IDENIX PHARMACEUTICALS LLC, UNIVERSITA DEGLI STUDI DI CAGLIARI, Plaintiffs-Appellants
GILEAD SCIENCES INC., Defendant-Appellee
from the United States District Court for the District of
Delaware in No. 1:14-cv-00846-LPS, Chief Judge Leonard P.
Gregory A. Castanias, Jones Day, Washington, DC, argued for
plaintiffs-appellants. Also represented by Jennifer Loraine
Swize; Lisa Lynn Furby, Chicago, IL; Calvin Griffith, Ryan
Boyd McCrum, Cleveland, OH; Anthony Insogna, San Diego, CA;
Jeffrey A. Lamken, Sarah Justine Newman, Michael Gregory
Pattillo, Jr., MoloLamken LLP, Washington, DC.
Joshua Rosenkranz, Orrick, Herrington & Sutcliffe LLP,
New York, NY, argued for defendant-appellee. Also represented
by Edmund Hirschfeld; Elizabeth Moulton, Menlo Park, CA;
Brian Philip Goldman, San Francisco, CA; Eric Shumsky,
Washington, DC; Frank Scherkenbach, Fish & Richardson,
PC, Boston, MA; Craig E. Countryman, W. Chad Shear, Jonathan
Elliot Singer, San Diego, CA.
Prost, Chief Judge, Newman and Wallach, Circuit Judges.
Pharmaceuticals LLC and Universita Degli Studi Di Cagliari
(collectively, "Idenix") appeal from the decision
of the U.S. District Court for the District of Delaware
granting judgment as a matter of law ("JMOL")
against Idenix and finding that U.S. Patent No. 7, 608, 597
is invalid for lack of enablement. Idenix Pharm. LLC v.
Gilead Scis., Inc., 2018 WL 922125, at *25 (D. Del. Feb.
16, 2018) ("JMOL Opinion"). Gilead Sciences Inc.,
("Gilead") argues that the patent is also invalid
for failure to meet the written description requirement, and
that the district court erred by failing to grant JMOL on
that ground as well. We affirm as to non-enablement and hold
that the patent is also invalid for lack of written
appeal stems from Idenix's December 2013 patent
infringement suit against Gilead, originally filed in the
U.S. District Court for the District of Massachusetts and
later transferred to the District of Delaware. J.A. 259-69.
At the time of the suit, both Idenix and Gilead were
researching and developing drugs for treatment of the
hepatitis C virus ("HCV"). HCV is a leading cause
of chronic liver disease, infecting hundreds of millions of
people worldwide, and accounting for tens of thousands of
deaths per year in the United States alone. Idenix alleged
that the imminent Food and Drug Administration approval, and
launch, of Gilead's HCV treatment drug sofosbuvir would
infringe Idenix's U.S. Pat. No. 7, 608, 597 (the
years of litigation, Chief Judge Stark held a two-week jury
trial in December 2016. Gilead stipulated to infringement
under the district court's claim construction but argued
that the '597 patent was invalid for failure to meet the
written description and enablement requirements. The jury
found for Idenix, upholding the validity of the patent and
awarding damages. After trial, Gilead filed a renewed motion
for JMOL with respect to written description and enablement.
The district court denied the motion with respect to written
description but granted JMOL on enablement, holding the
'597 patent invalid.
timely appealed. We have jurisdiction under 28 U.S.C. §
review the denial or grant of a motion for JMOL under
regional circuit law. See Tr. of Boston Univ. v.
Everlight Elecs. Co., 896 F.3d 1357, 1361 (Fed. Cir.
2018). Applying Third Circuit law, we "exercise plenary
review over a district court's rulings on motions for
JMOL, applying the same standard as the district court."
Agrizap, Inc. v. Woodstream Corp., 520 F.3d 1337,
1341-42 (Fed. Cir. 2008) (citing Gagliardo v. Connaught
Labs., Inc., 311 F.3d 565, 568 (3d Cir. 2002)).
A grant of JMOL is appropriate "where a party has been
fully heard on an issue during a jury trial and the court
finds that a reasonable jury would not have had a legally
sufficient evidentiary basis to find for the party on that
issue." Id. at 1342; see Fed. R. Civ.
requires that "the specification teach those in the art
to make and use the invention without undue
experimentation." In re Wands, 858 F.2d 731,
737 (Fed. Cir. 1988). A claim is not enabled when, "at
the effective filing date of the patent, one of ordinary
skill in the art could not practice their full scope without
undue experimentation." Wyeth & Cordis Corp. v.
Abbott Labs., 720 F.3d 1380, 1384 (Fed. Cir. 2013).
Whether a claim satisfies the enablement requirement is a
question of law that we review de novo. Tr. of Boston
Univ., 896 F.3d at 1361. However, "in the context
of a jury trial, we review the factual underpinnings of
enablement for substantial evidence." Id.
