DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s preliminary amendment to the claims, filed September 25, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Claims 1, 3-5, 7-11, 15, 17, and 20-26 are pending in the application.
Restriction/Election
Applicant's election with traverse of Group I, claims 1, 3-5, 7-11, and 15 in the reply filed September 25, 2026 is acknowledged. The traversal is on the ground(s) that claim 1 has been amended to exclude SEQ ID NO: 13 and the shared same or corresponding technical feature between the inventions of Groups I and II is a contribution over the prior art. This is not found persuasive because the shared same or corresponding technical feature between the inventions of Groups I and II is not a contribution over the prior art at least in view of Cheng, H. (WO 2021/093289 A1; cited on the attached Form PTO-892) disclosing the genetically engineered yeast cell of claim 1 as described in the below rejection under 35 U.S.C. 102.
The requirement is still deemed proper and is therefore made FINAL.
Claims 17 and 20-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Applicant’s election without traverse of the species SEQ ID NO: 38 (species election A), ER1 locus (species election B), and pyruvate kinase 1 promoter (species election C) in the reply filed September 25, 2026 is acknowledged.
Claims 1, 3-5, 7-11, and 15 are being examined on the merits with claims 1, 10, and 11 being examined only to the extent the claims read on the elected subject matter.
Priority
This application is filed under 35 U.S.C. 371 as a national stage of international application PCT/US2023/066628, filed May 5, 2023, which claims domestic priority under 35 U.S.C. 119(e) to U.S. provisional application no. 63/364,370, filed May 9, 2022.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on November 7, 2024 and May 12, 2025 are in compliance with the provisions of 37 CFR 1.97 and have been considered by the examiner.
Specification/Informalities
The disclosure is objected to because of the following informalities.
The use of the terms BLAST and GENESYS 20, which are trade names or marks used in commerce, have been noted in this application in paragraphs [0040], [0077], [0081], [0086], [0091], and [0096]. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1, 5, 10, and 15 are objected to because of the following informalities:
Claims 1 and 15 are objected to in the recitation of “a sequence at least…identical to” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite “a sequence having at least…sequence identity to.”
Claim 1 is also objected to in the recitation of “an exogenous polynucleotide sequence” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite “an exogenous polynucleotide comprising a nucleotide sequence” and for consistency, it is suggested that claims 9-11 be amended to delete “sequence” in the phrase “polynucleotide sequence.”
Claim 10 is objected to in the recitation of “a loci” and in the interest of improving claim form and grammar, it is suggested that claim 10 amended to replace the term “loci” with “locus.”
Claim 5 is objected to as not ending with a period. See MPEP 608.01(m).
Claim Rejections - 35 USC § 112(b)
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.
Claims 1, 3-5, 7-11, and 15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 (claims 3-5, 7-11, and 15 dependent therefrom) is indefinite in the recitation of “a sequence at least 90% identical to at least one of SEQ ID NOs: 34, 35, 36, 37, 38, and 39.” The noted limitation encompasses a sequence that is identical to a subset or all of SEQ ID NOs: 34, 35, 36, 37, 38, and 39, yet each of the sequences is distinct from the others. As such, one of skill in the art would recognize that there can be no sequence that is identical to a subset or all of SEQ ID NOs: 34, 35, 36, 37, 38, and 39. In the interest of advancing prosecution, it is suggested that the limitation “to at least one of SEQ ID NOs: 34, 35, 36, 37, 38, and 39” be amended to recite “to a sequence selected from the group consisting of SEQ ID NO: 34, 35, 36, 37, 38, and 39.”
Claim 3 is indefinite in the recitation of “yeast cell is an osmotolerant yeast cell.” The specification describes “osmotolerant” as referring to a yeast capable of growth and reproduction under conditions of high osmolarity, such as at least 10% (w/v), at least 20% (w/v), at least 30% (w/v), at least 40% (w/v), at least 50% (w/v), or at least 60% (w/v) glucose and/or at least 6% (w/v), at least 10% (w/v), at least 12% (w/v), at least 13% (w/v), at least 15% (w/v) sodium chloride. However, given that “high” in the phrase “high osmolarity” is a relative term and the specification discloses exemplary, non-limiting conditions of “high osmolarity,” one of skill in the art would not be able to ascertain the scope of yeast cells that are “osmotolerant.”
Claim 10 recites (in relevant part) the limitation "the ER1 locus.” There is insufficient antecedent basis for this limitation in the claim. In the interest of advancing prosecution, it is suggested that the noted phrase be amended to replace “the” with “an.”
