Eli Lilly and Company v. Actavis Elizabeth

NOTE: This disposition is nonprecedential
United States Court of Appeals
for the Federal Circuit
__________________________
ELI LILLY AND COMPANY,
Plaintiff-Appellant,
v.
ACTAVIS ELIZABETH LLC,
Defendant-Appellee,
AND
SUN PHARMACEUTICAL INDUSTRIES, LTD.,
Defendant-Appellee,
AND
SANDOZ, INC.,
Defendant-Appellee,
AND
MYLAN PHARMACEUTICALS INC.,
Defendant-Appellee,
AND
APOTEX INC.,
Defendant-Appellee,
AND
AUROBINDO PHARMA LTD.,
Defendant-Appellee,
ELI LILLY AND COMPANY v. ACTAVIS 2
AND
TEVA PHARMACEUTICALS USA, INC.,
Defendant-Appellee.
__________________________
2010-1500
__________________________
Appeal from the United States District Court for the
District of New Jersey in Case No. 07-CV-3770, Judge
Dennis M. Cavanaugh.
___________________________
Decided: July 29, 2011
___________________________
CHARLES E. LIPSEY, Finnegan, Henderson, Farabow,
Garrett & Dunner, LLP, of Reston, Virginia, argued for the
plaintiff-appellant. With him on the brief were L. SCOTT
BURWELL; ROBERT D. BAJEFSKY, LAURA P. MASUROVSKY, and
J. DEREK MCCORQUINDALE, of Washington, DC; and
JENNIFER S. SWAN, of Palo Alto, California. Of counsel on
the brief were MARK J. STEWART and TONYA L. COMBS, Eli
Lilly and Company, of Indianapolis, Indiana.
WILLIAM A. RAKOCZY, Rokaczy Molino Mazzochi Siwik
LLP, of Chicago, Illinois, argued for defendants-appellees
Sun Pharmaceutical Industries Ltd, Sandoz Inc. and
Aurobindo Pharma, Ltd. With him on the brief for defen-
dant-appellee Aurobindo Pharam Ltd was CHRISTINE J.
SIWIK. Of counsel were GREGORY A. DUFF and ROBERT M.
TEIGEN. On the brief were KEITH V. ROCKEY and KATHLEEN
A. LYONS, Rockey Depke, & Lyons, LLP, of Chicago, Illinois,
for defendant-appellee Sandoz Inc.; and THOMAS J. PARKER
and VICTORIA E. SPATARO, Alston & Bird LLP, of New York,
3 ELI LILLY AND COMPANY v. ACTAVIS
New York for defendant-appellee Mylan Pharmaceuticals
Inc.; ALAN B. CLEMENT, HUGH S. BALSAM, KEITH D. PARR,
ANDREA L. WAYDA, SCOTT, B. FEDER, KEVIN M. NELSON and
MYOKA K. GOODIN, Locke Lord Bissell & Liddell LLP, of
New York, New York, for defendant-appellee Apotex,Inc. Of
counsel on the brief was SHASHANK UPADHYE, Apotex, Inc, of
Toronto, Canada, for defendant-appellee Apotex, Inc. Also
on the brief were JAMES F. HURST, GAIL STANDISH, PETER E.
PERKOWSKI and ANDREW C. NICHOLS, Winston & Strawn
LLP, of Chicago, Illinois, for defendant-appellee Sun
Pharamaceutical Industries, Ltd. Of counsel was STEFFEN
JOHNSON.
CHAD A. LANDMON, Axinn, Veltop & Harkrider lLLP, of
Hartford, Connecticut, for defendant-appelle Actavis Eliza-
beth LLC. With him on the brief was MATTHEW J. BECKER.
__________________________
Before NEWMAN, FRIEDMAN, ∗ AND LOURIE, Circuit Judges.
NEWMAN, Circuit Judge.
