the preamble of claim 1 merely recites the purpose of the yeast host cell and does not limit the body of the claims, while the active steps of "a recombinant yeast cell comrpsiing a heterologous nucleic acid that produces a flavour compound, a native ethanol production pathway and accumulates at least 5 g/L during fermentation" fully and intrinsically“ set forth all of the limitations of the claimed invention. See MPEP 2111.02.II.
Regarding claim 114, it is acknowledged that Adachi et al. does not explicitly teach “wherein the majority of the carbohydrates in of the fermentation medium comprise maltose and maltotriose”; however, these limitations recite the process by which the recombinant yeast host cell is obtained. As stated above, the limitations, “is obtained from a brewing or distilling yeast parental cell”, are “product-by-process” limitations. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
Although Adachi et al. does not teach that the yeast host cell is a brewing or distilling yeast, this modification would have been obvious to one of ordinary skill in the art in view of Chen et al. and Stewart et al.
Chen et al. teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor [see Abstract]. Chen et al. teach a recombinant yeast host cell of Saccharomyces cerevisiae comprising a heterologous nucleic acid encoding a acetyl-CoA carboxylase, fatty acid synthase 1, and fatty acid synthase 2 for the production of ethyl caproate [see Abstract; p. 1262, column 2; Table 1]. Chen et al. teach that the yeast strain ais a Chinese liquor yeast S. cerevisiae [see Abstract; p. 1262, column 2; Table 1, and given that one of ordinary skill in the art associates liquor as a distilled product, the liquor yeast of Chen et al. can reasonably be interpreted as a distilling yeast.
Stewart et al. teach that the objectives of brewer’s and distiller’s wort fermentations are to consistently metabolize wort constituents into ethanol and other fermentation products [see p. 202, column 2]. Stewart et al. teach that the use of manipulated yeast strain will become commonplace through genetic modifications for the expression of various heterologous proteins [see p. 202 bridging to p. 203]. Stewart et al. teach several yeast strains useful in the brewing and distilling of alcoholic spirits [see Table 1].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to substitute the yeast of Adachi et al. with the brewer’s and distilling yeast of Chen et al. and Stewart et al. because Adachi et al. acknowledges that acidification during alcoholic fermentation using yeast is sometimes desirable for brewing and cider making and Chen et al. acknowledges flavor compounds in distilling yeast can be produced by genetically modifying distilling yeast and Stewart acknowledges several yeast strains useful in the brewing and distilling field. It would require simple substitution for one of ordinary skill in the art depending on the desired spirit and flavor to be made to choose an appropriate yeast strain for genetic modification based on the teachings of Stewart. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
20. Claims 1, 12, 91, 95, 97, 110, 113, and 114 are newly rejected under 35 U.S.C. 103 as being unpatentable over Farhi et al. (Metabolic Engineering, 2011; cited on PTO-892 mailed 01/25/2024) in view of Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
21. With respect to claim 1, Farhi et al. teach a recombinant Saccharomyces cerevisiae strain that has been transformed with heterologous nucleic acids encoding enzymes for the production of valencene flavor compound [see Abstract; p. 475, column 2; Figure 1; Figure 2]. Farhi et al. teach the recombinant yeast host cell wherein the one or more heterologous polypeptide comprises a farnesyl diphosphate synthase and a valencene synthase [see p. 475, column 2 bottom to column 1 of p. 476]. Given that Saccharomyces cerevisiae contains a natural ethanol production pathway, and given that Farhi et al. teach recombinant Saccharomyces cerevisiae that structurally meet the limitations of the claim, it is the examiner’s position that the strains of Saccharomyces cerevisiae taught by Farhi et al. would necessarily accumulate at least 5 g/L of ethanol during fermentation.
With respect to claim 12, Farhi et al. teach the recombinant yeast host cell wherein the flavor compound comprises valencene [see Abstract; p. 477; Figure 2]. Farhi et al. teach the recombinant yeast host cell wherein the one or more heterologous polypeptide comprises a farnesyl diphosphate synthase and a valencene synthase [see p. 475, column 2 bottom to column 1 of p. 476].
With respect to claim 91, Farhi et al. teach the recombinant yeast host cell is Saccharomyces cerevisiae [see Table 1; p. 476].