Claim 11 is indefinite in the recitation of (in relevant part) “SEQ ID NO: 86” in parenthesis because it is unclear as to whether the recitation of “SEQ ID NO: 86” in parenthesis is intended to be limiting or merely exemplary. If “SEQ ID NO: 86” in parenthesis is intended to be limiting, it is suggested that the phrase “pyruvate kinase 1 promoter (PYK1p; SEQ ID NO:86)” be amended to recite “pyruvate kinase 1 promoter (PYK1p) comprising the nucleotide sequence of SEQ ID NO:86.” If “SEQ ID NO: 86” in parenthesis is intended to be exemplary, applicant is advised that description of examples is properly set forth in the specification rather than the claims because if stated in the claims, examples may lead to confusion over the intended scope of a claim.
Claim 15 is indefinite in the recitation of “a sequence at least 95% identical to at least one of SEQ ID NOs: 34-39.” The noted limitation encompasses a sequence that is identical to a subset or all of SEQ ID NOs: 34, 35, 36, 37, 38, and 39, yet each of the sequences is distinct from the others. As such, one of skill in the art would recognize that there can be no sequence that is identical to a subset or all of SEQ ID NOs: 34, 35, 36, 37, 38, and 39. In the interest of advancing prosecution, it is suggested that the limitation “to at least one of SEQ ID NOs: 34, 35, 36, 37, 38, and 39” be amended to recite “to a sequence selected from the group consisting of SEQ ID NO: 34, 35, 36, 37, 38, and 39.”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 5, 8, 9, and 15 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Cheng, H. (WO 2021/093289 A1; cited on the attached Form PTO-892; hereafter “Cheng”) as evidenced by Rzechonek et al. (Genes 11:1424, 2020, 15 pages; cited on the IDS filed November 7, 2024; hereafter “Rzechonek”).
Cheng is a non-English language document and reference is made to US 2022/0259622 A1 as an English-language translation of Cheng.
The claims are drawn to (in relevant part) a genetically engineered yeast cell capable of producing ribitol, the engineered yeast cell comprising:
an exogenous polynucleotide sequence encoding a ribulose-5-phosphate reductase enzyme with a sequence at least 90% identical to SEQ ID NO: 38.
According to the instant specification, the term “exogenous” refers to genetic material or an expression product thereof that originates from outside of the host organism (paragraph [0036]).
Cheng is related to a construction method and recombinant yeast strain Yarrowia lipolytica for xylitol synthesis (see title).
Regarding instant claims 1, 5, and 15, Cheng teaches a gene encoding 5-p xylulose reductase from Lactobacillus plantarum with the nucleotide sequence of SEQ ID NO: 20 (US 2022/0259622 A1 at paragraphs [0044] and [0045]). SEQ ID NO: 20 of Cheng encodes an amino acid sequence that has 97% sequence identity to instant SEQ ID NO: 38 (see attached Appendix A for sequence alignment).
Cheng does not teach SEQ ID NO: 20 encodes a ribulose-5-phosphate reductase enzyme. However, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the amino acid sequence encoded by SEQ ID NO: 20 of Cheng is substantially identical to instant SEQ ID NO: 38, it is presumed that the polypeptide encoded by SEQ ID NO: 20 of Cheng is a ribulose-5-phosphate reductase enzyme.
Cheng teaches construction of a recombinant Yarrowia lipolytica strain expressing the 5-p xylulose reductase gene along with other genes for the production of xylitol (US 2022/0259622 A1 at paragraphs [0016] to [0021]). Cheng teaches Yarrowia lipolytica comprising the genes for xylitol production is capable of producing ribitol (US 2022/0259622 A1 at paragraph [0131]).
Regarding instant claim 3, Cheng does not teach the recombinant Yarrowia lipolytica strain is an osmotolerant yeast cell. However, evidentiary reference Rzechonek is cited in accordance with MPEP 2131.01.III to show that Yarrowia lipolytica is an osmotolerant yeast cell (see, e.g., Rzechonek at p. 10, bottom).
Regarding instant claim 8, Cheng does not teach the recombinant Yarrowia lipolytica strain is capable of producing ribitol at a titer of at least 20, 30, 50, 75, or 100 g/L when used in a fermentation process in the presence of dextrose for at least 96 hours. However, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the recombinant Yarrowia lipolytica strain of Cheng is substantially identical to the genetically engineered yeast cell of claim 1, it is presumed that the recombinant Yarrowia lipolytica strain of Cheng is capable of producing ribitol at a titer of at least 20, 30, 50, 75, or 100 g/L when used in a fermentation process in the presence of dextrose for at least 96 hours.
