H. Lundbeck A/S v. Lupin Ltd. ( 2023 )

Case: 22-1194 Document: 95 Page: 1 Filed: 12/07/2023
United States Court of Appeals
for the Federal Circuit
______________________
H. LUNDBECK A/S, TAKEDA PHARMACEUTICAL
COMPANY LIMITED, TAKEDA
PHARMACEUTICALS U.S.A., INC., TAKEDA
PHARMACEUTICALS INTERNATIONAL AG,
TAKEDA PHARMACEUTICALS AMERICA, INC.,
Plaintiffs-Appellants
v.
LUPIN LTD., LUPIN PHARMACEUTICALS, INC.,
MACLEODS PHARMA USA, INC., MACLEODS
PHARMACEUTICALS LTD., SANDOZ INC.,
SIGMAPHARM LABORATORIES, LLC, ZYDUS
PHARMACEUTICALS (USA) INC., ALEMBIC
GLOBAL HOLDING S.A., ALEMBIC
PHARMACEUTICALS INC., ALEMBIC
PHARMACEUTICALS LIMITED, CADILA
HEALTHCARELTD., LEK PHARMACEUTICALS,
D.D.,
Defendants-Cross-Appellants
______________________
2022-1194, 2022-1208, 2022-1246
______________________
Appeals from the United States District Court for the
District of Delaware in No. 1:18-cv-00088-LPS, Judge
Leonard P. Stark.
______________________
Decided: December 7, 2023
______________________
Case: 22-1194 Document: 95 Page: 2 Filed: 12/07/2023
2 H. LUNDBECK A/S v. LUPIN LTD.
BRIANNE BHARKHDA, Covington & Burling LLP, Wash-
ington, DC, argued for plaintiffs-appellants. Also repre-
sented by GEORGE FRANK PAPPAS, EINAR STOLE; KURT
CALIA, Palo Alto, CA.
DAVID BRIAN ABRAMOWITZ, Locke Lord LLP, Chicago,
IL, argued for defendants-cross-appellants Alembic Global
Holding S.A., Alembic Pharmaceuticals Inc., Alembic Phar-
maceuticals Limited, Cadila Healthcare Ltd., Lek Pharma-
ceuticals, d.d., Macleods Pharma USA, Inc., Macleods
Pharmaceuticals Ltd., Sandoz Inc., Sigmapharm Laborato-
ries, LLC, Zydus Pharmaceuticals (USA) Inc. Cadila
Healthcare Ltd., Zydus Pharmaceuticals (USA) Inc. also
represented by HUGH S. BALSAM, CAROLYN ANNE BLESSING,
MICHAEL GAERTNER, TIMOTHY FLYNN PETERSON, JONATHAN
B. TURPIN; AUGUST MELCHER, Weil, Gotshal & Manges
LLP, Redwood Shores, CA.
DEEPRO MUKERJEE, Katten Muchin Rosenman LLP,
New York, NY, argued for defendants-cross-appellants Lu-
pin Ltd., Lupin Pharmaceuticals, Inc. Also represented by
LANCE SODERSTROM; JOSEPH JANUSZ, JITENDRA MALIK,
Charlotte, NC.
BRADLEY C. GRAVELINE, Sheppard Mullin Richter &
Hampton LLP, for defendants-cross-appellants Alembic
Global Holding S.A., Alembic Pharmaceuticals Inc., Alem-
bic Pharmaceuticals Limited. Also represented by TODD E.
LUNDELL, Costa Mesa, CA; JESSE A. SALEN, San Diego, CA;
LAURA BURSON, O'Melveny & Myers LLP, Los Angeles, CA.