This case arises on the filing by each of the defendants
of an Abbreviated New Drug Application (ANDA), accompa-
nied by a Hatch-Waxman Act “Paragraph IV certification”
challenging the validity and enforceability and asserting
non-infringement of United States Patent No. 5,658,590 (the
’590 patent) owned by Eli Lilly and Company. The ’590
patent is directed to the use of the drug atomoxetine to treat
attention-deficit/hyperactivity disorder (ADHD). Lilly
obtained federal regulatory approval from the Food and
Drug Administration (FDA), and markets the product for
∗
Circuit Judge Friedman heard oral argument in this
appeal, but died on July 6, 2011 and did not participate in
the final decision. The case was decided by the remaining
judges of the panel, in accordance with Fed. Cir. Rule 47.11.
ELI LILLY AND COMPANY v. ACTAVIS 4
this use, with the brand name Strattera®. The defendants
seek to sell generic counterparts of this drug before the
expiration date of the ’590 patent.
The United States District Court for the District of New
Jersey sustained the ’590 patent against the defendants’
challenges on the grounds of inequitable conduct, anticipa-
tion, obviousness, and non-enablement. However, the court
held the claims invalid for lack of utility, which the court
called “enablement/utility.” The court also held that if the
claims were valid the defendants would be liable for in-
ducement to infringe, but that they would not be liable for
contributory infringement. The ruling of invalidity for lack
of utility, and the ruling that contributory infringement
does not also apply, are reversed. The district court’s other
rulings are affirmed. 1
I
THE PATENTED INVENTION
The ’590 patent is directed to the use of the compound
tomoxetine, 2 having the chemical name (R)-(–)-N-methyl-3-
(2-methylphenoxy)-3-phenylpropylamine, for treatment of
ADHD. Claim 1 is as follows:
1. A method of treating attention-
deficit/hyperactivity disorder comprising adminis-
tering to a patient in need of such treatment an ef-
fective amount of tomoxetine.
1 Eli Lilly & Co. v. Actavis Elizabeth LLC, 676 F.
Supp. 2d 352 (D.N.J. 2009); 731 F. Supp. 2d 348 (D.N.J.
2010).
2 The common names “atomoxetine” and “tomoxetine”
are both used in the record, and are used herein as they
appear in the record.
5 ELI LILLY AND COMPANY v. ACTAVIS
Claim 1 was treated by the parties and the district court as
dispositive of the issues. At the time the ’590 patent appli-
cation was filed, tomoxetine was a known compound, de-
scribed and claimed in Lilly’s U.S. Patent No. 4,314,081,issued February 2, 1982. Tomoxetine was studied through
Phase II clinical trials for the treatment of urinary inconti-
nence, and through Phase III clinical trials for treatment of
depression. See 21 C.F.R. §312.21 (explaining Phase I,
Phase II, and Phase III clinical trial criteria). Although the
clinical trials showed that tomoxetine was safe for human
use, the product did not provide the medicinal benefits for
which it was being evaluated.
In 1993 Lilly scientists Dr. John Heiligenstein and Dr.
Gary Tollefson suggested that tomoxetine might be effective
for treatment of ADHD. ADHD is a complex neurobiological
disorder characterized by developmentally inappropriate
levels of inattention, hyperactivity, and impulsiveness. The
district court explained that the occurrence of ADHD is
wide, the cause is unknown, and the mechanism of drug
treatment is unclear. Eli Lilly, 731 F. Supp. 2d at 352-53,
366. It was explained at the trial that research concerning
ADHD is difficult because there is no animal model for
experimental evaluation of the effect of any particular
treatment.