Regarding instant claim 9, Cheng teaches knockout or down-regulation of transketolase gene in the cell of Yarrowia lipolytica to lose or significantly decrease the ability to synthesize erythritol (US 2022/0259622 A1 at paragraphs [0022] and [0025]).
Therefore, Cheng anticipates claims 1, 3, 5, 8, 9, and 15 as written.
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.
Claims 4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng in view of de Troostenbergh et al. (EP 0136805; cited on the attached Form PTO-892; hereafter “de Troostenbergh”) and Rzechonek et al. (Critical Reviews in Biotechnology 38:620-633, 2018; cited on the attached Form PTO-892; hereafter “Rzechonek-2”).
Claim 4 is drawn to the yeast cell of claim 1, wherein the yeast cell is a cell of the subphylum Ustilaginomycotina.
Claim 7 is drawn to the yeast cell of claim 1, wherein the cell is a Moniliella pollinis cell.
The relevant teachings of Cheng and evidentiary reference Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 are set forth above.
Cheng does not teach or suggest a cell of the subphylum Ustilaginomycotina including a Moniliella pollinis cell.
De Troostenbergh relates to an industrial-scale process for the production of polyols including erythritol and/or ribitol by fermentation of a sugar with Moniliella tomentosa var. pollinis (see title; p. 1, first full paragraph).
Rzechonek-2 teaches the biotechnological production of the polyol erythritol by the yeast Moniliella pollinis (p. 622, column 2, top). Rzechonek-2 teaches genetic engineering to enhance productivity of erythritol (p. 629, column 1, top).
In view of the combined teachings of Cheng, de Troostenbergh, and Rzechonek-2, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Cheng to use Moniliella pollinis as the production host. One of ordinary skill would have expected success and could have used Moniliella pollinis for the production host of Cheng because while Cheng taught the yeast Yarrowia lipolytica for production of xylitol, de Troostenbergh taught Moniliella pollinis is a yeast for production of xylitol, and Rzechonek-2 taught Moniliella pollinis for production of a polyol (erythritol) and the concept of genetic engineering to enhance the production of the polyol. One of ordinary skill would have found it obvious to use Moniliella pollinis for the production host of Cheng because, based on the relevant teachings of Cheng, de Troostenbergh, and Rzechonek-2, an ordinarily skilled artisan would have predicted that Moniliella pollinis would be equivalent to Yarrowia lipolytica taught by Cheng.
Therefore, the invention of claims 4 and 7 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Cheng in view of Ishida et al. (Applied and Environmental Microbiology 71:1964-1970, 2005; cited on the attached Form PTO-892; hereafter “Ishida”).
Claim 10 is drawn to the yeast cell of claim 1, wherein the exogenous polynucleotide sequence is integrated into the genome of the yeast cell at a loci selected from the ER1 locus, the ER3 locus, the PDC1 locus, the pyrF locus, the TRP3 locus, the gpdIIA locus, and the gpdIIB locus.
The relevant teachings of Cheng and evidentiary reference Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 are set forth above.
Regarding claim 10, Cheng further teaches integrating the genes related to xylitol synthesis into the Yarrowia lipolytica cells (US 2022/0259622 A1 at paragraphs [0052] to [0054]).
Cheng does not teach or suggest integration into the genome at a PDC1 locus.
Ishida teaches metabolic engineering of S. cerevisiae through replacement of the PDC1 coding region with a gene of interest LDH via homologous recombination to efficiently produce lactic acid under the control of the native PDC1 promoter (p. 1964, Abstract).
In view of the combined teachings of Cheng and Ishida, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Cheng to integrate the gene encoding 5-p xylulose reductase into a PDC1 locus. One of ordinary skill would have been motivated and expected success to do so because Cheng taught integrating the genes related to xylitol synthesis into the yeast Yarrowia lipolytica cells and Ishida taught a PDC1 locus as a suitable site for integrating and expressing a heterologous gene in a yeast (S. cerevisiae).
Therefore, the invention of claim 10 would have been obvious to one of ordinary skill in the art before the effective filing date. In the interest of clarity, it is noted that the instant rejection is directed to a non-elected species. However, the non-elected species has yet to be searched and examined on the merits because the prior art directed to the non-elected species was identified during a search of the elected species of ER1 locus.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Cheng in view of Partow et al. (Yeast 27:955, 2010; cited on the attached Form PTO-892; herein “Partow”).
