Amgen Inc. v. Sanofi

United States Court of Appeals
for the Federal Circuit
______________________
AMGEN INC., AMGEN MANUFACTURING
LIMITED, AMGEN USA, INC.,
Plaintiffs-Appellees
v.
SANOFI, AVENTISUB LLC, REGENERON
PHARMACEUTICALS INC., SANOFI-AVENTIS U.S.,
LLC,
Defendants-Appellants
______________________
2017-1480
______________________
Appeal 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.
______________________
Decided: October 5, 2017
______________________
DARYL 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.
2 AMGEN INC. v. SANOFI
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.
PAUL 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, Washington, DC.
DUANE CHRISTOPHER MARKS, Eli Lilly and Company,
Indianapolis, IN, for amicus curiae Eli Lilly and Compa-
ny. Also represented by GREGORY ALAN COX, GILBERT
VOY, ALEXANDER WILSON.
BARBARA ANNE JONES, AARP Foundation Litigation,
Pasadena, CA, for amici curiae AARP and AARP Founda-
tion.
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 York, NY.
DAVID 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
AMGEN INC. v. SANOFI 3
Thompson, M.D., Rosa DeBernardo, Alina Wilson. Also
represented by MICHAEL JAY, Santa Monica, CA.
______________________
Before PROST, Chief Judge, TARANTO and HUGHES,
Circuit Judges.
PROST, Chief Judge.
Appellants Sanofi, Aventisub LLC, Regeneron Phar-
maceuticals Inc., and Sanofi-Aventis U.S., LLC (collective-
ly, “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 Appel-
lants’ Praluent® alirocumab (“Praluent”). 1 In particular,
Appellants argue that the district court improperly ex-
cluded 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’ evi-
dence 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 de-
scription and no enablement. We affirm the district
court’s grant of Appellees’ JMOL of non-obviousness.
Finally, we vacate the district court’s permanent injunc-
tion.
1 Appellants stipulated to infringement of the ’165
and ’741 patents. Appellants’ Br. 11.
4 AMGEN INC. v. SANOFI
I
A
The 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 cardio-
vascular 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 pa-
tient’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 recep-
tors, or LDL-Rs) that are responsible for extracting LDL-
C from the bloodstream.
Appellees 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.
The two patents at issue, both of which share the
same specification, are entitled “Antigen binding proteins
to proprotein convertase subtilisin kexin type 9
(PCSK9).” 2 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
2 All references are to the ’165 patent unless other-
wise indicated.
AMGEN INC. v. SANOFI 5
entire genus of antibodies that bind to specific amino acid
residues on PCSK9 and block PCSK9 from binding to
LDL-Rs. 3 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.
The patents disclose the trial-and-error process Appel-
lees 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 bind-
ing to wild-type PCSK9 to confirm stab[ility],” id. at col.
78 ll. 4–6, which were eventually narrowed to “85 antibod-
ies 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
3 A “residue” is a particular amino acid along
PCSK9’s amino acid sequence. Thus, the residue “S153”
refers to the amino acid serine, located at the 153rd posi-
tion of PCSK9’s sequence.
6 AMGEN INC. v. SANOFI
compete with these antibodies for binding to PCSK9. Id.
at figs. 2A–2D, figs. 3A–3JJ, col. 88 l. 30–col. 89 l. 37.
In 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.
B
In October 2014, Appellees sued Appellants, claiming
that Praluent infringed the patents in suit. Appellants
stipulated to infringement but challenged the patents’
validity on written description, enablement, and obvious-
ness grounds.
Over the course of litigation, the district court made
several rulings and decisions that are challenged here on
appeal. First, the district court excluded all of Appellants’
post-priority-date evidence proffered to show that the
patents in suit did not provide adequate written descrip-
tion. Second, the district court instructed the jury, over
Appellants’ objection, that written description can be
satisfied “by the disclosure of a newly-characterized
antigen . . . if you find that the level of skill and
knowledge in the art of antibodies at the time of filing was
such that production of antibodies against such an anti-
gen was conventional or routine.” J.A. 1580. Third, the
district court denied Appellants’ post-trial motions seek-
ing JMOL on written description and enablement.
Fourth, the district court excluded two purported prior art
references, Novartis and Schering, for being improper
prior art and granted Appellees’ motion seeking JMOL of
AMGEN INC. v. SANOFI 7
non-obviousness. And fifth, the district court issued a
permanent injunction removing Appellants’ Praluent from
the market.
