Trials@uspto.gov
`571.272.7822
`
`
`
`
`
`
`
` Paper No. 38
`
` Entered: August 12, 2020
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LIFESCAN GLOBAL CORPORATION,
`Petitioner,
`v.
`IKEDA FOOD RESEARCH, LTD., and PHC CORPORATION,
`Patent Owners.
`____________
`
`PGR2019-00032
`Patent 9,976,125 B2
`____________
`
`
`Before ERICA A. FRANKLIN, ROBERT A. POLLOCK, and
`DAVID COTTA, Administrative Patent Judges.
`
`COTTA, Administrative Patent Judge.
`
`
`
`DECISION
`Final Written Decision
`Granting-in-Part and Denying-in-Part
` Patent Owners’ Motion to Amend
`35 U.S.C. § 328
`
`
`
`
`
`
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`
` INTRODUCTION
`On January 30, 2019, Lifescan Global Corporation (“Petitioner”) filed a
`Petition requesting a post grant review of claims 1–10 of U.S. Patent No.
`9,976,125 B2 (Ex. 1005, “the ’125 patent”). Paper 1 (“Pet.”). On May 22, 2019,
`Ikeda Food Research Co., Ltd., and PHC Corporation (“Patent Owners”) filed a
`statutory disclaimer under 35 U.S.C. § 253(a) disclaiming claims 1–7, 9, and 10 of
`the ’125 patent. Ex. 2009. Shortly thereafter, Patent Owners filed a Preliminary
`Response to the Petition. Paper 6 (“Prelim. Resp.”). We determined, based on the
`information presented in the Petition and Preliminary Response, that there was a
`reasonable likelihood that Petitioner would prevail in showing that claim 8, the
`only remaining claim, was unpatentable. Pursuant to 35 U.S.C. § 324, the Board
`instituted trial on August 15, 2019. Paper 11 (“Institution Decision” or “Inst.
`Dec.”).
`Patent Owners did not file a Response to the Petition. Instead, Patent
`Owners filed a non-contingent Motion to Amend seeking cancellation of claim 8
`and proposing substitute claim 11. Paper 18, 1. Patent Owner’s motion included a
`request for preliminary guidance from the Board, in accordance with the New Pilot
`Program Concerning Motion to Amend Practice. Id. at 2; see also 84 Fed. Reg.
`9,497 (Mar. 15, 2019) (notice regarding New Pilot Program). Petitioner
`challenged the patentability of proposed new claim 11 in an Opposition (Paper 26),
`and we provided a Preliminary Guidance, in which we set forth our “preliminary,
`non-binding views” on whether Patent Owners had shown “a reasonable
`likelihood” that they had “satisfied the statutory and regulatory requirements
`associated with filing a motion to amend in a post-grant review” as well as our
`views on “whether Petitioner (or the record) establishe[d] a reasonable likelihood
`that the substitute claims are unpatentable” (Paper 27, 2).
`
`2
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`
`After entry of our Preliminary Guidance, Patent Owners filed a Revised
`Motion to Amend, reiterating their request for cancellation of claim 8 and
`proposing entry of a revised claim 11 on a “noncontingent basis.” Paper 28, 1 (“R.
`Mot.”). Petitioner filed an Opposition to Patent Owners’ Revised Motion to
`Amend (Paper 30, “Opp.”), Patent Owners filed a Reply to Petitioner’s Opposition
`(Paper 34, “Reply”), and Petitioner filed a Sur-reply to Patent Owner’s Reply
`(Paper 36, “Sur-reply”). On June 18, 2020, the parties presented arguments at an
`oral hearing. The transcript of the hearing has been entered into the record. Paper
`37 (“Tr.”).
`We have jurisdiction under 35 U.S.C. § 6. We issue this Final Written
`Decision pursuant to 35 U.S.C. § 328(a) and 37 C.F.R. § 42.73. For the reasons
`discussed below, Patent Owner’s Motion to Amend is granted with respect to
`cancellation of claim 8, and denied with respect to proposed substitute claim 11.
`
`Real Parties in Interest
`A.
