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 .
Claim Objections
Claims 13 & 21 are objected to because of the following informalities: reciting “a kit of part”. This is not a phrase with a clear meaning and is construed as “a kit comprising” for the purposes of examination. Appropriate correction is required.
Claim 15 is objected to because of the following informalities: reciting “a recombinant yeast according to claim 1”, claim 1 claims the composition of a recombinant yeast with at least 90% sequence identity to SEQ ID NO: 01. Claim 1 is not a process claim and does not recite any active steps thus claim 15 should recite “the protein of claim 11” or a statement of similar effect. Appropriate correction is required.
Claim 20 is objected to because of the following informalities: reciting “a protein according to claim 11”, claim 11 claims the composition of a protein with at least 90% sequence identity to SEQ ID NO: 01. Claim 11 is not a process claim and does not recite any active steps thus claim 20 should recite “the protein of claim 11” or a statement of similar effect. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: reciting “a kit according to claim 13”, claim 13 claims the composition of a kit of part comprising: a first and second recombinant yeast strain. Claim 13 is not a process claim and does not recite any active steps thus claim 21 should recite “the kit of part of claim 13” or a statement of similar effect. Appropriate correction is required.
Claim Rejections - 35 USC § 112
Indefiniteness
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.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 5 recites “wherein the recombinant yeast cell comprises one or more genetic modifications to functionally express a protein that functions in a metabolic pathway forming a non-native redox sink”, this language is vague and unclear what applicant is actually claiming. For the purposes of examination claim 5 is construed to claim the recombinant yeast cell of claim 1 with any further modification that results in the expression of any protein involved in any metabolic pathway that results in a redox reaction inside the yeast cell and the protein was not present before the modification. This is the only reasonable interpretation since there is no other definite limitation recited in this claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 11-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claims recite a glucoamylase with an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 01. This judicial exception is not integrated into a practical application because the claims are for the composition per se. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no further elements are recited in the claims. Applicant claims a naturally occurring enzyme from the turkey tail mushroom of the genus Trametes. The protein sequence has been known to occur in this organism since 2015 as evidenced by Couturier et al. (Enhanced degradation of softwood versus hardwood by the white-rot fungus Pycnoporus coccineus, Biotechnology for Biofuels, 18DEC15).
Claim Rejections - 35 USC § 102
Claims 1, 3-5, 11-12, 15, 18 & 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yazdi et al. (WO 2018/098381 A1, Improved Yeast For Ethanol Production, 31MAY18, hereafter “Yazdi”).
Yazdi teaches a recombinant yeast having a glucoamylase with greater than 90% sequence identity to SEQ ID NO: 01 (SEQ ID NO: 18 of Yazdi) of the instant application, for the purpose of producing ethanol from starch-containing material (Claim 10).
Regarding claims 1, 3-4, 11-12, 15, 18 & 20: A composition comprising a recombinant yeast cell encoding a glucoamylase with at least 90% sequence identity to SEQ ID NO: 01, that can break alpha-1,6-gylcosidic bonds, the glucoamylase itself, and a process for producing ethanol using the recombinant yeast or the glucoamylase, wherein the carbon source comprises disaccharides and or oligosaccharides. The composition itself is directly taught by claim 10 of Yazdi, which recites a fermenting organism (S. cerevisiae) encoding a glucoamylase comprising the polypeptided of SEQ ID NO: 18 (92% sequence identity to SEQ ID NO: 01 of the instant application), as well as the process of producing ethanol comprising the recombinant yeast, the glucoamylase and a starch containing material (starch is an oligosaccharide). Breaking alpha-1,6-gylcosidic bonds is an inherent feature of glucoamylase enzymes as evidenced by Sauer et al. (Glucoamylase: structure/function relationships, and protein engineering, Biochimica et Biophysica Acta (1543) 275-293, 28SEP00), although the activity is generally lower on breaking alpha-1,6 bonds compared to alpha-1,4 bonds. Breaking alpha-1,6 glycosidic bonds would also be an inherent property of an enzyme whether it were observed or not, and thus must have been present in the recombinant yeast and glucoamylase of claim 10 of Yazdi.
Regarding claim 5: the recombinant yeast cell of claim 1 with any further modification that results in the expression of any protein involved in any metabolic pathway that results in a redox reaction inside the yeast cell and the protein was not present before the modification; Claim 12 of Yazdi, which depends on claim 10, recites a yeast with an alpha-amylase with a glucoamylase linker and starch binding domain as shown in SEQ ID NO: 16. The alpha-amylase of claim 12 was not present before being modified, and is involved in the metabolic pathways of glycolysis, central metabolism and the electron transport chain since alpha-amylase frees glucose monomers from the starch polymer so that the cell can import them to fuel its metabolism. Thus, the alpha-amylase of claim 12 of Yazdi is a protein involved in a metabolic pathway that results in a redox reaction inside the yeast cell and the protein was not present before the modification. As such claim 5 of the instant application is anticipated by claim 12 of Yazdi.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Yazdi as applied to claims 1, 3-5, 11-12, 15, 18 & 20 above.