This court stayed the injunction pending appeal.
II
A
We first review whether the district court improperly
excluded Appellants’ evidence about antibodies, including
Appellants’ infringing Praluent, developed after the
patents’ priority date of January 9, 2008. Appellants
proffered this evidence to show that the patents lack 35
U.S.C. § 112 written description support. The district
court excluded this evidence, concluding that because the
evidence did not “illuminate[] the state of the art at the
time of filing,” it was not relevant “to determine whether
there is sufficient disclosure of the claimed invention.”
Amgen Inc. v. Sanofi, No. 14-1317, 2016 WL 675576, at *2
(D. Del. Feb. 18, 2016); see also J.A. 1030 (“I concluded
that, because the written description requirement is
tested as of the filing date, such evidence should be ex-
cluded.”). Because the district court’s decision was based
on a misapplication of the law, we reverse.
Section 112 states that “[t]he specification shall con-
tain a written description of the invention . . . in such full,
clear, concise, and exact terms as to enable any person
skilled in the art to which it pertains . . . to make and use
the same . . . .” This requirement ensures “that the inven-
tor actually invented the invention claimed.” Ariad
Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en banc). To show invention, a patentee must
convey in its disclosure that it “had possession of the
claimed subject matter as of the filing date.” Id. at 1350.
Demonstrating possession “requires a precise definition”
of the invention. Id. To provide this “precise definition”
for a claim to a genus, a patentee must disclose “a repre-
8 AMGEN INC. v. SANOFI
sentative number of species falling within the scope of the
genus or structural features common to the members of
the genus so that one of skill in the art can ‘visualize or
recognize’ the members of the genus.” Id.Here, the parties dispute whether a court may rely on
post-priority-date evidence to determine if a patent dis-
closes “a representative number of species.” Id. Appel-
lants argue that because the “written description
requirement protects against ‘attempts to preempt the
future before it has arrived,’” Appellants’ Br. 28 (quoting
Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)), it
“would make [no] sense if future innovators were barred
from introducing evidence of their own innovations in
written description challenges,” id. Appellees counter
that because “[w]ritten description and enablement are
judged at the time of filing,” Appellees’ Br. 34 (citing
Ariad, 598 F.3d at 1355), “post-priority-date evidence may
be relevant only if it illuminates the state of the art at the
filing date,” id. (first citing In re Koller, 613 F.2d 819, 825
(CCPA 1980); then citing In re Hogan, 559 F.2d 595, 605
(CCPA 1977)). And because Praluent and the other
antibodies Appellants proffered did not exist until after
the priority date, “they [were] not part of the state of the
art . . . and therefore cannot ‘illuminate’ it.” Id.Appellees are correct that written description is
judged based on the state of the art as of the priority date.
Ariad, 598 F.3d at 1355. Accordingly, evidence illuminat-
ing the state of the art subsequent to the priority date is
not relevant to written description. Id. Appellants,
however, are also correct that a patent claiming a genus
must disclose “a representative number of species falling
within the scope of the genus or structural features com-
mon to the members of the genus so that one of skill in
the art can ‘visualize or recognize’ the members of the
genus.” Id. at 1351. Evidence showing that a claimed
genus does not disclose a representative number of spe-
cies may include evidence of species that fall within the
AMGEN INC. v. SANOFI 9
claimed genus but are not disclosed by the patent, and
evidence of such species is likely to postdate the priority
date. If such evidence predated the priority date, it might
well anticipate the claimed genus.
Here, Appellants sought to introduce evidence not to
illuminate the state of the art on the priority date but to
show that the patent purportedly did not disclose a repre-
sentative number of species. Appellants’ Br. 12. As a
logical matter, such evidence is relevant to the represent-
ativeness question. Simply, post-priority-date evidence of
a particular species can reasonably bear on whether a
patent “fails to disclose a representative number of spe-
cies falling within the scope of the genus or structural
features common to the members of the genus so that one
of skill in the art can ‘visualize or recognize’ the members
of the genus.” Ariad, 598 F.3d at 1350.
