DETAILED OFFICE 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 .
Claims Status
Applicant’s preliminary amendment to the claims, filed on 5/30/2023, is
acknowledged. This listing of the claims replaces all prior versions and listings of the
claims.
Claims 1-2, 13-25, 28-30, and 54-55 are pending and are being examined on the merits.
Claims 3-12, 26-27, and 31-53 are cancelled.
Priority
This application is filed under 35 U.S.C. 371 as a national stage of international
application PCT/US2021/032251, filed on 5/13/2021, which claims benefit under 35 U.S.C. 119(e) to provisional application no. 63/024,392 filed on 5/13/2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 5/30/2023 and 12/12/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner and those references therein have been indicated as such.
Foreign patent document CA 2963300 A1 of the IDS filed 12/12/2023 is lined through because there is no copy of the reference in the application file.
Claim Objections
Claim 1 is objected to because of the recitation of “UDP-glycosyltransferase” without first writing out the full phrase for which the abbreviation “UDP” is used.
Claims 1, 14, 16-18, 20, and 54 are objected to for the recitation of “is at least 90% identical.” The Office recommends replacing the phrase with “has at least 90% amino acid sequence identity.”
Claim 21 is objected to because of the recitation of “EXG1” without first writing out the full phrase for which the abbreviation “EXG1” is used.
Claims 29-30 are objected to because of the recitation of “MIE1”, “MIA1”, “MIIA”, “MIIA1”, “MIIE”, “MIII”, “MIIIA1”, “MIIIE”, “MIIA1”, “MIIE1”, “MIE1”, “MIIIE”, and “MV” without first writing out the full phrases for which the abbreviations are used.
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 1-2, 13-25, 28-30, and 54-55 are rejected under 35 U.S.C. 103 as being unpatentable over Patron et al. (WO 2018/204483 A2; cited on the IDS from 5/30/2023; hereafter “Patron”) in view of A0A0X3XRP4_9ACTN (A0A0X3XRP4_9ACTN, Accession number A0A0X3XRP4, entry version 13, Uniprot, published December 11, 2019; cited on the IDS from 12/12/2023; hereafter “A0A0X3XRP4_9ACTN”).
Claims 1-2, 13-25, 28-30, and 54-55 are drawn to a host cell that comprises a heterologous polynucleotide encoding a UDP-glycosyltransferase (UGT), wherein the UGT comprises a sequence that is at least 90% identical to SEQ ID NO: 85.
Regarding claims 1 and 2, Patron teaches the methods of making mogroside compounds wherein recombinant host cells comprise one or more heterologous UDP-glycosyltransferase(s) (Abstract; para [0011, 0016, 0048]; Claim 22 and 30).
Regarding claim 13, Patron teaches the cell can comprise cucurbitadienol synthase (Abstract; para [0036, 0188, 0199, 0221, 0241, 0258]), a cytochrome p450 (para [0026, 0050, 0199]; Claims 53 and 164), a cytochrome p450 reductase (para [0043, 0058, 0199, 0205, 0405]), an epoxide hydrolase (para [0024-0025, 0027, 0036, 0058, 0199]; Claims 48 and 54), and a squalene epoxidase (para [0033, 0036, 0052, 0059, 0199, 0250, 400]; Claims 78, 81-82, 194).
Regarding claim 14, Patron teaches the cucurbitadienol synthase can be from Citrullus colocynthis with the amino acid sequence of SEQ ID NO: 331 that has 97.4% sequence identity with instant SEQ ID NO: 236 (para [0241, 0258]; SEQ ID NO: 331, amino acid residues 1-764 from the cucurbitadienol synthase from Citrullus colocynthis with the amino acid sequence of SEQ ID NO: 331 which has 97.4% identity with amino acid residues 1-764 of instant SEQ ID NO: 236, see alignment below).
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556
385
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Regarding claim 15, Patron teaches the cytochrome p450 can comprise the amino acid sequence of SEQ ID NO: 20 that is identical to instant SEQ ID NO: 280 (para [0026, 0050, 0199]; Claims 53 and 164)
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590
577
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Regarding claim 16, Patron teaches the cytochrome p450 reductase can comprise the CYP450 reductase from Siraitia grosvenorii with an amino acid sequence of SEQ ID NO: 874 that is identical to instant SEQ ID NO: 307 (SEQ ID NO: 874; see alignment below).
