Ikeda Food Research Co., Ltd.

Patent Trials and Appeals Board

Aug 12, 2020

PGR2019-00032 (P.T.A.B. Aug. 12, 2020)

Trials@uspto.gov Paper No. 38
571.272.7822 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

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Patent 9,976,125 B2

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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).
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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.
A. Real Parties in Interest
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
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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.
C. The ’125 Patent (Ex. 1005)
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
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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
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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.
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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).

E. The Asserted Grounds of Unpatentability
Petitioner challenges the patentability of substitute claim 11 on the following
grounds:
Claim(s) Challenged 35 U.S.C. § Reference(s)/Basis
11 103(a)1 Omura2, knowledge of POSA3
11 103(a) Omura, Tsuji4, knowledge of

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”).
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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.
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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.
E. Claim Construction
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
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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.
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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
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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
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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.
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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
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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).
C. Analysis
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.
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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.

“A biosensor comprising recombinant FAD-conjugated glucose
dehydrogenase . . .”

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.
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¶ 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-
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reply 6 (arguing that “[t]he substitution of one element known in the art for a
known equivalent is obvious”). Indeed, according to Petitioner, “any strain . . .
would have been obvious to use in a known biosensor construction for detecting
glucose.” Opp. 23. Petitioner contends that the POSA would have expected
success “based on the similarities in characteristics of the enzymes.” Ex. 1031
¶ 49 (cited at Opp. 23).
Patent Owners argue that there are over 185 species of Aspergillus and over
600 strains of Aspergillus orzyae and thus the POSA would have “no reason to
select the FAD-GDH of the NBRC 30104 strain to produce the claimed
recombinant sequence.” Reply 6. According to Patent Owners, “Petitioner and its
expert are throwing darts,” as there is no indication in the cited art which of the
possible 600 strains of Aspergillus orzyae would be most promising to try. Id. at
6–7. Patent Owners argue that “neither Petitioner nor its expert provide any
motivation as to why a POSA would have chosen the FAD-GDH of the NBRC
30104 strain over the other 599 strains.” Id. at 6.
Particularly given the relatively high degree of skill in the art, which
includes “research experience and/or knowledge in enzymology . . . and
biosensors,” we agree with Petitioner that it would have been obvious to a POSA
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.
As an initial matter, the evidence of record supports that it was known to use
FAD-conjugated glucose dehydrogenase from Aspergillus oryzae to detect glucose.
In particular, Tsuji discloses that glucose dehydrogenase sourced from Aspergillus
orzyae “does not act upon maltose in a broad sense,” “is suitable for the glucose
sensor,” and can be produced “on a large scale by the use of recombinant
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Escherichia coli.” Ex. 1007 ¶ 85; see also id. ¶¶ 7, 8; Ex. 1004, 4–5 (disclosing
that “[p]referred sources” of FAD-conjugated glucose dehydrogenase for sensing
glucose “include Aspergillus orzyae strain ATC 9102”); Ex. 1010, 3:28–31 (“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
orzyae.”); Ex. 1002, 3 (disclosing that FAD-conjugated GDH enzyme derived from
Aspergillus oryzae strain reacted with glucose but did not react with maltose “to
measurable extents”).
We recognize that Omura discloses that Aspergillus terreus strain FERM
BP-08578 is the most preferred source of FAD-conjugated glucose dehydrogenase,
but this does not negate the general teaching of the genus Aspergillus as a preferred
source. Ex. 1010, 3:53–56; Merck & Co. Inc. v. Biocraft Labs., Inc., 874 F.2d 804,
807 (Fed. Cir. 1989) (“[I]n a section 103 inquiry, ‘the fact that a specific
[embodiment] is taught to be preferred is not controlling, since all disclosures of
the prior art, including unpreferred embodiments, must be considered.’”) (quoting
In re Lamberti, 545 F.2d 747, 750 (CCPA 1976)); see also, Syntex (U.S.A.) LLC v.
Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005) (“A statement that a particular
combination is not a preferred embodiment does not teach away absent clear
discouragement of that combination.”). Moreover, as discussed above, Tsuji
discloses that glucose dehydrogenase sourced from Aspergillus orzyae “does not
act upon maltose in a broad sense,” “is suitable for the glucose sensor,” and can be
produced “on a large scale by the use of recombinant Escherichia coli. Ex. 1007
¶ 85.
We also acknowledge that there is no evidence of record that Aspergillus
orzyae strain NBRC 30104 was used to sense glucose prior to the filing of Patent
Owner’s priority application. However, the record does include evidence
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supporting that the POSA would have understood that enzyme activity toward
glucose and maltose is preserved across the genus Aspergillus and, more
specifically, that glucose dehydrogenase enzymes derived from different species of
Aspergillus can be used in a glucose biosensor. Ex. 1010, 3:53–54 (Omura
identifying the “genus Aspergillus” as a preferred microorganism source of
“coenzyme-binding glucose dehydrogenase” for use in Omura’s invention), 3:28–
55 (identifying Aspergillus orzyae as a source of FAD-conjugated glucose
dehydrogenase and singling out Aspergillus terreus strain FERM BP-08578 as the
most preferred source of FAD-conjugated glucose dehydrogenase because it
exhibits high stability and is conveniently quenched);9 Ex. 1004, 3–4 (disclosing
sensing glucose, teaching that the “glucose dehydrogenase enzymes may be
obtained from any microorganism containing these enzymes,” and identifying the
genus Aspergillus as a source of E.C.1.1.99.10, i.e., FAD-conjugated glucose
dehydrogenase); Ex. 1030, 5–6 (disclosing that FAD-conjugated glucose
dehydrogenase sourced from Aspergillus niger has low maltose activity as
compared to glucose). This evidence supports Dr. LaBelle’s testimony that “there
appears to be some appreciation in the art that functional difference[s], while they
do exist, are relatively minor and do not vary much with respect to activity toward
glucose and maltose at the genus and even species level.” Ex. 1031 ¶ 27.
In view of the evidence that enzyme functionality is preserved at the genus
level, Dr. LaBelle persuasively concludes that “it would . . . follow that little
difference would . . . exist among the strains within a particular species.” Id. More