`Petitioner identifies LifeScan Global Corporation and its affiliates, as the
`real parties-in-interest. According to Petitioner these parties include:
`Platinum Equity Capital Partners IV, L.P.; Platinum LifeScan
`Principals, LLC; DUV Holding Corporation; DUV Intermediate
`Holding Corporation; DUV Intermediate Holding II Corporation;
`LifeScan, Inc.; LifeScan China, LLC; LifeScan IP Holdings, LLC;
`LifeScan Holding Limited; LifeScan Holding II Limited; LifeScan
`Europe GmbH; LifeScan Scotland Limited;LifeScan Institute, LLC;
`LifeScan Foreign Holdings, LLC; LifeScan U.K. Limited; LifeScan
`Canada ULC; LifeScan Deutschland GmbH; LifeScan Italy S.R.L.;
`LifeScan Belgium BVBA; LifeScan France SAS; LifeScan Malaysia
`SDN. BHD; LifeScan Spain, S.L.; LifeScan U.K. Limited LIFESCAN
`– podružnica Croatia; LifeScan U.K. Limited, LIFESCAN
`ΥΙΙΟΚΑΤΑΣΤΗΜΑ ΕΛΛΑΔΣ; LifeScan U.K. Limited (spółka z
`ograniczoną odpowiedzialnością) Oddział w Polsce; LifeScan U.K.
`Limited Ireland Branch; LifeScan U.K. Limited South Africa Branch;
`LifeScan U.K. Limited Argentina Branch; LifeScan Russia Limited
`
`3
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`
`Liability Company; LifeScan Czech Republic s.r.o.; LifeScan Mexico,
`S. de R.L. de C.V.; LifeScan Mexico Servicios S. de R.L. de C.V.;
`LifeScan Japan KK; LifeScan Brasil Equipamentos para diagnosticos,
`pesquisa e desenvolvimento Ltd; LifeScan Portugal, Unipessoal LDA;
`and LIFESCAN MEDICAL DEVICES INDIA PRIVATE LIMITED.
`Pet. 7–8.
`Patent Owners identify Ikeda Food Research Co., Ltd.; PHC Corporation;
`Ikeda Tohka Industries Co., Ltd.; PHC Holdings Corporation; and Ascensia
`Diabetes Care Holdings AG as the real parties in interest. Paper 3, 1.
`B.
`Related Proceedings
`Petitioner represents that it is unaware of any other matters related to the
`’125 patent. Pet. 8. Patent Owners identify U.S. Patent Nos. 8,492,130, 8,882,978,
`9,340,816, and 9,663,811; U.S. Patent Application No. 15/955,650; PCT
`Publication No. WO 2008/001903 A1; and Japanese Publication Nos. 4665235 B2,
`4773578 B2, 5209087 B2, 5792214 B2, 6438519 B2, 2016019529 A, and
`2018093872 A (now Japanese Patent No. 6535075) as relating to the ’125 patent.
`Paper 3, 2; Paper 16, 1–2.
`The ’125 Patent (Ex. 1005)
`C.
`The ’125 patent issued May 22, 2018, identifying Takako Yada, Koji
`Miyamoto, and Michinari Honda as joint inventors. Ex. 1005, code (72). The
`patent “relates to a novel gene (polynucleotide) encoding a flavin adenine
`dinucleotide (FAD) conjugated glucose dehydrogenase. . . [and] a biosensor for
`use in the determination of glucose . . . characterized by using the enzyme.” Id. at
`1:6–14.
`
`The ’125 patent teaches that “blood glucose level is an important marker for
`diabetes” and that diagnostic kits using glucose dehydrogenase were
`“recommended” for determining blood glucose levels. Id. at 1:18–32. Glucose
`dehydrogenase may be coenzyme-conjugated or coenzyme-unconjugated. Id. at
`
`4
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`1:33–39. Coenzyme-conjugated glucose dehydrogenase is preferred because its
`determination sensitivity is high, it is less likely to be affected by impurities than
`coenzyme-unconjugated glucose dehydrogenase, and it can, in principle, be used to
`produce a low cost point-of-care testing device. Id. at 1:33–45. Coenzyme-
`conjugated glucose dehydrogenase “requires pyrroloquinoline quinone (PQQ),
`flavin adenine dinucleotide (FAD) or the like as a coenzyme.” Id. at 1:33–39.