Yazdi teaches a recombinant yeast having a glucoamylase with greater than 90% sequence identity to SEQ ID NO: 01 (SEQ ID NO: 18 of Yazdi) of the instant application, for the purpose of producing ethanol from starch-containing material (Claim 10). While Yazdi does not explicitly teach the DNA sequence of SEQ ID NO: 02 which codes for SEQ ID NO: 01 of the instant application, it is obvious to one of ordinary skill in the art that the specific DNA sequence of an enzyme of interest is a matter of choice, since DNA synthesis services are widely available. Many different DNA sequences can encode the same polypeptide, and in the age of widely available gene synthesis services one can select their DNA sequence of choice for any given peptide sequence, usually for the purpose of codon optimization or GC content matching foreign genes for expression in a new host. Thus, the DNA sequence of SEQ ID NO: 02 is obvious even though it was not directly taught by Yazdi.
Claims 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Yazdi as applied to claims 1-5, 11-12, 15, 18 & 20 above, and further in view of De Waal et al. (WO 2018/172328 A1, Improved Glycerol Free Ethanol Production, 20MAR18, hereafter “De Waal”).
Yazdi teaches a recombinant yeast having a glucoamylase with greater than 90% sequence identity to SEQ ID NO: 01 (SEQ ID NO: 18 of Yazdi) of the instant application, for the purpose of producing ethanol from starch-containing material (Claim 10). While Yazdi does not explicitly teach the inclusion of the following enzymes: RuBisCo, ribulokinase, chaperones of RuBisCo, phosphoketolase, phosphotransacetylase, acetate kinase, NAD+ dependent acetylating acetaldehyde dehydrogenase, glycerol dehydrogenase, dihydroxyacetone kinase or a glycerol transporter, nor does it teach the deletion of glycerol-3-phosphate dehydrogenase or glycerol phosphate phosphatase. De Waal teaches all of those with a recombinant yeast for ethanol production.
De Waal specifically teaches the inclusion of the following enzymes: RuBisCo (page 28 line 24), phosphoketolase, phosphotransacetylase, acetate kinase (Claim 4), NAD+ dependent acetylating acetaldehyde dehydrogenase (Claims 1 & 6-7) and a glycerol dehydrogenase, dihydroxyacetone kinase or a glycerol transporter (Claims 1-3, page 35 lines 19-24). De Waal also teaches the deletion of glycerol-3-phosphate dehydrogenase or glycerol phosphate phosphatase (Claims 12-13, page 21 line 12).
Regarding claims 6-10: the inclusion of the following enzymes: RuBisCo, ribulokinase, chaperones of RuBisCo, phosphoketolase, phosphotransacetylase, acetate kinase, NAD+ dependent acetylating acetaldehyde dehydrogenase, glycerol dehydrogenase, dihydroxyacetone kinase or a glycerol transporter, and the deletion of glycerol-3-phosphate dehydrogenase or glycerol phosphate phosphatase in a recombinant yeast with a glucoamylase with at least 90% sequence identity to SEQ ID NO: 01. This suggests that it would be obvious to one of ordinary skill in the art to combine the recombinant yeast for glycerol free ethanol production of De Waal with the glucoamylase expressing recombinant yeast of Yazdi with the expectation of nothing but success. Especially since the genetic modification of yeast is standard within the field and the techniques are well known to the ordinary artisan. One would have been motivated to do since both recombinant strains of yeast address separate well known issues of ethanol production, unwanted side products (glycerol) and the requirement for pre-processing carbon sources (starch) down to glucose, and combining the two would improve efficiency of ethanol production.
Claims 13, 16-17, 19 & 21 are rejected under 35 U.S.C. 103 as being unpatentable over Yazdi as applied to claims above 1-12, 15, 18 & 20, and further in view of De Bruijn et al. (WO 2019/063543 A1, Improved Glycerol Free Ethanol Production, 04APR19, hereafter “De Bruijn”).
Yazdi teaches a recombinant yeast having a glucoamylase with greater than 90% sequence identity to SEQ ID NO: 01 (SEQ ID NO: 18 of Yazdi) of the instant application, for the purpose of producing ethanol from starch-containing material (Claim 10). While Yazdi does not explicitly teach the process for ethanol production comprising external dosing of a glucoamylase at a concentration of 0.05g/L or less, or explicitly without external dosing, nor does it teach the total weight of disaccharides or oligosaccharides as greater than or equal to 1% of total saccharides.
