Trials@uspto.gov
`571-272-7822
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`Paper: 14
`Date: January 19, 2021
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`SWEEGEN, INC.,
`Petitioner,
`
`v.
`
`PURECIRCLE USA INC. and PURECIRCLE SDN BHD,
`Patent Owner.
`____________
`
`PGR2020-00070
`Patent 10,485,257 B2
`____________
`
`
`
`Before SUSAN L. C. MITCHELL, JENNIFER MEYER CHAGNON, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`WISZ, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`35 U.S.C. § 324
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`571-272-7822
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`Paper: 14
`Date: January 19, 2021
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`SWEEGEN, INC.,
`Petitioner,
`
`v.
`
`PURECIRCLE USA INC. and PURECIRCLE SDN BHD,
`Patent Owner.
`____________
`
`PGR2020-00070
`Patent 10,485,257 B2
`____________
`
`
`
`Before SUSAN L. C. MITCHELL, JENNIFER MEYER CHAGNON, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`WISZ, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`35 U.S.C. § 324
`
`
`
`
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`PGR2020-00070
`Patent 10,485,257 B2
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`I.
`
`INTRODUCTION
`
`SweeGen, Inc. (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
`requesting a post-grant review of claims 1–7 of U.S. Patent No. 10,485,257
`B2 (Ex. 1001, “the ’257 patent”). PureCircle USA Inc. and PureCircle SDN
`BHD (collectively, “Patent Owner”) filed a Preliminary Response (Paper 10,
`“Prelim. Resp.”). After receiving our authorization to do so (see Paper 11),
`Petitioner filed a Reply to Patent Owners’ Preliminary Response addressing
`discretionary denial under 35 U.S.C. § 325(d) (Paper 12) and Patent Owner
`filed a Sur-Reply (Paper 13).
`We may not authorize a post-grant review to be instituted “unless . . .
`the information presented in the petition filed under section 321, if such
`information is not rebutted, would demonstrate that it is more likely than not
`that at least 1 of the claims challenged in the petition is unpatentable.”
`35 U.S.C. § 324(a).
`Upon consideration of the arguments and evidence, we determine
`Petitioner has not shown that the ’257 patent is eligible for post-grant
`review. Accordingly, we do not institute a post-grant review of the
`challenged claims of the ’257 patent.
`Real Parties-in-Interest
`A.
`Petitioner identifies SweeGen, Inc., Phyto Tech Corp. d/b/a Blue
`California, and Conagen, Inc. as the real parties-in-interest. Pet. 89. Patent
`Owner states that “PureCircle Sdn Bhd and PureCircle USA Inc. are the sole
`assignee and exclusive licensee, respectively, of [the ’257 patent], based on
`recorded assignments from the inventors and the Coca-Cola Company.”
`Paper 3, 2. Patent Owner also states that “PureCircle Sdn Bhd and
`PureCircle USA Inc. are both wholly owned subsidiaries of parent-company
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`PureCircle Limited, which is a majority-owned subsidiary of Ingredion
`Incorporated.” Id.
`Related Proceedings
`B.
`The parties indicate that the ’257 patent is the subject of PureCircle
`USA Inc. and PureCircle Sdn Bhd v. SweeGen, Inc. and Phyto Tech Corp
`d/b/a Blue California, Case No. 8:18-cv-1679 JVS (C.D. Cal.). Pet. 89;
`Paper 3, 2. The parties also indicate that IPR2019-01017 was filed for
`related U.S. Patent No. 9,243,273 (“the ’273 patent) and was not instituted.
`Id. Patent Owner also indicates that U.S. Pat. App. No. 16/694,893 claims
`priority through the ’273 patent. Paper 3, 2.
`
`C.
`
`The Asserted Grounds of Unpatentability
`Petitioner asserts that claims 1–7 of the ’257 patent are unpatentable
`in view of the following grounds. Pet. 4.