We have not ruled on that question to date, but the
common-sense logic of admissibility finds support in
AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc.,
759 F.3d 1285 (Fed. Cir. 2014). There, Centocor, the
accused infringer of AbbVie’s functional claim to a genus
of antibodies, stipulated to infringement and challenged
validity based on written description. Centocor argued
that the antibodies disclosed in AbbVie’s patents were
“not representative of the entire genus,” id. at 1298, and it
relied heavily on its own accused antibody to support the
unrepresentativeness argument, introducing evidence
that its antibody “differ[ed] considerably from
the . . . antibodies described in [the asserted] patents,” id.
at 1300. The jury found that the patents lacked adequate
written description, and both the district court and this
court relied heavily on that evidence in upholding the
invalidity verdict. See AbbVie, 759 F.3d at 1301; Abbott
GmBH & Co., KG v. Centocor Ortho Biotech, Inc., 971
F.3d 171, 176–80 (D. Mass. 2013). That is significant
because, at the time of trial, the timing of Centocor’s
antibody in relation to AbbVie’s priority date was unset-
10 AMGEN INC. v. SANOFI
tled: the PTO, in an interference, had found that Cento-
cor’s antibody postdated AbbVie’s invention, as AbbVie
argued, and the subsequent litigation of the question
under 35 U.S.C. § 146 was unresolved. See Abbott, 870 F.
Supp. 2d at 246. The Centocor antibody, in short, was a
basis for the unrepresentativeness ruling without regard
to whether it postdated the patent’s priority date.
Appellees argue, and the district court held, that our
predecessor court’s decision in In re Hogan prohibits the
use of post-priority-date evidence to show that a patent
fails to disclose a representative number of species. See
Appellees’ Br. 34 (“[P]ost-priority-date evidence may be
relevant only if it illuminates the state of the art at the
filing date.”); J.A. 1032 (“By giving its imprimatur to the
jury’s verdict [in AbbVie], the Federal Circuit arguably
departed from its own precedent, established in In re
Hogan, 559 F.2d 595 (CCPA 1977), that later-developed or
later-discovered products should not be used to test
compliance with 35 U.S.C. § 112[, ¶] 1.”). But the district
court and Appellees misread In re Hogan by conflating the
difference between post-priority-date evidence proffered to
illuminate the post-priority-date state of the art, which is
improper, with post-priority-date evidence proffered to
show that a patent fails to disclose a representative
number of species. In re Hogan prohibits the former but
is silent with respect to the latter.
In In re Hogan, the U.S. Patent and Trademark Office
(“PTO”) rejected an application directed to “Solid Polymer
of Olefins” for failing to enable the claimed invention. 559
F.3d at 597. The relevant claim at issue recited, in its
entirety, “[a] normally solid homopolymer of 4-methyl-1-
pentene.” Id. The application disclosed “a method of
making the crystalline form” of the claimed homopolymer
which was “the only then existing way to make such a
polymer.” Id. at 606. The PTO rejected the application,
however, because the application did not disclose a sec-
ond, “amorphous form” of making the polymer “which . . .
AMGEN INC. v. SANOFI 11
did not exist” as of the priority date. Id. Our predecessor
court reversed the PTO, holding that “[t]o now say that
appellants should have disclosed in 1953 the amorphous
form which on this record did not exist until 1962, would
be to impose an impossible burden on inventors and thus
on the patent system.” Id. Further, because the appli-
cant had claimed the homopolymer and not a particular
method of making the polymer, the court further held that
“[t]o restrict appellants to the crystalline form disclosed,
under such circumstances, would be a poor way to stimu-
late invention, and particularly to encourage its early
disclosure.” Id.
Here, unlike in In re Hogan, Appellants were not of-
fering post-priority-date evidence to show that Appellees’
claimed genus is not enabled because of a change in the
state of the art. Instead, Appellants offered Praluent and
other post-priority-date antibodies to argue that the
claimed genus fails to disclose a representative number of
species. As explained above, the use of post-priority-date
evidence to show that a patent does not disclose a repre-
sentative number of species of a claimed genus is proper.
It was thus legal error for the district court to categorical-
ly preclude all of Appellants’ post-priority-date evidence of
Praluent and other antibodies. Accordingly, we reverse
the district court’s decision and remand for a new trial on
written description.
For many of the same reasons, the district court’s im-
proper exclusion of post-priority-date evidence requires a
new trial on enablement as well. Under the enablement
requirement, “the specification of a patent must teach
those skilled in the art how to make and use the full scope
of the claimed invention without undue experimentation.”
Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1365
(Fed. Cir. 1997). Appellants purportedly sought to intro-
duce post-priority-date evidence showing that Appellees
engaged in lengthy and potentially undue experimenta-
tion to enable the full scope of the claims. Such evidence
12 AMGEN INC. v. SANOFI
could have been relevant to determining if the claims
were enabled as of the priority date and should not have
been excluded simply because it post-dated the claims’
priority date. See, e.g., White Consol. Indus., Inc. v. Vega
Servo-Control, Inc., 713 F.2d 788, 791 (Fed. Cir. 1983)
(determining, based on post-priority-date expert evidence
that “1½ to 2 man years of effort” would be needed to
practice an invention, that patent claims were not ena-
bled). Accordingly, we reverse the district court’s decision
excluding Appellants’ post-priority-date evidence of
enablement and remand for a new trial on enablement.
B
We next consider whether the trial court improperly
instructed the jury on written description. The district
court correctly instructed the jury that in order to satisfy
the written description requirement, a patentee may
disclose either a representative number of species falling
within the scope of the genus or disclose structural fea-
tures common to the members of the genus so that one of
skill in the art can visualize or recognize the members of
the genus. Additionally, however, the district court
further instructed the jury that:
In the case of a claim to antibodies, the correlation
between structure and function may also be satis-
fied by the disclosure of a newly characterized an-
tigen by its structure, formula, chemical name, or
physical properties if you find that the level of
skill and knowledge in the art of antibodies at the
time of filing was such that production of antibod-
ies against such an antigen was conventional or
routine.
J.A. 1580. Appellants argue that this instruction is
erroneous because disclosing an antigen does not satisfy
the written description requirement for a claim to an
antibody. Appellees respond that the instruction was
proper because it merely restates the law as set forth in
AMGEN INC. v. SANOFI 13
Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed.
Cir. 2002), Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir.
2004), and Centocor Ortho Biotech, Inc. v. Abbott Labs.,
636 F.3d 1341 (Fed. Cir. 2011). As discussed below, the
district court’s instruction is not legally sound and is not
based on any binding precedent. Accordingly, we con-
clude that the instruction was improper.
The district court’s instruction traces its roots back to
PTO guidelines first discussed by this court in Enzo
Biochem. That case involved claims directed to nucleic
acid probes that were defined by their function of selec-
tively hybridizing to the genetic material of certain bacte-
ria. Enzo Biochem, 323 F.3d at 960. We noted in that
case that not “all functional descriptions of genetic mate-
rial fail to meet the written description requirement.” Id.
at 964. Instead, we cited the PTO’s Guidelines on written
description for the proposition that “functional character-
istics when coupled with a known or disclosed correlation
between function and structure” may satisfy the written
description requirement. Id. (citing Guidelines for Exam-
ination of Patent Applications Under the 35 U.S.C. 112, ¶
1, “Written Description” Requirement 66 Fed. Reg. 1099–
01, 1106 (“Guidelines”)). 4 We further noted, in dicta, that
4 The Guidelines were first published on Feb. 28,
2000 as the Revised Interim Written Description Guide-
lines Training Materials. In March 2008, the training
materials were revised and republished as Written De-
scription Training Materials, Revision 1, available at
https://www.uspto.gov/sites/default/files/web/menu/
written.pdf. The PTO now notes that the Training Mate-
rials have been “archived” and that “[a] new version will
be prepared to reflect changes in the law since 2008,
including any required clarifications due to developments
in the law relating to 35 U.S.C. 112.” Examination Guid-
ance and Training Materials, United States Patent and
14 AMGEN INC. v. SANOFI
“the PTO would find compliance with 112, [¶] 1, for a
claim to an isolated antibody capable of binding to antigen
X, notwithstanding the functional definition of the anti-
body, in light of the well-defined structural characteristics
for the five classes of antibody, the functional characteris-
tics of antibody binding, and the fact that the antibody
technology is well developed and mature.” Id. (citing
Synopsis of Application of Written Description Guidelines,
at 60, available at https://web.archive.org/
web/20041101121800/http://www.uspto.gov/web/menu/wri
tten.pdf).