However, De Bruijn teaches the production of ethanol using a recombinant yeast expressing a glucoamylase further comprising the external dosing of glucoamylase at a concentration of 0.05 g/L, and explicitly without external dosing of the glucoamylase (claim 16, page 20 lines 4-21). De Bruijn also teaches the production of ethanol using the recombinant yeast encoding a glucoamylase in Simultaneous Saccharification Fermentation (SSF) mode (page 24 lines 11-13, table 4) wherein the recombinant yeast are directly cultured on corn mash which according to the preparation recipe (page 23 lines 22-26) would far exceed 1% of the total saccharides being oligo or disaccharides. De Bruijn further teaches a recombinant yeast for the production of ethanol with a sequence identity of 97% to that of SEQ ID NO: 03 of the instant application (claim 1-8 & 11-16).
Regarding claims 16-17 & 19: a process for producing ethanol comprising a recombinant yeast encoding a glucoamylase with at least 90% sequence identity to SEQ ID NO: 01, and either the external dosing of glucoamylase at a concentration of 0.05 g/L or less or explicitly without external dosing of glucoamylase. Also, the process wherein the disaccharides and oligosaccharides makeup greater than of equal to 1% of the total saccharides.
Yazdi teaches the recombinant yeast encoding a glucoamylase with at least 90% sequence identity to SEQ ID NO: 01, for the production of ethanol, while De Bruijn teaches the process of ethanol production using a recombinant yeast encoding a different glucoamylase, further comprising/excluding the external dosing of a glucoamylase, as well as the production of ethanol wherein the carbon source is greater than or equal to 1% oligo or disaccharides. This suggests that it would be obvious to one of ordinary skill in the art to combine the recombinant yeast of Yazdi with the process of De Bruijn with the expectation of nothing but success. Especially since the genetic modification of yeast is standard within the field and the techniques are well known to the ordinary artisan. One would have been motivated to do so since the methods of De Bruijn allow for SSF mode which can save time, effort and expense in the preprocessing of starchy materials for ethanol production.
Regarding claims 13 & 21: a kit comprising two recombinant yeasts, the first encoding a protein with at least 90% sequence identity to SEQ ID NO: 01 and the second yeast encoding a protein with at least 70% sequence identity to SEQ ID NO: 03, as well as the process of producing ethanol using the same.
Yazdi teaches the recombinant yeast encoding a glucoamylase with at least 90% sequence identity to SEQ ID NO: 01, for the production of ethanol, while De Bruijn teaches the process of ethanol production using a recombinant yeast encoding a different glucoamylase with 97% identity to SEQ ID NO: 03 of the instant application. This suggests that it would have been obvious to one of ordinary skill in the art to combine the two with the expectation of success. Especially since the genetic modification of yeast is standard within the field and the techniques are well known to the ordinary artisan. One would have been motivated to do so since the recombinant yeast of De Bruijn also encodes for genes that increase the efficiency of ethanol production by reducing or eliminating the production of the unwanted side product, glycerol. Especially since the recombinant yeast of De Bruijn can transport and metabolize the glycerol produced by the recombinant yeast of Yazdi.
Discussion of Relevant Prior Art
The following documents which are not cited in this office action teach a glucoamylase with at least 90% sequence identity to SEQ ID NO: 01 of the instant application, for the purposes of ethanol production: WO 2011/066576 A1 (SEQ ID NO: 02, 96%, SEQ ID NO: 04, 94%, SEQ ID NO: 06, 94%), WO 2016196202 A1 (SEQ ID NO: 08, 93%), WO 2015 007639 (SEQ ID NO: 16, 93%), US 20120214197 A1 (SEQ ID NO: 02, 96%, SEQ ID NO: 04, 94%, SEQ ID NO: 06, 94%) US 20180208917 A1 (SEQ ID NO: 10, 93%), US 20170051265 A1 (SEQ ID NO: 16, 93%).
The following documents which are not cited teach a protein with at least 70% sequence identity to SEQ ID NO: 03: WO 2019063542 A1 (SEQ ID NO: 18, 100%, SEQ ID NO: 19, 97%, SEQ ID NO: 17, 97%), WO 2020043497 A1 (SEQ ID NO: 02, 100%).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GREGORY WILLKEEN whose telephone number is (571)272-6184. The examiner can normally be reached 9:00-5:00 Mon-Fri.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie L. Gordon can be reached at (571) 272-1113. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/G.A.W./ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651