`Ground Claims Challenged
`35 U.S.C. §
`1
`1–7
`112(a)
`2
`1–7
`112(a)
`3
`1–7
`101
`4
`1–7
`102
`5
`1–2, 6–7
`102
`
`Reference(s)/Basis
`Enablement
`Written Description
`Eligibility
`Markosyan1
`Kishore2
`
`
`Petitioner relies on the Declarations of Kim Friis Olsson, Ph.D. (Ex. 1007),
`David Nunn, Ph.D. (Ex. 1009), and Enrique Arevalo (Ex. 1010) in support
`
`
`1 Markosyan et al., US 2015/0031869 A1, published Jan. 29, 2015
`(Ex. 1012, “Markosyan”).
`2 Kishore et al., WO 2011/153378 A1, published Dec. 8, 2011 (Ex. 1013,
`“Kishore”).
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`of its contentions. Patent Owner relies on the Declarations of Professor J.
`Martin Bollinger, Jr., Ph.D. (Ex. 2003) and Professor Joe P. Foley
`(Ex. 2005) in support of its Preliminary Response.
`The ’257 Patent
`D.
`The ’257 patent is directed to biocatalytic methods for preparing
`steviol glycosides from other steviol glycosides. Ex. 1001, 4:15–18. Steviol
`glycosides are a class of compounds found in the leaves of the Stevia
`rebaudiana Bertoni plant. Id. at 1:28–30. Purified steviol glycosides can be
`used in consumable products as non-caloric sweeteners. Id. at code (57),
`3:30–31.
`The ’257 patent discloses the conversion of Rebaudioside D
`(“Reb D”) to Rebaudioside X (“Reb X”) by contacting Reb D with a
`UDP-glucosyltransferase (“UGT”) enzyme, such as UGT76G1, which
`catalyzes the reaction of UDP-glucose and Reb D to produce Reb X.
`Ex. 1001, 13:13–17, 25–26. As shown in the figure below, Reb D is
`converted to Reb X through the addition of a glucose unit to the disaccharide
`at the C19 position of Reb D. Id. at 13:17–19, Fig. 2. A portion of Figure 2
`from the ’257 patent, which shows this reaction, is reproduced below:
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`Ex. 1001, Fig. 2. Figure 2 above shows the conversion of Reb D to Reb X.
`Examples 1, 2, and 7–12 of the ’257 patent describe the in vivo and in
`vitro production of UGT76G1. Ex. 1001, 20:58–22:21, 24:22–26:67.
`Examples 6 and 14 of the ’257 patent describe catalytic reactions of Reb D
`to Reb X using in-vitro produced UGT76G1. Id. at 24:1–22, 27:28–57. The
`’257 patent also describes the use of high-performance liquid
`chromatography to separate the components of the reaction mixture of
`Example 14 and the use of nuclear magnetic resonance and high resolution
`mass spectrometry to describe the structure of the reaction components. Id.
`at 27:49–57, 30:15–32:59.
`Illustrative Claim
`E.
`Petitioner challenges claims 1–7 of the ’257 patent. Claim 1, which is
`the only independent claim of the ’257 patent, is illustrative of the
`challenged claims, and is reproduced below:
`1. A method for adding at least one glucose unit to a steviol
`glycoside substrate to provide a target steviol glycoside,
`comprising contacting the steviol glycoside substrate with a
`recombinant biocatalyst protein
`enzyme
`comprising
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`the
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`target
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`UDP-glucosyltransferase, wherein
`glycoside is Rebaudioside X.
`Ex. 1001, 35:31–36. Challenged claims 2–7 depend, directly or indirectly,
`from claim 1.
`
`steviol
`
`II.
`
`BACKGROUND
`
`A.
`
`Person of Ordinary Skill in the Art
`In determining the level of skill in the art, we consider the type of
`problems encountered in the art, the prior art solutions to those problems, the
`rapidity with which innovations are made, the sophistication of the
`technology, and the educational level of active workers in the field. Custom
`Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962 (Fed. Cir.
`1986).
