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 .
DETAILED ACTION
The amendment filed 01/30/2026 has been entered. Claim 26 has been cancelled.
Claims 1-25, and 27-30 are pending.
Election/Restrictions
Applicant's election with traverse of Group I and the species: "in vitro" of claim 1, amino acids of species 2A of claim 12, amino acid motif of SEQ ID NO:5 of claim 13, geranylgeranyl diphosphate synthase of claim 30, and Rebaudioside DG of claim 8, in the reply filed on 01/30/2026 is acknowledged. The traversal is on the grounds that that both claims 1 and 30 are drawn to methods of forming a glycosylated steviol glycoside using a glycosyltransferase. This is not found persuasive as the common technical feature was proven not to be special, as set forth in the requirement for restriction dated 10/30/2025.
The requirement is still deemed proper and is therefore made FINAL.
Claims 22-25, and 27-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/3.
Claims 1-21 are under examination.
Claim Objections
Claims 3 objected to because of the following informalities:
In claims 3 and 4, “b” represents “beta” and therefore Glu-b-Xyl and -b-Glu-b-Xyl-R5 should be amended to recite Glu-β-Xyl and -β-Glu-β-Xyl-R5.
Claims 19 and 21 contain convoluted language.
Claim 19 may be amended to recite: The method of claim 14, wherein the reaction is performed for 1 hour to 10 days at a temperature of 25-40˚C.
Claim 21 may be amended to recite: The method of claim 1, wherein forming the glycosylated steviol glycoside of Formula II is performed in an engineered cell capable of making the steviol glycoside of Formula I…
Appropriate correction is required.
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.
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 1-21 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 1 recites a method for forming a glycosylated steviol glycoside comprising forming a compound of Formula II from a compound of Formula I. It is unclear if Formula II is the glycosylated steviol glycoside referred to in the preamble.
Claim 1 recites: using a glycosyltransferase…. wherein the glucosyltransferase… Therefore, it is unclear which enzyme the claim requires, as glucosyltransferase is a type of glycosyltransferase.
Claim 1 also recites: R2 comprises one or more sugar residues or is a hydrogen and (ii) an activated xylose. The claim language is indefinite as it is unclear if it means that R2 is a sugar residue, a hydrogen, or an activated xylose, or if the activated xylose is a separate entity from Formula I, as there is no item (i).
Claims 2-21 are also rejected as they depend from claim 1.
Claim 13 recites: wherein the glycosyltransferase comprises one or more of the following amino acid motifs relative to SEQ ID NO:1… However, the claim does not define where in SEQ ID NO:1 the motifs should be inserted. It is unclear if the motifs should be added at either end of the amino acid sequence of SEQ ID NO:1, within the amino acid sequence of SEQ ID NO:1, or if they should replace an amino acid stretch of SEQ ID NO:1. Therefore, it is unclear what amino acid sequence the glycosyltransferase requires.
Claim 14 is indefinite because it is a “use” claims that attempts to claim a process without setting forth any steps involved in the process. MPEP § 2173.05(q) states that attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Claim 15 recites: where the compound of Formula I constitutes more than 50% (mol) of steviol glycoside in the reaction. It is unclear if the term in parentheses is a required, or an optional and thus not required, limitation of the instant claim.
A broad range together with a narrow range that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 16 recites the broad recitation of more than 60% of the steviol glycoside compound of Formula I is converted to the xylosylated steviol glycoside of Formula II, and the claim also recites more than 65% of the steviol glycoside compound of Formula I is converted to the xylosylated steviol glycoside of Formula II which is the narrower statement of the range. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 18 recites: a polypeptide (wt) to UDP-X (mol) ratio, and a polypeptide (wt) to SGI (mol) ratio. It is unclear if the terms in parentheses are required, or optional and thus not required, units for the ratio limitation of the instant claim.
Claim 21 recites: wherein the activated xylose is fed (externally). It is unclear if the term in parentheses is a required, or an optional and thus not required, limitations of the instant claims.
Claim Interpretation
Based on the information found in the instant specification, it is interpreted that the method of claim 1 is a method for forming a glycosylated steviol glycoside of Formula II from Formula I and activated xylose, i.e., UDP-xylose, using a glycosyltransferase having UDP-xylose:19-steviol xylosyltransferase activity, wherein UDP-xylose:19-steviol xylosyltransferase activity refers to the enzymatic activity which transfers a xylose moiety from UDP-xylose to the 19C atom or a saccharide residue directly or indirectly attached to (and extending from) the 19C atom to the a steviol acceptor molecule (p. 11, para. [0040] of the instant specification).
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
Claims 1-21 are drawn to a method of forming a glycosylated steviol glycoside comprising forming a compound of Formula II from a compound of Formula I using a glycosyltransferase having UDP-xylose:19-steviol xylosltransferase activity, wherein the glycosyltransferase transfers xylose from an activated xylose to Formula I. Claim 10 limits the glycosyltransferase to a sequence having at least 75% sequence identity to SEQ ID NO:1. Claim 11 limits the glycosyltransferase to a sequence having 85% sequence identity to SEQ ID NO:1 Claim 12 limits the glycosyltransferase to having amino acid residues of (A) or (B) relative to SEQ ID NO:1 Claim 5 limits Formula I to stevioside, rebaudioside A, rebaudioside C, rebaudioside D, rebaudioside F, rebaudioside G, or dulcoside-A. Claim 6 limits Formula I to stevioside, rebaudioside A, or rebaudioside C. Claim 7 limits Formula I to rebaudioside A. Claims 8 and 17 limit Formula II to the compound named rebaudioside DG (Formula III).