`Notably, in biosensors using glucose dehydrogenase to determine blood
`glucose levels, it is desirable that glucose dehydrogenase not react with maltose.
`Id. at 1:46–56. “Maltose is a sugar used in an infusion, and when . . . glucose
`dehydrogenase reacts with maltose, a blood glucose POCT [point-of-care testing]
`device displays a higher blood glucose level than the actual value.” Id. at 1:48–50.
`According to the ’125 patent, FAD-conjugated glucose dehydrogenase has
`been purified from several different bacterial strains. Id. at 2:4–3:22. FAD-
`conjugated glucose dehydrogenase enzymes purified from Agrobacterium
`tumefaciens, Cytophaga marinoflava, Agaricus bisporus, and Macrolepiota
`rhacodes “have a high activity for maltose, and have a low selectivity for glucose.”
`Id. at 2:4–18. FAD-conjugated glucose dehydrogenase purified from Burkholderia
`cepacia similarly has a “high activity for maltose.” Id. at 2:19–21. In contrast,
`FAD-conjugated glucose dehydrogenase purified from Aspergillus terrus “has
`excellent substrate (glucose) recognition performance, . . . and also has a low
`activity for maltose,” but “the production amount of the enzyme is extremely
`small” and, because of the sugars linked to the enzyme, “the activity of the enzyme
`is difficult to detect (the enzymatic activity is low).” Id. at 2:28–61. The
`“existence of a coenzyme-conjugated glucose dehydrogenase derived
`from Aspergillus oryzae was suggested in 1967,” however, “only partial enzymatic
`
`5
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`properties were revealed, . . . although a property that the enzyme does not act on
`maltose was suggested.” Id. at 2:62–67.
`
`The ’125 patent states that “an object of the invention is to . . . provide a
`novel gene (polynucleotide) encoding an FAD-conjugated glucose dehydrogenase
`having . . . excellent reactivity to glucose, excellent thermal stability, . . . excellent
`substrate-recognition performance and . . . a low activity for maltose.” Id. at 3:59–
`65. The ’125 patent discloses that:
`The present inventors made intensive studies in order to achieve the
`above object, and as a result, they found that in order to significantly
`express an FAD-conjugated glucose dehydrogenase in an Aspergillus
`oryzae strain, it was necessary that an amino acid sequence
`(AGVPWV) be contained in a polypeptide encoding a gene of the
`enzyme, and also confirmed that the activity was substantially lost
`when at least one amino acid residue in the amino acid sequence was
`deleted, and thus, the invention was completed.
`Id. at 4:7–15. According to the ’125 patent, “using the polynucleotide of the
`invention, an FAD-conjugated glucose dehydrogenase having excellent properties
`that it has excellent substrate (glucose) recognition performance and also has a low
`activity for maltose can be produced uniformly in a large amount by, for example,
`a recombinant DNA technique.” Id. at 5:34–39.
`
`D.
`Challenged Claim
`At the time of our Institution Decision, following Patent Owners’
`statutory disclaimer of claims 1–7, 9, and 10 (Ex. 2009), claim 8 was the only
`claim remaining in the ’125 patent. For the reasons discussed infra, we grant
`Patent Owners’ request to cancel claim 8. As the patentability of claim 8 is thus
`no longer at issue, we focus our analysis on the patentability of proposed
`substitute claim 11. Proposed substitute claim 11 is reproduced below, with
`strikeout text indicating text that has been deleted from original claim 8 and
`underlined text indicating text that has been added to original claim 8.
`
`6
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`
`11. A biosensor comprising a recombinant FAD-conjugated
`glucose dehydrogenase, wherein the recombinant FAD-conjugated
`glucose dehydrogenase is selected from: (a) a polypeptide which
`comprises the amino acid sequence represented by SEQ ID NO: 1;
`and (b) consists of a polypeptide which comprises an amino acid
`sequence having the sequence of an FAD-conjugated glucose
`dehydrogenase of Aspergillus oryzae NBRC 30104, wherein the
`sequence is set forth in SEQ ID NO:1 except that amino acid residue
`R at position 121 is replaced with an S and amino acid residue V at
`position 129 is replaced with an I, a homology of 90% or more to the
`amino acid sequence (a) and has an FAD-conjugated glucose
`dehydrogenase activity;
`wherein the recombinant FAD-conjugated glucose
`dehydrogenase has a value of enzymatic activity for maltose of 10%
`5% or less with a value of enzymatic activity for D-glucose taken as
`100%; and
`wherein the biosensor is capable of detecting glucose by a pH
`change.