`Petitioner, relying on the testimony of Dr. Olsson, contends that a
`person of ordinary skill in the art as of the relevant date would have been a
`person with:
`[A] bachelor’s degree, master’s degree, or Ph.D. in chemistry,
`biochemistry, molecular biology, chemical engineering, genetic
`engineering, or a related field, and would have at least several
`years of experience researching and developing methods for
`enzyme expression in recombinant microorganisms, including
`bacteria and yeast. The person would have familiarity with
`modifying naturally occurring nucleic acid sequences encoding
`one or more enzyme(s) of interest to optimize their expression in
`the recombinant microorganism. The person would also have
`familiarity with using such recombinant enzymes as catalysts for
`biotransformation of organic compounds such as steviol
`glycosides and subsequent purification of the products to
`produce food additives such as artificial sweeteners (including
`but not limited to rebaudiosides).
`Pet. 14–15 (citing Ex. 1007 ¶ 33) (citations omitted).
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`Patent Owner points out that Petitioner’s proposed definition differs
`from the one found by the Board in IPR2019-01017, which involved the
`grandparent ’273 patent, and asserts that there is no substantive difference
`between the technology claimed in the ’273 and ’257 patents “and thus no
`reason the level of ordinary skill in the art should change.” Prelim. Resp.
`13–14 (citing Ex. 2003 ¶¶ 22–26).
`We agree with Patent Owner that the technology claimed in the ’273
`and ’257 patents is substantively similar and the level of skill in the art
`should be the same for both patents. Compare Ex. 2001, 35:2–5, with
`Ex. 1001, 35:31–36. Therefore, consistent with the decision in
`IPR2019-01017, we find that a person of ordinary skill in the art would have
`had an advanced degree in chemistry, biotechnology, biochemistry, or
`molecular biology, and research experience and knowledge of recombinant
`techniques and chemical process manufacturing involving the use of
`enzymes. This definition is consistent with the level of ordinary skill in the
`art at the time of the invention as reflected in the prior art in this proceeding.
`See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (explaining
`that specific findings regarding ordinary skill level are not required “where
`the prior art itself reflects an appropriate level and a need for testimony is
`not shown”) (quoting Litton Indus. Prods., Inc. v. Solid State Sys. Corp.,
`755 F.2d 158, 163 (Fed. Cir. 1985)).
`Although we do not fully adopt Petitioner’s definition of a person of
`ordinary skill in the art, our determination regarding Petitioner’s challenge
`does not turn on the differences between Petitioner’s definition and the
`adopted definition above, and we note that our conclusions would be the
`same under either definition.
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`B.
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`Claim Construction
`We interpret a claim “using the same claim construction standard that
`would be used to construe the claim in a civil action under 35 U.S.C.
`[§] 282(b).” 37 C.F.R. § 42.200(b) (2019). Under this standard, we
`construe the claim “in accordance with the ordinary and customary meaning
`of such claim as understood by one of ordinary skill in the art and the
`prosecution history pertaining to the patent.” Id.
`Petitioner proposes constructions for claim 1 as a whole as well as for
`the terms “steviol glycoside substrate,” “recombinant biocatalyst protein
`enzyme,” “UDP-glucosyltransferase,” “Rebaudioside X,” and “synthetic
`steviol glycosides.” Pet. 15–25. Patent Owner generally disagrees with
`Petitioner’s proposed constructions and provides constructions for the terms
`“Rebaudioside X,” “recombinant,” and “UDP-glucosyltransferase.” Prelim.
`Resp. 12–14.
`Upon review of the parties’ arguments and the evidence of record, we
`determine that no terms of the ’257 patent require express construction for
`purposes of this Decision. See Nidec Motor Corp. v. Zhongshan Broad
`Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (citing Vivid Techs.,
`Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly
`those terms need be construed that are in controversy, and only to the extent
`necessary to resolve the controversy.”)).