At the time of this invention, all of the products that
were being used to treat ADHD exhibited deficiencies. The
’590 patent explains that the stimulants that were being
used require multiple doses per day, produce a rebound
effect between doses, and cause undesirable side effects; and
the tricyclic antidepressants that were being used also
produce undesirable side effects, and require careful super-
vision and dosage titration. The record states that the
suggestion of Drs. Heiligenstein and Tollefson that tomoxet-
ine might be an effective treatment for ADHD was met with
ELI LILLY AND COMPANY v. ACTAVIS 6
skepticism. However, arrangements were made to conduct
clinical tests at Massachusetts General Hospital, and on
December 1, 1994 the investigators submitted to the FDA
an Investigational New Drug (IND) application for treat-
ment of ADHD with tomoxetine. On January 3, 1995 the
FDA authorized the investigation. The ’590 patent applica-
tion was filed on January 11, 1995, and the clinical investi-
gation commenced. By May 1995 initial positive results
were obtained, and in October 1995 the investigators re-
ported their preliminary results at a meeting of the Ameri-
can Association of Child and Adolescent Psychiatry.
Clinical investigation continued over the next seven
years, including treatment of patients of various ages and
ADHD severity, determination of possible side effects and of
the cumulative effect of treatment, the development and
evaluation of formulations, schedules, and dosages, and
other studies relevant to determination of efficacy and
safety. On November 26, 2002 the FDA approved the use of
tomoxetine for treatment of ADHD in adults, children, and
adolescents, at dosages of 10, 18, 25, 40, and 60 mg/day of
oral administration; on February 14, 2005 the FDA also
approved dosages of 80 and 100 mg/day. The record states
that the product has achieved wide use.
II
OBVIOUSNESS
The defendants challenged patent validity on the ground
of obviousness, arguing that atomoxetine was a known
norepinephrine inhibitor and thus that it would have been
obvious to test this product for treatment of ADHD. The
defendants argued that the inventors simply “substituted
one potent selective norepinephrine reuptake inhibitor
(atomoxetine) for another (desipramine) known to be effec-
7 ELI LILLY AND COMPANY v. ACTAVIS
tive in treating ADHD.” Eli Lilly, 731 F. Supp. 2d at 356(quoting Defendants’ Post-Trial Brief, at 7).
The district court, discussing this argument, referred to
the reports of sudden death of children taking desipramine,
and found that these “negative reports concerning desip-
ramine. . . . must weigh to some extent away from using
atomoxetine as a potential ADHD treatment” although
“desipramine was functionally a similar compound to ato-
moxetine.” Id. at 365. The court found that “while the prior
art demonstrated that norepinephrine reuptake inhibition
was relevant to ADHD treatment, the literature does not
appear to indicate that it was alone sufficient.” Id. at 362.
The court stated that “it is impermissible to pick and choose
from any one reference only so much of it as will support a
given position, to the exclusion of other parts necessary to
the full appreciation of what such reference fairly suggests
to one of ordinary skill in the art.” Id. at 365-66 (quoting In
re Weslau, 353 F.2d 238, 241 (CCPA 1965)).
The district court observed that the entirety of the prior
art must be considered in determining obviousness. There
was no evidence that the advantageous and effective proper-
ties of atomoxetine to treat ADHD, devoid of the negative
effects of known and similar products, would have been
obvious from the prior art. The district court found that
treatment of ADHD with atomoxetine would not have been
predicted by skilled artisans with a reasonable degree of
certainty, and concluded that there was not clear and con-
vincing evidence that the effective use of atomoxetine to
treat ADHD would have been obvious to a person of ordi-
nary skill in the field of the invention.
The defendants argue that, at the very least, it would
have been “obvious to try” atomoxetine for this use. How-
ever, applying the guidance of KSR International Co. v.
ELI LILLY AND COMPANY v. ACTAVIS 8
Teleflex Inc., 550 U.S. 398 (2007), there was no evidence
that use of atomoxetine had been identified as a possible
solution to the problems of treating ADHD, nor that the
exercise of common sense would have led a person of ordi-
nary skill to test atomoxetine for treatment of ADHD. See
id. at 420-21. The evidence was contrary to the likelihood
that atomoxetine would be effective to treat ADHD, for
atomoxetine was known not to be an effective antidepres-
sant, and the known norepinephrine inhibitor despiramine
was associated with sudden death in children. The experts
for both sides were in agreement that they would not have
expected that atomoxetine would be a successful treatment
of ADHD.