With respect to claim 95, Farhi et al. teach a recombinant Saccharomyces cerevisiae strain that has been transformed with heterologous nucleic acids encoding enzymes for the production of valencene flavor compound [see Abstract; p. 475, column 2; Figure 1; Figure 2] in a growth medium comprising 2% glucose (nutrient) [see p. 476, column 1, bottom].
With respect to claim 97, Farhi et al. teach combinations of recombinant yeast host cells and wild type host cells (interpreted as non-genetically modified yeast) [see p. 476; Table 1; Figure 2].
With respect to claim 110, Farhi et al. teach the recombinant yeast host cell, wherein the heterologous nucleic acid is operatively associated with a heterologous promoter [see p. 475, column 2].
With respect to claim 113, it is acknowledged that Farhi et al. does not explicitly teach wherein the flavoured alcoholic beverage is a beer or a distilled spirit; however, the recitation of "wherein the flavoured alcoholic beverage is a beer or a distilled spirit" limits the intended use of “for making a flavoured alcoholic beverage in the preamble of claim 1 merely recites the purpose of the yeast host cell and does not limit the body of the claims, while the active steps of "a recombinant yeast cell comrpsiing a heterologous nucleic acid that produces a flavour compound, a native ethanol production pathway and accumulates at least 5 g/L during fermentation" fully and intrinsically“ set forth all of the limitations of the claimed invention. See MPEP 2111.02.II.
Regarding claim 114, it is acknowledged that Farhi et al. does not explicitly teach “wherein the majority of the carbohydrates in of the fermentation medium comprise maltose and maltotriose”; however, these limitations recite the process by which the recombinant yeast host cell is obtained. As stated above, the limitations, “is obtained from a brewing or distilling yeast parental cell”, are “product-by-process” limitations. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
Although Farhi et al. does not teach that the yeast host cell is a brewing or distilling yeast, this modification would have been obvious to one of ordinary skill in the art in view of Chen et al. and Stewart et al.
Chen et al. teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor [see Abstract]. Chen et al. teach a recombinant yeast host cell of Saccharomyces cerevisiae comprising a heterologous nucleic acid encoding a acetyl-CoA carboxylase, fatty acid synthase 1, and fatty acid synthase 2 for the production of ethyl caproate [see Abstract; p. 1262, column 2; Table 1]. Chen et al. teach that the yeast strain ais a Chinese liquor yeast S. cerevisiae [see Abstract; p. 1262, column 2; Table 1, and given that one of ordinary skill in the art associates liquor as a distilled product, the liquor yeast of Chen et al. can reasonably be interpreted as a distilling yeast.
Stewart et al. teach that the objectives of brewer’s and distiller’s wort fermentations are to consistently metabolize wort constituents into ethanol and other fermentation products [see p. 202, column 2]. Stewart et al. teach that the use of manipulated yeast strain will become commonplace through genetic modifications for the expression of various heterologous proteins [see p. 202 bridging to p. 203]. Stewart et al. teach several yeast strains useful in the brewing and distilling of alcoholic spirits [see Table 1].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to substitute the yeast of Farhi et al. with the brewer’s and distilling yeast of Chen et al. and Stewart et al. because Farhi et al. acknowledges that that valencene is desirable as a flavoring compound and Chen et al. acknowledges flavor compounds in distilling yeast can be produced by genetically modifying distilling yeast and Stewart acknowledges several yeast strains useful in the brewing and distilling field. It would require simple substitution for one of ordinary skill in the art depending on the desired spirit and flavor to be made to choose an appropriate yeast strain for genetic modification based on the teachings of Stewart. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
22. Claims 1, 17, 91, 95, 97, 110, 113, and 114 are newly rejected under 35 U.S.C. 103 as being unpatentable over Gavira et al. (Metabolic Engineering, 2013; cited on PTO-892 mailed 01/25/2024) in view of Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
23. With respect to claim 1, Gavira et al. teach a recombinant Saccharomyces cerevisiae strain that has been transformed with heterologous nucleic acids encoding enzymes for the production of nootkatone flavor compound [see Abstract; p. p. 28; Figure 2]. Gavira et al. teach the recombinant Saccharomyces cerevisiae strain that has been transformed with heterologous nucleic acids encoding enzymes for the production of nootkatone flavor compound [see Abstract; p. p. 28; Figure 2], wherein the one or more heterologous polypeptide comprises a cytochrome P450 reductase and CYP71D51v2 that oxidizes valencene [see Abstract; p. 26, column 2; p. 28; Figures 2-4]. Given that Saccharomyces cerevisiae contains a natural ethanol production pathway, and given that Gavira et al. teach recombinant Saccharomyces cerevisiae that structurally meet the limitations of the claim, it is the examiner’s position that the strains of Saccharomyces cerevisiae taught by Gavira et al. would necessarily accumulate at least 5 g/L of ethanol during fermentation.