`
`III. ELIGIBILITY FOR POST-GRANT REVIEW
`
`As a threshold matter, we must determine whether the ’257 patent is
`eligible for post-grant review. The post-grant review provisions set forth in
`section 6(d) of the Leahy-Smith America Invents Act, Pub. L. No. 112–29,
`125 Stat. 284 (September 16, 2011) (“AIA”), apply only to patents subject to
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`the first-inventor-to-file provisions of the AIA. See AIA § 6(f)(2)(A)
`(stating that the provisions of section 6(d) “shall apply only to patents
`described in section 3(n)(1)”). Patents subject to the first-inventor-to-file
`provisions are those that issue from applications that contain or contained at
`any time—
`(A) a claim to a claimed invention that has an effective filing
`date as defined in section 100(i) of title 35, United States Code,
`that is on or after [March 16, 2013]; or
`(B) a specific reference under section 120, 121, or 365(c) of
`title 35, United States Code, to any patent or application that
`contains or contained at any time such a claim.
`AIA § 3(n)(1).
`Our rules require that each petitioner for post-grant review certify that
`the challenged patent is available for post-grant review. 37 C.F.R.
`§ 42.204(a) (“The petitioner must certify that the patent for which review is
`sought is available for post-grant review . . . .”). In addition, “[a] petition for
`a post-grant review may only be filed not later than the date that is 9 months
`after the date of the grant of the patent or of the issuance of a reissue patent
`(as the case may be).” 35 U.S.C. § 321(c).
`Determining whether a patent is subject to the first-inventor-to-file
`provisions of the AIA, and therefore eligible for post-grant review, is
`straightforward when the patentee filed the application from which the
`patent issued before March 16, 2013, or when the patentee filed the
`application on or after March 16, 2013 without any priority claim. The
`determination is more complex, however, for a patent that issues from a
`“transition application,” that is, an application filed on or after March 16,
`2013, that claims the benefit of an earlier filing date. See MPEP § 2159.04
`(9th ed. Rev. 10.2019, June 2020). Entitlement to the benefit of an earlier
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`date under 35 U.S.C. §§ 119, 120, 121, or 365 is premised on disclosure of
`the claimed invention “in the manner provided by § 112(a) (other than the
`requirement to disclose the best mode)” in the earlier application. See
`35 U.S.C. §§ 119(e), 120. Thus, a patent that issues from a transition
`application is not available for post-grant review if the claimed subject
`matter complies with the written description and enablement requirements of
`§ 112(a) for an ancestor application filed prior to March 16, 2013.
`The application that matured into the ’257 patent is a transition
`application, as it was filed after March 16, 2013, but claims priority to
`applications filed before March 16, 2013. Specifically, the ’257 patent
`issued November 26, 2019 from U.S. Application No. 15/400,325 (“the ’325
`application”), filed January 6, 2017. Ex. 1001, codes (45), (21), (22). The
`’325 application was filed as a continuation of U.S. Application No.
`14/954,213 (“the ’213 application”), filed on November 30, 2015. Id. at
`code (60). This parent ’213 application claims priority to U.S. Application
`No. 14/469,076, filed August 26, 2014, now U.S. Patent No. 9,243,273 (the
`same ’273 patent discussed above), which claims priority to PCT
`Application No. PCT/US2013/030439 (“the ’439 PCT application”), filed
`March 12, 2013, which claims priority to provisional Application No.
`61/649,978 (“the ’978 provisional application”), filed May 22, 2012. Id. at
`code (60). Therefore, the ’439 PCT application and the ’978 provisional
`application are pre-AIA applications because they were filed before
`March 16, 2013.
`Petitioner asserts that the ’257 patent is eligible for post-grant review
`because claims 1–7 are not enabled by any of the priority applications,
`including the pre-AIA applications (i.e., the ’439 PCT application and the
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`’978 provisional application), and there is no written description support for
`claims 1–7 in any of the priority applications. Pet. 25–26. According to
`Petitioner, the effective filing date of each of the ’257 patent claims is
`January 6, 2017, the actual filing date of the patent, and the ’257 patent is,
`therefore, eligible for post-grant review. Id. at 26.
`Patent Owner asserts that the ’257 patent is not subject to post-grant
`review because it claims priority to the pre-AIA ’439 PCT application which
`has “text that is essentially identical to the ’257 Patent’s specification, and
`has claims with essentially the same scope as the ’257 Patent’s claims.”