MARY LAFLEUR, Crowell & Moring, LLP, Chicago, IL,
for defendants-cross-appellants Lek Pharmaceuticals, d.d.,
Macleods Pharma USA, Inc., Macleods Pharmaceuticals
Ltd., Sandoz Inc. Also represented by LAURA A. LYDIGSEN,
MARK HERBERT REMUS. Macleods Pharma USA, Inc., Mac-
leods Pharmaceuticals Ltd. also represented by
Case: 22-1194 Document: 95 Page: 3 Filed: 12/07/2023
H. LUNDBECK A/S v. LUPIN LTD. 3
CHRISTOPHER J. SORENSON, Merchant & Gould P.C., Min-
neapolis, MN.
DONALD J. MIZERK, Husch Blackwell LLP, Chicago, IL,
for defendant-cross-appellant Sigmapharm Laboratories,
LLC. Also represented by MATTHEW KAMPS, PHILIP D.
SEGREST, JR., MARC RICHARD WEZOWSKI; THOMAS P.
HENEGHAN, Madison, WI.
______________________
Before DYK, PROST, and HUGHES, Circuit Judges.
DYK, Circuit Judge.
H. Lundbeck A/S (“Lundbeck”), Takeda Pharmaceuti-
cal Company Ltd., Takeda Pharmaceuticals U.S.A., Inc.,
Takeda Pharmaceuticals International AG, and Takeda
Pharmaceuticals America, Inc. (collectively “plaintiffs”) ap-
peal the final judgment of the United States District Court
for the District of Delaware.
The district court held that defendants’ Abbreviated
New Drug Applications (“ANDAs”) did not infringe two pa-
tents owned by plaintiffs, one for the use of the drug vorti-
oxetine in patients who have previously taken certain other
antidepressant medications and had to cease or reduce use
due to sexually related adverse events, U.S. Patent No.
9,278,096 (“the ’096 patent”), and one for using vortioxetine
to treat cognitive impairment, U.S. Patent No. 9,125,910(“the ’910 patent”).
Defendants Lupin Ltd., Lupin Pharmaceuticals, Inc., 1
Macleods Pharma USA, Inc., Macleods Pharmaceuticals
Ltd., Sandoz Inc., 2 Sigmapharm Laboratories, LLC, Zydus
1 “Lupin” refers to Lupin Ltd. and Lupin Pharma-
ceuticals, Inc. collectively.
2 “Sandoz” refers to Sandoz Inc. and Lek Pharmaceu-
ticals d.d. collectively.
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4 H. LUNDBECK A/S v. LUPIN LTD.
Pharmaceuticals (USA) Inc., Alembic Global Holding S.A.,
Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals
Ltd., Cadila Healthcare Ltd., and Lek Pharmaceuticals,
d.d. (collectively “defendants”), conditionally cross appeal
the district court judgment that the ’096 and ’910 patents
are not invalid.
Lupin also cross appeals the district court’s determina-
tion that Lupin’s ANDA will infringe plaintiffs’ U.S. Patent
No. 9,101,626 (“the ’626 patent”), covering a process for
making vortioxetine, and the district court’s construction
of the term “reacting.”
We affirm the judgment of non-infringement of the ’096
and ’910 patents and the determination that Lupin in-
fringed claim 12 of the ’626 patent. We do not reach the
question of the validity of the ’096 and ’910 patents.
BACKGROUND
I
A new drug cannot be marketed for use unless the Food
and Drug Administration (“FDA”) has approved a New
Drug Application (“NDA”) for the proposed use of that
drug. See 21 U.S.C. § 355(a)–(b). The Hatch-Waxman Act
allows generic manufacturers to “piggy-back[]” on a
branded drug’s FDA-approved NDA by submitting an
ANDA showing that the generic drug has the same active
ingredients and is bioequivalent to the brand-name drug.
See Caraco Pharm. Lab’ys, Ltd. v. Novo Nordisk A/S, 566
U.S. 399, 404–05 (2012) (discussing Drug Price Competi-
tion and Patent Term Restoration Act of 1984, Pub. L. No.
98-417, 98 Stat. 1585). Under this streamlined approach,
the ANDA may rely on the safety and efficacy information
for an approved use of the brand-name drug. Id. at 405.