9 Dr. LaBelle explains, in persuasive and unrebutted testimony, that these teachings
from Omura would have suggested to a POSA that “FAD-conjugated GDH of
Aspergillus oryzae does not differ functionally from Aspergillus terreus in relation
to activity toward glucose and maltose but that differences rested with stability.”
Ex. 1031 ¶ 27.
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specifically, Dr. LaBelle testifies that the POSA “would recognize the high
probability that FAD-conjugated GDH would be functionally the same toward
glucose across Aspergillus oryzae strains.” Ex. 1031 ¶ 28. This testimony is
unrebutted and persuasive.
Patent Owners do not direct us to persuasive evidence that the POSA would
expect active glucose dehydrogenase sourced from different strains of Aspergillus
orzyae to function differently when used to sense glucose that would undermine
Petitioner’s persuasive showing. Indeed, Patent Owners concede that strains of
Aspergillus orzyae with active glucose dehydrogenase are functionally equivalent.
Tr. 29 (“JUDGE COTTA: So, counsel, as between those strains that do have
activity, is there any evidence that they are not functional equivalents of each
other? MR. GEORGE: No, I mean, the strains that have activity are functionally
equivalent of each other.”).
At oral argument, the parties and the panel discussed whether Table 1 of the
’125 patent, which is reproduced below, showed differences among strains of
Aspergillus orzyae. Tr. 10:24–13:16, 15:21–17:8, 21:10–23:12, 30:3–30:26.
Table 1 presents results from the inventors’ attempts to confirm glucose
dehydrogenase activity for each of twelve strains of Aspergillus orzyae. Ex. 1005,
19:50–20:19. Table 1 also correlates these results with the presence or absence of
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amino acid sequence AGVPWV, a sequence that the ’125 patent teaches is critical
to glucose dehydrogenase activity. Id. at 4:6–16, 6:14–19, and 21:10–14. The
results provided in Table 1 indicate that the inventors were able to confirm glucose
dehydrogenase activity in 9 out of 12 strains of Aspergillus orzyae.
Patent Owners did not provide argument that Table 1 evidenced differences
among strains of Aspergillus orzyae in their briefing on their motion to amend. See
generally R. Mot.; Reply. Accordingly, any such argument is waived.10 However,
even if we were to consider it, and to credit Table 1 as showing that some strains of
Aspergillus orzyae lack active glucose dehydrogenase,11 we would still find the
claimed biosensor obvious. When balanced against the evidence that several
strains of Aspergillus orzyae were understood to produce active glucose

