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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-4 and 9-17 in the reply filed on 07/14/2026 is acknowledged.
Claims 5-8 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/14/2026.
Priority
The instant application claims benefit to PCT/KR2022/021327 filed on 12/26/2022 and KR10-2021-0187435 filed 12/24/2021 and is acknowledged. The instant claims herein are examined using the effective filing date of 12/24/2021 for the basis of any prior art rejections.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 06/21/2024 and 07/14/2026 were properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) were considered.
Claim Objections
Claims 10 and 13 objected to because of the following informalities: claim 10 recites “the composition further comprises at least a substat. . .” The claim should be amended to recite “substrate”.
Claim 13 recites “UGT761” and should be amended to recite “UGT76G1”. Appropriate correction is required.
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 1-4 and 9-17 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 claim(s) contains 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 inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
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). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
Independent claim 1 (and thus the dependent claims) recite “an enzyme protein having a uridine diphosphate-glucosyltransferase (UDP-glucoslyl transferase) activity to transfer glucose to steviol glycoside substrate, wherein at least one amino acid selected from the group consisting of the 201st and 202nd amino acids from the N- terminus in the amino acid sequence of SEQ ID NO: 1 is substituted with at least one amino acid selected from the group consisting of serine and leucine”. Instant claim 4 requires “wherein the enzyme protein has 101% or higher of an activity, based on 100% of an activity of the wild-type enzyme containing an amino acid sequence of SEQ ID NO: 1 for converting Rebaudioside A substrate to Rebaudioside D in an enzyme reaction for 2 to 24 hours.”
Under broadest reasonable interpretation, the claim requires substitution either (or both) of the 201st and 202nd amino acids in SEQ ID NO: 1 with serine or leucine (i.e., substituting the amino acid at position 201 with S or L, and/or substituting the amino acid at position 202 with S or L) while still retaining or having increased UDP-glucosyl transferase activity to transfer glucose to steviol glycoside substrate. This is problematic because the specification fails to teach an art-recognized correlation between structure (i.e., the claimed genus of amino acid substitutions) and function between the ability of the enzyme synthase to perform its claimed function.
In support of the claimed genus of mutated enzymes, the specification discloses engineering of UDP-glucosyl transferase by creating a T201S mutant, V202L mutant, and a T201S/V202L mutant (see Examples 1 and 2) for expression in recombinant microorganisms. Applicant also demonstrates conversion of Reb A to Reb D between wildtype and mutated enzymes, in which the mutant enzymes harboring either T201S or T201S/V202L demonstrated relative conversion rate of Reb D at 110.3% and 129.1% (respectively) in comparison to the wildtype (see Table 5, example 4, Table 6).
As discussed above, the instant claims require the specific functional language of “wherein the enzyme protein has 101% or higher of an activity, based on 100% of an activity of the wild-type enzyme containing an amino acid sequence of SEQ ID NO: 1 for converting Rebaudioside A substrate to Rebaudioside D”. However, Applicant fails to demonstrate that, e.g., a T201L or V202S or V202L (or a combination of the mutations) can retain glucosyltransferase activity, much less exceeding such activity in comparison to the wildtype. The specification only demonstrates the comparison of a mutated TaUGT enzyme harboring T201S or T201S/V202L double mutant to the wildtype enzyme (see Table 5) but fails to provide any information on whether the V202L single mutant (encompassed by the instant claims) provides 100%+ enzyme activity as required by the claims.
As such, the use of only the T201S or T201S/V202L UDP-glucosyltransferase mutants cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of enzymes useful for increased UDP-glycosyltransferase activity, because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
Even with knowledge in the art regarding modification of amino acids, one of ordinary skill would not reasonably know, based on the disclosure provided, what structures other than the mutations described in the specification are required for the outcome of creating an enzyme retaining UDP-glucosyl transferase activity to transfer glucose to steviol glycoside substrate without a recognized correlation between structure and function.
The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the claimed genus of superoxide dismutase enzyme fragments, i.e., additional complete or partial structures, other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or some combination thereof demonstrating possession of the claimed genus.