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513
384
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Regarding claim 17, Patron teaches the epoxide hydrolase can be the EPH1 epoxide hydrolase with an amino acid sequence SEQ ID NO: 21 that is identical to SEQ ID NO: 291 (SEQ ID NO: 21; see alignment below).
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275
384
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Regarding claim 18, Patron teaches the squalene epoxidase can be the squalene epoxidase with an amino acid sequence SEQ ID NO: 909 that is identical to SEQ ID NO: 293 (para [0059, 0250, 0400]; Claim 194; SEQ ID NO: 909; see alignment below).
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395
390
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Regarding claims 19-20, Patron teaches one of the UDP-glucosyltransferases can be UGT98 with an amino acid sequence of SEQ ID NO: 9 that has 97.7% sequence identity to instant SEQ ID NO: 121 (para [0017, 0019, 0042-0043]; Claim 32; SEQ ID NO: 121; see alignment below).
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530
578
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Regarding claim 21, Patron teaches the recombinant cell can have a deletion in EXG1 gene to prevent reduction of glucanase activity which may lead to deglucosylation of mogrosides (para [0142]).
Regarding claims 22-25, Patron teaches the host cell can comprise bacteria cells, yeast cells, plant cells, Escherichia coli, Yarrowia lipolytica, or Yarrowia (para [0037, 00143, 0168, 0195; Claim 101-102).
Regarding claims 28-30, Patron teaches production of the mogroside includes contacting the cell with: mogroside IIA to produce mogroside IIIE (para [0269]; Claim 20); mogrol, mogroside IIA, mogroside IIA1, mogroside IIE, mogrocide III, or mogrocide IIIE to produce siamensoide 1 (para [0265]); mogroside IIA, mogroside IIA1, mogroside IIE, mogrocide III, or mogrocide IIIE to produce mogrocide IIIA1 (para [0276]).
Regarding claims 54 and 55, Patron teaches one of the UDP-glycosyltransferases can comprise UGT1697 with the sequence of SEQ ID NO: 18 which is identical to instant SEQ ID NO: 321 (para [0017]; Claim 24; SEQ ID NO: 18; see alignment below).
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352
389
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The difference between Patron and claims 1-2, 13-25, 28-30, and 54-55 is that Patron does not teach wherein the UGT comprises a sequence that is at least 90% identical to instant SEQ ID NO: 85.
A0A0X3XRP4_9ACTN teaches a glycosyl transferase that has UDP–glycosyltransferase activity; the amino acid sequence of A0A0X3XRP4_9ACTN is identical to instant SEQ ID NO: 85 (p. 1; see alignment below).
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814
772
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In view of the combined teachings of Patron and A0A0X3XRP4_9ACTN, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the recombinant host cells comprising one or more heterologous UDP-glycosyltransferase to produce mogrocides taught by Patron by a simple substitution of a heterologous UDP-glycosyltransferase for the A0A0X3XRP4 UDP-glycosyltransferase taught by A0A0X3XRP4_9ACTN, thereby arriving at the invention of claim 1-2, 13-25, 28-30, and 54-55.
An ordinary artisan would have been motivated to modify the recombinant host cells comprising one or more heterologous UDP-glycosyltransferase to produce mogrocides taught by Patron by substituting one known UDP-glycosyltransferase for another known known UDP-glycosyltransferase in the prior art like the A0A0X3XRP4 UDP-glycosyltransferase taught by A0A0X3XRP4_9ACTN and have generated predictable results because the enzymes have the same activity. This is an application of KSR rationale B (See MPEP 2143; As discussed in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), a simple substitution of one known element for another to obtain predictable results is considered obvious.).
An ordinary artisan would have had a reasonable expectation of success of expressing the A0A0X3XRP4 UDP-glycosyltransferase in the recombinant cell of Patron since Patron taught experimental methodology for expressing a recombinant UDP-glycosyltransferase in a host cell.
Consequently, the invention of claim 1-2, 13-25, 28-30, and 54-55 would have been obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
No claims are currently allowed for the reasons as stated above. Applicants must
respond to the objections/rejections in this Office action to be fully responsive in
prosecution.
The instant Office Action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SCOTT E. MULDER whose telephone number is (571)272-2372. The examiner can normally be reached Monday - Friday 7:30 AM - 3:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath 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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/SCOTT E. MULDER/Examiner, Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656