With respect to claim 17, Gavira et al. teach the recombinant yeast host cell wherein the flavor compound comprises nootkatone [see Abstract; p. p. 28; Figure 2]. Gavira et al. teach the recombinant Saccharomyces cerevisiae strain that has been transformed with heterologous nucleic acids encoding enzymes for the production of nootkatone flavor compound [see Abstract; p. p. 28; Figure 2], wherein the one or more heterologous polypeptide comprises a cytochrome P450 reductase and CYP71D51v2 that oxidizes valencene [see Abstract; p. 26, column 2; p. 28; Figures 2-4].
With respect to claim 91, Gavira et al. teach the recombinant yeast host cell is Saccharomyces cerevisae [see p. 26, column 2].
With respect to claim 95, Gavira et al. teach the recombinant yeast host cell cultured in a minimum medium comprising glucose (nutrient) [see p. 26, column 2].
With respect to claim 97, Gavira et al. teach the recombinant Saccharomyces cerevisiae strain that has been transformed with heterologous nucleic acids encoding enzymes for the production of nootkatone flavor compound and control yeast (non-genetically modified yeast) [see p. 27, column 2].
With respect to claim 110, Gavira et al. teach the recombinant yeast host cell, wherein the heterologous nucleic acid is operatively associated with a heterologous promoter [see p. 26, column 2].
With respect to claim 113, it is acknowledged that Gavira et al. does not explicitly teach wherein the flavoured alcoholic beverage is a beer or a distilled spirit; however, the recitation of "wherein the flavoured alcoholic beverage is a beer or a distilled spirit" limits the intended use of “for making a flavoured alcoholic beverage in the preamble of claim 1 merely recites the purpose of the yeast host cell and does not limit the body of the claims, while the active steps of "a recombinant yeast cell comrpsiing a heterologous nucleic acid that produces a flavour compound, a native ethanol production pathway and accumulates at least 5 g/L during fermentation" fully and intrinsically“ set forth all of the limitations of the claimed invention. See MPEP 2111.02.II.
Regarding claim 114, it is acknowledged that Gavira et al. does not explicitly teach “wherein the majority of the carbohydrates in of the fermentation medium comprise maltose and maltotriose”; however, these limitations recite the process by which the recombinant yeast host cell is obtained. As stated above, the limitations, “is obtained from a brewing or distilling yeast parental cell”, are “product-by-process” limitations. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
Although Gavira et al. does not teach that the yeast host cell is a brewing or distilling yeast, this modification would have been obvious to one of ordinary skill in the art in view of Chen et al. and Stewart et al.
Chen et al. teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor [see Abstract]. Chen et al. teach a recombinant yeast host cell of Saccharomyces cerevisiae comprising a heterologous nucleic acid encoding a acetyl-CoA carboxylase, fatty acid synthase 1, and fatty acid synthase 2 for the production of ethyl caproate [see Abstract; p. 1262, column 2; Table 1]. Chen et al. teach that the yeast strain ais a Chinese liquor yeast S. cerevisiae [see Abstract; p. 1262, column 2; Table 1, and given that one of ordinary skill in the art associates liquor as a distilled product, the liquor yeast of Chen et al. can reasonably be interpreted as a distilling yeast.
