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 .
The amendment filed 04/10/2026 has been entered. Claims 3, 7 and 12 have been amended. Claims 21-27 have been added. Claims 8-9 and 16-20 have been cancelled. Claims 1-7, 10-15 and 21-27 are pending. Claims 13-15, 26 and 27 are withdrawn. Claims 1-7, 10-12, and 21-25 are under examination.
Election/Restrictions
Applicant’s election of Group I (claims 1-12 and 21-25) and the species drawn to a genetically inactivated Abd1 gene and a heterologous methyltransferase, SEQ ID NO: 16 and nsp14 in the reply filed on 04/10/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 13-15, 26 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04/10/2026.
Information Disclosure Statement
The information disclosure statement filed 03/29/2024 has been considered and an initialed copy is enclosed.
Claim Objections
Claim 3 is objected to because of the following informalities: “wherein the plasmid encoding the heterologous methyltransferase comprises at least 95% sequence identity” should be “wherein the plasmid encoding the heterologous methyltransferase comprises a nucleic acid sequence comprising at least 95% sequence identity”. Similar changes should be made to parts b and c of claim 3 for the guanylyltransferase and RNA triphosphate, respectively.
Claim 11 is objected to because of the following informalities: Please include the full meaning “FOA” which is shorthand or fluoroacetic acid according to the specification. Appropriate correction is required.
Claim 25 “the heterologous methyltransferase is encoded by a plasmid comprising at least 95% sequence identity” should be “the heterologous methyltransferase is encoded by a plasmid comprising a nucleic acid sequence comprising at least 95% sequence identity”.
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) 1-2, 4-7, 10-12 and 21-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. Proc. Natl. Acad. Sci. U.S.A. 106 (9) 3484-3489, 2009 cited in IDS as evidenced by Saha et al. Journal of Biological Chemistry, 1999; 274, 16553-16562 cited in IDS as evidenced by NCBI Reference sequence YP_009725309.1 18-July 2020.
Claim 1: Chen et al disclose an isolated non-native yeast YBS40 strain comprising:
a genetically inactivated Abd1 gene – YBS40 strain has the chromosomal abd1 gene deleted and cell growth is thus contingent on the maintenance of the corresponding yeast gene on a plasmid carrying URA3 gene as a selection marker; and a heterologous methyltransferase gene i.e. nsp14 from SARS-CoV-2 strain WHU.
See page 3484 under results to page 3485 left column first paragraph.
Claim 2: Chen et al disclose the isolated non-native YB40 strain of claim 1 wherein the heterologous methyltransferase is encoded by a plasmid and wherein the heterologous methyltransferase is a full-length methyltransferase. See p. 3484 disclosing cloning the coding sequence of nsp14 of SARS-CoV-2 strain WHU(19) into plasmid pMceK294A, p. 3485 figure 1 legend disclosing YBS40 could be complemented by SARS-CoV-nsp14 p. 3488 under cloning, expression and purification of recombinant proteins.
Claim 4: Chen et al disclose the isolated non-native yeast of claim 1 wherein the heterologous methyltransferase is fused to an RNA polymerase complex targeting gene. Chen et al disclose that the coding sequence of viral proteins was fused with the N terminus of the GTase domain of the mammalian capping enzyme (aminoacid211–597 of Mce1), so that the fusion protein can be targeted to the RNA polymerase II complex. See p. 3484 under functional screening for coronavirus cap-forming enzymes.
Claim 5: Chen et al disclose the YBS40 strain further comprising an Abd1 plasmid comprising a second Abd1 gene operably linked to a promoter: YBS40 has the chromosomal abd1 gene are deleted and cell growth is thus contingent on the maintenance of the corresponding yeast gene on a plasmid carrying URA3 gene as a selection marker. See p. 3484 under results to p. 3485 column 1 first paragraph and p. 3488 under yeast strains and functional screening: Strain YBS40 is deleted at the chromosomal Abd1 locus encoding the yeast cap MTase (16) and its growth depends on the maintenance of plasmid p360-ABD1 (URA3) which comprises a second abd1 gene.
Claim 6: Chen et al disclose The isolated non-native yeast of claim 5 the Abd 1 plasmid further comprises a yeast Ura3 gene; and wherein the Abd1 plasmid is curable. Chen et al disclose the YBS40 strain further comprising an Abd1 plasmid comprising a second Abd1 gene operably linked to a promoter: YBS40 has the chromosomal abd1 gene deleted and cell growth is thus contingent on the maintenance of the corresponding yeast gene on a plasmid carrying URA3 gene as a selection marker. See p. 3484 under results to p. 3485 column 1 first paragraph and p. 3488 under yeast strains and functional screening: Strain YBS40 is deleted at the chromosomal Abd1 locus encoding the yeast cap MTase (16) and its growth depends on the maintenance of plasmid p360-ABD1 (URA3) which comprises the second abd1 gene.