Claim 11 is drawn to (in relevant part) the yeast cell of claim 1, wherein the exogenous polynucleotide sequence is operably linked to a heterologous or artificial promoter selected from the group consisting of pyruvate kinase 1 promoter (PYK1p; SEQ ID NO:86).
The relevant teachings of Cheng and evidentiary reference Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 are set forth above.
Cheng does not teach or suggest a pyruvate kinase 1 promoter.
Partow teaches various constitutive glucose-based promoters including PYK1 for expression in S. cerevisiae (p. 956, column 2, middle).
In view of the combined teachings of Cheng and Partow, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify Xu to use a PYK1 promoter for expression of the gene encoding 5-p xylulose reductase. One of ordinary skill would have been motivated and expected success to do so because Cheng taught expressing a gene encoding 5-p xylulose reductase in the yeast Yarrowia lipolytica and Partow taught a PYK1 promoter for expressing a heterologous gene in a yeast (S. cerevisiae).
Therefore, the invention of claim 11 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 1, 3, 5, 8, 9, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (US 2021/0002620 A1; cited on the IDS filed November 7, 2024; hereafter “Xu”) in view of UniProt Accession Number A0A2S9VZQ6 (April 2021, 2 pages; cited on the attached Form PTO-892; hereafter “UniProt”) and as evidenced by Rzechonek.
Xu is related to methods and materials for producing polyols and electron rich compounds (see title).
Regarding instant claims 1, 5, and 15, Xu teaches a recombinant microorganism comprising a polynucleotide encoding Pyp1 and further comprising a polynucleotide encoding an enzyme with sugar phosphate dehydrogenase activity (paragraphs [0011] to [0013]). Xu teaches the microorganism is a yeast including S. cerevisiae and Y. lipolytica (paragraphs [0012] and [0068]). Xu teaches the enzyme with sugar phosphate dehydrogenase activity is a ribitol-5-phosphate dehydrogenase (paragraph [0022]). Xu teaches ribitol-5-phosphate dehydrogenase has been found in gram positive pathogens including Haemophilus influenza (accession number Q48230) and Staphylococcus aureus (accession number ADL64305) (paragraph [0074]). Xu teaches a combinatory over-expression of the enzyme encoded by the PYP1 gene and a gene encoding a sugar phosphate dehydrogenase represents a novel engineering pathway for polyol production and that this approach can be applied to the production of many polyols (paragraph [0061]), noting that polyols include ribitol (paragraph [0006]). Xu teaches Pyp1 has phosphatase activity on ribitol-5-phosphate to produce ribitol (paragraph [0114]).
The difference between Xu and claim 1 is that Xu does not teach a ribulose-5-phosphate reductase with a sequence at least 90% identical to SEQ ID NO: 38.
UniProt teaches a ribulose-5-phosphate reductase (p. 1, top) with an amino acid sequence that has greater than 99% sequence identity to instant SEQ ID NO: 38 (see attached Appendix B for sequence alignment). UniProt teaches ribulose-5-phosphate reductase has the alternative name ribitol-5-phosphate dehydrogenase (p. 1, top).
In view of the combined teachings of Xu and UniProt, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Xu to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase. One of ordinary skill would have expected success and could have used the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase of Xu because Xu taught the sugar phosphate dehydrogenase is a ribitol-5-phosphate dehydrogenase and UniProt taught a ribitol-5-phosphate dehydrogenase. One of ordinary skill would have found it obvious to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase of Xu because, based on the relevant teachings of Xu and UniProt, an ordinarily skilled artisan would have predicted that the ribitol-5-phosphate dehydrogenase of UniProt would be equivalent to the ribitol-5-phosphate dehydrogenase of Xu.
Regarding instant claim 3, the combination of Xu and UniProt does not teach Yarrowia lipolytica is an osmotolerant yeast cell. However, evidentiary reference Rzechonek is cited in accordance with MPEP 2131.01.III to show that Yarrowia lipolytica is an osmotolerant yeast cell (see, e.g., Rzechonek at p. 10, bottom).
Regarding instant claim 8, the combination of Xu and UniProt does not teach the recombinant yeast of Xu modified to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase is capable of producing ribitol at a titer of at least 20, 30, 50, 75, or 100 g/L when used in a fermentation process in the presence of dextrose for at least 96 hours. However, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the recombinant yeast of Xu modified to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase is substantially identical to the genetically engineered yeast cell of claim 1, it is presumed that the recombinant yeast of Xu modified to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase is capable of producing ribitol at a titer of at least 20, 30, 50, 75, or 100 g/L when used in a fermentation process in the presence of dextrose for at least 96 hours.