In Noelle, the patent owner claimed an antibody and
sought to claim priority to an earlier filed patent. 355
F.3d at 1349. Noelle argued that “because antibodies are
defined by their binding affinity to their antigens, he
sufficiently described [the claimed antibody] by stating
that it binds to [a disclosed antigen].” Id. We rejected this
argument and concluded that the claims were not entitled
to the earlier priority date because “Noelle failed to dis-
close the structural elements of [the] antibody or antigen
in his earlier . . . application.” Id. In reaching this con-
clusion, we acknowledged that according to Enzo, “as long
as an applicant has disclosed a ‘fully characterized anti-
gen,’ either by its structure, formula, chemical name, or
physical properties, or by depositing the protein in a
public depository, the applicant can then claim an anti-
body by its binding affinity to that described antigen.” Id.But because Noelle did not disclose structure for the
antibody or the antigen, we did not rely on Enzo to find
that the patentee had satisfied the written description
requirement.
Trademark Office, available at https://www.uspto.
gov/patent/laws-and-regulations/examination-
policy/examination-guidance-and-training-materials.
AMGEN INC. v. SANOFI 15
Then, in Centocor, we examined Enzo and Noelle as
well as the PTO Guidelines and held that the antibody
claims at issue were invalid for lack of written descrip-
tion. 636 F.3d at 1351–53. We noted that under the
PTO’s Guidelines, “an applicant can claim an antibody to
novel protein X without describing the antibody when
(1) the applicant fully discloses the novel protein and
(2) generating the claimed antibody is so routine that
possessing the protein places the applicant in possession
of an antibody.” Id. at 1351–52. The patentee there had
claimed a “class of antibodies containing a human varia-
ble region that have particularly desirable therapeutic
properties: high affinity, neutralizing activity, and A2
specificity.” Id. at 1352. The claimed antibodies could
bind to “the human TNF-α protein.” Id. at 1351. The
patentee there argued that under Noelle and the PTO
Guidelines, “fully disclosing the human TNF-α protein
provides adequate written description for any antibody
that binds to human TNF-α.” Id. We held, however, that
even though the patentee had disclosed the human TNF-α
protein, the claims were still invalid. Id. at 1352–53. We
questioned the propriety of the “newly characterized
antigen” test and concluded that instead of “analogizing
the antibody-antigen relationship to a ‘key in a lock,’” it
was more apt to analogize it to a lock and “a ring with a
million keys on it.” Id. at 1352.
Centocor is the only case where we examined the
“newly characterized antigen” test in some detail. The
test was not central to the holding in either Enzo or Noelle
and neither case explored it in much depth. And in
Noelle, we cautioned that “each case involving the issue of
written description[] ‘must be decided on its own facts.
Thus, the precedential value of cases in this area is ex-
tremely limited.’” Id. at 1349 (quoting Vas–Cath Inc. v.
Mahurkar, 935 F.2d 1555, 1562 (Fed. Cir. 1991)).
The essential problem with the jury instruction given
in this case is that it effectively permitted the jury to
16 AMGEN INC. v. SANOFI
dispense with the required finding of a “written descrip-
tion of the invention.” 35 U.S.C. § 112. Our en banc
decision in Ariad, reflecting earlier decisions such as
Schriber-Schroth Co. v. Cleveland Trust Co., 305 U.S. 47,
56–57 (1938), and In re Ruschig, 379 F.2d 990, 991–95
(CCPA 1967), made clear that, to satisfy the statutory
requirement of a description of the invention, it is not
enough for the specification to show how to make and use
the invention, i.e., to enable it. Ariad, 598 F.3d at 1345–
46, 1347–48. Yet the instruction in this case invites just
that improper equation. A jury would naturally under-
stand the instruction to permit it to deem any antibody
within the claim adequately described merely because the
antibody could easily be “produc[ed]” (and, implicitly,
used as an antibody). J.A. 1580 (requirement “may . . . be
satisfied” if antigen is newly characterized and “produc-
tion of antibodies against such an antigen was conven-
tional or routine”). Indeed, the instruction does not even
require any particular antibody to be easily made; all it
requires is that “production of antibodies”—some, not
all—“against [a newly characterized] antigen” be conven-
tional or routine. By permitting a finding of adequate
written description merely from a finding of ability to
make and use, the challenged sentence of the jury instruc-
tion in this case ran afoul of what is perhaps the core
ruling of Ariad.