`Prelim. Resp. 16 (citing Ex. 1001, 1). Petitioner acknowledges that “the
`specifications of the ’439 PCT Application and the ’257 patent are nearly
`identical” and include “only minor, non-substantive differences.” Pet. 47.
`Therefore, Petitioner’s arguments regarding the lack of priority to the pre-
`AIA ’439 PCT application are the same as those made by Petitioner with
`regard to lack of enablement and lack of written description of the ’257
`patent itself.3 Id.
`We analyze the priority issue below.
`Analysis of Priority Date of the Challenged Patent
`Petitioner asserts that the ’257 patent priority applications do not
`provide enablement or written description support for the claims of the ’257
`patent. We analyze each of these arguments in turn below.
`
`A.
`
`
`3 As a result of the similarities between the specifications of the ’439 PCT
`application and the ’257 patent, some of Petitioner and Patent Owner’s
`priority arguments discuss the disclosure of the ’257 patent without referring
`to the similar disclosure in the pre-AIA ’439 PCT application.
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`1. Asserted Lack of Enablement of Claims 1–7
`Petitioner contends that claims 1–7 of the ’257 patent are not enabled
`by any of the priority applications (or the ’257 patent itself). Pet. 26–42.
`Patent Owner disputes Petitioner’s contentions. Prelim. Resp. 18–55.
`
`a. Principles of Law
`Under 35 U.S.C. § 112(a), enablement is separate and distinct from
`the written description requirement. Ariad Pharms., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336, 1344 (Fed. Cir. 2010) (en banc). “The test of enablement is
`whether one reasonably skilled in the art could make or use the invention
`from the disclosures in the patent coupled with information known in the art
`without undue experimentation.” U.S. v. Telectronics, Inc., 857 F.2d 778,
`785 (Fed. Cir. 1988). “[A] patent specification complies with the statute
`even if a ‘reasonable’ amount of routine experimentation is required in order
`to practice a claimed invention . . . .” Enzo Biochem, Inc. v. Calgene, Inc.,
`188 F.3d 1362, 1371 (Fed. Cir. 1999). Whether undue experimentation is
`needed is not a single, simple factual determination, but rather is a
`conclusion reached by weighing many factual considerations. In re Wands,
`858 F.2d 731, 737 (Fed. Cir. 1988). These factors, referred to as the Wands
`factors, include:
`(1) the quantity of experimentation necessary, (2) the amount of
`direction or guidance presented, (3) the presence or absence of
`working examples, (4) the nature of the invention, (5) the state
`of the prior art, (6) the relative skill of those in the art, (7) the
`predictability or unpredictability of the art, and (8) the breadth of
`the claims.
`
`Id.
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`b. Petitioner’s Position
`Petitioner asserts that, despite only a single example in the ’257 patent
`of producing Reb X by contacting Reb D with UGT76G1 (encoded by the
`DNA sequence listed in SEQ ID NO: 1), the challenged claims “are so broad
`that they encompass at least billions of combinations of steviol glycoside
`substrates and UGTs, including many that would not, in fact, be capable of
`producing Reb X.” Pet. 1, 27. Petitioner further contends that “neither the
`claims nor the [priority applications] provide guidance sufficient to direct a
`POSITA to the combinations that can successfully lead to Reb X.” Id. at
`27–28. According to Petitioner, “[t]o practice claim 1, a POSITA must
`undertake an iterative process to identify every steviol glycoside substrate
`that can be contacted by every UGT (and all variants thereof) to create
`Reb X without proper guidance from the specification.” Id. at 28.
`With regard to the breadth of the claims, Petitioner contends that the
`claims are exceedingly broad because “claim 1 encompasses at least billions,
`if not trillions or even more, of UGTs.” Pet. 28 (citing Ex. 1007 ¶ 86).