Regarding instant claim 9, the combination of Xu and UniProt does not teach the recombinant yeast of Xu modified to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase has reduced erythritol production. However, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the recombinant yeast of Xu modified to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase is substantially identical to the genetically engineered yeast cell of claim 1, it is presumed that the recombinant yeast of Xu modified to use the ribitol-5-phosphate dehydrogenase of UniProt as the sugar phosphate dehydrogenase has reduced erythritol production.
Therefore, the invention of claims 1, 3, 5, 8, 9, and 15 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Xu in view of UniProt and as evidenced by Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 above, and further in view of de Troostenbergh and Rzechonek-2.
The relevant teachings of Xu and UniProt and evidentiary reference Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 are set forth above.
The combination of Xu and UniProt does not teach or suggest a cell of the subphylum Ustilaginomycotina including a Moniliella pollinis cell.
De Troostenbergh relates to an industrial-scale process for the production of polyols including erythritol and/or ribitol by fermentation of a sugar with Moniliella tomentosa var. pollinis (see title; p. 1, first full paragraph).
Rzechonek-2 teaches the biotechnological production of the polyol erythritol by the yeast Moniliella pollinis (p. 622, column 2, top). Rzechonek-2 teaches genetic engineering to enhance productivity of erythritol (p. 629, column 1, top).
In view of the combined teachings of Xu, UniProt, de Troostenbergh, and Rzechonek-2, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify Xu to use Moniliella pollinis as the yeast. One of ordinary skill would have expected success and could have used Moniliella pollinis for the recombinant microorganism of Xu because Xu taught the recombinant microorganism is a yeast and is genetically modified to produce ribitol, de Troostenbergh taught Moniliella pollinis is a yeast for production of ribitol, and Rzechonek-2 taught Moniliella pollinis for production of a polyol (erythritol) and the concept of genetic engineering to enhance the production of the polyol. One of ordinary skill would have found it obvious to use Moniliella pollinis for the recombinant microorganism of Xu because, based on the relevant teachings of Xu, de Troostenbergh, and Rzechonek-2, an ordinarily skilled artisan would have predicted that Moniliella pollinis would be equivalent to yeasts taught by Xu.
Therefore, the invention of claims 4 and 7 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Xu in view of UniProt and as evidenced by Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 above, and further in view of Ishida.
The relevant teachings of Xu and UniProt and evidentiary reference Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 are set forth above.
The combination of Xu and UniProt does not teach or suggest integration into the genome at a PDC1 locus.
Ishida teaches metabolic engineering of S. cerevisiae through replacement of the PDC1 coding region with a gene of interest LDH via homologous recombination to efficiently produce lactic acid under the control of the native PDC1 promoter (p. 1964, Abstract).
In view of the combined teachings of Xu, UniProt, and Ishida, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify Xu to integrate the polynucleotide encoding ribitol-5-phosphate dehydrogenase into a PDC1 locus. One of ordinary skill would have been motivated and expected success to do so because Xu taught S. cerevisiae comprising a heterologous polynucleotide encoding a ribitol-5-phosphate dehydrogenase and Ishida taught a PDC1 locus as a suitable site for integrating and expressing a heterologous gene in S. cerevisiae.
Therefore, the invention of claim 10 would have been obvious to one of ordinary skill in the art before the effective filing date. In the interest of clarity, it is noted that the instant rejection is directed to a non-elected species. However, the non-elected species has yet to be searched and examined on the merits because the prior art directed to the non-elected species was identified during a search of the elected species of ER1 locus.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Xu in view of UniProt and as evidenced by Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 above, and further in view of Partow.
The relevant teachings of Xu and UniProt and evidentiary reference Rzechonek as applied to claims 1, 3, 5, 8, 9, and 15 are set forth above.
The combination of Xu and UniProt does not teach or suggest a pyruvate kinase 1 promoter.
Partow teaches various constitutive glucose-based promoters including PYK1 for expression in S. cerevisiae (p. 956, column 2, middle).
In view of the combined teachings of Xu, UniProt, and Partow, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify Xu to use the PYK1 promoter of Partow for expression of ribitol-5-phosphate dehydrogenase. One of ordinary skill would have been motivated and expected success to do so because Xu taught S. cerevisiae comprising a heterologous polynucleotide encoding a ribitol-5-phosphate dehydrogenase and Partow taught a PYK1 promoter for expressing a heterologous gene in S. cerevisiae.
Therefore, the invention of claim 11 would have been obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
Status of the claims:
Claims 1, 3-5, 7-11, 15, 17, and 20-26 are pending.