We cannot say that this particular context, involving
a “newly characterized antigen” and a functional genus
claim to corresponding antibodies, is one in which the
underlying science establishes that a finding of “make and
use” (routine or conventional production) actually does
equate to the required description of the claimed products.
For us to draw such a conclusion, and transform a factual
issue into a legally required inference, we would have to
declare a contested scientific proposition to be so settled
as to be entitled to judicial notice. That we cannot do.
AMGEN INC. v. SANOFI 17
An adequate written description must contain enough
information about the actual makeup of the claimed
products—“a precise definition, such as by structure,
formula, chemical name, physical properties, or other
properties, of species falling within the genus sufficient to
distinguish the genus from other materials,” which may
be present in “functional” terminology “when the art has
established a correlation between structure and function.”
Ariad, 598 F.3d at 1350. But both in this case and in our
previous cases, it has been, at the least, hotly disputed
that knowledge of the chemical structure of an antigen
gives the required kind of structure-identifying infor-
mation about the corresponding antibodies. See, e.g., J.A.
1241 (549:5–16) (Appellants’ expert Dr. Eck testifying
that knowing “that an antibody binds to a particular
amino acid on PCSK9 . . . does not tell you anything at all
about the structure of the antibody”); J.A. 1314 (836:9–11)
(Appellees’ expert Dr. Petsko being informed of Dr. Eck’s
testimony and responding that “[m]y opinion is that [he’s]
right”); Centocor, 636 F.3d at 1352 (analogizing the anti-
body-antigen relationship as searching for a key “on a
ring with a million keys on it”) (internal citations and
quotation marks omitted).
A court may take judicial notice of a fact only when it
is either “generally known” or “accurately and readily
[discernible] from sources whose accuracy cannot reason-
ably be questioned.” Fed. R. Evid. 201(b); see B.V.D.
Licensing Corp. v. Body Action Design, Inc., 846 F.2d 727,
728 (Fed. Cir. 1988) (“Courts may take judicial notice of
facts of universal notoriety, which need not be proved, and
of whatever is generally known within their jurisdictions.”
(citing Brown v. Piper, 91 U.S. 37 (1875))). Because the
scientific premise behind the “newly characterized anti-
gen” test stated in the instruction in this case was neither
“generally known” nor “accurately and readily” ascertain-
able, we cannot take judicial notice of the premise and
displace the required fact finding with what amounts to a
18 AMGEN INC. v. SANOFI
rule of law. We are not required to conclude otherwise,
and depart from the plain restriction on judicial notice, by
the statement in Enzo, which was unnecessary to its
holding, about what PTO Guidelines indicated the PTO
would find.
Further, the “newly characterized antigen” test flouts
basic legal principles of the written description require-
ment. Section 112 requires a “written description of the
invention.” But this test allows patentees to claim anti-
bodies by describing something that is not the invention,
i.e., the antigen. The test thus contradicts the statutory
“quid pro quo” of the patent system where “one describes
an invention, and, if the law’s other requirements are
met, one obtains a patent.” Ariad, 598 F.3d at 1345.
Indeed, we have generally eschewed judicial exceptions to
the written description requirement based on the subject
matter of the claims. See Univ. of Rochester v. G.D. Searle
& Co., 358 F.3d 916, 925 (Fed. Cir. 2004) (noting that “the
statute applies to all types of inventions”). And Congress
has not created a special written description requirement
for antibodies as it has, for example, for plant patents.
See, e.g., 35 U.S.C. § 162 (exempting plant patents from
§ 112 “if the description is as complete as is reasonably
possible”).
For those reasons, it was improper for the district
court to instruct the jury as it did in the sentence at issue
here. On remand, the district court should amend its jury
instructions accordingly.
C
Next, we consider whether the district court improp-
erly denied Appellants’ post-trial motion seeking JMOL of
no written description and no enablement. Appellants
argue that the asserted patents fail to provide written
description support because they merely teach “where an
antibody binds to an antigen” which “tells one nothing
about the structure of any other antibody.” Appellants’
AMGEN INC. v. SANOFI 19
Br. 53. Appellants also argue that the patents are not
enabling because one must engage in several steps includ-
ing a trial-and-error process of generating and screening
antibodies, performing x-ray crystallography, and still
potentially failing to “get a sufficient number of antibod-
ies that enable the full scope of the claims.” Id.