We discern no error in the district court’s ruling that the
claims had not been proved invalid on the ground of obvi-
ousness.
III
ENABLEMENT/SCOPE
The defendants argue that the ’590 specification does
not enable the full scope of claim 1, pointing out that the
claim’s words “administering to the patient an effective
amount” are not limited to the formulations that are specifi-
cally exemplified in the specification. The defendants argue
that the patent enables only the immediate release products
and dosages in the specific examples, and that claim 1 is
invalid because it is not so limited. The defendants’ expert
witness testified that formulations and dosages for treat-
ment of ADHD are not routine, and thus that undue ex-
perimentation would be required to determine the specific
formulation and effective amount to be administered to a
specific patient.
9 ELI LILLY AND COMPANY v. ACTAVIS
The ’590 patent describes the formulation and admini-
stration of tomoxetine as follows:
Since tomoxetine is readily orally absorbed and
requires only once/day administration, there is little
or no reason to administer it in any other way than
orally. It may be produced in the form of a clean,
stable crystal, and thus is easily formulated in the
usual oral pharmaceutical forms, such as tablets,
capsules, suspensions, and the like. The usual
methods of pharmaceutical scientists are applicable.
It may be usefully administered, if there is any rea-
son to do so in a particular circumstance, in other
pharmaceutical forms, such as injectable solutions,
depot injections, suppositories and the like, which
are well known to and understood by pharmaceuti-
cal scientists. It will substantially always be pre-
ferred, however, to administer tomoxetine as a
tablet or capsule and such pharmaceutical forms are
recommended.
’590 patent, col. 2 ll.20-33. The patent’s description of
dosages for treatment of ADHD with tomoxetine includes:
The effective dose of tomoxetine for ADHD is in
the range from about 5 mg/day to about 100 mg/day.
The preferred adult dose is in the range from about
10 to about 80 mg/day, and a more highly preferred
adult dose is from about 20 to about 60 mg/day. The
children’s dose of course is smaller, in the range
from about 5 to about 70 mg/day, more preferably
from about 10 to about 50 mg/day. The optimum
dose for each patient, as always, must be set by the
physician in charge of the case, talking into account
the patient’s size, other medications which the pa-
ELI LILLY AND COMPANY v. ACTAVIS 10
tient requires, severity of the disorder and all of the
other circumstances of the patient.
Id. at col. 2 ll.7-19.
The district court found that “the various conceivable
formulations are standard—and they were not part of the
basis for the invention’s patentability.” Eli Lilly, 731 F.
Supp. 2d at 375. The court observed that the particular
dosage form is not the invention, and is routinely deter-
mined:
a dosage formulator as defined by the parties—a
scientist with at least a bachelor’s degree in phar-
macy or some closely related field, at least three to
five years of work experience in developing a par-
ticular pharmaceutical dosage form, and the ability
to consult with others skilled in other particular
disciplines (e.g., physicians, analytical chemists,
and biopharmaceutical scientists)—would be able to
do so without undue experimentation.
Id. at 376. In In re Wands, 858 F.2d 731 (Fed. Cir. 1988),
this court identified several factors that may assist in
determining whether experimentation is “undue”:
(1) the quantity of experimentation necessary, (2)
the amount of direction or guidance presented, (3)
the presence or absence of working examples, (4) the
nature of the invention, (5) the state of the prior art,
(6) the relative skill of those in the art, (7) the pre-
dictability or unpredictability of the art, and (8) the
breadth of the claims.
858 F.2d at 737. The district court applied this precedent,
and concluded that “reliance on formulation-related disclo-
11 ELI LILLY AND COMPANY v. ACTAVIS
sures in the prior art [is] appropriate.” Eli Lilly, 731 F.