Claims 17 and 20-26 are withdrawn from consideration.
Claims 1, 3-5, 7-11, and 15 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MANJUNATH N RAO can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX A
US-17-737-012-20
Sequence 20, US/17737012
Publication No. US20220259622A1
GENERAL INFORMATION
APPLICANT: Shanghai Jiao Tong University
TITLE OF INVENTION: Construction method and recombinant yeast stain Yarrowia
TITLE OF INVENTION: lipolytica for xylitol synthesis
FILE REFERENCE: KAG38307
CURRENT APPLICATION NUMBER: US/17/737,012
CURRENT FILING DATE: 2022-05-04
NUMBER OF SEQ ID NOS: 79
SEQ ID NO 20
LENGTH: 1026
TYPE: DNA
ORGANISM: Lactobacillus plantarum
Alignment Scores:
Length: 1026
Score: 1702.00 Matches: 326
Percent Similarity: 99.1% Conservative: 12
Best Local Similarity: 95.6% Mismatches: 3
Query Match: 97.0% Indels: 0
Gaps: 0
US-18-863-699-38 (1-341) x US-17-737-012-20 (1-1026)
Qy 1 MetLeuAsnGlnValTyrArgLeuValAspProArgGlnIleGluValGlnThrValAla 20
||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||
Db 1 ATGTTGAACCAAGTTTACAGATTGGTTGACCCAAGACAATTCGAAGTTCAAACTGTTGCT 60
Qy 21 GluGluIleThrAspAsnAspIleValValArgProLysTyrLeuSerValCysHisAla 40
||||||||||||:::|||||||||:::|||||||||::::::||||||||||||||||||
Db 61 GAAGAAATCACTAACAACGACATCATCGTTAGACCAAGATTCTTGTCTGTTTGTCACGCT 120
Qy 41 AspThrArgTyrPheThrGlyGlnArgProGlnAlaThrLeuArgGlnLysLeuProMet 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GACACTAGATACTTCACTGGTCAAAGACCACAAGCTACTTTGAGACAAAAGTTGCCAATG 180
Qy 61 AlaLeuIleHisGluGlyValGlyGluValValLysAspProGlnAsnLysPheLysPro 80
|||||||||||||||||||||||||||||||||||||||||||||:::||||||||||||
Db 181 GCTTTGATCCACGAAGGTGTTGGTGAAGTTGTTAAGGACCCACAAGACAAGTTCAAGCCA 240
Qy 81 GlyThrLeuValAlaMetValProAsnThrProPheGluThrAspProIleIleLysGlu 100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GGTACTTTGGTTGCTATGGTTCCAAACACTCCATTCGAAACTGACCCAATCATCAAGGAA 300
Qy 101 AsnTyrLeuProThrSerLysPheArgSerSerGlyTyrAspGlyPheMetGlnGluTyr 120
||||||||||||:::|||||||||||||||||||||||||||||||||||||||||||||
Db 301 AACTACTTGCCATCTTCTAAGTTCAGATCTTCTGGTTACGACGGTTTCATGCAAGAATAC 360
Qy 121 ValThrLeuHisArgAspArgAlaIleValValProAspAsnPheAspHisGlnMetSer 140
|||:::||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GTTTCTTTGCACAGAGACAGAGCTATCGTTGTTCCAGACAACTTCGACCACCAAATGTCT 420
Qy 141 AlaPheIleGluMetValSerValGlyValHisAlaLeuThrGlnLeuGluAlaValMet 160
||||||||||||||||||||||||||||||||||||||||||||||||||| ||||||
Db 421 GCTTTCATCGAAATGGTTTCTGTTGGTGTTCACGCTTTGACTCAATTGGAAGGTGTTATG 480
Qy 161 AspAlaAspArgLysIleIleGlyIleTrpGlyAspGlyAsnLeuGlyPheIleThrAla 180
|||||||||||||||:::||||||||||||||||||||||||||||||||||||||||||
Db 481 GACGCTGACAGAAAGGTTATCGGTATCTGGGGTGACGGTAACTTGGGTTTCATCACTGCT 540
Qy 181 ThrLeuValLysGlnIlePheProAspSerGlnLeuMetIlePheGlyArgHisArgSer 200
||||||||||||||||||||||||||||||||||||||||||||||||||||||:::|||
Db 541 ACTTTGGTTAAGCAAATCTTCCCAGACTCTCAATTGATGATCTTCGGTAGACACCAATCT 600
Qy 201 LysLeuAspTyrPheSerPheAlaAspLysThrTyrLeuValAspAspIleProSerAsp 220
||||||||||||||||||||||||||||||||||||||||||||||||||||||:::|||
Db 601 AAGTTGGACTACTTCTCTTTCGCTGACAAGACTTACTTGGTTGACGACATCCCAAACGAC 660
Qy 221 LeuGlnValSerGlnAlaLeuGluCysThrGlyGlyArgGlySerGluSerAlaIleAla 240
|||:::||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 TTGAAGGTTTCTCAAGCTTTGGAATGTACTGGTGGTAGAGGTTCTGAATCTGCTATCGCT 720