JMOL is proper when “a reasonable jury would not
have a legally sufficient evidentiary basis to find for the
party.” Fed. R. Civ. P. 50(a)(1). “A determination that a
patent is invalid for failure to meet the written descrip-
tion requirement of 35 U.S.C. § 112, ¶ 1 is a question of
fact, and we review a jury’s determinations of facts relat-
ing to compliance with the written description require-
ment for substantial evidence.” Ariad, 598 F.3d at 1355
(citing PIN/NIP, Inc. v. Platte Chem. Co., 304 F.3d, 1235,
1243 (Fed. Cir. 2002)). And “[t]o be enabling, the specifi-
cation of a patent must teach those skilled in the art how
to make and use the full scope of the claimed invention
without undue experimentation.” Genentech, 108 F.3d at
1365 (internal quotation marks omitted). But
“[e]nablement is not precluded by the necessity for some
experimentation such as routine screening” of antibodies.
In re Wands, 858 F.2d 731, 736–37 (Fed. Cir. 1988).
Here, the jury did not hear relevant post-priority-date
evidence regarding written description and enablement.
This evidence may show, for example, that practicing the
invention did not require undue experimentation or that
the disclosed species are representative of the claimed
genus. Because we are presented with an incomplete
record on these issues, the court is unable to determine
whether the jury would have a “legally sufficient eviden-
tiary basis” to determine if the patents provide sufficient
written description or if the claims are enabled. Fed. R.
Civ. P. 50(a)(1). We therefore reject Appellants’ argu-
ments and conclude that Appellants are not entitled to
JMOL of no written description and no enablement.
20 AMGEN INC. v. SANOFI
D
We next address whether the district court improperly
granted Appellees’ JMOL of non-obviousness. Because
the district court correctly excluded Appellants’ proffered
references as improper prior art, we conclude that the
district court’s grant of Appellees’ motion seeking JMOL
of non-obviousness was proper.
During litigation, Appellants sought to invalidate the
asserted patents by proffering two published PCT applica-
tions: Novartis (WO 2008/12563) and Schering (WO
2009/055783). Neither reference predates the January 9,
2008 priority date of the asserted patents. But both
applications claim priority to provisional applications that
do predate the asserted patents’ priority date. 5 In the
district court, Appellants attempted to rely on these PCT
applications as pre-AIA § 102(e)(1) art. 35 U.S.C.
§ 102(e)(1) (providing “an application for patent, pub-
lished under section 122(b), by another filed in the United
States before the invention by the applicant for patent”).
Appellees argued, however, that the references were not
proper prior art because Appellants had not shown that
the provisional applications provided written description
support for the claims of the PCT applications. The
district court agreed, excluded the two references, and
granted JMOL of non-obviousness.
Appellants argue that the district court erred by mis-
applying our decision in Dynamic Drinkware, LLC v.
National Graphics, Inc., 800 F.3d 1375 (Fed. Cir. 2015).
According to Appellants, that case only related to whether
“a patent asserted as prior art under § 102(e)(2) was prior
art as of the filing date of a parent application” but does
5 It is undisputed that the provisional applications
are not themselves prior art under § 102(e)(1) because
they are not applications published under § 122(b).
AMGEN INC. v. SANOFI 21
not relate to whether “published patent applications
asserted as prior art under § 102(e)(1)” were prior art as
of the filing date of their provisional applications. Appel-
lants’ Br. 46. Appellants are incorrect.
In Dynamic Drinkware, we clearly explained that for
a non-provisional application to claim priority to a provi-
sional application for prior art purposes, “the specification
of the provisional [application] must contain a written
description of the invention . . . in such full, clear, concise,
and exact terms, to enable an ordinarily skilled artisan to
practice the invention claimed in the non-provisional
application.” 800 F.3d at 1378. Further, we have previ-
ously stated that “for the non-provisional utility applica-
tion to be afforded the priority date of the provisional
application, . . . the written description of the provisional
must adequately support the claims of the non-provisional
application.” New Railhead Mfg., L.L.C. v. Vermeer Mfg.
Co., 298 F.3d 1290, 1294 (Fed. Cir. 2002).