Stewart et al. teach that the objectives of brewer’s and distiller’s wort fermentations are to consistently metabolize wort constituents into ethanol and other fermentation products [see p. 202, column 2]. Stewart et al. teach that the use of manipulated yeast strain will become commonplace through genetic modifications for the expression of various heterologous proteins [see p. 202 bridging to p. 203]. Stewart et al. teach several yeast strains useful in the brewing and distilling of alcoholic spirits [see Table 1].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to substitute the yeast of Gavira et al. with the brewer’s and distilling yeast of Chen et al. and Stewart et al. because Gavira et al. acknowledges that nootkatone is desirable as a flavoring compound because of its grapefruit flavor and odor and Chen et al. acknowledges flavor compounds in distilling yeast can be produced by genetically modifying distilling yeast and Stewart acknowledges several yeast strains useful in the brewing and distilling field. It would require simple substitution for one of ordinary skill in the art depending on the desired spirit and flavor to be made to choose an appropriate yeast strain for genetic modification based on the teachings of Stewart. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
24. Claims 1, 47, 62, 91, 95, 97, 110-111, and 113-114 are newly rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Microbial Cell Factories, 2016; cited on PTO-892 mailed 01/25/2024) in view of Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
25. With respect to claim 1, Lee et al. teach a de novo pathway for the production of raspberry ketone (4-(4-hydroxphenyl)butan-2-one) comprising four heterologous genes encoding phenylalaine/tyrosine ammonia lyase, cinnamate-4-hydrxylase, coumarate-CoA ligase and benzalacetone synthase in Saccharomyces cerevisiae [see Abstract; p. 2; Figure 1]. Given that Saccharomyces cerevisiae contains a natural ethanol production pathway, and given that Lee et al. teach recombinant Saccharomyces cerevisiae that structurally meet the limitations of the claim, it is the examiner’s position that the strains of Saccharomyces cerevisiae taught by Lee et al. would necessarily accumulate at least 5 g/L of ethanol during fermentation.
With respect to claim 47, Lee et al. teach a de novo pathway for the production of raspberry ketone (4-(4-hydroxphenyl)butan-2-one) comprising four heterologous genes encoding phenylalaine/tyrosine ammonia lyase, cinnamate-4-hydrxylase, coumarate-CoA ligase and benzalacetone synthase in Saccharomyces cerevisiae [see Abstract; p. 2; Figure 1].
With respect to claim 62, Lee et al. teach a de novo pathway for the production of raspberry ketone (4-(4-hydroxphenyl)butan-2-one) comprising four heterologous genes encoding phenylalaine/tyrosine ammonia lyase, cinnamate-4-hydrxylase, coumarate-CoA ligase and benzalacetone synthase in Saccharomyces cerevisiae [see Abstract; p. 2; Figure 1]. Lee et al. also teach that yeast have been show to display efficient benzalacetone reductase activity.
With respect to claim 91, Lee et al. teach the recombinant yeast host cell is Saccharomyces cerevisiae [see Abstract; p. 2; Figure 1].
With respect to claim 95, Lee et al. teach the production of raspberry ketone under winemaking conditions (interpreted as the recombinant yeast host cell and a nutrient) [see p. 2].
With respect to claim 97, Lee et al. teach recombinant strains of the recombinant yeast host cell and a control (interpreted as a non-genetically modified yeast) [see Abstract; p. 2; Figure 4].
With respect to claim 110, Lee et al. teach the recombinant yeast host cell wherein the nucleic acid molecule is operatively linked to a heterologous promoter [see p. 2 and 3].
With respect to claim 111, Lee et al. teach the recombinant yeast host cell wherein the heterologous promoter is pgk1 [see p. 3].
With respect to claim 113, the recitation of "wherein the flavoured alcoholic beverage is a beer or a distilled spirit" limits the intended use of “for making a flavoured alcoholic beverage in the preamble of claim 1 merely recites the purpose of the yeast host cell and does not limit the body of the claims, while the active steps of "a recombinant yeast cell comrpsiing a heterologous nucleic acid that produces a flavour compound, a native ethanol production pathway and accumulates at least 5 g/L during fermentation" fully and intrinsically“ set forth all of the limitations of the claimed invention. See MPEP 2111.02.II. Nevertheless, Lee et al. teach the production of raspberry ketone for flavoring of wine and distillates [see Abstract].
Regarding claim 114, it is acknowledged that Lee et al. does not explicitly teach “wherein the majority of the carbohydrates in of the fermentation medium comprise maltose and maltotriose”; however, these limitations recite the process by which the recombinant yeast host cell is obtained. As stated above, the limitations, “is obtained from a brewing or distilling yeast parental cell”, are “product-by-process” limitations. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
Although Lee et al. does not teach that the yeast host cell is a brewing or distilling yeast, this modification would have been obvious to one of ordinary skill in the art in view of Chen et al. and Stewart et al.