Qy 241 GlnIleIleGlnHisIleArgProMetGlyThrAlaIleLeuMetGlyValSerGluAsp 260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 CAAATCATCCAACACATCAGACCAATGGGTACTGCTATCTTGATGGGTGTTTCTGAAGAC 780
Qy 261 ProValGlyIleAspThrArgSerValLeuAlaGluGlyLeuThrLeuArgGlyValSer 280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 CCAGTTGGTATCGACACTAGATCTGTTTTGGCTGAAGGTTTGACTTTGAGAGGTGTTTCT 840
Qy 281 ArgSerGlyArgAlaAspPheGlnArgAlaIleAspIleLeuThrLysSerProValThr 300
||||||||||||||||||||||||||||||:::|||||||||||| ||||||||||||
Db 841 AGATCTGGTAGAGCTGACTTCCAAAGAGCTGTTGACATCTTGACTGACTCTCCAGTTACT 900
Qy 301 ArgGluArgLeuGlnAsnLeuValGlyPheThrArgLysValSerThrIleGlnAspIle 320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 AGAGAAAGATTGCAAAACTTGGTTGGTTTCACTAGAAAGGTTTCTACTATCCAAGACATC 960
Qy 321 ThrAspPhePheGluGlyAlaLeuThrAsnTyrTrpGlyLysAlaValMetGluTrpAsp 340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 ACTGACTTCTTCGAAGGTGCTTTGACTAACTACTGGGGTAAGGCTGTTATGGAATGGGAC 1020
Qy 341 Val 341
|||
Db 1021 GTT 1023
APPENDIX B
A0A2S9VZQ6_LACPE
ID A0A2S9VZQ6_LACPE Unreviewed; 341 AA.
AC A0A2S9VZQ6;
DT 18-JUL-2018, integrated into UniProtKB/TrEMBL.
DT 18-JUL-2018, sequence version 1.
DT 10-JUN-2026, entry version 28.
DE RecName: Full=Ribulose-5-phosphate reductase {ECO:0000256|HAMAP-Rule:MF_02069};
DE Short=Ribulose-5-P reductase {ECO:0000256|HAMAP-Rule:MF_02069};
DE EC=1.1.1.405 {ECO:0000256|HAMAP-Rule:MF_02069};
DE AltName: Full=Ribitol-5-phosphate dehydrogenase {ECO:0000256|HAMAP-Rule:MF_02069};
GN Name=tarJ {ECO:0000256|HAMAP-Rule:MF_02069};
GN ORFNames=C6Y08_14050 {ECO:0000313|EMBL:PRO91239.1};
OS Lactiplantibacillus pentosus (Lactobacillus pentosus).
OC Bacteria; Bacillati; Bacillota; Bacilli; Lactobacillales; Lactobacillaceae;
OC Lactiplantibacillus.
OX NCBI_TaxID=1589 {ECO:0000313|EMBL:PRO91239.1, ECO:0000313|Proteomes:UP000238378};
RN [1] {ECO:0000313|EMBL:PRO91239.1, ECO:0000313|Proteomes:UP000238378}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IG2 {ECO:0000313|EMBL:PRO91239.1,
RC ECO:0000313|Proteomes:UP000238378};
RA Calero-Delgado B., Martin-Platero A.M., Perez-Pulido A.J.,
RA Benitez-Cabello A., Casimiro-Soriguer C.S., Martinez-Bueno M.,
RA Arroyo-Lopez F.N., Rodriguez-Gomez F., Bautista-Gallego J.,
RA Garrido-Fernandez A., Jimenez-Diaz R.;
RT "Draft Genome Sequences of six Lactobacillus pentosus Strains Isolated from
RT Brines of Traditionally Fermented Spanish-Style Green Table Olives.";
RL Submitted (MAR-2018) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the NADPH dependent reduction of D-ribulose 5-
CC phosphate to D-ribitol 5-phosphate. {ECO:0000256|HAMAP-Rule:MF_02069}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-ribitol 5-phosphate + NADP(+) = D-ribulose 5-phosphate +
CC NADPH + H(+); Xref=Rhea:RHEA:19921, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57695, ChEBI:CHEBI:57783, ChEBI:CHEBI:58121,
CC ChEBI:CHEBI:58349; EC=1.1.1.405; Evidence={ECO:0000256|HAMAP-
CC Rule:MF_02069};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|ARBA:ARBA00001947,
CC ECO:0000256|HAMAP-Rule:MF_02069};
CC -!- PATHWAY: Cell wall biogenesis; poly(ribitol phosphate) teichoic acid
CC biosynthesis. {ECO:0000256|HAMAP-Rule:MF_02069}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000256|ARBA:ARBA00008072, ECO:0000256|HAMAP-
CC Rule:MF_02069}.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:PRO91239.1}.