Here, Appellants challenged the district court’s appli-
cation of Dynamic Drinkware, but did not proffer any
evidence showing that the provisional applications con-
tained representative species or common structural
elements sufficient to satisfy the written description
requirement for the monoclonal antibodies claimed in the
PCT applications. Similarly, Appellants provided no
evidence that the claims of the PCT applications were
enabled by the provisional application. Because the
district court properly excluded Novartis and Schering
under Dynamic Drinkware, the court’s grant of JMOL of
non-obviousness was proper.
E
Finally, we address the district court’s permanent in-
junction removing Appellants’ Praluent from the market.
As noted earlier, we stayed this injunction pending reso-
lution of this appeal. Because we vacate the district
court’s judgment as to written description and enable-
22 AMGEN INC. v. SANOFI
ment and remand for a new trial, we also vacate the
permanent injunction.
We write to note, however, that the district court’s
permanent injunction analysis in this case was improper
for two distinct reasons. First, the district court misap-
plied eBay, Inc. v. MercExchange, L.L.C., 547 U.S. 388(2006). In that case, the Supreme Court explained that:
[A] plaintiff seeking a permanent injunction must
satisfy a four-factor test before a court may grant
such relief. A plaintiff must demonstrate: (1) that
it has suffered an irreparable injury; (2) that rem-
edies available at law, such as monetary damages,
are inadequate to compensate for that injury;
(3) that, considering the balance of hardships be-
tween the plaintiff and defendant, a remedy in
equity is warranted; and (4) that the public inter-
est would not be disserved by a permanent injunc-
tion.
Id. at 391 (emphases added). Here, the district court
concluded that issuing a permanent injunction would
disserve the public interest. Despite that finding, the
court issued a permanent injunction. J.A. 33–34. That
was in clear violation of eBay. If a plaintiff fails to show
“that the public interest would not be disserved by a
permanent injunction,” then the district court may not
issue an injunction. eBay, 547 U.S. at 391.
Second, the district court also erred in its analysis of
the “public interest” factor. In reaching its conclusion
that the injunction would disserve the public, the district
court weighed “being a patent holder and a verdict win-
ner” on the one hand and “taking an independently devel-
oped, helpful drug off the market” on the other. J.A. 33.
It then “conclude[d] that the public interest of having a
choice of drugs should prevail.” J.A. 33–34.
AMGEN INC. v. SANOFI 23
But eliminating a choice of drugs is not, by itself, suf-
ficient to disserve the public interest. Under such an
approach, courts could never enjoin a drug because doing
so would always reduce a choice of drugs. That, of course,
is not the law. See 35 U.S.C. § 271(e)(4)(B) (“[I]njunctive
relief may be granted against an infringer to prevent the
commercial manufacture, use, offer to sell, or sale within
the United States or importation into the United States of
an approved drug, veterinary biological product, or biolog-
ical product.”). We previously rejected such reasoning in
WBIP, LLC v. Kohler Co. and explained that:
The district court’s decision is based on its reason-
ing that having more manufacturers of a lifesav-
ing good in the market is better for the public
interest. But this reasoning is true in nearly eve-
ry situation involving such goods, such that, if it
alone is sufficient, it would create a categorical
rule denying permanent injunctions for life-saving
goods, such as many patented pharmaceutical
products. As the Supreme Court has warned, cat-
egorical rules regarding permanent injunctions
are disfavored.
829 F.3d 1317, 1343 (Fed. Cir. 2016). Just as a patent
owner does not automatically receive an injunction merely
by proving infringement, see eBay, 547 U.S. at 394, an
accused infringer cannot escape an injunction merely by
producing infringing drugs. Accordingly, a reduction in
choice of drugs cannot be the sole reason for a district
court to deny an injunction.
III
For the foregoing reasons, we conclude that the dis-
trict court erred by (i) categorically excluding Appellants’
evidence of written description and enablement, and
(ii) improperly instructing the jury on written description.
For these reasons we reverse the district court’s decision
to exclude Appellants’ evidence of written description and
24 AMGEN INC. v. SANOFI
enablement and remand for a new trial consistent with
this opinion. We conclude that Appellants are not enti-
tled to JMOL of no written description and no enable-
ment. We also conclude that the district court properly
granted Appellees’ JMOL of non-obviousness. Finally, we
vacate the permanent injunction and remand for further
proceedings consistent with this opinion.
REVERSED IN PART, AFFIRMED IN PART,
VACATED IN PART, AND REMANDED