`Petitioner asserts that “[t]here are thousands of known naturally occurring
`UDP-glycosyltransferases that have been identified to date, and many of
`these are UGTs capable of catalyzing transfers of a glucose unit to an
`acceptor molecule.” Id. at 29 (citing Ex. 1007 ¶ 92). Petitioner further
`asserts that the claims “also encompass variants of the UGT having one or
`more substitutions, deletions, or insertions within the amino acid sequence
`of the enzyme.” Id. (citing Ex. 1007 ¶ 99). For example, Petitioner and
`Dr. Olsson assert that there are 1922 (or 1.35 x 1028) UGT variants with at
`least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1
`and this number becomes even larger when including variants with less than
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`95% identity and all of the other naturally occurring UGTs and their
`variants. Id. at 29–30 (citing Ex. 1007 ¶ 102).
`Petitioner further contends that claim 1 also “encompasses at least
`millions of steviol glycoside substrates.” Pet. 30 (citing Ex. 1007 ¶ 110).
`According to Petitioner, there are more than 41 known, naturally occurring
`steviol glycosides from Stevia rebaudiana and millions of synthetic steviol
`glycosides that could theoretically be synthesized. Id. (citing Ex. 1007
`¶¶ 87, 108, 110–119; Ex. 1015, 1202 (Table 1); Ex. 1030, 4–6 (Table 1)).
`Petitioner concludes that “claim 1 covers all combinations of the at least
`billions of UGTs and at least millions of steviol glycoside substrates, further
`broadening the scope of claim 1 to an almost immeasurably large number.”
`Id. at 31 (citing Ex. 1007 ¶¶ 85, 134).
`Petitioner also asserts that “the field of biocatalytic processing using
`enzymes and steviol glycoside substrates is an unpredictable field” and “it is
`not possible to reliably predict the activity of a UGT, including related
`variants, on a steviol glycoside substrate based on phylogeny or structure of
`the UGT.” Pet. 31–32 (citing Ex. 1007 ¶¶ 104–106, 140–143; Ex. 1020, 63).
`Therefore, according to Petitioner, “a POSITA would be required to
`empirically test each individual UGT to determine its catalytic activity with
`a particular steviol glycoside substrate in providing Reb X.” Id. at 32 (citing
`Ex. 1007 ¶ 95). Petitioner also contends that “the catalytic activity of an
`enzyme can be greatly altered by making only a few amino acid
`substitutions” and that “individual UGTs within the same family, and even
`subfamily, can have distinct catalytic activity.” Id. (citing Ex. 1007 ¶¶ 93,
`141).
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`According to Petitioner, predictability is even more difficult because
`“UGTs, including UGT76G1, can act on numerous steviol glycoside
`substrates” and that “[t]his known promiscuity of UGTs would not allow a
`POSITA to reliably predict without experimentation how any given UGT
`would react with any given steviol glycoside.” Pet. 33 (citing Ex. 1007
`¶¶ 145–146). In support of this contention, Petitioner cites to Ex. 1031, a
`reference authored by Dr. Olsson, which states:
`Reb D and Reb [X]4 are not formed in a linear pathway from
`steviol, but are formed as products in a metabolic glycosylation
`grid and their formation is directly dependent on the catalytic
`activity of UGT76G1 to convert 1,2-stevioside to Reb A, and
`Reb D to Reb [X]. However, UGT76G1 acts like a chameleon
`enzyme in the pathway, catalyzing different reactions in the
`metabolic glycosylation grid.
`Id. (citing Ex. 1007 ¶ 145; Ex. 1031, 3).
`Petitioner further contends that “any attempt by a POSITA to practice
`the full scope of the Challenged Claims would require an extensive,
`non-routine experimental program to empirically determine which
`combinations, if any, of billions of UGTs and millions of steviol glycoside
`substrates are capable of providing Reb X.” Pet. 34 (citing Ex. 1007
`¶¶ 130–132). According to Petitioner, “[w]hile it is typical to screen
`enzymes and enzyme variants for a given enzyme activity, it is not routine to
`screen such vast numbers of enzymes and variants” and that “[s]creening at
`least billions of UGTs—as would be required to determine the scope of the
`claims of the ‘257 patent—would be a massive undertaking, requiring years
`of work on the part of the POSITA.” Id. at 34–35 (citing Ex. 1007 ¶ 131).
`
`4 Ex. 1031 refers to Reb M, which is the same as Reb X. Pet. 5; Prelim.