10 At oral argument, Patent Owners also discussed Tsuji’s inability to obtain
functional glucose dehydrogenase from Aspergillus orzyae strain RIB 40. Tr.
27:14–28:21, 30:18–31:5. To the extent Patent Owners argue that the RIB 40
strain evidence differences among strains of Aspergillus orzyae, such argument is
waived because it was not included in Patent Owners’ briefing. But even if we
were to consider Tsuji’s discussion of the RIB 40 strain, and credit it as evidence
that the strain does not have active glucose dehydrogenase rather than simply as
evidence that Tsuji failed to sequence glucose dehydrogenase from the RIB 40
strain, we would consider it cumulative of the evidence provided by Table 1 of the
’125 patent.
11 Dr. LaBelle testifies that the absence of glucose dehydrogenase activity in some
of the strains in Table 1 may be due to growth conditions and/or the medium on
which the organism is cultured. Ex. 1031 ¶¶ 30–32. This testimony is potentially
at odds with the teaching in the ’125 patent that the amino acid sequence
AGVPWV is critical to expression of glucose dehydrogenase and that the three
inactive strains in Table 1 lack this critical sequence. Ex. 1005, 4:6–16, 6:14–19,
20:1–19, and 21:10–14. While we note this potentially conflicting evidence, for
purposes of our discussion of the evidence in Table 1, we credit Table 1 as
evidencing a lack of activity in three strains of Aspergillus orzyae.
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dehydrogenase (see, e.g., Ex. 1001, 1;12 Ex. 1004, 4; 1007 ¶ 7, 8, 85; Ex. 1010
3:28–31) and that that glucose dehydrogenase activity was understood to be
preserved at the genus level (see, e.g., Ex. 1010, 3:53–54, 3:28–32, 3:53–55; Ex.
1004, 3–4; Ex. 1031 ¶ 27), the existence of certain strains of Aspergillus orzyae
that lack glucose dehydrogenase activity does not defeat the reasonable expectation
of success of a POSA in practicing the claimed invention. See Ex. 1031 ¶ 28
(unrebutted testimony of Dr. LaBelle that the POSA “would recognize the high
probability that FAD-conjugated GDH would be functionally the same toward
glucose across Aspergillus oryzae strains”).
Moreover, methods of testing the activity of glucose dehydrogenase with
respect to glucose were known well before Patent Owners filed their priority
application. See e.g., Ex. 1001, 2 (“Glucose dehydrogenase activity was measured
as described previously . . .”); Ex. 1002, 2; Ex. 1003, 2; Ex. 1007 ¶¶ 62–64 (“the
glucose dehydrogenase activity is measured under the following condition[s] . . .”);
Ex. 1010, 17:45–18:16 (describing “Enzymatic Activity Measurement Method 1”
and “Enzymatic Activity Measurement Method 2”); Ex. 1004, 7–8, 9.
Accordingly, the POSA would have known to identify strains of Aspergillus
oryzae that have active glucose dehydrogenase using known methods and to use
strains of Aspergillus oryzae with active rather than inactive glucose
dehydrogenase as a source of enzymes for use in biosensor. Ex. 1031 ¶ 29 (Dr.
LaBelle testimony that “so long as there is a functional FAD-conjugated glucose
dehydrogenase isolated from Aspergillus oryzae, a POSA would be able to utilize
it within the biosensor as recited in PO’s substitute claim 11 and have a reasonable
expectation of achieving success.”). Accordingly, even if we were to consider