“[T]his process is designed to speed the introduction of low-
cost generic drugs to market.” Id.“To facilitate the approval of generic drugs as soon as
patents allow, the Hatch-Waxman Amendments and FDA
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H. LUNDBECK A/S v. LUPIN LTD. 5
regulations direct brand manufacturers to file information
about their patents” in what is called the Orange Book. Id.;
see also 21 U.S.C. § 355(b)(1)(A)(viii). If an ANDA appli-
cant wishes to market a drug before the expiration of the
patents listed in the Orange Book, the applicant has two
options. See Caraco, 566 U.S. at 406.
First, if the ANDA applicant believes that a patent “is
invalid or will not be infringed by the manufacture, use, or
sale of the new drug for which the application is submit-
ted,” the applicant may submit a “Paragraph IV” certifica-
tion. 21 U.S.C. § 355(j)(2)(A)(vii)(IV). Filing a Paragraph
IV certification gives the brand manufacturer a right to sue
the ANDA filer for infringement. Caraco, 566 U.S. at 407
(citing 35 U.S.C. § 271(e)(2)(A)). Infringement can then be
“determined by traditional patent infringement analysis.”
Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365
(Fed. Cir. 2003). Under the patent statute, it is an act of
direct infringement to make, use, offer to sell, or sell a pa-
tented invention without authorization. 35 U.S.C.
§ 271(a). The patent statute also provides for indirect in-
fringement, which can be found in cases where the defend-
ant “actively induces” another to infringe or in cases where
a “contributory infringer” sells “a material . . . for use in
practicing a patented process.” 35 U.S.C. § 271(b)–(c). Sale
of a material that is “suitable for substantial noninfringing
use” is not contributory infringement. § 271(c).
Second, for patents that claim a method of use, the
ANDA applicant may propose a label that “carves out” a
patented use and submit a “section viii” statement to that
effect. Caraco, 566 U.S. at 406 (citing 21 U.S.C.
§ 355(j)(2)(A)(viii)). If the FDA approves the carved-out la-
bel, the ANDA applicant may market the drug “only for a
subset of approved uses—i.e., those not covered by the
brand’s patents.” Id. “The Hatch-Waxman Amendments
authorize the FDA to approve the marketing of a generic
drug for particular unpatented uses; and section viii pro-
vides the mechanism for a generic company to identify
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6 H. LUNDBECK A/S v. LUPIN LTD.
those uses, so that a product with a label matching them
can quickly come to market. The statutory scheme, in
other words, contemplates that one patented use will not
foreclose marketing a generic drug for other unpatented
ones.” Id. at 415.
II
Takeda U.S.A., Inc. holds the approved NDA for the
branded drug Trintellix® (“Trintellix”) for the treatment of
major depressive disorder (“MDD”) in adults. Trintellix’s
active ingredient is a salt of vortioxetine. Plaintiffs’ pa-
tents on the drug compound and on a method of use for
treating depression, U.S. Patent Nos. 7,144,884 and
8,476,279 (the “compound patents”), have expiration dates
of June 17, 2026, and October 2, 2022, respectively.
Following the initial FDA approval of the use of Trin-
tellix to treat MDD, plaintiffs secured the ’096 and ’910
method of use patents at issue in this case, which concern
the treatment of MDD in patients who have previously
taken certain other drugs but had to cease or reduce use
due to sexually related adverse events and the treatment
of cognitive impairment, respectively. The plaintiffs then
listed the ’096 and ’910 patents in the FDA’s Orange Book.
Their expiration dates are March 21, 2032, and June 15,
2027, respectively. Defendants have submitted ANDAs
seeking approval to market vortioxetine for only one indi-
cation, the treatment of MDD in adults, a method of use
not covered by the ’096 and ’910 patents, and the ANDAs
will become effective after the expiration of the compound
patents. 3 Plaintiffs nonetheless contended that the ’096
3 As to the compound patents, some defendants sub-
mitted so-called “Paragraph III” certifications indicating
that those defendants are not seeking approval to market
vortioxetine prior to the expiration of the patents, see 21
U.S.C. § 355(j)(2)(A)(vii)(III), and other defendants are
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H. LUNDBECK A/S v. LUPIN LTD. 7
and ’910 patents preclude approval of defendants’ ANDAs. 4
It is useful to understand the background of these two pa-
tents.
