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
Applicant’s election without traverse of Invention I (claims 1-4, 6-8, 10-16, 18 and 19) and species of SEQ ID NO: 296 (GAPN), SEQ ID NO: 323 (glycerol transporter) and glucoamylase in the reply filed on 02/18/2026 is acknowledged.
Claims 22, 23, 25 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/18/2026.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 7, 10 and 19 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 7 is indefinite for depending from cancelled claim 5 (i.e. any one claims 1-6). A claim depending from a cancelled claim is indefinite as far as it is not clear what the features of the cancelled claim are.
Regarding claim 19, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). That is, it is unclear if embodiments of claim 19 require a surfactant, emulsifier, etc.
Claims 6 and 10 recite “a mature polypeptide comprising or consisting of the amino acid sequence of any one of.” Recitation of “comprising or consisting of” is not understood as reciting a Markush group, since the purpose of a transitional phrase is set forth whether a claim is open or closed to unrecited claim elements rather than be a claim element as may be recited in a Markush group. It is unclear if “comprising or consisting of” simply means “comprising,” i.e. open claim language, or if “comprising or consisting of” is a hybrid transitional phrase having some undefined meaning different from either “comprising” or “consisting of.” For this reason, an ordinarily skilled artisan cannot determine how to avoid infringement.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-4, 6-7, 12-16 and 18-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skinner et al. (WO 2020/115716 A1). The sequence listing for Skinner is also available in U.S. 2021/0380989 A1.
Skinner, abstract, states:
The present disclosure concerns recombinant yeast host cells having a first genetic modification for downregulating a first metabolic pathway that converts NADP+ to NADPH, as well as a second genetic modification for upregulating a second metabolic pathway that converts NADP+ to NADPH. The second genetic modification allows the expression of a glyceraldehyde-3-phosphate dehydrogenase lacking phosphorylating activity, which can, in some embodiments, be from enzyme commission 1.2.1.9 or 1.2.1.90. The second pathway is distinct from the first metabolic pathway. The present disclosure also concerns a process for making and improving the yield of a fermented product, such as ethanol, using the recombinant yeast host cell.
Table beginning on page 47 of Skinner presents the following S. cerevisiae strains:
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“Native enzymes that function to transport glycerol synthesis include, but are not limited to, the FPS1 polypeptide as well as the STL1 polypeptide. The FPS1 polypeptide is a glycerol exporter and the STL1 polypeptide functions to import glycerol in the recombinant yeast host cell.” Skinner, page 39. “The present disclosure provides an alternative for reducing glycerol by diverting more carbon flux towards pyruvate by introducing a heterologous glyceraldehyde-3-phosphate dehydrogenase gene into the recombinant yeast host cell.” Skinner, page 8.
The above description of Skinner anticipates claims 1 and 18.
Regarding claim 3, the GAPN gene/polynucleotide in the table above is linked to a tpi1p promoter that is a foreign the GAPN gene.
Regarding claim 6, SEQ ID NO: 1 of Skinner is a nucleotide sequence encoding SEQ ID NO: 2 of Skinner. SEQ ID NO: 2 of Skinner is over 99% identical to recited SEQ ID NO: 279.
Regarding claim 7, the STL1 glycerol transporter gene/polynucleotide in the table above is linked to a hxt3p/qcr8p promoter that is operable linkage to a foreign promoter as recited.
Regarding claim 19, claim 67 of Skinner presents a process for converting biomass into a fermentation product by contacting/combining a yeast cell as described by Skinner with biomass, which produces a composition meeting the features of claim 19.
Regarding claims 12 and 13, a “fifth genetic modification for expressing a fifth polypeptide for increasing saccharolytic activity in an embodiment, the fifth polypeptide comprises an enzyme having alpha-amylase activity and/or an enzyme having glucoamylase activity. “In some embodiments, the recombinant yeast host cel! can include a fifth genetic modification allowing the expression of an heterologous saccharolytic enzyme. As used in the context of the present disclosure, a “saccharolytic enzyme” can be any enzyme involved in carbohydrate digestion, metabolism and/or hydrolysis, including amylases, cellulases, hemicellulases, cellulolytic and amylolytic accessory enzymes, inulinases, levanases, and pentose sugar utilizing enzymes amylolytic enzyme. In an embodiment, the saccharolytic enzyme is an amylolytic enzyme. As used herein, the expression “amylolytic enzyme” refers to a class of enzymes capable of hydrolyzing starch or hydrolyzed starch. Amylolytic enzymes include, but are not limited to alpha-amylases (EC 3.2.1 .1 , sometimes referred to fungal alpha-amylase, see below), maltogenic amylase (EC 3.2.1 .133), glucoamylase (EC 3.2 1 .3).” Skinner, page 37.