12 Exhibits 1002 and 1003 also disclose active glucose dehydrogenase sourced
from Aspergillus orzyae, but appear to rely on the same strain of Aspergillus
orzyae as Ex. 1001. See, Ex. 1002, 2 n.2; Ex. 1003, 2 n.1.
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Patent Owner’s argument that Table 1 of the ’125 patent illustrates active and
inactive strains of Aspergillus oryzae, we would still find that it obvious to use
glucose dehydrogenase derived from the NBRC 30104 in a biosensor.
In sum, the evidence supports that FAD-conjugated glucose dehydrogenase
from the genus Aspergillus and, more specifically, from the species Aspergillus
oryzae, was known to have active FAD-conjugated glucose dehydrogenase that
could be used in a glucose sensor. The evidence also supports that the POSA
“would recognize the high probability that FAD-conjugated GDH would be
functionally the same toward glucose across Aspergillus oryzae strains.” Ex. 1031
¶ 28. In view of this evidence, we agree with Dr. LaBelle that it would have been
obvious to use the claimed strain of Aspergillus orzyae in Omura’s biosensor.
Dr. LaBelle explains:
Given the known properties of FAD-conjugated GDH from
Aspergillus in general, and specifically Aspergillus oryzae, a POSA
would have been motivated to use the FAD-conjugated GDH from
any Aspergillus oryzae strain, including NBRC 30104 instead of the
FAD-conjugated GDH from Aspergillus terreus in the FAD-
conjugated GDH-based biosensors described in Omura based on the
similarities in characteristics of the enzyme and the desire to
industrially produce a coenzyme-binding glucose dehydrogenase in a
commercial expression vector.
Id. ¶ 41; see also id. ¶¶ 47–49 (discussing motivation provided by Tsuji). We
further agree with Dr. LaBelle that the POSA would reasonably have expected this
substitution of known equivalents to be successful “based on the similarities in
characteristics of the enzymes.” Id. ¶ 49; see also id. ¶ 42.

“. . . 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 . . .”