III
Some drugs for the treatment of depression are associ-
ated with high rates of sexual dysfunction. Treatment
Emergent Sexual Dysfunction (“TESD”) is a term used for
sexual dysfunction caused by antidepressant drugs. Plain-
tiffs conducted clinical studies regarding the effects of Trin-
tellix on sexual function, which concluded that it had
shown less adverse effects on sexual function as compared
to other antidepressants.
Using findings from some of these studies, Lundbeck
and Takeda filed the application that became the ’096 pa-
tent. The ’096 patent concerns a method of treatment in-
volving the use of vortioxetine by a patient who “has
previously received medication or is still receiving medica-
tion for the treatment of [depression and other diseases]”
who has “ceased or reduced [use of the medication] due to
sexually related adverse events.” ’096 patent, cl. 1. The
Patent and Trademark Office (“PTO”) issued the ’096 pa-
tent on March 8, 2016. Claim 7 of the ’096 patent depends
from independent claim 1 and dependent claim 6. The
claims recite:
1. A method for the treatment of a disease selected
from the group consisting of depression, anxiety,
abuse and chronic pain, comprising the admin-
istration of a therapeutically effective amount of
subject to a district court order that the ANDAs not be ap-
proved before the expiration of the compound patents,
which is not an issue on appeal.
4 Sandoz filed a Paragraph III certification as to the
’910 patent and so is not a party with respect to the ’910
patent issues on appeal.
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8 H. LUNDBECK A/S v. LUPIN LTD.
[Compound I] 5 or a pharmaceutically acceptable
salt thereof to a patient in need thereof,
wherein said patient has previously received med-
ication or is still receiving medication for the treat-
ment of said disease, the medication is ceased or
reduced or has to be ceased or reduced due to sex-
ually related adverse events, and the medication is
selected from the group consisting of selective ser-
otonin reuptake inhibitors, selective noradrenaline
reuptake inhibitors, noradrenaline/serotonin
reuptake inhibitors, and tri-cyclics.
6. The method according to claim 1, wherein Com-
pound I or a pharmaceutically acceptable salt
thereof is administered to the patient in unit doses
of about 1–50 mg.
7. The method according to claim 6, wherein the
patient is administered between about 1 and 20 mg
per day of the hydrobromic acid salt of Compound
I orally.
The second patent at issue is the ’910 patent concern-
ing treatment of cognitive impairment. Cognitive impair-
ment is very common in MDD patients. The PTO issued
the ’910 patent on September 8, 2015. Claim 6 of the ’910
patent depends from independent claim 1 and dependent
claim 3. The claims recite in relevant part:
1. A method of treating cognitive impairment in-
volving decline in speed of processing, executive
function, attention, or verbal learning and memory
in a patient diagnosed with depression, the method
5 The patents at issue define 1-[2-(2,4-dimethylphen-
ylsulfanyl)phenyl]piperazine, also known as vortioxetine,
and pharmaceutically acceptable salts thereof as Com-
pound I.
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H. LUNDBECK A/S v. LUPIN LTD. 9
comprising administering a therapeutically effec-
tive amount of Compound I or a pharmaceutically
acceptable salt thereof to the patient, wherein . . .
the method alleviates a symptom or complication of
the cognitive impairment or delays the progression
of the cognitive impairment.
3. The method of claim 1, wherein the depression is
major depressive disorder.
6. The method of claim 3, wherein the method com-
prises administering a hydrobromide salt of Com-
pound I to the patient.