MPEP 2163.05 II states “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us].’”
The instant specification reduces to practice 5 glycosyltransferase enzymes (SEQ ID NOs:1-4 and UGT76G1, the sequence of which is not disclosed) that were capable of glycosylating rebaudioside A (Example 4). The specification does not disclose the entire genus of glycosyltransferase enzymes that are capable of transferring xylose to the 19C of a steviol acceptor molecule. The instant specification also only discloses a limited number of species of steviol glycoside acceptors, stevioside, rebaudioside A, rebaudiocide C, rebaudioside D, rebaudioside F, rebuadioside G, and dulcoside A, that were capable of being glycosylated with activated xylose by the enzyme of SEQ ID NO:1 (Example 1).
The instant specification does not disclose what structural properties are required for the glycosyltransferase to transfer xylose to the 19C atom of all steviol acceptor molecules, or disclose which regions of SEQ ID NO:1 are the active site residue(s) for conserving the claimed enzyme activity. The instant specification does not disclose amino acid sequences with up to 75% or 85% divergence from SEQ ID NO:1 that are capable of performing the claimed enzyme activity. Therefore, the disclosed species are not representative of the entire genus of claimed glycosyltransferase variants and steviol glycoside acceptors.
Urai et al., (US Pub. No. 2022/0256902 A1) teaches Formula I, which is identical to instant Formula II, and is described as a novel steviol glycoside that contains xylose (para. [0028]). Urai also teaches steviol glycosides that are identical to instant Formula III (para. [0031]). Urai teaches the chemical synthesis of the compounds of instant Formulas II and III, but does not teach the enzymatic xyolsylation of Formula I to form Formula II or III. Urai does teach that the steviol glycoside of the present invention may be obtained by using a glycosylation enzyme and steviol, steviol glycoside, UDP-glucose and/or UDP-xylose as a substrate (para. [0097]). However, Urai does not teach a glycosyltransferase enzyme that is capable of xyolsylation, or disclose enzyme variants with up to 25% or 15% sequence divergence from instant SEQ ID NO:1 that are capable of transferring xylose from UDP-xylose to a steviol glycoside. Urai does not disclose all steviol glycosides that are capable of being xylosylated at C19.
In summary, neither the instant specification, nor the prior art, discloses a structure-function relationship between conserved amino acid residues in the claimed enzyme structure and the claimed glycosyltransferase activity. Neither the specification, nor the prior art, disclose a structure-function relationship between steviol glycoside structure its ability to be glycosylated with a xylose at C19. One of ordinary skill in the art cannot reasonably predict which residues of SEQ ID NO:1 may be modified to generate a glycosyltransferase capable of transferring xylose to C19 of a steviol glycoside acceptor molecule, and cannot reasonably predict all possible steviol glycosides that are capable of accepting a xylose at C19. Based on the instant disclosure, those skilled in the art would not conclude that the applicant was in possession of all claimed variants.
Pertinent Prior Art
The closest prior art references are that of Urai et al., (US Pub. No. 2022/0256902 A1), Purkayashtha et al., (WO 2019/099118 A1), and Zhao et al., (US Patent No. 11,091,743 B2).
Urai et al., (US Pub. No. 2022/0256902 A1) teaches Formula I, which is identical to instant Formulas II, and is described as a novel steviol glycoside that contains xylose (para. [0028]). Urai also teaches steviol glycosides that are identical to instant Formula III (para. [0031]). However, Urai teaches the chemical synthesis of the compounds of instant Formulas II and III, but does not teach the enzymatic xyolsylation of Formula I to form Formula II or III. Although Urai does teach that the steviol glycoside of the present invention may be obtained by using a glycosylation enzyme and steviol, steviol glycoside, UDP-glucose and/or UDP-xylose as a substrate (para. [0097]), “glycosylation enzymes” encompass a broad genus of enzymes and Urai does not specifically teach the use of a glycosyltransferase enzyme, does not specifically teach enzymes capable of xylosylation, and does not teach a compound of Formula I as a substrate for xylosylation.
Purkayashtha et al., (WO 2019/099118 A1) teaches novel diterpene glycosides and methods of purifying and using said glycosides. Purkayashtha teaches a compound named Rebaudioside U (p. 49, Fig. 19), which is identical to instant Formulas II and III. However, Purkayashtha does not teach the chemical or enzymatic synthesis of Rebaudioside U. Purkayashtha teaches that the novel diterpene glycosides were isolated from Stevia plants (p. 3, Summary of the Invention).
Zhao et al., (US Patent No. 11,091,743 B2) teaches a method of producing steviol glycosides using a Setaria glycosyltransferase for the production of rebaudioside D and rebaudioside M. Zhao does not teach a steviol glycoside comprising a xylose at C19, i.e., Zhao does not teach a compound of instant Formula II or III.
There are no prior art references that disclose that the glycosyltransferase enzyme of SEQ ID NO:1 is capable of transferring xylose from UDP-xylose to C19 of stevioside, rebaudioside A, rebaudioside C, rebaudioside D, rebaudioside F, rebaudioside G, or dulcoside-A to form xylosated stevioside, rebaudioside A, rebaudioside C, rebaudioside D, rebaudioside F, rebaudioside G, or dulcoside-A.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657
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