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Substitute claim 11 recites that the polypeptide 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.” Petitioner contends
that “the sequence recited in claim 11 is necessarily present in the NBCR 30104
strain, is well within the skill of a POSA to obtain, and would therefore necessarily
be 100% identical to that of the FAD-conjugated GDH found in the NBRC 30104
strain.” Opp. 6 (citing Ex. 1031 ¶¶ 33, 34), 19–20 (citing Ex. 1007 ¶¶ 24–28; Ex.
1010, 17:19–36). Petitioner then asserts that with the sequence in hand, a POSA
would have been able to produce the FAD-conjugated GDH recombinantly. Id. at
9 (“a POSA only needs to obtain the amino acid sequence for the FAD-conjugated
GDH of Aspergillus oryzae in order to produce a recombinant GDH enzyme”), 20
(“a POSA can obtain the amino acid sequence of FAD-conjugated GDH of
Aspergillus oryzae . . . in order to produce a recombinant GDH enzyme thereof.”).
Patent Owners do not contest that the claimed sequence is inherently present
in Aspergillus oryzae NBRC 30104. Nor do Patent Owners contest that with the
claimed sequences, the POSA would be able to produce a recombinant enzyme.
Instead, Patent Owners contend that Petitioner and Dr. LaBelle “improperly
conflate (i) the prior existence of the A. oryzae NBRC 30104 mold organism with
(ii) possession of the requisite NBRC 30104 FAD-GDH amino acid sequence or
gene sequence information (which was not known), and possession of recombinant
NBRC 30104 FAD-GDH itself (which was also not known).” Reply 2. According
to Patent Owner, “[s]imply being in possession of A. oryzae NBRC 30104 mold
does not put a POSA in possession of NBRC 30104 FAD-GDH amino acid
sequence information, which is needed to produce the claimed recombinant FAD-
GDH.” Id.
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We agree with Petitioner that the claimed sequence is necessarily present in
the NBCR 30104 strain, that it would have been well within the skill of a POSA to
obtain, and that once in possession of the sequence, the POSA would have been
able to produce FAD-conjugated GDH recombinantly.
With respect to the identity of the claimed sequence to the sequence present
in FAD-conjugated glucose dehydrogenase derived from NBCR 30104,
Petitioner’s position is supported by the testimony of Dr. LaBelle, who testifies:
The specific amino acid sequence of FAD-conjugated GDH enzyme
from a known source, Aspergillus oryzae NBRC 30104, is
inherent[ly] present. As such, the FAD-conjugated GDH of NBRC
30104 would therefore necessarily have 100% identity with the amino
acid sequence recited in PO’s substitute claim 11.
Ex. 1031 ¶ 34. Dr. LaBelle’s testimony on this point is consistent with the record,
including the description in the ’025 patent of the claimed sequences as being
“derived from Aspergillus oryzae NBRC 30104.” See e.g, Ex. 1005, 20:31–41.
Patent Owners do not direct us to contradictory evidence or provide argument that
calls Dr. LaBelle’s testimony into question. Accordingly, we credit Dr. LaBelle’s
testimony that FAD-conjugated glucose dehydrogenase derived from Aspergillus
oryzae strain NBRC 30104 would have an amino acid sequence 100% identical to
that recited in substitute claim 11.
With respect to the ability of the POSA to obtain the claimed sequence,
Omura teaches that “[t]hose skilled in the art can obtain the coenzyme-binding
glucose dehydrogenase readily based on the disclosure of the protein or its salt
derived from the physiochemical characteristics of the inventive coenzyme.” Ex.
1010, 17:19–23. Omura also discloses that its coenzyme may be “recombinant”
and can be produced “industrially using a gene engineering method in which a
gene segment of the coenzyme-binding glucose dehydrogenase is inserted into a
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known expression vector.” Id. at 17:15–36. This supports that the POSA would
have been able to obtain the claimed sequence and express it recombinantly.
Tsuji also supports that the POSA would have been able to obtain the
claimed sequence. It discloses a method by which the gene and amino acid
sequence of FAD-conjugated glucose dehydrogenase derived from Aspergillus
orzyae was determined, even though “the amino acid sequence and the base
sequence encoding the Flavin-binding glucose dehydrogenase derived from
Aspergillus oryzae were not specified in the NCBI database.” Ex. 1007, ¶¶ 24
(disclosing absence of sequence in NCBI database), 69–71 (summarizing method
of obtaining sequence), 75–79 (detailed discussion of obtaining the sequence).
In addition to the disclosures in the art supporting that a POSA would have