Supp. 2d at 375.
The defendants cite ALZA Corp. v. Andrx Pharmaceuti-
cals LLC, 603 F.3d 935 (Fed. Cir. 2010), in which this court
found that the patent did not “provide sufficient guidance
for a person of ordinary skill in the art to make the non-
osmotic dosage forms as claimed.” Id. at 940. However, in
that case the court described the field of ascending release
dosage forms as “not mature” and “a ‘breakaway’ from the
prior art.” Id. at 941. Such characteristics were not here
demonstrated. There was no evidence that known proce-
dures for determination of dosages and formulation did not
apply. See Spectra-Physics, Inc. v. Coherent, Inc., 827 F.2d
1524, 1534 (Fed. Cir. 1987) (“A patent need not teach, and
preferably omits, what is well known in the art.”).
Enablement is not negated if a reasonable amount of
experimentation is required to establish dosages and formu-
lation of an active ingredient. See Enzo Biochem, Inc. v.
Calgene Inc., 188 F.3d 1362, 1371 (Fed. Cir. 1999). Lack of
enablement must be proved by clear and convincing evi-
dence. Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501
F.3d 1274, 1281 (Fed. Cir. 2007). Error has not been shown
in the district court’s finding and conclusion that the scope
of the claims is enabled. That ruling is affirmed.
IV
ENABLEMENT/UTILITY
The district court held all of the ’590 patent claims inva-
lid for lack of “enablement/utility.” The court held that
utility was not established because experimental data
showing the results of treatment of ADHD were not in-
cluded in the specification. The court held that “the court
ELI LILLY AND COMPANY v. ACTAVIS 12
cannot conclude that a person of skill in the art would have
recognized the method of treatment’s utility in view of the
specification and prior art.” Eli Lilly, 731 F. Supp.2d at
389.
The patent statute requires that the specification “dis-
close as a matter of fact a practical utility for the invention.”
In re Ziegler, 992 F.2d 1197, 1201 (Fed. Cir. 1993). Lilly
points out that the utility to treat ADHD was fully disclosed
and correctly described and enabled in the specification.
The ’590 patent describes the use of tomoxetine to treat
ADHD in humans, and states that “tomoxetine is a notably
safe drug, and its use in ADHD, in both adults and children,
is a superior treatment for that disorder because of im-
proved safety.” Col.1 ll.66 to col.2 l.1. The patent refers to
the two recognized types of ADHD, inattentive type and
hyperactive-impulsive type, and states: “Treatment with
tomoxetine is effective in patients who are primarily suffer-
ing from either component or from the combined disorder.”
Col.3 ll.38-40. The patent states:
The method of the present invention is effective in
the treatment of patients who are children, adoles-
cents or adults, and there is no significant difference
in the symptoms or the details of the manner of
treatment among patients or different ages.
Col.4 ll.14-18. No criticism of the correctness of these
statements has been offered. The defendants do not dispute
that the ’590 patent describes the utility of tomoxetine for
treatment of ADHD, and that the utility is correctly de-
scribed. Lilly agrees that human test data were not avail-
able at the time the patent application was filed, because
human tests were prohibited without FDA authorization.
13 ELI LILLY AND COMPANY v. ACTAVIS
Dr. Heiligenstein, one of the inventors, testified about
his uncertainty whether this treatment of ADHD would be
effective, when he and Dr. Tollefson suggested experimental
testing for this purpose:
Q: At the time of this filing, did you have a reason-
able expectation that tomoxetine would work to
treat ADHD?
A: It was a hypothesis.
Q: Did you have a reasonable expectation?
A: Reasonable? Can you define reasonable?
Q: Did you believe it was going to work for ADHD?
A: No, I wasn’t sure at all that it would work.