`Resp. 8. For clarity, we use the terminology of “Rebaudioside X” or “Reb
`X” in this Decision.
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`Petitioner further contends that “the screening would need to encompass
`screening for the ability of each UGT to add a glucose to a steviol glycoside
`substrate at any step along any possible pathway to Reb X” and that
`“[s]creening such large numbers of enzymes and enzyme variants for
`multiple, distinct, enzyme activities is not routine.” Id. at 35 (citing
`Ex. 1007 ¶ 132).
`According to Petitioner:
`At a minimum, in order to determine which steviol glycosides
`substrates are convertible to Reb X according to the process
`claimed in the ‘257 patent, a POSITA would be required to:
`1) test which of the millions of theoretical steviol glycoside
`configurations can actually be synthesized, and 2) test each of
`the at least millions of natural or synthetic steviol glycoside
`substrates with each of the at least billions of UGTs to determine
`which combinations result in the successful conversion of the
`steviol glycoside substrate to Reb X.
`Pet. 36 (citing Ex. 1007 ¶ 124).
`Petitioner further asserts that, despite the breadth of the claims, the
`priority applications disclose only one “example of a single UGT
`(UGT76G1 encoded by SEQ ID NO: 1) that can be used in a single step
`enzymatic pathway to convert one steviol glycoside substrate (Reb D) to
`Reb X” as illustrated below:
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`Pet. 37 (citing Ex. 1005, 424–473, 480; Ex. 1006, 6–22, 28; Ex. 1007
`¶¶ 136–137; Ex. 1011, 1). According to Petitioner “the disclosure of a
`single UGT capable of converting Reb D to Reb X is wholly inadequate to
`enable a POSITA to practice the full scope of the claimed invention without
`undue experimentation” because screening all variants with at least 99%
`identity to the amino acid sequences encoded by SEQ ID NO: 1 would
`require screening 194 (or 130,321) variants. Id. at 38 (citing Ex. 1007
`¶¶ 100, 102, 104). Petitioner further contends that “no further guidance or
`roadmap is given to determine other combinations of UGTs and steviol
`glycoside substrates capable of providing Reb X.” Id. (citing Ex. 1007
`¶ 139).
`
`Petitioner also argues that the ’257 patent does not disclose or enable
`how to make Reb X by adding a glucose using a UGT to the following
`substrates, which are recited in claim 2: steviolmonoside, steviolbioside,
`rebaudioside E, rebaudioside G, rebaudioside I, and the vast majority of the
`compounds that would be encompassed by the term “synthetic steviol
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`glycosides.” Pet. 39 (citing Ex. 1007 ¶¶ 126–128). Petitioner further
`contends that “no methods for converting rebaudioside G or rebaudioside I
`to Reb X by contacting these compounds with a UGT were known in the
`scientific literature at the time the priority applications were filed.” Id.
`(citing Ex. 1007 ¶ 126).
`
`According to Petitioner, the challenged claims encompass inoperative
`embodiments because, “[f]or a number of the steviol glycoside substrates
`encompassed by claim 1 and specifically claimed in claim 2 there is no
`known pathway for bioconversion to Reb X.” Pet. 40 (citing Ex. 1007
`¶ 147). Petitioner cites to Figure 1 of Ex. 1031 to support the argument that
`there is not pathway to Reb X (referred to as Reb M) from Reb G or Reb I
`(recited in claim 2) or from Reb Q or 1,3-bioside (within the scope of claim
`1):
`
`Pet. 40–41 (citing Ex. 1031, Figure 1; Ex. 1007 ¶ 147). Petitioner also cites
`to a portion of Ex. 1031 which states that, while UGT76G1 is a “chameleon
`enzyme catalyzing at least eight different glucosylation steps in the
`metabolic glycosylation grid of steviol glycosides,” none of “1,3-bioside,
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`Reb G, Reb Q, and Reb I . . . can be converted to the premium steviol
`glucosides Reb D and Reb [X].” Id. at 41 (citing Ex. 1031, 12; Ex. 1007
`¶ 148). According to Petitioner, “[t]he fact that these substrates cannot be
`converted into Reb X by contacting them with a UGT provides additional
`evidence that practicing the full scope of the Challenged Claims would
`require undue experimentation.” Id.