Regarding claim 14, “The recombinant yeast host cell of the present disclosure can include an optional sixth genetic modification for limiting glycerol production and/or facilitating the transport (and in an embodiment, the export) of glycerol. . . . Native enzymes that function to produce glycerol include, but are not limited to, the GPD1 and the GPD2 polypeptide (also referred to as GPD1 and GPD2 respectively) as well as the GPP1 and the GPP2 polypeptides (also referred to as GPP1 and GPP2 respectively). . . . In some embodiments, the recombinant yeast host cell can have a genetic modification in the gpd1 gene and the gpd2 gene resulting is a recombinant yeast host cell being knock-out for the gpd1 gene and the gpd2 gene.” Skinner, page 38-39.
Regarding claim 15, “The present disclosure also concerns a process for making and improving the yield of a fermented product, such as ethanol, using the recombinant yeast host cell.” Skinner, abstract. “[I]t was then determined if the co-expression of STL1 with GAPN could further increase the fermentation yield in a corn mash fermentation. When STL1 is co-expressed with GAPN, an improvement in the ethanol yield and a reduction in glycerol production is observed (when compared to the parental strain). This is seen in Figure 10, when STL1 is co-expressed with a glucoamylase (strains M19994 and M20365) as well as in Figure 11 when STL1 is expressed with GAPN (strain M19687), ADHE (M2Q17Q) or in combination with the reuterin complex (strains M20296 and M20300).” Skinner, page 53. The preceding is understood as a description of co-expression of STL1 (glycerol transporter) with GAPN has improved ethanol production that the same corresponding strain expressing GAPN without STL1 as to meet the features of claim 15. Further, strain M18913 expresses 2 copies of GAPN and strain M19687 is a corresponding strain expressing 2 copies of GAPN and 4 copies of STL1 (glycerol transporter). Fig. 10 of Skinner shows strain M19687 producing over 153 g/L of ethanol and Fig. 9 of Skinner shows strain M18913 producing less than 145 g/L of ethanol, which meets the features of claim 15.
Regarding claim 16, strain M19506 express two copies of STL1 and strain M22889 is a corresponding strain expressing 4 copies of GAPN and 2 copies of STL1. See Skinner, Table beginning pg. 47. Fig. 14A of Skinner showing that strain M22889 produces more ethanol that strain M19506 under the same conditions meets the features of claim 16.
Further regarding claims 15 and 16, Skinner in general, regardless of specific working embodiments as discussed above, teaches that expression of STL1 (glycerol transporter) and GAPN, separately or together, is associated with increased ethanol production as compared to the same strain lacking expression of STL1 or GAPN. Specifically, “the recombinant yeast host cell increases ethanol
production compared to a corresponding native yeast host cell lacking the first genetic
modification and the second genetic modification [GAPN expression].” Skinner, claim 71. “When STL 1 is co-expressed with GAPN, an improvement in the ethanol yield and a reduction in glycerol production is observed.” Skinner, page 53. The preceding further meets the features of claims 15 an 16.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-4, 6-8, 10, 12-16 and 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Skinner et al. (WO 2020/115716 A1) as applied to claims 1-4, 6-7, 12-16 and 18-19 above, and further in view of Uniprot, Accession No. G8ZQF7, 2020, www.uniprot.org.
Regarding claims 8 and 10, “The STL1 polypeptide is natively expressed in yeasts and fungi, therefore the heterologous polypeptide functioning to import glycerol can be derived from yeasts and fungi. STL1 genes encoding the STL1 polypeptide include, but are not limited to . . . Toruiaspora deibrueckii Gene ID: 11505245.
As such, Skinner directly suggests and teaches that the STL1 polypeptide/gene from S. cerevisiae employed in the working examples of Skinner can be replaced with other specified STL1 genes including “Toruiaspora deibrueckii Gene ID: 11505245.” More specifically, an ordinarily skilled artisan would have been motived to employ any polynucleotide encoding a protein associated with Toruiaspora deibrueckii Gene ID: 1150524” including the glycerol transport protein described in Uniprot G8ZQF7 described as associated with “GeneID; 11505245,” since Skinner directly suggests that other specified STL1 genes including “Toruiaspora deibrueckii Gene ID: 11505245” can be used in embodiments of Skinner. The glycerol transport protein taught in Uniprot G8ZQF7 is 100% identical to recited SEQ ID NO: 319.
Claims 8 and 10 are understood as stating that the amino acid sequence of SEQ ID NO: 319 is “a mature polypeptide sequence” as recited.
Claim(s) 1-4, 6-7, 11-16 and 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Skinner et al. (WO 2020/115716 A1) as applied to claims 1-4, 6-7, 12-16 and 18-19 above, and further in view of Argyros et al. (U.S. 2016/0194669 A1).
