AMGEN INC., AMGEN MANUFACTURING LIMITED, AMGEN USA, INC., Plaintiffs-Appellees
SANOFI, AVENTISUB LLC, REGENERON PHARMACEUTICALS INC., SANOFI-AVENTIS U.S., LLC, Defendants-Appellants
from the United States District Court for the District of
Delaware in Nos. 1:14-cv-01317-SLR, 1:14-cv-01349-SLR,
1:14-cv-01393-SLR, 1:14-cv-01414-SLR, Judge Sue L. Robinson.
Joseffer, King & Spalding LLP, Washington, DC, argued for
plaintiffs-appellees. Also represented by Christopher Robert
Healy, Joshua Nathaniel Mitchell; Merritt Ellen McAlister,
Atlanta, GA; Katherine Nicole Clouse, Sarah Chapin Columbia,
McDermott, Will & Emery LLP, Boston, MA; William G.
Gaede, III, Menlo Park, CA; Eric W. Hagen, Los Angeles, CA;
Emily Curtis Johnson, Erica S. Olson, Dennis J. Smith, Steven
D. Tang, Stuart L. Watt, Wendy A. Whiteford, Amgen Inc.,
Thousand Oaks, CA; Christopher Mead, London & Mead,
Washington, DC; Melanie K. Sharp, Young, Conaway, Stargatt
& Taylor LLP, Wilmington, DE.
D. Clement, Kirkland & Ellis LLP, Washington, DC, argued
for defendants-appellants. Also represented by George W.
Hicks, Jr., Nathan S. Mammen; Siew Yen Chong, Vishal C.
Gupta, John J. Molenda, Steptoe & Johnson, LLP, New York,
NY; Richard Praseuth, Los Angeles, CA; Kiley Ann White,
Christopher Marks, Eli Lilly and Company, Indianapolis, IN,
for amicus curiae Eli Lilly and Company. Also represented by
Gregory Alan Cox, Gilbert Voy, Alexander Wilson.
Barbara Anne Jones, AARP Foundation Litigation, Pasadena, CA,
for amici curiae AARP and AARP Foundation.
Dimitrios T. Drivas, White & Case LLP, New York, NY, for
amicus curiae Pfizer Inc. Also represented by Eric M.
Majchrzak, Amit Thakore; Jeffrey Neil Myers, Pfizer Inc., New
A. Kelly, Hunton & Williams LLP, Atlanta, GA, for amicus
curiae Ipsen Pharma S.A.S.
Melissa Arbus Sherry, Latham & Watkins LLP, Washington,
DC, for amicus curiae AbbVie Inc. Also represented by Michael
A. Morin, Emily K. Sauter.
William Marsillo, Boies, Schiller & Flexner, LLP, Armonk,
NY, for amici curiae Luis Aparicio, M.D., W. Ross Davis,
M.D., Avichai Eres, M.D., Norman Lepor, M.D., Mary McGowan,
M.D., Narendra Singh, M.D., Paul
Thompson, M.D., Rosa DeBernardo, Alina Wilson. Also
represented by Michael Jay, Santa Monica, CA.
Prost, Chief Judge, Taranto and Hughes, Circuit Judges.
Sanofi, Aventisub LLC, Regeneron Pharmaceuticals Inc., and
Sanofi-Aventis U.S., LLC (collectively,
"Appellants") appeal from a final judgment of the
district court holding U.S. Patent Nos. 8, 829, 165
("'165 patent") and 8, 859, 741 ("'741
patent") not invalid and granting a permanent injunction
enjoining sales of Appellants' Praluent® alirocumab
("Praluent"). In particular, Appellants argue that
the district court improperly excluded evidence regarding
written description and ena-blement, improperly instructed
the jury on written description, improperly denied
Appellants' motion seeking JMOL of no written description
and no enablement, improperly granted Appellees' motion
seeking JMOL of non-obviousness, and improperly issued the
permanent injunction. Appellants' Br. 1. Because we
conclude that the district court (i) erred by excluding
Appellants' evidence regarding written description and
enablement, and (ii) improperly instructed the jury on
written description, we reverse-in-part and remand for a new
trial on written description and enablement. We also conclude
that Appellants are not entitled to JMOL of no written
description and no enablement. We affirm the district
court's grant of Appellees' JMOL of non-obviousness.