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DR EMBL; PVOB01000278; PRO91239.1; -; Genomic_DNA.
DR RefSeq; WP_088769495.1; NZ_BOUG01000007.1.
DR Proteomes; UP000238378; Unassembled WGS sequence.
DR GO; GO:0050256; F:ribitol-5-phosphate 2-dehydrogenase [NAD(P)+] activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:1902012; P:poly(ribitol phosphate) teichoic acid biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd08237; ribitol-5-phosphate_DH; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR HAMAP; MF_02069; TarJ; 1.
DR InterPro; IPR013154; ADH-like_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR034710; TarJ.
DR PANTHER; PTHR43350:SF19; D-GULOSIDE 3-DEHYDROGENASE; 1.
DR PANTHER; PTHR43350; NAD-DEPENDENT ALCOHOL DEHYDROGENASE; 1.
DR Pfam; PF08240; ADH_N; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE 3: Inferred from homology;
KW Cell wall biogenesis/degradation {ECO:0000256|HAMAP-Rule:MF_02069};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW Rule:MF_02069}; NADP {ECO:0000256|HAMAP-Rule:MF_02069};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002, ECO:0000256|HAMAP-
KW Rule:MF_02069}; Reference proteome {ECO:0000313|Proteomes:UP000238378};
KW Teichoic acid biosynthesis {ECO:0000256|HAMAP-Rule:MF_02069};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|HAMAP-Rule:MF_02069}.
FT DOMAIN 25..133
FT /note="Alcohol dehydrogenase-like N-terminal"
FT /evidence="ECO:0000259|Pfam:PF08240"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_02069"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_02069"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_02069"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_02069"
SQ SEQUENCE 341 AA; 38216 MW; 6A25CC07129985DA CRC64;
Query Match 99.8%; Score 1751; Length 341;
Best Local Similarity 99.7%;
Matches 340; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLNQVYRLVDPRQIEVQTVAEEITDNDIVVRPKYLSVCHADTRYFTGQRPQATLRQKLPM 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLNQVYRLVDPRQIEVQTVAEEITDNDIVVRPKYLSVCHADTRYFTGQRPQATLRQKLPM 60
Qy 61 ALIHEGVGEVVKDPQNKFKPGTLVAMVPNTPFETDPIIKENYLPTSKFRSSGYDGFMQEY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ALIHEGVGEVVKDPQNKFKPGTLVAMVPNTPFETDPIIKENYLPTSKFRSSGYDGFMQEY 120
Qy 121 VTLHRDRAIVVPDNFDHQMSAFIEMVSVGVHALTQLEAVMDADRKIIGIWGDGNLGFITA 180
|:||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VSLHRDRAIVVPDNFDHQMSAFIEMVSVGVHALTQLEAVMDADRKIIGIWGDGNLGFITA 180
Qy 181 TLVKQIFPDSQLMIFGRHRSKLDYFSFADKTYLVDDIPSDLQVSQALECTGGRGSESAIA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TLVKQIFPDSQLMIFGRHRSKLDYFSFADKTYLVDDIPSDLQVSQALECTGGRGSESAIA 240
Qy 241 QIIQHIRPMGTAILMGVSEDPVGIDTRSVLAEGLTLRGVSRSGRADFQRAIDILTKSPVT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 QIIQHIRPMGTAILMGVSEDPVGIDTRSVLAEGLTLRGVSRSGRADFQRAIDILTKSPVT 300
Qy 301 RERLQNLVGFTRKVSTIQDITDFFEGALTNYWGKAVMEWDV 341
|||||||||||||||||||||||||||||||||||||||||
Db 301 RERLQNLVGFTRKVSTIQDITDFFEGALTNYWGKAVMEWDV 341