IV
Plaintiffs sued seeking to enjoin defendants from mar-
keting a generic version of Trintellix until after the expira-
tion of the ’096 and ’910 patents, alleging induced and
contributory infringement of the ’096 patent and contribu-
tory infringement of the ’910 patent. Following a bench
trial, the district court determined that the defendants’
ANDAs neither induced infringement of nor contributorily
infringed the ’096 and ’910 patents. Plaintiffs timely ap-
pealed. We have jurisdiction pursuant to 28 U.S.C.
§ 1295(a)(1).
V
A third patent at issue in this case is the ’626 patent
concerning a process for manufacturing vortioxetine.
Claim 12 of the ’626 patent depends from independent
claim 1 and dependent claim 11. Claim 1 recites in rele-
vant part:
1. A process for the preparation of [compound I] or
a pharmaceutically salt thereof, the process com-
prising reacting compound II . . ., with a compound
of formula III . . ., and a compound [IV] . . ., in the
presence of a solvent, a base and a palladium cata-
lyst consisting of a palladium source and a
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10 H. LUNDBECK A/S v. LUPIN LTD.
phosphine ligand at a temperature between 60° C.
and 130° C.
Lupin filed an ANDA seeking approval to market vor-
tioxetine prepared by a process that plaintiffs contend will
infringe claim 12 of the ’626 patent. Plaintiffs sued Lupin
for infringement and to bar Lupin from using the process
before the expiration of the ’626 patent. The parties dis-
puted the construction of the term “reacting.” After a
bench trial, the district court agreed with plaintiffs’ con-
struction and found that Lupin infringes under that con-
struction. Lupin timely cross appealed. We have
jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).
DISCUSSION
“This court reviews a district court’s judgment follow-
ing a bench trial for errors of law and clearly erroneous
findings of fact.” Allen Eng’g Corp. v. Bartell Indus., Inc.,
299 F.3d 1336, 1343–44 (Fed. Cir. 2002).
I
A
Typically, under the Hatch-Waxman Act, plaintiffs sue
ANDA filers for direct, induced, and/or contributory in-
fringement. See, e.g., Allergan, Inc. v. Alcon Lab’ys, Inc.,
324 F.3d 1322, 1331 (Fed. Cir. 2003) (“The only difference
in the analysis of a traditional infringement claim and a
claim of infringement under section 271(e)(2) is the
timeframe under which the elements of infringement are
considered.”). Plaintiffs argue that the district court erred
in not finding infringement of the ’096 and ’910 patents be-
cause section 271(e)(2)(A) creates a separate cause of ac-
tion that does not require a showing of direct, induced, or
contributory infringement by the ANDA filer. Section
271(e)(2)(A) provides:
It shall be an act of infringement to submit an ap-
plication under [the Hatch-Waxman Act] for a drug
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H. LUNDBECK A/S v. LUPIN LTD. 11
. . . the use of which is claimed in a patent . . . if the
purpose of such submission is to obtain approval
under such Act to engage in the commercial manu-
facture, use, or sale of a drug . . . the use of which
is claimed in a patent before the expiration of such
patent.
Thus, plaintiffs argue, defendants infringe under the plain
text of section 271(e)(2)(A) because they filed ANDAs seek-
ing approval to market vortioxetine; some uses of vortiox-
etine—for the treatment of patients that have previously
taken other drugs but had to cease or reduce use due to
sexually related adverse events and for the treatment of
cognitive impairment—are covered by the ’096 and ’910 pa-
tents; and the labels do not prohibit prescribing vortiox-
etine for those uses, even though the defendants do not
propose to market the drug for those patented uses. In
other words, according to plaintiffs it makes no difference
that the drug is proposed to be sold for a use not covered by
the ’096 and ’910 patents because the drug could be pre-
scribed for those patented uses. We disagree. Our cases
establish that “the use . . . claimed in a patent” under sec-
tion 271(e)(2)(A) must be the use for which an applicant is
seeking marketing approval.
As an initial matter, we note that plaintiffs did not
make this statutory interpretation argument before the
district court, and defendants argue that plaintiffs forfeited
the argument by not raising it below. Because the con-
struction of a statute is a pure question of law, we nonethe-
less elect to address plaintiffs’ arguments. See Singleton v.