Heiligenstein Dep. 127:4-12, August 7, 2008. It was not
disputed that persons experienced in this field would re-
quire actual human tests to verify the effectiveness of this
use. As the Court discussed in Daubert v. Merrell Dow
Pharmaceuticals, Inc., 509 U.S. 579, 593 (1993): “Scientific
methodology today is based on generating hypotheses and
testing them to see if they can be falsified; indeed, this
methodology is what distinguishes science from the other
fields of human inquiry.” (quoting Michael D. Green, 86 Nw.
U. L. Rev. 643, 645 (1992)).
Although it was recognized that Dr. Heiligenstein’s hy-
pothesis required testing, Lilly points out that support for
the testing was provided, patent procedures were initiated,
and the FDA authorized proceeding with human clinical
trials. The Manual of Patent Examining Procedure in-
structs examiners to give presumptive weight to the utility
for which human trials have been initiated:
ELI LILLY AND COMPANY v. ACTAVIS 14
MPEP §2107.03 (8th ed. 2008). IV. . . . Before a
drug can enter human clinical trials, the sponsor, of-
ten the applicant, must provide a convincing ration-
ale to those especially skilled in the art (e.g., the
Food and Drug Administration) that the investiga-
tion may be successful. Such a rationale would pro-
vide a basis for the sponsor’s expectation that the
investigation may be successful. In order to deter-
mine a protocol for phase I testing, the first phase of
clinical investigation, some credible rationale of how
the drug might be effective or could be effective
would be necessary. Thus, as a general rule, if an
applicant has initiated human clinical trials for a
therapeutic product or process, Office personnel
should presume that the applicant has established
that the subject matter of that trial is reasonably
predictive of having the asserted therapeutic utility.
(Emphases in original.) During examination of the ’590
application, the patent examiner did not require the sub-
mission of data showing treatment of ADHD with atomoxet-
ine, although it is not disputed that such data were obtained
shortly after the patent application was filed. The utility of
this product to treat ADHD is not so incredible as to war-
rant the special procedures that are authorized for use when
the examiner doubts the described utility, as in In re
Swartz, 232 F.3d 862 (Fed. Cir. 2000) (cold fusion); Newman
v. Quigg, 877 F.2d 1575, modified 886 F.2d 329 (Fed. Cir.
1987) (perpetual motion); and for subject matter in once
notoriously intractable areas such as cures for baldness or
cancer. In deciding whether additional information is
required for examination purposes, deference is owed to the
“qualified agency presumed to have properly done its job.”
Am. Hoist & Derrick Co. v. Sowa & Sons, Inc., 725 F.2d
1350, 1359 (Fed. Cir. 1984).
15 ELI LILLY AND COMPANY v. ACTAVIS
In this case, evidence of the described utility of tomoxet-
ine was not requested by the patent examiner, although
experimental verification was obtained soon after the filing
of the patent application. The examination of the ’590
patent was in accordance with the rules, as the court has
explained:
[A] specification which contains a disclosure of util-
ity which corresponds in scope to the subject matter
sought to be patented must be taken as sufficient to
satisfy the utility requirement of §101 for the entire
claimed subject matter unless there is reason for
one skilled in the art to question the objective truth
of the statement of utility or its scope.
In re Langer, 503 F.2d 1380, 1391 (CCPA 1974) (emphases
in original). In In re Brana, 51 F.3d 1560 (Fed. Cir. 1995)
the court again explained that:
A specification disclosure which contains a teaching
of the manner and process of making and using the
invention in terms which correspond to those used
in describing and defining the subject matter sought
to be patented must be taken as in compliance with
the enabling requirement of the first paragraph of
§112 unless there is reason to doubt the objective
truth of the statements contained therein which
must be relied on for enabling support.
51 F.3d at 1566 (quoting In re Marzocchi, 439 F.2d 220, 223
(CCPA 1971)) (emphases in original). In Brana, where the
utility was antitumor activity in humans, the court reaf-
firmed the practice that: “Only after the PTO provides
evidence showing that one of ordinary skill in the art would
reasonably doubt the asserted utility does the burden shift
to the applicant to provide rebuttal evidence sufficient to
ELI LILLY AND COMPANY v. ACTAVIS 16
convince such a person of the invention’s asserted utility.”
