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 .
Priority
This application claims benefit of priority to Provisional Application 63/222,597 filed 07/16/2021 and is also a 371 of PCT/US2022/073759 filed 07/15/2022. Support for the instant claims can be found in the Provisional Application, therefore, the effective filing date of the claimed invention for the purposes of applying prior art is 07/16/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 03/17/2025 and 03/11/2026 have been acknowledged and considered.
Drawings
The drawings filed 01/11/2024 are objected to. The drawings are objected to because they are blurry and illegible, specifically, in Figure 1 the terminal group on multiple chemical compounds is illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-2 and 5-12, in the reply filed on 03/11/2026 is acknowledged.
Regarding the species elections, Applicant’s election without traverse of one nucleic acid encoding an amino acid sequence (1), SEQ ID NO: 3 as the specific amino acid sequence encoded by the nucleic acid sequence (2), one transcriptional regulator as the specific number of transcriptional regulators (3) and Saccharomyces cerevisiae as the specific yeast cell or strain (4) in the reply filed on 03/11/2026 is acknowledged.
Applicant further stated claims 1-2, 5-9 and 11-12 read on the elected species.
Claim Status
As stated above, Applicant elected Group I, encompassing claims 1-2 and 5-12. Claim 10 is not encompassed by the election of species. Therefore, claims 3-4, 10 and 13-16 are withdrawn by the Examiner as they are not encompassed by the elections.
Claims 1-16 are currently pending.
Claims 3-4, 10 and 13-16 are withdrawn.
Claims 1-2, 5-9 and 11-12 are under examination.
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.
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.
Claims 1-2, 5-9 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Schalk et al. (WO 2020011883 A1, 01/16/2020) (IDS Reference of 03/17/2025) in view of UniProt (A0A7U2EY07_PHANO, 06/02/2021) (IDS Reference of 03/17/2025).
Regarding claims 1-2 and 11-12, Schalk et al. disclose a method for synthesizing terpene compounds, including copalol (See entire document, Abstract). More specifically, Schalk et al. disclose the production of copalol in Saccharomyces cerevisiae cells, reading on the elected cell/strain, using a copalyl-pyrophosphate phosphatase and different alcohol dehydrogenases (Page 83, Example 9). For the production of copalol, multiple genes were cDNA optimized for expression in yeast, including the geranylgeranyl-pyrophosphate (GGPP) synthase CrtE from Pantoea agglomerans, the copalyl-pyrophosphate (CPP) synthase SmCPS2 from Salvia miltiorrhiza, the copalyl-pyrophosphate phosphatase TalVeTPP from Talaromyces verruculosus and different alcohol dehydrogenases were expressed in engineered S. cerevisiae cells with increased levels of endogenous farnesyl-diphosphate (Page 83, Example 9). The utilized TalVeTPP from Talaromyces verruculosus was predicted to be a member of the protein tyrosine phosphatase family because it contains the signatures of protein tyrosine phosphatase family proteins (Page 75, Lines 21-31). Regarding TalVeTPP, Schalk et al. disclose the polypeptides of the invention having terpenyl diphosphate phosphatase activity, converting CPP to copalol, are members of the Protein tyrosine phosphatase family, in particular, the Y_phosphatase3 family having the Pfam ID number PF13350 (Page 11, Lines 7-9). To determine if the prediction was correct, Schalk et al. integrated TalVeTPP into a host cell, cultivated the cell and analyzed the products for the presence of copalol (Page 76, Lines 24-27). The host cells with the integrated TalVeTPP were able to effectively express copalol (Page 76, Lines 30-31). Thus, TalVeTPP was shown to be able to enzymatically convert copalyl-diphosphate pyrophosphatase (CPP) to copalol and can be used to produce copalol in engineered cells (Page 78, Lines 18-21). Additionally, all of the enzymes discussed above are from microorganisms other than S. cerevisiae, which are integrated into the genome of the host cell (Page 15, Lines 26-28), thus, they are all heterologous nucleic acids encoding an amino acid sequence.
Schalk et al. do not disclose the genetically modified host cell comprises an enzyme with an amino acid sequence that is at least 90% identical to or is the sequence of instant SEQ ID NO: 3.