Regarding claim 11, similar to Skinner Argyros teach yest strains engineered for reduced glycerol production to assist in increased ethanol production. Argyros, abstract:
The present invention provides for novel metabolic pathways to reduce or modulate glycerol production and increase product formation. More specifically, the invention provides for a recombinant microorganism comprising one or more native and/or heterologous proteins that function to import glycerol and one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to convert a carbohydrate source, such as lignocellulose, to a product, such as ethanol, wherein the one or more native and/or heterologous proteins or enzymes is activated, upregulated, or downregulated. The invention also provides for a recombinant microorganism comprising one or more native or heterologous proteins that function to regulate glycerol synthesis and one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to convert a carbohydrate source to ethanol, wherein said one or more native and/or heterologous proteins or enzymes is activated, upregulated or downregulated. Also provided are methods for increasing cellular glycerol uptake and increasing recombinant production of fuels and other chemicals using the recombinant microorganisms of the invention.
As in Skinner, the recombinantly expressed protein to import glycerol is STL1. “In some embodiments, the one or more native and/or heterologous proteins that function to import glycerol is STL1.” Argyros, para. [0014].
Regarding “one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to convert a carbohydrate source to ethanol,” “the microorganism further comprises one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to convert xylose to xylulose-5-phosphate and/or arabinose to xylulose-5-phosphate, wherein said one or more native and/or heterologous enzymes is activated, upregulated or downregulated. In some embodiments, the one or more native and/or heterologous enzymes that function to convert xylose to xylulose-5-phosphate is xylose isomerase. In certain embodiments, the one or more native and/or heterologous enzymes that function to convert arabinose to xylulose-5-phosphate is selected from the group consisting of arabinose isomerase, ribulokinase, and ribulose 5-phosphate epimerase.” Argyros, para. [0022]. “In some embodiments, the PE-2 strain overexpresses a hemicellulase and/or a gene encoding a protein of the xylose fermentation pathway. In some embodiments, the gene encoding a protein of the xylose fermentation pathway is selected from the group consisting of xylose isomerase (XylA), xylulokinase (XKS1), transketolase (TKL2), transaldolase (TAL1), and any combination thereof.” Argyros, para. [0063].
A xylose fermentation pathway is an active pentose fermentation pathway. Claims 1 and 43 direct that the glycerol import protein (i.e. STL1) and xylose/pentose fermentation pathway be embodied in the same strain.
As such, Argyros expressly teaches that it is advantageous to modify a yeast cell for production of ethanol having further modifications to decrease glycerol production (i.e. expression of STL1 glycerol import protein) be combined with a xylose/pentose fermentation pathway heterologously expressed in the same S. cerevisiae strain. In view of such direct teachings, an ordinarily skilled artisan at the time of filing would have been motivated to modify embodiments of Skinner as discussed above to further express a heterologous xylose/pentose fermentation pathway in order to achieve the benefit of ethanol production from lignocellulose materials that contain xylose that can be fermented to ethanol.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-8, 10-16 and 18-19 (all non-withdrawn claims) are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 17/924,917 in view of Skinner et al. (WO 2020/115716 A1) (see IDS), Uniprot, Accession No. G8ZQF7, 2020, www.uniprot.org and Argyros et al. (U.S. 2016/0194669 A1).
The rejections under 35 U.S.C. 102 and 103 stated above are incorporated herein by reference. Copending or patented claims are referred to as “reference claims.”
The reference claims recite:
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As discussed above, the cited prior art teach that it is advantageous to combine a xylose fermentation/metabolism pathway, expression of heterologous GAPN gene and a STL1 glycerol transporter, along with all of the other features of the rejected claims, to produce a S. cerevisiae cell with reduced glycerol production and therefore increased ethanol production with ability to utilize xylose as found in lignocellulose. Argyros, paras. [0197]-[0201] further teach that an arabinose metabolism pathway can further be present instead of or in combination with a xylose metabolism pathway. As such, the prior art further teaches that it is advantageous to combine an arabinose fermentation/metabolism pathway, expression of heterologous GAPN gene and a STL1 glycerol transporter. As far as the cited prior art teaches that an advantageous embodiment of the reference claims is an S. cerevisiae cell engineered to combine an arabinose fermentation/metabolism pathway, expression of heterologous GAPN gene and a STL1 glycerol transporter and all of the other features of the rejected claims, an ordinarily skilled artisan at the time of filing would have been motivated to form embodiments of the reference claims meeting all of the features of the rejected claims in order to achieve the advantages suggested by the cited prior art discussed above being a S. cerevisiae cell with reduced glycerol production and therefore increased ethanol production with ability to utilize xylose and/or arabinose as found in lignocellulose
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TODD M EPSTEIN whose telephone number is (571)272-5141. The examiner can normally be reached Mon-Fri 9:00a-5:30p.
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652