`R. Mot. 18 (proposed substitute claim 11); Ex. 1005, 35:10–27, 36:22–23 (original
`claim 8).
`
`
`Reference(s)/Basis
`Omura2, knowledge of POSA3
`Omura, Tsuji4, knowledge of
`
`The Asserted Grounds of Unpatentability
`E.
`Petitioner challenges the patentability of substitute claim 11 on the following
`grounds:
`Claim(s) Challenged
`11
`11
`
`35 U.S.C. §
`103(a)1
`103(a)
`
`1 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29, 125 Stat.
`284, 287–88 (2011), amended 35 U.S.C. § 103, effective March 16, 2013. Because
`the application from which the ’987 patent issued was filed before this date, the
`pre-AIA version of § 103 applies.
`2 Omura et al., U.S. Patent No. 7,514,250 B2, issued Apr. 7, 2009 (Ex. 1010,
`“Omura”).
`3 Person of ordinary skill in the art (“POSA”).
`4 Tsuji et al., U.S. Patent Publication No. 2008/0014612 A1, published Jan 17,
`2008 (Ex. 1007, “Tsuji”).
`
`7
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`
`Claim(s) Challenged
`
`35 U.S.C. §
`
`Reference(s)/Basis
`
`POSA
`
`
`Petitioner submits the Second Declaration of Dr. Jeffrey T. LaBelle (Ex.
`1031) in support of its Opposition to Patent Owners’ Revised Motion to Amend.5
`F.
`Person of Ordinary Skill in the Art
`Factual indicators of the level of ordinary skill in the art include “the various
`prior art approaches employed, the types of problems encountered in the art, the
`rapidity with which innovations are made, the sophistication of the technology
`involved, and the educational background of those actively working in the field.”
`Jacobson Bros., Inc. v. United States, 512 F.2d 1065, 1071 (Ct. Cl. 1975); see also
`Orthopedic Equip. Co., v. United States, 702 F.2d 1005, 1011 (Fed. Cir. 1983)
`(quoting with approval Jacobson Bros.).
`Petitioner contends that the person of ordinary skill would have “a PhD in
`molecular biology (or a related discipline, such as biochemistry) with at least 2
`years of post-doctoral experience, or an equivalent amount of combined education
`and laboratory experience.” Pet. 22–23. Petitioner contends that the person of
`ordinary skill would also have “experience using recombinant DNA techniques to
`express proteins and a familiarity with protein chemistry and biosensors.” Id.
`In their Preliminary Response, Patent Owners asserted that Petitioner used
`
`“an overly broad and insufficiently experienced definition of a POSA [person of
`ordinary skill in the art].” Prelim. Resp. 9. According to Patent Owners,
`Petitioner’s proposal that the POSA would have a “PhD in molecular biology” was
`insufficiently specific for an invention “directed to the use of enzymes in
`biosensors for measuring glucose levels.” Id. at 10. Patent Owners asserted that
`
`
`5 Petitioner also provided the Declarations of Dr. Jeffrey T. LaBelle (Ex. 1008) and
`Dr. Anthony Edward George Cass (Ex. 1021) in support of its Petition.
`8
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`the POSA should have more than just a “familiarity” with enzyme-based
`biosensors and protein chemistry. Id. Rather, the POSA should have ordinary skill
`in enzymology and biosensors. Id. Thus, according to Patent Owners:
`[A] POSA would have a PhD in the field of biological chemistry or a
`related discipline. The POSA would also have research experience
`and/or knowledge in enzymology, recombinant DNA techniques, and
`biosensors. The POSA would further understand that enzyme-based
`glucose biosensors were known and would understand how they work.
`
`Id.
`
`In our Institution Decision, we agreed with the position Patent Owners took
`in their Preliminary Response – i.e, that the focus of the challenged claims was
`enzyme-based biosensors and thus the POSA would have more than just a
`familiarity with enzyme-based biosensors and protein chemistry. Inst. Dec. 8–9.