However, UniProt discloses A0A7U2EY07_PHANO, a tyrosine specific protein phosphatase domain-containing protein (Top of Page 1) belonging to Pfam PF13350 and the Y_phosphatase3 family (Top of Page 4). A0A7U2EY07_PHANO disclosed by UniProt shares 100% sequence identity to instant SEQ ID NO: 3, the elected amino acid sequence. A sequence alignment is provided below wherein Qy is instant SEQ ID NO: 3 and Db is A0A7U2EY07_PHANO disclosed by UniProt.
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Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the tyrosine specific protein phosphatase domain-containing protein A0A7U2EY07_PHANO, belonging to Pfam PF13350 and the Y_phosphatase3 family, as the enzyme for converting CPP to copalol in the host cell of Schalk et al. because it was a known tyrosine specific protein phosphatase domain-containing protein as taught by UniProt and would be expected, absent evidence to the contrary, to have the same function and effect as other similarly annotated proteins, motivated by the desire to effectively produce copalol as it amounts to simple substitution of one known element for another to obtain predictable results. Exemplary rationales that may support a conclusion of obviousness include simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I)(B).
Regarding claims 5-6, as discussed above, Schalk et al. disclose the production of copalol in Saccharomyces cerevisiae cells using a copalyl-pyrophosphate phosphatase and different alcohol dehydrogenases wherein the genes encoding for the GGPP synthase CrtE, the copalyl-pyrophosphate synthase SmCPS2, the copalyl-pyrophosphate phosphate TalVeTPP and different alcohol dehydrogenases were expressed in engineered S. cerevisiae cells with increased levels of endogenous farnesyl-diphosphate (Page 83, Example 9). As Schalk et al. disclose SmCPS2 is involved in the production of copalol, SmCPS2 reads on an enzyme of a pathway for making E-copalol. The SmCPS2 from Salvia miltiorrhiza, reading on a heterologous nucleic acid, is SEQ ID NO: 63 (Page 83, Example 9). SEQ ID NO: 63 of Schalk et al. is a nucleic acid sequence and SEQ ID NO: 64 of Schalk et al. is the amino acid sequence encoded by SEQ ID NO: 63 of Schalk et al. SEQ ID NO: 64 of Schalk et al. shares 100% sequence identity to instant SEQ ID NO: 43. An alignment is provided below wherein Qy is instant SEQ ID NO: 43 and Db is SEQ ID NO: 64 of Schalk et al.
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Regarding claims 7-8, as discussed above, Schalk et al. disclose the engineered S. cerevisiae cells have increased levels of endogenous farnesyl-diphosphate (FPP) (Page 83, Example 9). Schalk et al. further disclose to increase the level of endogenous FPP in the S. cerevisiae cells, an extra copy of all yeast endogenous genes involved in the mevalonate pathway, ERG10 to ERG20, were integrated into the genome of the specific S. cerevisiae strain utilized, CEN.PK2-1C (Page 84, Lines 7-9). It is noted the instant Specification states “the term ‘heterologous’ refers to what is not normally found in nature” and “the term ‘heterologous compound’ refers to the production of a compound by a cell that does not normally produce the compound, or to the production of a compound at a level not normally produced by the cell” (Specification, Page 6, Lines 9-12). Thus, the inclusion of an extra copy of ERG20 being integrated into the genome of the S. cerevisiae strain reads on heterologous because the extra copy is not what is normally found in nature. Additionally, Schalk et al. disclose ERG20 converts isopentenyl-diphosphate (IPP) and dimethylallyl-diphosphate (DMAPP) into FPP (Page 74, Lines 14-16), thus, ERG20 reads on an enzyme capable of converting IPP and DMAPP into FPP.
Regarding claim 9, Schalk et al. disclose the coding sequence of TalVeTPP which was codon optimized for its expression in S. cerevisiae was under the control of the bidirectional yeast promoter, GAL10/GAL1 (Page 87, Lines 16-18). The GAL10/GAL1 promoter reads on a single transcriptional regulator.
Conclusion
Claims 1-2, 5-9 and 11-12 and rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY T WHITE whose telephone number is (571)272-0683. The examiner can normally be reached Monday - Friday 8:30 - 5:00 EST.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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