Wulff, 428 U.S. 106, 121 (1976) (“The matter of what ques-
tions may be taken up and resolved for the first time on
appeal is one left primarily to the discretion of the courts
of appeals, to be exercised on the facts of individual
cases.”); Columbia Sportswear N. Am., Inc. v. Seirus Inno-
vative Accessories, Inc., 80 F.4th 1363, 1374 (Fed. Cir.
2023) (“[W]hether to excuse a forfeiture is generally within
our discretion.”); Cemex, S.A. v. United States, 133 F.3d
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12 H. LUNDBECK A/S v. LUPIN LTD.
897, 902 (Fed. Cir. 1998) (addressing an argument not
raised below “because an issue of statutory interpretation
is involved”).
In Warner-Lambert and its progeny, we considered
and rejected plaintiffs’ interpretation of section
271(e)(2)(A). 316 F.3d at 1354–62. The plaintiff in Warner-
Lambert, which owned a patent on methods of treatment
for neurodegenerative disease that was listed in the Or-
ange Book, sued to block a generic company from securing
approval of an ANDA that would allow the marketing of
the drug for another use not covered by the patent. Id. at
1352. The plaintiff argued that, because the generic com-
pany sought FDA approval “for a drug,” “the use of which
is claimed in” a patent, the company infringed “irrespective
of whether approval is sought to market the drug for the
patented use.” Id. at 1355. We disagreed, holding that
such an interpretation “eviscerated an important part of
the statutory provision” by severing the phrase beginning
“if the purpose . . .” from the rest of the statute. Id.We explained that “‘the use’ in § 271(e)(2)(A) refers to
the use for which the FDA has granted an NDA” and for
which the ANDA was submitted. Id. at 1356. Thus, it is
not “an act of infringement under 35 U.S.C. § 271(e)(2)(A)
to submit an ANDA for a drug if just any use of that drug
were claimed in a patent.” Id. at 1358–59. If it were, a
brand could “maintain its exclusivity merely by regularly
filing a new patent application claiming a narrow method
of use not covered by its NDA,” which “would confer sub-
stantial additional rights on pioneer drug patent owners
that Congress quite clearly did not intend to confer.” Id. at
1359. Rather, actions for infringement of method of use
patents under section 271(e)(2)(A) are limited to patents
that claim an indication of the drug for which indication
the applicant is seeking approval. Id. at 1361.
Plaintiffs argue that the Warner-Lambert line of cases
are distinguishable, at least as to the ’096 patent, because
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H. LUNDBECK A/S v. LUPIN LTD. 13
the use covered by the ’096 patent still involves the treat-
ment of MDD and will not be an off-label use. Our other
section 271(e)(2)(A) cases confirm that Warner-Lambert is
not limited to cases in which the “patent at issue is for a
use not approved under the NDA.” Id. at 1355; see, e.g.,
AstraZeneca Pharms. LP v. Apotex Corp., 669 F.3d 1370,
1379 (Fed. Cir. 2012) (“Although [plaintiff] is correct that
the patent at issue in Warner-Lambert claimed an off-label
use for a drug, that distinction is irrelevant for purposes of
§ 271(e)(2).”).
Here, the district court found that defendants are not
seeking approval for an indication claimed by the ’096 and
’910 patents. Defendants solely seek approval to market
the drug for the treatment of MDD pursuant to the meth-
ods of expiring patents—that is the “purpose” of the ANDA
submissions. Thus, the patented uses are not those for
which ANDA approval is sought. Plaintiffs have failed to
establish that section 271(e)(2)(A) provides an independent
basis of infringement.
B
Plaintiffs next argue that the district court erred in
finding no induced infringement of claim 7 of the ’096 pa-
tent. Under the law of induced infringement, “[w]hoever
actively induces infringement of a patent shall be liable as
an infringer.” 35 U.S.C. § 271(b). “The accused infringer
must have ‘knowingly aided and abetted’ direct infringe-
ment” and taken active steps to encourage, recommend, or
promote infringement. Takeda Pharms. U.S.A., Inc. v.