`Accordingly, based on the record before us at the time, we accepted the definition
`provided in Patent Owners’ Preliminary Response, which was consistent with the
`level of skill reflected in the asserted prior art references and in the specification of
`the ‘987 patent. See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001)
`(the prior art itself can reflect the appropriate level of ordinary skill in the art).
`Neither party challenges the identification of the POSA set forth in our
`Institution Decision. See generally, R. Mot.; Opp.; Reply; Sur-reply.
`Additionally, we find that the fully developed trial record supports the POSA
`identification we made in our Institution Decision. Accordingly, in this decision,
`we apply the identification of the POSA set forth in our Institution Decision. Inst.
`Dec. 9.
`
`Claim Construction
`E.
`In a post grant review, we construe the claims “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. Therefore, we construe the
`
`9
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`challenged claims under the framework set forth in Phillips v. AWH Corp., 415
`F.3d 1303, 1312–19 (Fed. Cir. 2005) (en banc). Under this framework, claim
`terms are given their ordinary and customary meaning, as would be understood by
`a person of ordinary skill in the art, at the time of the invention, in light of the
`language of the claims, the specification, and the prosecution history of record. Id.
`Only those terms that are in controversy need be construed, and only to the
`extent necessary to resolve the controversy. 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)). For
`purposes of this decision, we need not expressly construe any claim terms.
`
` CANCELLATION OF CLAIM 8
`Patent Owners’ Motion to Amend requests that claim 8 be cancelled.6
`R. Mot. 1. The Motion is not contingent on any finding by the Board regarding the
`patentability of claim 8. Id. Rather, the Motion seeks to replace challenged claim
`8 with substitute claim 11 without precondition. Id. (“Patent Owners . . . request
`cancellation of claim 8 of U.S. Patent No. 9,976,125 (‘the ’125 Patent,’ Ex. 1005)
`and entry of new claim 11 on a noncontingent basis.”).
`“A motion to amend may cancel a challenged claim . . . .” 35 U.S.C.
`§ 316(d)(1)(A); 37 C.F.R. § 42.121(a)(3). Petitioner does not oppose the
`cancelation of claim 8. Accordingly, we grant Patent Owner’s Revised Motion
`to Amend with respect to the request to cancel challenged claim 8.
`
` PATENTABILITY OF SUBSTITUTE CLAIM 11
`
`
`6 Petitioner challenged claims 1–10 in the Petition. As noted above, prior to our
`decision on institution, Patent Owners filed a statutory disclaimer under 35 U.S.C.
`§ 253(a) disclaiming claims 1–7, 9, and 10 of the ’125 patent. Accordingly, we
`declined to institute post-grant review with respect to disclaimed claims 1–7, 9 and
`10. Inst. Dec. 6–7.
`
`10
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`
`Petitioner contends that substitute claim 11 is unpatentable on two grounds:
`first, substitute claim 11 would have been obvious over Omura in view of the
`knowledge of the POSA, and second, substitute claim 11 would have been obvious
`over the combination of Omura and Tsuji in view of the knowledge of the POSA.
`Opp. 7–24. We have considered the question of patentability in view of all the
`evidence and arguments presented in this proceeding. Based on the record
`developed during this proceeding, we determine that Petitioner has shown by a
`preponderance of the evidence that substitute claim 11 would have been obvious
`over the combination of Omura, Tsuji, and the knowledge of the POSA. Because
`Petitioner has proven that substitute claim 11 would have been obvious, as
`discussed in detail below, we do not consider whether Patent Owners’ motion
`otherwise complies with the statutory and regulatory requirements for a motion to
`amend. See, 35 U.S.C. § 326(d)(1)(B) (requiring that the amendment propose a
`“reasonable number of substitute claims” and requiring that the substitute claims
`do “not enlarge the scope of the claims of the patent or introduce new matter”); 37
`C.F.R. § 42.221 (additionally providing, inter alia, that a motion to amend “may be
`denied where . . . [t]he amendment does not respond to a ground of unpatentability
`involved in the trial”). Similarly, because we have determined that substitute claim
`11 would have been obvious over the combination of Omura, Tsuji, and the
`knowledge of the POSA, as discussed in detail below, we do not reach the question
`of whether substitute claim 11 would also have been obvious over only Omura in
`view of knowledge of the POSA.