'597 patent claims a method of treating HCV by
administering nucleoside compounds having a specific chemical
and stereochemical structure. The nucleosides claimed in the
'597 patent contain a sugar ring having five carbon
atoms, numbered 1' (one prime) to 5' (five prime), as
well as a base. At each carbon, substituent atoms or groups
of atoms can be added in either the "up" or
"down" position. This structure is illustrated
below, with a hydroxyl group (OH) shown attached at the
2'-down and 3'-down positions:
Br. 8. The parties' arguments focus on the presence of
various possible substituents at the 2'-up and
argues that the key to its invention, and to treatment of
HCV, is the use of 2'-methyl-up nucleosides: nucleosides
"having a methyl substitution ('CH3') at the
2' 'up' position of the molecule's sugar
ring," illustrated below.
Appellant's Br. 7-8.
argues that this characterization is overly broad, as the
'597 patent provides no guidance in determining which of
the billions of potential 2'-methyl-up nucleosides are
effective in treating HCV. See Appellee's Br. 8.
According to Gilead, the '597 patent primarily describes
2'-methyl-up nucleosides that have a hydroxyl group (OH)
at the 2'-down position. But Gilead's accused product
has fluorine (F), not OH, at the 2'-down position.
Id. According to Gilead, the '597 patent cannot
enable the full scope of effective 2'-methyl-up
nucleosides at least because its accused embodiment,
2'-methyl-up 2'-fluoro- down, is not disclosed in or
enabled by the specification.
1. A method for the treatment of a hepatitis C virus
infection, comprising administering an effective amount of a
purine or pyrimidine β-D-2'-methyl-ribofuranosyl
nucleoside or a phosphate thereof, or a pharmaceutically
acceptable salt or ester thereof.
'597 patent claim 1. The district court construed the
to require "a methyl group in the 2' up position and
non-hydrogen substituents at the 2' down and 3' down
positions." Idenix Pharm., Inc. v. Gilead Scis.,
Inc., 2015 WL 9048010, at *6 (D. Del. Dec. 16, 2015)
("Claim Construction Order"). Thus, while the claim
requires methyl at the 2'-up position, it allows nearly
any imaginable substituent at the 2'-down
Idenix's urging, the district court also construed the
preamble, "[a] method for the treatment of a hepatitis C
virus infection," as a narrowing functional limitation.
Idenix Pharm. LLC v. Gilead Scis., Inc., 2016 WL
6802481, at *5 (D. Del. Nov. 16, 2016). In combination with
the requirement to administer an "effective
amount," this claim language "limit[s] the scope of
the claims to the use of some set of compounds that are
effective for treatment of HCV." Id. at *6.
party challenges the district court's claim constructions
in this appeal. Claim 1, therefore, encompasses any β-D
nucleoside meeting both the structural limitations (including
a methyl group at 2'-up) and the functional limitations
(efficacy in treating HCV). It is undisputed, however, that
there are billions of potential 2'-methyl-up nucleosides.
The key enablement question is whether a person of ordinary
skill in the art would know, without undue experimentation,
which 2'-methyl-up nucleosides would be effective for
treating HCV. We conclude that they would not. Taking into
account the evidence presented at trial, a reasonable jury
would not have had a legally sufficient basis to find
analyzing undue experimentation, we consider the factors
first enumerated in In re Wands. The uncontested
jury instructions in this case formulate the Wands
factors as follows:
(1) the quantity of experimentation necessary;
(2) how routine any necessary experimentation is in the
(3) whether the patent discloses specific working examples of
the claimed invention;
(4) the amount of guidance presented in the patent;
(5) the nature and predictability of the field;
(6) the level of ordinary skill; and
(7) the scope of the claimed invention.
J.A. 179; see Wands, 848 F.3d at 737. The parties
agree that the level of ordinary skill in the art is high,
but dispute the impact of the remaining factors. We discuss
each in turn.
agree with the district court that the quantity of
experimentation required to determine which 2'-methyl-up
nucleosides meet claim 1 is very high, which favors a finding
of non-enablement. The evidence presented to the jury could
not support any other finding. At trial, Gilead presented
expert testimony that because the claim allows for nearly any
substituent to be attached at any position (other than
2'-up), a person of ordinary skill in the art would
understand that "billions and billions" of
compounds literally meet the structural limitations of the
claim. J.A. 37545.
did not dispute that math, but argued to the jury that this
approach was merely "theoretical," because a person
of ordinary skill in the art ("POSA") would not
attach substituents at random. See J.A. 37734.
Instead, Idenix argued, a POSA would know to "take into
account the patent as a whole" to focus on a
"significantly smaller" set of candidate compounds.