been able to obtain the claimed sequence, Dr. LaBelle testifies that it was “well
within the knowledge of a POSA to obtain an amino acid sequence of an enzyme
known to exist in an organism” or to obtain “the DNA sequence encoding that
particular enzyme.” Ex. 1031 ¶ 34. As this testimony is consistent with the art, and
not persuasively rebutted, we credit it.
To counter this evidence, Patent Owners direct us to the disclosure in Tsuji
that one of the methods that Tsuji used to try to obtain the sequence of FAD-
conjugated glucose dehydrogenase from Aspergillus orzyae was unsuccessful.
According to Patent Owners, “Tsuji shows that in 2006, POSAs encountered
insurmountable technical hurdles in trying to directly obtain even a partial amino
acid sequence of FAD-GDH from both Aspergillus terreus and Aspergillus oryzae
using conventional sequencing techniques.” Reply 9. Patent Owners argue that
Tsuji’s “contemporaneous statements regarding the POSA’s complete failure with
conventional sequencing methods in 2006 directly contradict the Petitioner’s (and
Prof. LaBelle’s) blasé assertions 13 years later that ‘a POSA only needs to obtain
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the amino acid sequence for the FAD-conjugated GDH of Aspergillus oryzae in
order to produce a recombinant GDH enzyme.’” Id.
We acknowledge that one of the methods used by Tsuji was unsuccessful in
obtaining the sequence of FAD-conjugated glucose dehydrogenase. See Ex. 1007
¶ 26 (disclosing that the inventors “had no choice but to give up the cloning
utilizing the partial amino acid sequence”); see also, id. ¶¶ 67, 68, 73, 74.
However, we do not find this persuasive of the inability of the POSA to obtain the
claimed sequence because Tsuji’s disclosure also includes a method that was
successful in obtaining the sequence of FAD-conjugated glucose dehydrogenase.
Id. ¶¶ 27 (“the present inventors isolated the gene encoding the flavin-binding
glucose dehydrogenase derived from Aspergillus orzyae and completed the present
invention”), 69–71, 75–79.
Patent Owners argue that Tsuji’s second, successful method does not
provide a viable path by which a POSA could obtain the claimed sequence. Reply
10–11. In Tsuji’s second method, Tsuji’s inventors used a FAD-conjugated
glucose dehydrogenase amino acid sequence from P. lilacinoechinulatum, a
microorganism from an entirely different genus, as a base for comparing to
polypeptides isolated from Aspergillus orzyae. Ex. 1007 ¶¶ 77–79. Patent Owners
argue that this should not have worked as the sequence from P.
lilacinoechinulatum had only 49% sequence similarity when compared to
Aspergillus orzyae’s sequence, far below the 80% similarity that Patent Owners
contend is the “yardstick for homology cloning.” Reply 11 (citing Ex. 2022).
Patent Owners thus contend that a “POSA would have viewed Tsuji’s experiments
as a lucky break, and would not view them as a viable path forward.” Id. at 11.
This argument is not persuasive for two reasons.
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First, Patent Owners neglect to consider that Tsuji is prior art, and thus the
POSA would have knowledge of all that Tsuji discloses, including an amino acid
sequence for FAD-linked glucose dehydrogenase derived from Aspergillus orzyae.
See, e.g., Ex. 1007 (SEQ ID NO: 4).13 The availability of this sequence as a
starting point for sequencing efforts vitiates Patent Owners’ argument that the
POSA would not have viewed Tsuji’s as providing a “viable path forward.”
Second, Patent Owners’ contention is based entirely on attorney argument.
As discussed above, Petitioner’s position is supported by the testimony of Dr.
LaBelle and by the prior art of record. Particularly given the relatively high level
of skill in the art, which includes experience with “recombinant DNA techniques,”
we credit Dr. LaBelle’s well supported testimony that it was “well within the
knowledge of a POSA to obtain an amino acid sequence of an enzyme known to
exist in an organism” and also to “obtain the DNA sequence encoding that
particular enzyme,” over Patent Owners’ unsupported attorney argument to the
contrary. Ex. 1031 ¶ 34.
In sum, the evidence supports Petitioner’s position that “the sequence recited
in claim 11 is necessarily present in the NBCR 30104 strain, is well within the skill
of a POSA to obtain, and would therefore necessarily be 100% identical to that of
the FAD-conjugated GDH found in the NBRC 30104 strain.” Opp. 6.
The evidence also supports that once such sequence was obtained, a POSA
would capable of, and motivated to, use the sequence to produce the enzyme
recombinantly industrially. Ex. 1007 ¶ 85; Ex. 1010, 17:15–36.