`
`A.
`
`Principles of Law
`
`In a post grant review, amended claims are not added to a patent as of right,
`but rather must be proposed as a part of a motion to amend. 35 U.S.C. § 326(d).
`The Board must assess the patentability of proposed substitute claims “without
`
`11
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`placing the burden of persuasion on the patent owner.” Aqua Prods., Inc. v. Matal,
`872 F.3d 1290, 1328 (Fed. Cir. 2017) (en banc); see also Lectrosonics, Inc. v.
`Zaxcom, Inc., IPR2018-01129, Paper 15 at 3‒4 (PTAB Feb. 25, 2019)
`(precedential). Subsequent to the issuance of Aqua Products, the Federal Circuit
`issued a decision in Bosch Automotive Service Solutions, LLC v. Matal, 878 F.3d
`1027 (Fed. Cir. 2017) (“Bosch”), as well as a follow-up order amending that
`decision on rehearing. See Bosch Auto. Serv. Sols., LLC v. Iancu, No. 2015-1928
`(Fed. Cir. Mar. 15, 2018) (Order on Petition for Panel Rehearing).
`In accordance with Aqua Products, Bosch, and Lectrosonics, a patent owner
`does not bear the burden of persuasion to demonstrate the patentability of the
`substitute claims presented in the motion to amend. Rather, ordinarily, “the
`petitioner bears the burden of proving that the proposed amended claims are
`unpatentable by a preponderance of the evidence.” Bosch, 878 F.3d at 1040 (as
`amended on rehearing); Lectrosonics, Paper 15 at 3–4. In determining whether a
`petitioner has proven unpatentability of the substitute claims, the Board focuses on
`“arguments and theories raised by the petitioner in its petition or opposition to the
`motion to amend.” Nike, Inc. v. Adidas AG, No. 2019-1262, 2020 WL 1802796, at
`*6 (Fed. Cir. Apr. 9, 2020).
`A patent claim is unpatentable under 35 U.S.C. § 103(a) if the differences
`between the claimed subject matter and the prior art are such that the subject
`matter, as a whole, would have been obvious at the time the invention was made to
`a person having ordinary skill in the art to which said subject matter pertains. KSR
`Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). The question of obviousness is
`resolved on the basis of underlying factual determinations, including (1) the scope
`and content of the prior art; (2) any differences between the claimed subject matter
`and the prior art; (3) the level of skill in the art; and (4) objective evidence of
`
`12
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966). Objective
`evidence of nonobviousness may include the following: “commercial success,
`long felt but unsolved needs, failure of others, etc.”7 Id.
`We analyze the patentability of substitute claim 11 in accordance with the
`above-stated principles.
`B.
`Scope and Content of the Prior Art
`
`Knowledge of the POSA
`FAD-conjugated glucose dehydrogenase purified from Aspergillus oryzae
`was known at least as early as 1966. Ex. 1001, 1 (journal article published in 1967
`stating: “[a] glucose dehydrogenase which catalyzes the oxidation by 2,6-
`dichlorophenol indophenol (DCIP) of glucose to gluconic acid was purified from
`induced mycelia of Aspergillus oryzae . . . The enzyme contained I mole of FAD
`as prosthetic group per mole of enzyme”); see also, Ex. 1031 ¶ 25 (Dr. LaBelle’s
`well supported testimony that “[g]lucose reactivity of FAD-conjugated GDH
`[glucose dehydrogenase] derived from Aspergillus oryzae and biosensors using
`that reactivity were known well in advance of the ’125 Patent’s earliest priority
`dates”); see also Ex. 1002, 1; Ex. 1003, 1; Ex. 1004, 4–5; Ex. 1007. 3:28–32 (“it
`has already been observed that a glucose dehydrogenase whose coenzyme is a
`flavin adenine dinucleotide exists in a cytoplasm fraction and a culture of
`Aspergillus oryzae”).
`The Aspergillus orzyae strain NBRC 30104 was known at least as early as
`1976, when it was submitted to the NBRC culture collection database by Hideya
`Murakami after he successfully characterized and classified various strains of
`
`
`7 We do not address objective indicia of nonobviousness in this opinion because
`Patent Owners did not present any evidence or arguments directed to objective
`indicia of nonobviousness during this proceeding.