Chen et al. teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor [see Abstract]. Chen et al. teach a recombinant yeast host cell of Saccharomyces cerevisiae comprising a heterologous nucleic acid encoding a acetyl-CoA carboxylase, fatty acid synthase 1, and fatty acid synthase 2 for the production of ethyl caproate [see Abstract; p. 1262, column 2; Table 1]. Chen et al. teach that the yeast strain is a Chinese liquor yeast S. cerevisiae [see Abstract; p. 1262, column 2; Table 1, and given that one of ordinary skill in the art associates liquor as a distilled product, the liquor yeast of Chen et al. can reasonably be interpreted as a distilling yeast.
Stewart et al. teach that the objectives of brewer’s and distiller’s wort fermentations are to consistently metabolize wort constituents into ethanol and other fermentation products [see p. 202, column 2]. Stewart et al. teach that the use of manipulated yeast strain will become commonplace through genetic modifications for the expression of various heterologous proteins [see p. 202 bridging to p. 203]. Stewart et al. teach several yeast strains useful in the brewing and distilling of alcoholic spirits [see Table 1].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to substitute the yeast of Lee et al. with the brewer’s and distilling yeast of Chen et al. and Stewart et al. because Lee et al. acknowledges production of raspberry ketone under winemaking conditions as a flavoring agent and Chen et al. acknowledges flavor compounds in distilling yeast can be produced by genetically modifying distilling yeast and Stewart acknowledges several yeast strains useful in the brewing and distilling field. It would require simple substitution for one of ordinary skill in the art depending on the desired spirit and flavor to be made to choose an appropriate yeast strain for genetic modification based on the teachings of Stewart. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Although the combination of Lee et al., Chen et al. and Stewart et al. do not explicitly teach the recombinant yeast host cell of claim 62 overexpressing a native benzalactone reductase, this modification would have been obvious to one of ordinary skill in the art based on the teachings of Lee et al. because Lee et al. teach that yeast have benzalacetone reductase that converts benzalacetone into raspberry ketone. One of ordinary skill in the art would desire to overexpress a native benzalecetone reductase in order to maximize raspberry ketone production formation. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
26. Claims 1, 66, 91, 95, 97, and 110-114 are newly rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (J. Ind. Microbiol. Biotechnol., 2017, available online 10/21/2016; cited on PTO-892 mailed 01/25/2024) in view of Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
27. With respect to claims 1 and 66, Wang et al. teach the production of the flavor compound phenylethyl alcohol via the overexpression of ARO8 and ARO10 in Saccharomyces cerevisiae [see Abstract; p. 132; Table 1]. Given that Saccharomyces cerevisiae contains a natural ethanol production pathway, and given that Wang et al. teach recombinant Saccharomyces cerevisiae that structurally meet the limitations of the claim, it is the examiner’s position that the strains of Saccharomyces cerevisiae taught by Wang et al. would necessarily accumulate at least 5 g/L of ethanol during fermentation. Since the Office does not have the facilities for examining and comparing applicants’ yeast host cell with the yeast host cell of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the yeast host cell of the prior art does not possess the same material structural and functional characteristics of the claimed yeast host cell). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 91, Wang et al. teach the recombinant yeast host cell is Saccharomyces cerevisiae [see Table 1].
With respect to claim 95, Wang et al. teach fermenting agent comprising the recombinant yeast host cell and a medium comprising glucose (nutrient) [see Abstract; p. 131].
With respect to claim 97, Wang et al. teach the recombinant yeast host cell and control yeast cells (non-genetically modified yeast) [see Table 1].
With respect to claims 110-112, Wang et al. teach the recombinant yeast host cell wherein the nucleic acid molecule is operatively linked to an adh1 gene promoter [see p. 131, column 2].
With respect to claim 113, it is acknowledged that Wang et al. does not explicitly teach wherein the flavoured alcoholic beverage is a beer or a distilled spirit; however, the recitation of "wherein the flavoured alcoholic beverage is a beer or a distilled spirit" limits the intended use of “for making a flavoured alcoholic beverage in the preamble of claim 1 merely recites the purpose of the yeast host cell and does not limit the body of the claims, while the active steps of "a recombinant yeast cell comprising a heterologous nucleic acid that produces a flavour compound, a native ethanol production pathway and accumulates at least 5 g/L during fermentation" fully and intrinsically“ set forth all of the limitations of the claimed invention. See MPEP 2111.02.II.