Id. at 1566 (citing In re Bundy, 642 F.2d 430, 433 (CCPA
1981)). Such evidence was not here provided by the PTO,
and rebuttal evidence was not required.
The district court’s statement that “there was no credi-
ble disclosure of utility to begin with,” Eli Lilly, 731 F.
Supp. 2d at 386 n.18, does not comport with the specifica-
tion’s extensive disclosure of utility. The district court
appears to have accepted the defendants’ argument that in
view of the absence of experimental data in the specifica-
tion, the disclosed utility must be deemed incredible. The
district court apparently also accepted the defendants’
position that such data were required to be included in the
specification. However, the purported authority cited by the
defendants concerned quite different issues, where, for
various reasons, it was appropriate to offer experimental
evidence. For example, the district court relied on patent
“interference” cases, as in Rasmusson v. SmithKline
Beecham Corp., 413 F.3d 1318, 1324 (Fed. Cir. 2005), where
evidence of actual reduction to practice was required to
establish a priority date earlier than that of an adverse
claimant.
When priority is not at issue, generally the applicant
may provide data obtained either before or after the patent
application was filed. With reference to demonstration of
utility, in Brana, 51 F.3d at 1567 n.19 the court noted that
post-filing evidence “can be used to substantiate any doubts
as to the asserted utility since this pertains to the accuracy
of a statement already in the specification.” Here, the
utility of tomoxetine is accurately stated in the specification;
there is no allegation of falsity in the disclosed utility, and
the patent examiner did not require the presentation of
additional data. In In re Marzocchi, 439 F.2d 220 (CCPA
1971) the court had explained that:
17 ELI LILLY AND COMPANY v. ACTAVIS
The only relevant concern of the Patent Office under
these circumstances should be over the truth of any
such assertion. The first paragraph of §112 requires
nothing more than objective enablement. How such
a teaching is set forth, either by the use of illustra-
tive examples or by broad terminology, is of no im-
portance.
439 F.2d at 223. The ’590 patent describes and enables the
utility of tomoxetine to treat ADHD. The disclosure is not
“on its face, contrary to generally accepted scientific princi-
ples.“ Id. at 223. Lilly’s expert testified that the utility of
tomoxetine to treat ADHD “had not been ruled out,” Trial
Tr. 1099:4, and even the defendants’ expert testified that “it
could work.” Trial Tr. 200:22.
The defendants rely on Janssen Pharmaceutica N.V. v.
Teva Pharmaceuticals USA, Inc., 583 F.3d 1317 (Fed. Cir.
2009) where the court held that the use of galantamine to
treat Alzheimer’s disease was a “mere research proposal.”
The specification summarized six scientific articles on the
properties of galantamine to raise blood levels of cortisol
and ACTH, and reporting brain effects in mammals, and the
court held that because the animal tests were “not finished .
. . by the time the ‘318 patent was allowed,” enablement was
not shown. The court held that there was not “a reasonable
correlation between a compound’s activity and its asserted
therapeutic use,” in the words of MPEP §2107.03. In the
case of atomoxetine, however, the norepinephrine relation-
ship was known, safety for antidepressant activity had been
established, the specification contained a full description of
the utility, experimental verification had been obtained
before the patent was granted, and the examiner had not
requested additional information. There was no evidence
that the disclosure is “on its face, contrary to generally
accepted scientific principles.” Marzocchi, 439 F.2d at 223.
ELI LILLY AND COMPANY v. ACTAVIS 18
As stated in Brana, 51 F.3d 1566-67: “Even if one skilled in
the art would have reasonably questioned the asserted
utility, i.e., even if the PTO met its initial burden thereby
shifting the burden to the applicants to offer rebuttal evi-
dence, applicants proffered sufficient evidence to convince
one of skill in the art of the asserted utility.”