`13
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`Aspergillus oryzae. Ex. 1037; Ex, 1031 ¶ 22 (Dr. LaBelle testimony regarding
`NBRC culture collection database).
`Omura
`Omura discloses, in relevant part, a “biosensor [that] may be any sensor
`having a reaction layer containing the inventive coenzyme-binding glucose
`dehydrogenase as an enzyme.” Ex. 1010, 18:54–55. Omura states, “[t]he
`coenzyme which is bound to the inventive glucose dehydrogenase may for
`example be a flavin compound, including a coenzyme such as flavin adenine
`dinucleotide.” Id. at 3:10–13. Omura also states, “the inventive coenzyme-binding
`glucose dehydrogenase may also be a synthetic coenzyme-binding glucose
`dehydrogenase or a recombinant coenzyme-binding glucose dehydrogenase
`obtained by a gene engineering technology.” Id. at 17:15–19. Omura teaches that
`“a biosensor can be constructed so that the chromogenic intensity or pH change is
`detected.” Id. at 19:3–4.
`As to the source of its coenzyme-binding glucose dehydrogenase, Omura
`discloses that “[i]t has already been observed that a glucose dehydrogenase whose
`coenzyme is a flavin dinucleotide exists in a cytoplasm fraction and a culture of
`Aspergills oryzae.” Id. at 3:28–32. According to Omura, this enzyme has “poor
`stability” and can only be quenched using a heavy metal, which creates problems
`with waste disposal. Id. at 3:35–41. Omura discloses that the “coenzyme-binding
`glucose dehydrogenase discovered in [its] invention is characterized by its higher
`stability when compared with that of the known Aspergillus orzyae-derived
`coenzyme-binding glucose dehydrogenase, and also by a favorably convenient
`handling for quenching.” Id. at 3:41–48. The microorganism from which Omura’s
`coenzyme-binding glucose dehydrogenase is derived is “preferably a eukaryotic
`microorganism, more preferably, genus Aspergillus, further preferably, Aspergillus
`
`14
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`terreus, and most preferably, the deposited strain FERM BP-08578.” Id. at 3:51–
`56.
`Tsuji8
`Tsuji discloses that “[i]t is an object of [Tsuji’s] invention to provide a
`method for efficiently producing the practically more advantageous enzyme for the
`blood glucose sensor.” Ex. 1007 ¶ 7. To this end, the inventors in Tsuji, “isolated
`the gene encoding the flavin-binding glucose dehydrogenase derived from
`Aspergillus oryzae.” Id. ¶ 27; id. ¶ 8 (disclosing that Tsuji’s inventors “acquired a
`glucose dehydrogenase gene derived from Aspergillus oryzae by utilizing [the]
`database of [the] National Center for Biotechnology Information (NCBI) and
`found that glucose dehydrogenase derived from Aspergillus oryzae could be
`acquired from Escherichia coli using the gene”). The enzyme isolated in Tsuji
`“does not act upon maltose in a broad sense and is suitable for the glucose sensor.”
`Id. ¶ 85; see also, id. ¶ 81 Table 1 (showing glucose reactivity of 100 and maltose
`reactivity of 0.4).
`
`Analysis
`C.
`Omura discloses a biosensor similar to that recited in substitute claim 11,
`with the principal differences between Omura’s biosensor and the claimed
`biosensor being that Omura does not disclose the use FAD-conjugated glucose
`dehydrogenase derived from the claimed strain of Aspergillus oryzae, and that the
`FAD-conjugated glucose dehydrogenase in Omura’s biosensor does not have the
`
`8 At one point in this proceeding, Patent Owner challenged the status of Tsuji as
`prior art. See, e.g., R. Mot. 12–13. At the hearing, Patent Owner represented that
`it no longer contends that Tsuji is not prior art. Tr. 32:21–33:4; see also, Opp. 15–
`18 (explaining Petitioner’s position as to why Tsuji constitutes prior art). As this
`point is no longer contested, and for the reasons set forth in our analysis in the
`Preliminary Guidance on the Motion to Amend (Paper 27, 7–8), we treat Tsuji as
`prior art to the ’125 patent.