Regarding claim 114, it is acknowledged that Wang et al. does not explicitly teach “wherein the majority of the carbohydrates in of the fermentation medium comprise maltose and maltotriose”; however, these limitations recite the process by which the recombinant yeast host cell is obtained. As stated above, the limitations, “is obtained from a brewing or distilling yeast parental cell”, are “product-by-process” limitations. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
Although Wang et al. does not teach that the yeast host cell is a brewing or distilling yeast, this modification would have been obvious to one of ordinary skill in the art in view of Chen et al. and Stewart et al.
Chen et al. teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor [see Abstract]. Chen et al. teach a recombinant yeast host cell of Saccharomyces cerevisiae comprising a heterologous nucleic acid encoding a acetyl-CoA carboxylase, fatty acid synthase 1, and fatty acid synthase 2 for the production of ethyl caproate [see Abstract; p. 1262, column 2; Table 1]. Chen et al. teach that the yeast strain is a Chinese liquor yeast S. cerevisiae [see Abstract; p. 1262, column 2; Table 1, and given that one of ordinary skill in the art associates liquor as a distilled product, the liquor yeast of Chen et al. can reasonably be interpreted as a distilling yeast.
Stewart et al. teach that the objectives of brewer’s and distiller’s wort fermentations are to consistently metabolize wort constituents into ethanol and other fermentation products [see p. 202, column 2]. Stewart et al. teach that the use of manipulated yeast strain will become commonplace through genetic modifications for the expression of various heterologous proteins [see p. 202 bridging to p. 203]. Stewart et al. teach several yeast strains useful in the brewing and distilling of alcoholic spirits [see Table 1].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to substitute the yeast of Wang et al. with the brewer’s and distilling yeast of Chen et al. and Stewart et al. because Wang et al. acknowledges production of phenylethyl alcohol as a flavor compound through genetic modification of a yeast and Chen et al. acknowledges flavor compounds in distilling yeast can be produced by genetically modifying distilling yeast and Stewart acknowledges several yeast strains useful in the brewing and distilling field. It would require simple substitution for one of ordinary skill in the art depending on the desired spirit and flavor to be made to choose an appropriate yeast strain for genetic modification based on the teachings of Stewart. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
28. Claims 1, 30, 91, 95, 97, 110-111, and 113-114 are newly rejected under 35 U.S.C. 103 as being unpatentable over Strucko et al. (Metabolic Engineering Communications, 2015; cited on PTO-892 mailed 01/25/2024) in view of Yang et al. (PLoS One, 2013; cited on PTO-892 mailed 01/25/2024) Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
29. With respect to claim 1, Strucko et al. teach the construction of a de novo vanillin b-glucoside pathway in two Saccharomyces cerevisiae strains comprising transforming the strains with genes encoding the enzymes aromatic carboxylic acid reductase, phosphopantetheine transferase, O-methyltransferase, and 3-dehydroshikimate dehydratase [see Abstract; Figure 1; p. 100, column 2]. Given that Saccharomyces cerevisiae contains a natural ethanol production pathway, and given that Strucko et al. teach recombinant Saccharomyces cerevisiae that structurally meet the limitations of the claim, it is the examiner’s position that the strains of Saccharomyces cerevisiae taught by Strucko et al. would necessarily accumulate at least 5 g/L of ethanol during fermentation.
With respect to claim 30, Strucko et al. teach the construction of a de novo vanillin b-glucoside pathway in two Saccharomyces cerevisiae strains comprising transforming the strains with genes encoding the enzymes aromatic carboxylic acid reductase, phosphopantetheine transferase, O-methyltransferase, and 3-dehydroshikimate dehydratase [see Abstract; Figure 1; p. 100, column 2].
With respect to claim 91, Strucko et al. teach the recombinant yeast host cell is Saccharomyces cerevisiae [see Abstract; p. 100, column 2].
With respect to claim 95, Strucko et al. teach a fermenting agent comprising the recombinant yeast host cell and glucose as a carbon source (nutrient) [see p. 102, column 1].