“. . . and has an FAD-conjugated glucose dehydrogenase activity; wherein the
recombinant FAD-conjugated glucose dehydrogenase has a value of enzymatic

13 Petitioner asserts that SEQ ID NO:4 of Tsuji was 100% identical to SEQ ID
NO:1 of the ’125 patent. Pet. 42; see also Ex. 1008 ¶ 34; Ex. 1021 ¶ 32.
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activity for maltose of 5% or less with a value of enzymatic activity for D-glucose
taken as 100% . . .”

Substitute claim 11 recites that the polypeptide “has an FAD-conjugated
glucose dehydrogenase activity” and that “the recombinant FAD-conjugated
glucose dehydrogenase has a value of enzymatic activity for maltose of 5% or less
with a value of enzymatic activity for D-glucose taken as 100%.” Petitioner
contends that the relative enzymatic activity is “an inherent functional property that
necessarily results from a known FAD-conjugated GDH enzyme.” Opp. 11–12.
More specifically, Petitioner contends that a biosensor that uses a sequence
identical to that recited in substitute claim 11 would “necessarily possess the
[claimed] relative enzymatic activity toward maltose and glucose.” Id. at 12.
Petitioner also provides evidence that it was known that “the FAD-conjugated
GDH enzyme present in Aspergillus generally, and more specifically Aspergillus
oryzae, exhibited low or reduced enzymatic activity towards maltose as compared
to glucose.” Id.
Patent Owners do not contest that a biosensor having the recited amino acid
sequence would necessarily have the claimed relative enzymatic activity. See
generally R. Mot.; Reply.
We find that the evidence of record supports that a biosensor that used FAD-
conjugated glucose dehydrogenase having the recited amino acid sequence would
necessarily have the claimed relative activity level. Ex. 1031 ¶ 35 (Dr. LaBelle’s
unrebutted testimony that “the activity level demonstrated in FAD-conjugated
glucose dehydrogenase enzymes from Aspergillus oryzae flows directly as a result
of the protein sequence” and that “the activity level demonstrated toward glucose
and maltose are properties of the particular protein sequence”).

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“. . . and wherein the biosensor is capable of detecting glucose by a pH change.”

Substitute claim 11 recites that “the biosensor is capable of detecting glucose
by a pH change.” Petitioner contends that Omura discloses this element. Opp. 13,
21.
Patent Owners do not contest that Omura discloses this element. See
generally R. Mot.; Reply.
We find that the evidence of record supports that Omura discloses a
biosensor capable of detecting glucose by a pH change. Ex. 1010, 19:3–4 (Omura
disclosure that “a biosensor can be constructed so that the chromogenic intensity or
pH change is detected.”); Ex. 1031 ¶ 45 (Dr. LaBelle’s testimony that “[g]lucose
biosensors operable by detecting a pH change [are] also known in the art and
described in Omura.”).

D. Summary with Respect to Obviousness
Having fully considered the parties’ arguments and the evidence of record,
we find that it would have been obvious to use FAD-conjugated glucose
dehydrogenase from any strain of Aspergillus orzyae having active glucose
dehydrogenase, including strain NBRC 30104, in a biosensor like that described in
Omura that detects glucose by a pH change. We further find that a POSA would
have been capable of obtaining the amino acid sequence of FAD-conjugated
glucose dehydrogenase in strain NBRC 30104, and motivated to do so in order to
express it recombinantly at scale. Finally we find that FAD-conjugated glucose
dehydrogenase so expressed would inherently have the claimed sequence and
relative activity toward glucose and maltose. We thus find that the Petitioner has
established, by a preponderance of the evidence, that a POSA would have found
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substitute claim 11 obvious over the combination of Omura, Tsuji, and the
knowledge in the art. Accordingly, we deny Patent Owners’ motion to enter
proposed substitute claim 11.

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CONCLUSION
For the foregoing reasons, we grant Patent Owners’ request to cancel claim
8, and deny Patent Owners’ request to enter proposed substitute claim 11, as
summarized in the following table:
Motion to Amend Outcome Claim(s)
Original Claims Cancelled by Amendment 8
Substitute Claims Proposed in the Amendment 11
Substitute Claims: Motion to Amend Granted
Substitute Claims: Motion to Amend Denied 11
Substitute Claims: Not Reached

IV. ORDER
Accordingly, it is
ORDERED that Patent Owners’ Motion to Amend is granted as to its non-
contingent request to cancel claim 8;
FURTHER ORDERED that Patent Owners’ Motion to Amend is
denied as to substitute claims 11.

PGR2019-00032
Patent 9,976,125 B2

34
PETITIONER:
Aaron Eckenthal
Brian Tomkins
Alyssa D’Antonio
Lerner, David, Littenberg, Krumholz & Mentlik, LLP
aeckenthal.ipr@ldlkm.com
btomkins.ipr@ldlkm.com
adantonio@lernerdavid.com

PATENT OWNER:

Kenneth George
Brian Comack
Amster, Rothstein & Ebenstein LLP
kgeorge@arelaw.com
bcomack@arelaw.com