Claim 7: Chen et al disclose the isolated non-native yeast of claim 1, wherein a) the heterologous methyltransferase is nsp14. See page 3484 under results to page 3485 left column first paragraph.
Claim 10: The YBS40 strain is haploid as evidenced by Saha et al. Journal of Biological Chemistry, 1999; 274, 16553-16562. Saha et al disclose YBS40 were derived by targeted gene disruptions in the diploid strain W303 followed by tetrad dissection and genotyping of haploid progeny. See under yeast strains on p. 16555.
Claim 11: Chen et al disclose a composition comprising the isolated non-native YBS40 strain and a carrier; wherein the carrier comprises a solid medium; and wherein the composition further comprises 5-FOA (5-fluoroacetic acid). See figure 1B.
Claim 12: Chen et al disclose a kit comprising: the YBS40 strain which comprises genetically/chromosomal inactivated Abd1, and a) a plasmid comprising a methyltransferase nsp14 gene, wherein incorporating the plasmid into the a yeast comprising genetically inactivated Abd1 results in the isolated non-native yeast of claim 1.
Chen et al disclose the isolated non-native YB40 strain of claim 1 wherein the heterologous methyltransferase is encoded by a plasmid and wherein the heterologous methyltransferase is a full-length methyltransferase. See p. 3484 disclosing cloning the coding sequence of nsp14 of SARS-CoV-2 strain WHU(19) into plasmid pMceK294A, p. 3485 figure 1 legend disclosing YBS40 could be complemented by SARS-CoV-nsp14 p. 3488 under cloning, expression and purification of recombinant proteins.
Claim 21: As evidenced by Saha et al the YBS40 strain is Saccharomyces cerevisiae. See Saha et al p. 16556 figure 2 disclosing S. pombe pcm1p replaces S. cerevisiae YBS40 Abd1p in vivo.
Claim 22: Chen et al disclose the YBS40 comprising the genetically inactivated Abd1 gene and the heterologous methyltransferase nsp14 is from Sars-CoV-2 strain WHU which is SARS-CoV-2.
Claim 24: The nsp14 from SARS-CoV-2 (NCBI Reference sequence YP_009725309.1) comprises an amino acid sequence that is 96.4% identical to the amino acid sequence of SEQ ID NO: 4. See Appendix A for sequence alignment with SEQ ID NO: 4.
Claim(s) 1-7, 10-12 and 21-25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ornelas et al. ACS Synth Biol 2022, November 18; 11(11): 3759-3771 cited in IDS as evidenced by GenBank accession number QIX07429.1 ORF1ab polyprotein (527 aa region 5962-6452) 10-June-2020.
Claim 1: Ornelas et al disclose an isolated non-native Saccharomyces cerevisiae (S. cerevisiae), comprising: a) a genetically inactivated Abd1 gene and a heterologous nsp14 methyltransferase. See page 5 second paragraph to page 6 under “building YeRCOM-nsp14 for SARS-CoV-2 nsp14 nT-MTase activity.
Claim 2: Ornelas et al disclose the isolated non-native yeast of claim 1 wherein the heterologous methyltransferase is encoded by a plasmid and wherein the heterologous methyltransferase is a full-length methyltransferase or a functional methyltransferase fragment i.e. deletion of amino acids 292-258 of full length nsp14, or a codon optimized methyltransferase for expression in yeast i.e. double stranded nsp14 was codon optimized for S. cerevisiae. See page 11 “pMO2” under construction of plasmids; page 6 under “building YeRCOM-nsp14 for SARS-CoV-2 nsp14 nT-MTase activity; page 7 under Using YeRC0M-nsp14 platform to determine key domains necessary for SARS-CoV-2 nsp14 N7-MTase activity.
Claim 3: Ornelas et al disclose the isolated non-native yeast of claim 2 wherein the plasmid encoding the heterologous methyltransferase nsp14 comprises an nucleic acid sequence 100% sequence identity to SEQ ID NO: 16. See sequence alignment in appendix C. See nsp14 sequence disclosed in table S2 of supporting information of Ornelas et al (Appendix D).
Claim 4: Ornelas et al disclose the isolated non-native yeast of claim 1 wherein the heterologous nsp14 methyltransferase is fused to mce1 gene which is a RNA polymerase complex targeting gene. See under “Building YeRC0M-nsp14 for SARS-CoV-2 nsp14 N7-MTase activity” on page 6 disclosing “we generated fusion between SARS-CoV-2 nsp14 sequence and human mce1 gene which was expected to direct the viral nsp14 to RNA polymerase II complex”.