Finally, we vacate the district court's permanent
patents at issue generally relate to antibodies that help
reduce low-density lipoprotein cholesterol (LDL-C), or
"bad cholesterol." High levels of LDL-C in the
bloodstream can cause heart attacks, strokes, and
cardiovascular disease. Typically, high LDL-C is treated
using small molecules called statins. In some cases, however,
statins have adverse side effects or cannot reduce a
patient's LDL-C to a healthy level, requiring alternative
treatment. One such alternative treatment is a PCSK9
inhibitor-the medicine claimed by the patents at issue. PCSK9
is a naturally occurring protein that binds to and causes the
destruction of liver cell receptors (LDL receptors, or
LDL-Rs) that are responsible for extracting LDL-C from the
Amgen Inc., Amgen Manufacturing, Ltd., and Amgen USA, Inc.
(collectively, "Appellees") first began studying
PCSK9 in early 2005. This research resulted in the
development of Appellees' drug Repatha' which uses
the active ingredient "evolocumab." Evo-locumab is
a monoclonal antibody that targets PCSK9 to prevent it from
destroying LDL-R proteins. Appellees filed for FDA approval
on August 27, 2014. The FDA approved Repatha in August 2015.
patents at issue, both of which share the same specification,
are entitled "Antigen binding proteins to proprotein
convertase subtilisin kexin type 9
(PCSK9)." The '165 patent issued on September 9,
2014, and the '741 patent issued on October 14, 2014. The
patents have an undisputed priority date of January 9, 2008.
Appellants' Br. 12. The relevant claims cover the entire
genus of antibodies that bind to specific amino acid residues
on PCSK9 and block PCSK9 from binding to
LDL-Rs. The patents do not specifically claim
Repatha, or any other antibody, by amino acid sequence. Claim
1 of the '165 patent is representative. It recites:
An isolated monoclonal antibody, wherein, when bound to
PCSK9, the monoclonal antibody binds to at least one of the
following residues: S153, I154, P155, R194, D238, A239, I369,
S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID
NO:3, and wherein the monoclonal antibody blocks binding of
PCSK9 to LDL[-]R.
'165 patent col. 427 ll. 47-53.
patents disclose the trial-and-error process Appellees used
to generate and screen antibodies that bind to PCSK9 and
block PCSK9 from binding to LDL-Rs. Id. at col. 73
l. 29-col. 124 l. 31. In particular, the specification
explains that to discover the claimed antibodies, 3, 000
human monoclonal antibodies were "rescreened for binding
to wild-type PCSK9 to confirm stab[ility], "
id. at col. 78 ll. 4-6, which were eventually
narrowed to "85 antibodies that blocked interaction
between the PCSK9 . . . and the LDLR [at] greater than 90%,
" id. at col. 80 ll. 35-37. The specification
also discloses the three-dimensional structures, obtained via
x-ray crystallography, of two antibodies known to bind to
residues recited in the claims-21B12 (Repatha) and 31H4.
Id. at fig. 3E, fig. 3JJ, col. 99 l. 29-col. 103 l.
60. Finally, the specification discloses the amino acid
sequences of twenty-two other antibodies that "bin"
with Repatha or 31H4, meaning they compete with these
antibodies for binding to PCSK9. Id. at figs. 2A-2D,
figs. 3A-3JJ, col. 88 l. 30-col. 89 l. 37.
September 2007, Appellants also started exploring antibodies
targeting PCSK9. This research resulted in development of
Praluent. The active ingredient in Praluent is a monoclonal
antibody that targets PCSK9 to prevent it from binding to and
destroying LDL-R proteins. The LDL-R proteins then extract
LDL-C thereby lowering overall LDL-C levels in the
bloodstream. In November 2011, the PTO issued Appellants a
patent that claimed Praluent by its amino acid sequence.
Appellants filed for FDA approval of Praluent in November
2014. The FDA approved Praluent in July 2015.
October 2014, Appellees sued Appellants, claiming that
Praluent infringed the patents in suit. Appellants stipulated
to infringement but challenged the patents' validity on