With respect to claim 97, Strucko et al. teach recombinant yeast strains of CEN,PK112-11C and X2180-1A and control strains (non-genetically modified) [see p. 100, column 2; Table 3].
With respect to claims 110-111, Strucko et al. teach the recombinant yeast host cell wherein the nucleic acid molecule is operatively linked to a pgk1 gene promoter [see p. 100].
With respect to claim 113, it is acknowledged that Strucko et al. does not explicitly teach wherein the flavoured alcoholic beverage is a beer or a distilled spirit; however, the recitation of "wherein the flavoured alcoholic beverage is a beer or a distilled spirit" limits the intended use of “for making a flavoured alcoholic beverage in the preamble of claim 1 merely recites the purpose of the yeast host cell and does not limit the body of the claims, while the active steps of "a recombinant yeast cell comprising a heterologous nucleic acid that produces a flavour compound, a native ethanol production pathway and accumulates at least 5 g/L during fermentation" fully and intrinsically“ set forth all of the limitations of the claimed invention. See MPEP 2111.02.II.
Regarding claim 114, it is acknowledged that Strucko et al. does not explicitly teach “wherein the majority of the carbohydrates in of the fermentation medium comprise maltose and maltotriose”; however, these limitations recite the process by which the recombinant yeast host cell is obtained. As stated above, the limitations, “is obtained from a brewing or distilling yeast parental cell”, are “product-by-process” limitations. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
However, Strucko et al. does not explicitly teach the yeast host cell of claims 1 and 30, as a brewing or distilling yeast and wherein the flavor compound comprises vanillin and wherein the one or more heterologous polypeptide comprises a heterologous feruloyl-CoA synthase enzyme; a heterologous enoyl-CoA hydratase; and/or a heterologous vanillin synthase enzyme.
Yang et al. teach that vanillin is one of the most important flavoring agents used in the world that is widely used in foods, beverages, perfumes, and pharmaceuticals [see p. 1, column 1]. Yang et al. further teach the heterologous expression of the genes encoding a feruloyl CoA synthetase and enoyl-CoA hydratase in E. coli for the production of vanillin [see Abstract; p.2; Figure 2].
Chen et al. teach that ethyl esters formed during yeast fermentation play a key role in the development of flavor profiles of Chinese liquor [see Abstract]. Chen et al. teach a recombinant yeast host cell of Saccharomyces cerevisiae comprising a heterologous nucleic acid encoding a acetyl-CoA carboxylase, fatty acid synthase 1, and fatty acid synthase 2 for the production of ethyl caproate [see Abstract; p. 1262, column 2; Table 1]. Chen et al. teach that the yeast strain is a Chinese liquor yeast S. cerevisiae [see Abstract; p. 1262, column 2; Table 1, and given that one of ordinary skill in the art associates liquor as a distilled product, the liquor yeast of Chen et al. can reasonably be interpreted as a distilling yeast.
Stewart et al. teach that the objectives of brewer’s and distiller’s wort fermentations are to consistently metabolize wort constituents into ethanol and other fermentation products [see p. 202, column 2]. Stewart et al. teach that the use of manipulated yeast strain will become commonplace through genetic modifications for the expression of various heterologous proteins [see p. 202 bridging to p. 203]. Stewart et al. teach several yeast strains useful in the brewing and distilling of alcoholic spirits [see Table 1].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art desiring to produce vanillin to combine the teachings of Strucko et al., Yang et al., Chen et al. and Stewart et al. according to the teachings of Yang et al., Chen et al. and Stewart et al. because Strucko et al. teach heterologous expression of enzymes in Saccharomyces for the production of vanillin glucoside. Yang et al. teach that vanillin is an important flavoring agent widely used in foods, beverages, perfumes, and pharmaceuticals and teach the heterologous expression of two enzymes feruloyl CoA synthetase and enoyl-CoA hydratase in E. coli. It would require only routine skill for one of ordinary skill in the art to substitute the E. coli of Yang et al. with a brewing or distilling yeast to produce vanillin and one of ordinary skill in the art would desire to do so because Yang et al. acknowledges that vanillin is an important flavoring agent widely used in foods, beverages, perfumes, and pharmaceuticals, and one of ordinary skill in the art desiring to add vanillin as a flavoring agent in an alcoholic beverage would look to the teachings of Chen et al. and Stewart et al. because Chen et al. acknowledges flavor compounds in distilling yeast can be produced by genetically modifying distilling yeast and Stewart acknowledges several yeast strains useful in the brewing and distilling field. It would require simple substitution for one of ordinary skill in the art depending on the desired spirit and flavor to be made to choose an appropriate yeast strain for genetic modification based on the teachings of Stewart. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
30. Claim 39 is newly rejected under 35 U.S.C. 103 as being unpatentable over Strucko et al. (Metabolic Engineering Communications, 2015; cited on PTO-892 mailed 01/25/2024) in view of Yang et al. (PLoS One, 2013; cited on PTO-892 mailed 01/25/2024) Chen et al. (J. Ind. Microbiol. Biotechnol., 2016; cited on PTO-892 mailed 01/25/2024) and Stewart et al. (J. Inst. Brew., 2013; examiner cited) as applied to claims 1, 30, 91, 95, 97, 110-111, and 113-114 above, and further in view of Gallage et al. (Nature Communication, 2014; cited on PTO-892 mailed on 01/25/2024). This new grounds of rejection is necessitated upon further consideration of the claims in view of applicants’ remarks and declaration.