`
`c. Patent Owner’s Position
`Patent Owner contends that Petitioner failed to perform a complete
`Wands factor analysis because they only discussed a few of the Wands
`factors. Prelim. Resp. 18. Patent Owner also asserts that “[w]here, as here,
`conventional and routine experimentation, and well-known computational
`modeling that was available in 2012, is all that is needed to identify operable
`UDP-glucosyltransferases, the claims are enabled.” Id. at 20. According to
`Patent Owner, analyzing all the Wands factors weighs in favor of finding
`enablement. Id.
`First, Patent Owner contends that the advanced state of the art and
`high level of skill support enablement. Prelim. Resp. 21. Patent Owner cites
`to deposition testimony from Dr. Eric Walters, Petitioner’s declarant in the
`concurrent litigation, as support for the assertions that homology modeling
`was available in 2012, the use and generation of recombinant enzymes was
`well-understood in 2012, the expression of UDP-glucosyltransferases in host
`organisms was well-understood and conventional at the time, and that it was
`known that homology modeling would narrow the UDP-glucosyltransferases
`that needed to be screened. Id. at 22–23 (citing Ex. 2010, 102:15–103:16,
`106:1–8, 197:9–14). Patent Owner concludes that, “the art was so advanced
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`in 2012 that no further teaching of how to screen UDP-glucosyltransferase
`mutants was needed in 2012.” Id. at 23 (citing Ex. 2003 ¶¶ 101–116).
`Patent Owner further asserts that the art’s predictability supports the
`claims’ breadth. Prelim. Resp. 36–37. According to Patent Owner,
`“methods for making the steviol glycoside precursors to Rebaudioside [X]
`(such as Rebaudioside D and Rebaudioside E) and the
`UDP-glucosyltransferases needed to do so, were all well-known in the art by
`2012.” Id. at 36 (citing Ex. 1013, 132, Fig. 2C; Ex. 1031, 2, Fig. 1).
`Furthermore, according to Patent Owner, the ’257 patent contains working
`examples that provide sufficient guidance given the advanced state of the
`art. Id. at 37–38 (citing Ex. 1001, 14:58–17:19, 20:60–32:60).
`Patent Owner further asserts that the quantity of experimentation is
`low, which favors a finding of enablement. Prelim. Resp. 42–55. According
`to Patent Owner, “determining whether a UDP-glucosyltransferase will
`transfer a glucose from UDP-glucose to steviol glycoside is conventional,
`routine, and straightforward,” citing to statements from Petitioner’s
`declarants to support this contention. Id. (citing Ex. 1007 ¶¶ 131, 190, 191;
`Ex. 2010, 98:6–21, 100:25–101:13, 101:22–102:14, 106:1–107:8; Ex. 2011,
`136:9–13). Patent Owner also cites to the deposition testimony of
`Petitioner’s declarant in the concurrent litigation to support the assertions
`that robots could be used to automate the testing of
`UDP-glucosyltransferases, so that very large numbers of enzymes could be
`easily tested in parallel (Ex. 2010, 102:2–14); computational modeling could
`be used in 2012 to narrow the field of UDP-glucosyltransferases that would
`work (Ex. 2010, 102:15–103:16); and mutant versions of
`UDP-glucosyltransferases were generally expected to work (Ex. 2010,
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`126:23–127:25). Id. Lastly, Patent Owner contends that the four glycosides
`that Petitioner argues to be inoperative embodiments would work with the
`invention. Id. at 52–54.
`
`d. Analysis
`We analyze the Wands factors for enablement below.
`
`i. Nature of the Invention and Relative Skill in the Art
`The nature of the invention is the production of Reb X by adding
`glucose units to a steviol glycoside substrate using a recombinant
`UDP-glucosyltransferase. See Ex. 1001, 35:31–36. As discussed supra, the
`level of skill in the art is high, requiring an “advanced degree in chemistry,
`biotechnology, biochemistr
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