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.
Claim 15 is 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 15 recites “the composition comprises a glucose donor (glycosyl donor).” The use of parentheses renders the claims indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention, or if it is an exemplary embodiment of glucose donors.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 9-13 and 17 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 7-8, and 18 of copending Application No. 18/722905 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below.
Regarding instant claim 1, 4, 9, and 13, copending claim 1 and 7 recites “A composition for producing steviol glycosides containing Rebaudioside M, which comprises a biocatalyst comprising a first uridine diphosphate- glucosyltransferase(UDP-glucosyltransferase) that has 92% or higher of amino acid sequence identity with an amino acid sequence of SEQ ID NO: 1 and transfers glucose to steviol glycoside substrate, and UGT76G1; and a reaction substrate; wherein Rebaudioside M is contained in 10% by weight or more of the steviol glycosides reaction product”. Copending claim 2 requires “the first UDP-glucosyltransferase comprises an amino acid sequence of SED ID NO: 1, or an amino acid sequence comprising at least a substitution of amino acid in which at least an amino acid selected from the group consisting of 201st amino acid and 202nd amino acid from N-terminus in an amino acid sequence of SEQ ID NO: 1, is substituted with at least one selected from serine and leucine”. Please note that instant SEQ ID NO: 1 and copending SEQ ID NO: 1 are the same sequence of UDP-glucosyltransferase. Also note that as the copending claims recite the same mutation as required by the instant claims, absent evidence tot eh contrary, the copening claims also encompass the limitation of instant claim 4 requiring “101% or higher of an activity. . . for convering rebaudioside A to rebaudioside D”.
Regarding claim 2 and 10-11, copending claim 13 recites “the reaction substrate includes at least one steviol glycosides selected from the group consisting of stevioside and Rebaudioside A”
Regarding claim 3, copending claim 8 recites “30% or more of a total conversion rate of Reb M and Reb D”.
Regarding claim 17, copending claim 1 recites “the composition of Claim 1, further comprising at least one selected from the group consisting of uridine diphosphate (UDP) and sucrose”
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Examiner’s Note
The instant claims recite “An enzyme protein having a uridine diphosphate-glucosyltransferase (UDP-glucoslyl transferase) activity to transfer glucose to steviol glycoside substrate, wherein at least one amino acid selected from the group consisting of the 201st and 202nd amino acids from the N- terminus in the amino acid sequence of SEQ ID NO: 1 is substituted with at least one amino acid selected from the group consisting of serine and leucine”. The closest prior art of record (Vroom et al US20180223264 A1; cited in Applicant’s 06/21/2024 IDS) discloses engineered glycosyltransferase (GT) enzymes, polypeptides having GT activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides (see abstract). Vroom also teaches compositions and methods for the production of rebaudiosides (e.g., rebaudioside M, rebaudioside A, rebaudioside I, and rebaudioside D) (see abstract, claims, throughout).
While the prior art broadly teaches a 201S mutation in glucosyltransferase of SEQ ID NO: 3346 or SEQ ID NO: 2510 (a similar mutation as encompassed by the instant claims; see paragraphs 0050 and 0073 of Vroom), the art fails to adequately provide a PHOSITA the necessary teaching, suggestion or motivation to mutate the amino acid at that position in the amino acid sequence of SEQ ID NO: 1 (the wildtype UDP-glucosyltransferase). Please note the sequence alignment for instant SEQ ID NO: 1 and the disclosed SEQ ID NOs: 2510 and 3346 below showing that the disclosed sequences are completely different enzymes.
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794
813
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SEQ ID NO: 2510 of Vroom
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1042
874
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SEQ ID NO: 3346 of Vroom
The art also fails to teach or suggest a mutation at position 202 in SEQ ID NO: 1 where the amino acid at that position is mutated to, e.g., leucine. Please note that while no prior art rejections have been made, the claims are not allowable for the reasons set forth in the rejections above.
Conclusion
NO CLAIMS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
US 11639497 B2
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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