On the entirety of the evidence, invalidity for lack of en-
ablement/utility was not shown by clear and convincing
evidence. The district court’s holding of invalidity on this
ground is reversed.
V
INFRINGEMENT
The district court held that the defendants would be li-
able for inducement to infringe the ’590 patent by providing
atomoxetine bearing the FDA-approved label authorizing
use to treat ADHD. The defendants argue that “the mere
distribution of generic atomoxetine products cannot estab-
lish inducement liability, even though the labeling includes
the legally required statement of FDA-approved use.” Lilly
responds that the label use to treat ADHD is the only le-
gally approved use, and the only use for which the defen-
dants are authorized to provide the product.
The defendants rely on Warner-Lambert Co. v. Apotex
Corp., 316 F.3d 1348 (Fed. Cir. 2003), for its finding of non-
infringement, although in that case the patent on the only
FDA-authorized use had expired, and the court held that
the provider of the generic product, labeled for the author-
ized use on which the patent had expired, did not infringe a
different (unexpired) patent on an unauthorized use:
19 ELI LILLY AND COMPANY v. ACTAVIS
[T]he request to make and sell a drug labeled with a
permissible (non-infringing) use cannot reasonably
be interpreted as an act of infringement (induced or
otherwise) with respect to a patent on an unap-
proved use, as the ANDA does not induce anyone to
perform the unapproved acts required to infringe.
316 F.3d at 1364-65.
The defendants also argue that there are off-label uses
of atomoxetine, stated by the defendants to be as high as
29% of the total, and conceded by Lilly as possibly as high as
8% of the total. However, the product sold by the defen-
dants is labeled solely for the patented use to treat ADHD.
We have long held that the sale of a product specifically
labeled for use in a patented method constitutes inducement
to infringe that patent, and usually is also contributory
infringement. See Astrazeneca LP v. Apotex, Inc., 633 F.3d
1042, 1060 (Fed. Cir. 2010) (finding intent to induce in-
fringement based on the product label authorizing the
patented use, which “would inevitably lead some consumers
to practice the claimed method”); see also DSU Med. Corp. v.
JMS Co. Ltd., 471 F.3d 1293, 1305-06 (Fed. Cir. 2006) (en
banc in relevant part) (finding liability for induced in-
fringement when an entity “offers a product with the object
of promoting its use to infringe, as shown by clear expres-
sion or other affirmative steps taken to foster infringe-
ment”).
No clear error has been shown in the district court’s
findings and conclusion regarding inducement. We affirm
the judgment that the provision of atomoxetine labeled
solely for use to treat ADHD constitutes inducement to
infringe the ’590 patent.
ELI LILLY AND COMPANY v. ACTAVIS 20
As for contributory infringement, the district court held
that liability is avoided if the product has any “frequent”
non-infringing use. Lilly argues that atomoxetine is not a
“staple article of commerce suitable for substantial non-
infringing use,” the words of 35 U.S.C. §271(c), for the only
authorized use of atomoxetine is the patented use to treat
ADHD. The defendants are restricted from selling a feder-
ally regulated drug for unapproved uses. See 21 C.F.R.
§202.1(e)(4). The defendants respond that physicians may
nonetheless prescribe atomoxetine for unauthorized use.
Such unauthorized activity does not avoid infringement by a
product that is authorized to be sold solely for the infringing
use.
We conclude that the district court erred in its applica-
tion of the law of contributory infringement. That aspect of
the district court’s decision is reversed.
SUMMARY
The judgment that the ’590 patent claims are invalid for
lack of “enablement/utility” is reversed. The district court’s
rulings of validity on other grounds, and the judgment of
infringement, are affirmed. We remand for further proceed-
ings.
AFFIRMED-IN-PART, REVERSED-IN-PART, and
REMANDED