Id. The district court accepted this argument, but
concluded that even taking into account the knowledge and
approach of a POSA, the candidate compounds number
"likely millions or at least many, many
thousands." JMOL Opinion, at *12.
evidence presented, a reasonable jury could only have
concluded that at least "many, many thousands" of
candidate compounds exist. Idenix's evidence, which
supports at best an unspecified number "significantly
smaller" than "billions," could not lead a
reasonable jury to any other conclusion. As Gilead points
out, even hundreds of millions is a "significantly
smaller" number when the starting point is
"billions and billions." Appellee's Br. 35-36.
Idenix's counsel conceded that in its "best
case," considering the knowledge of a POSA, the
structural limitations still encompass "some number of
thousands" of compounds. J.A. 40013.
conclusion is supported by the '597 patent itself, which
discloses enormous quantities of 2'-methyl-up nucleosides
that would need to be tested for efficacy against HCV. The
specification contains 18 Formulas, each of which is
represented by a diagram with variables at multiple
positions. For example, Formula XVII, described as the
"eleventh principal embodiment," provides:
compound of Formula XVII, or a pharmaceutically acceptable
salt or prodrug thereof:
Base is a purine or pyrimidine base as defined herein;
R1 and R2 are independently H;
phosphate (including monophosphate, diphosphate,
triphosphate, or a stabilized phosphate prodrug); acyl
(including lower acyl); alkyl (including lower alkyl);
sulfonate ester including alkyl or arylalkyl sulfonyl
including methanesulfonyl and benzyl, wherein the phenyl
group is optionally substituted with one or more substituents
as described in the definition of aryl given herein; a lipid,
including a phospholipid; an amino acid; a carbohydrate; a
peptide; a cholesterol; or other pharmaceutically acceptable
leaving group which when administered in vivo is capable of
providing a compound wherein R1 or R2 is independently H or
R6 is hydrogen, hydroxy, alkyl (including lower
alkyl), azido, cyano, alkenyl, alkynyl, Br-vinyl, -
C(O)O(alkyl), -C(O)O(lower alkyl), -O(acyl), - O(lower acyl),
-O(alkyl), -O(lower alkyl), - O(alkenyl), chloro, bromo,
fluoro, iodo, NO2, NH2, -NH(lower
alkyl), -NH(acyl), -N(lower alkyl)2,
R7 and R9 are independently hydrogen,
OR2, hydroxy, alkyl (including lower alkyl),
azido, cyano, alkenyl, alkynyl, Br-vinyl, -C(O)O(alkyl), -
C(O)O(lower alkyl), -O(acyl), -O(lower acyl), - O(alkyl),
-O(lower alkyl), -O(alkenyl), chlorine, bromine, iodine,
NO2, NH2, -NH(lower alkyl), - NH(acyl),
-N(lower alkyl)2, -N(acyl)2;
R10 is H, alkyl (including lower alkyl), chlorine,
bromine or iodine;
alternatively, R7 and R9, or
R7 and R10 can come together to form a
pi bond; and
X is O, S, SO2 or CH2.
'597 patent col. 12 ll. 20-67. The 2'-up position in
this formula, represented as R6, includes a methyl
group as one of two dozen possible
substituents. Even limiting this formula only to its
2'-methyl-up variations, however, the formula provides
more than a dozen options at the R1 position, more
than a dozen independent options at the 2'-down position,
more than a dozen independent options at the 3'- down
position, and multiple independent options for the base.
district court meticulously calculated, this formula alone
discloses more than 7, 000 unique configurations of
2'-methyl-up nucleosides. JMOL Opinion, at
Other formulas in the specification provide equally large
numbers of compounds. Idenix argues that a POSA would have
focused on only a narrow subset of billions of possible
candidates, but the jury was not free to adopt a number lower
than the many, many thousands of configurations identified as
"principal embodiment[s]" in the patent itself.
See, e.g., '597 patent col. 12 ll. 20-22.
Testing the compounds in the specification alone for efficacy
against HCV requires enough experimentation for this factor
to weigh in favor of non-enablement.
relatedly argues that a POSA would understand the
"focus" of the claim to be "the inhibition of
the NS5B polymerase" to effectively cure HCV.
Appellant's Br. 16. Therefore, Idenix argues, a POSA
would know which candidates were likely to inhibit NS5B, and
would test only those, resulting in a "predictable and
manageable" group of candidate compounds. Id.
This argument improperly attempts to narrow the claim to only
those nucleosides that would inhibit the NS5B polymerase. But
the district court's claim construction, not challenged
in this appeal, made clear that "as a matter of law,
NS5B activity is not a claim limitation." JMOL
Opinion, at *26 (emphasis in original).
it would be improper to rely on a POSA's knowledge of
NS5B to fill the gaps in the specification. "It is the
specification, not the knowledge of one skilled in the art,
that must supply the novel aspects of an invention in order
to constitute adequate enablement." Genentech, Inc.
v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir.
1997). Idenix's attempt to treat NS5B as a claim
limitation, based on the knowledge ...