31. The relevant teachings of Strucko et al., Yang et al. and Lilly et al. as applied to claims 1, 30, 91, 95, 97, 110-111, and 113-114 are set forth above.
With respect to claims 39, Strucko et al. teach the construction of a de novo vanillin b-glucoside pathway in two Saccharomyces cerevisiae strains comprising transforming the strains with genes encoding the enzymes aromatic carboxylic acid reductase, phosphopantetheine transferase, O-methyltransferase, and 3-dehydroshikimate dehydratase [see Abstract; Figure 1; p. 100, column 2].
However, the combination of Strucko et al., Yang et al., Chen et al. and Stewart et al. does not explicitly teach the recombinant yeast host cell of claim 39, lacking a phenyacrylic acid decarboxylase enzymatic activity.
Gallage et al. teach that vanillin is a popular and valuable flavor compound and that vanillin synthase catalyzes the conversion of ferulic acid to vanillin [see Abstract]. Gallage et al. teach that concomitant with the conversion of ferulic acid and its glucoside into vanillin and vanillin glucoside, yeasts are able to metabolize ferulic acid into 4-vinylguaiacol through phenylacrylate decarboxylase and that increased levels of vanillin production in yeast would thus be envisioned following disruption or downregulation of the two genes encoding phenylacrylate decarboxylase and ferrulate decarboxylase [see p. 5, column 2].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art desiring to produce vanillin to combine the teachings of Strucko et al., Yang et al., Chen et al., Stewart et al. and Gallage et al. according to the teachings of Gallage et al. to downregulate phenylacrylic acid decarboxylase acitivty because Strucko et al., Yang et al., Chen et al. and Stewart et al. teach heterologous expression of enzymes in brewer’s Saccharomyces for the production of vanillin. Gallage et al. teach that increased levels of vanillin production in yeast would thus be envisioned following disruption or downregulation of the two genes encoding phenylacrylate decarboxylase and ferrulate decarboxylase. One of ordinary skill in the art would have a reasonable expectation of success, a reasonable level of predictability and would be motivated to combine the teachings of Strucko et al., Yang et al., Chen et al., Stewart et al. and Gallage et al. because Gallage et al. acknowledges that increased levels of vanillin production in yeast would thus be envisioned following disruption or downregulation of the two genes encoding phenylacrylate decarboxylase and ferrulate decarboxylase. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Remarks Regarding Prior Art Rejections
32. Applicants’ remarks regarding the prior art rejections have been fully considered; however, they are rendered moot in view of the new rejections set forth above, which are necessitated upon further consideration of the claims in view of applicants’ arguments.
Claim Objections
33. Claims 63 and 78 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
34. Status of the claims:
Claims 1-2, 12, 17, 30, 39-40, 47, 62-63, 66, 78, 91, 95, 97, 99, 104, and 110-114 are pending.
Claims 99 and 104 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 1-2, 12, 17, 30, 39-40, 47, 62, 66, 91, 95, 97, 110-114 are rejected.
Claims 63 and 78 are objected to.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656