Claim 5: Ornelas et al disclose the isolated non-native yeast of claim 1: a) further comprising an Abd1 pMO1 plasmid comprising a second Abd1 gene operably linked to a promoter: If the SARS-CoV-2 nsp14 MEC1 fusion catalyzes the RNA cap 0 N7-methylation of the native yeast mRNAs, then S. cerevisiae abd1::kanMX4 pMO1 pMO2 haploid will survive in presence of 5-FOA where the abd1 expressing plasmid pMO1 is cured. See under Building YeRC0M-nsp14 for SARS-CoV-2 nsp14 N7-MTase activity on page 6.
Claim 6: Ornelas et al disclose the isolated non-native yeast of claim 5, wherein the Abd1 plasmid further comprises a yeast Ura3 gene; and wherein the Abd1 plasmid is curable - Since pMO1 has a ura3 marker, it can be cured in presence of 5-fluorooratic acid (5-FOA) See page 5, starting from the 12th to the last line.
Claim 7: As set forth above, Ornelas et al disclose the heterologous methyltransferase comprises nsp14.
Claim 10: Ornelas et al disclose the isolated non-native yeast is haploid. If the SARS-CoV-2 nsp14 MEC1 fusion catalyzes the RNA cap 0 N7-methylation of the native yeast mRNAs, then S. cerevisiae abd1::kanMX4 pMO1 pMO2 haploid will survive in presence of 5-FOA where the abd1 expressing plasmid pMO1 is cured. See under Building YeRC0M-nsp14 for SARS-CoV-2 nsp14 N7-MTase activity on page 6.
Claim 11: Ornelas et al disclose a composition comprising the isolated non-native yeast of claim 1 and a carrier; wherein the carrier comprises a solid (agar plates) or liquid (growing cultures) medium; and wherein the composition further comprises 5-FOA: Plasmids containing ura3 marker were cured by growing cultures in synthetic defined medium containing 1 mg/mL 5-fluoroorotic acid (5FOA) and uracil 0.02 mg/mL for 48 hours or by plating onto synthetic media agar plates containing 1mg/mL 5-fluoroorotic acid (5FOA) and uracil 0.02 mg/mL and incubating at 30°C for 48 hours. See under “plasmid curing procedure” on page 11.
Claim 12: Ornelas et al disclose a kit comprising: a yeast comprising genetically inactivated Abd1, and a) a plasmid comprising a nsp14 methyltransferase gene, wherein incorporating the plasmid into the yeast comprising genetically inactivated Abd1 results in the isolated non-native yeast of claim 1: We transformed pMO2 and pMO3 into S. cerevisiae abd1::kanMX4 pMO1 haploid to generate S. cerevisiae abd1::kanMX4 pMO1 pMO2 haploid and comprises and S. cerevisiae abd1::kanMX4 pMO1 pMO3 haploid respectively. Abd1 gene is replaced by G418 resistance marker (referred to as S. cerevisiae abd1::kanMX4 haploid). See page 5 second paragraph.
Claim 21: As stated above the yeast is Saccharomyces cerevisiae.
Claim 22: As stated above the isolated non-native yeast of claim 1 comprises the genetically inactivated Abd1 gene and the heterologous methyltransferase and Ornelas et al disclose the heterologous methyltransferase comprises a Coronaviridae virus methyltransferase nsp14 from SARS-CoV-2.
Claim 24: Ornelas et al disclose the isolated non-native yeast of claim 7 comprising the heterologous methyltransferase comprising SARS-CoV-2 nsp14, wherein the nsp14 comprises or consists of an amino acid sequence as evidenced by GenBank accession number QIX07429.1 (DBSource accession MT318827.1 cited in IDS and cited in Ornelas et al figure 6 legend on p. 24) wherein the amino acid sequence comprises 96.4% sequence identity to SEQ ID NO: 4. See figure 6 and figure S5 and Appendix B.
Claim 25: Ornelas et al disclose the isolated non-native yeast of claim 1 comprising the genetically inactivated Abd1 gene and the heterologous methyltransferase, wherein the heterologous methyltransferase is nsp14 and the heterologous methyltransferase nsp14 comprises an nucleic acid sequence 100% sequence identity to SEQ ID NO: 16. See sequence alignment in appendix C. See nsp14 sequence disclosed in table S2 of supporting information of Ornelas et al (Appendix D).
Status of Claims
Claims 13-15, 26 and 27 are withdrawn. Claims 1-7, 10-12, and 21-25 are rejected.
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/OLUWATOSIN A OGUNBIYI/Primary Examiner, Art Unit 1645
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