`
`15
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`amino acid sequence recited in substitute claim 11. The contested issues in this
`case focus principally on these differences. In particular, the parties dispute: 1)
`whether it would have been obvious to use FAD-conjugated glucose
`dehydrogenase derived from the claimed strain of Aspergillus oryzae, and 2)
`whether, as Patent Owners contend, the POSA would have faced insurmountable
`obstacles in trying to obtain the claimed amino acid sequence from Aspergillus
`oryzae strain NCBR 30104. We address these arguments in the context of
`analyzing the record with respect to each individual claim limitation recited in
`claim 11. We address each limitation in the sequence in which it is presented in
`the claim.
`
`comprising
`biosensor
`“A
`dehydrogenase . . .”
`
`
`recombinant FAD-conjugated
`
`glucose
`
`Substitute claim 11 recites a “biosensor comprising a recombinant FAD-
`conjugated glucose dehydrogenase.” Petitioner contends that both Omura and
`Tsuji disclose biosensors using recombinant FAD-conjugated glucose
`dehydrogenase. Opp. 7–8, 18–19.
`Patent Owners do not contest that Omura and Tsuji disclose this element.
`See generally, R. Mot.; Reply.
`We find that the evidence of record supports that both Omura and Tsuji
`disclose biosensors using recombinant FAD-conjugated glucose dehydrogenase.
`Ex. 1010, 18:54–55 (Omura disclosing biosensor containing “coenzyme-binding
`glucose dehydrogenase”); id. at 3:10–13 (disclosing that the coenzyme may be
`“flavin adenine dinucleotide.”); id. at 17:15–19 (disclosing that the coenzyme-
`binding glucose dehydrogenase may be obtained recombinantly); Ex. 1007 ¶ 7
`(Tsuji disclosing objective to obtain an enzyme for the blood glucose sensor); id.
`
`16
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`¶ 27 (disclosing isolation of gene encoding flavin-binding glucose dehydrogenase);
`id. ¶ 8 (disclosing that enzyme can be produced in Escherichia coli).
`
` “. . . wherein the recombinant FAD-conjugated glucose dehydrogenase consists of
`a polypeptide having the sequence of an FAD-conjugated glucose dehydrogenase
`of Aspergillus oryzae NBRC 30104 . . .”
`
`
`Substitute claim 11 recites that the “recombinant FAD-conjugated glucose
`dehydrogenase consists of a polypeptide having the sequence of an FAD-
`conjugated glucose dehydrogenase of Aspergillus oryzae NBRC 30104.” Neither
`Omura nor Tsuji disclose a biosensor that uses FAD-conjugated glucose
`dehydrogenase from the specifically recited strain of Aspergillus oryzae. Petitioner
`contends, however, that the POSA would have been aware that Aspergillus oryzae
`was a source for FAD-conjugated glucose dehydrogenase, and that a POSA,
`“equipped with the disclosure of recombinant FAD-conjugated GDH-based
`biosensors as in Tsuji and Omura[,] would have found it obvious to produce a
`biosensor having FAD-conjugated GDH comprising the amino acid sequence
`[from] . . . a previously known strain of Aspergillus oryzae, NBRC 30104.” Opp.
`21–22.
`More specifically, Petitioner contends that “[t]he functionality of the FAD-
`conjugated GDH from Aspergillus oryzae NBRC 30104 is indistinguishable from
`other strains of Aspergillus oryzae.” Opp. 22 (citing Ex. 1031 ¶¶ 26, 43); id. at 10–
`11 (“The ’125 Patent fails to demonstrate the advantage of NBRC 30104 over any
`of the other active FAD-conjugated GDH enzymes isolated from Aspergillus
`oryzae.”). Petitioner thus argues that it would have been obvious and “relatively
`simple” to substitute FAD-conjugated glucose dehydrogenase derived from the
`claimed strain of Aspergillus oryzae for FAD-conjugated glucose dehydrogenase
`derived from Aspergillus terreus as disclosed in Omura. Id. at 23; see also Sur-
`
`17
`
`

`

`PGR2019-00032
`Patent 9,976,125 B2
`
`reply 6 (arguing that “[t]he substitution of one element know