West-Ward Pharm. Corp., 785 F.3d 625, 630–31 (Fed. Cir.
2015) (quoting Warner-Lambert, 316 F.3d at 1363). Exam-
ples of active steps include “advertising an infringing use
or instructing how to engage in an infringing use.” Metro-
Goldwyn-Mayer Studios Inc. v. Grokster, Ltd., 545 U.S.
913, 936 (2005). In order to support inducement liability,
instructions may not merely describe an infringing mode;
they must “evidence ‘intent to encourage infringement.’”
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14 H. LUNDBECK A/S v. LUPIN LTD.
Takeda, 785 F.3d at 631 (emphasis omitted) (quoting Vita-
Mix Corp. v. Basic Holding, Inc., 581 F.3d 1317, 1329 (Fed.
Cir. 2009)).
Here, plaintiffs’ inducement case relied solely on de-
fendants’ proposed ANDA labels as the inducing conduct.
Because plaintiffs did not identify any advertising or pro-
motional materials that encouraged infringement, this
case is unlike GlaxoSmithKline LLC v. Teva Pharmaceuti-
cals USA, Inc., 7 F.4th 1320, 1333 (Fed. Cir. 2021), and
other cases where we have found infringement based on
communications outside the ANDA label. Here the district
court found the label in question is not a label that induces
infringement of the ’096 patent. It is the label FDA re-
quired for the sale of the drug to treat MDD—a label that
the patentee itself proposed for that purpose in connection
with its NDA for treating MDD and that preexisted the is-
suance of the ’096 patent.
Nonetheless, plaintiffs contend that because the ’096
patent exists and clinicians will prescribe the ANDA prod-
ucts for the uses claimed in the ’096 patent, defendants
have induced infringement and cannot obtain approval for
their ANDAs. However, it cannot be, as plaintiffs suggest,
that a patentee can bar the sale of a drug for a use covered
only by patents that will have expired simply by securing
a new patent for an additional, narrower use, as we recog-
nized in Warner-Lambert. 316 F.3d at 1359. Such an ap-
proach to indirect infringement would be inconsistent with
a stated purpose of the Hatch-Waxman Act—“to enable ge-
neric manufacturers to be ready to enter the market once
patents expired.” Id. at 1357. A patentee may not use
Hatch-Waxman to “maintain its exclusivity merely by reg-
ularly filing a new patent application claiming a narrow
method of use not covered by its NDA.” Id. at 1359. Ac-
cordingly, we do not see how, in the normal course, a label
required to market the drug for a use covered by expired
patents could demonstrate the required specific intent to
encourage infringement of new patents covering different
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H. LUNDBECK A/S v. LUPIN LTD. 15
uses. This is particularly so here since plaintiffs’ infringe-
ment theory depends entirely on the “Adverse Reactions”
section of the defendants’ ANDA labels, which was essen-
tial to FDA approval to market the drug for the treatment
of MDD and has been present in the Trintellix label since
FDA first approved the drug for the treatment of MDD on
September 30, 2013 6—years before the PTO issued the ’096
patent in 2016. 7
To be sure, there may be situations where the owner of
an expired compound patent or expired method of use pa-
tent makes a new discovery that requires a new method of
use to ensure patient safety. If FDA requires, in order to
protect patient safety, that the new method of use must be
included in the label, the ANDA label may induce infringe-
ment of the new safety patents. Our cases have considered
instances where the ANDA label includes necessary safety
instructions, for example instructions to titrate to a lower
dose, AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060–
61 (Fed. Cir. 2010), to request a lab test and adjust the dose
in response, Vanda Pharms. Inc. v. West-Ward Pharms.
Int’l Ltd., 887 F.3d 1117, 1131 (Fed. Cir. 2018), or to take a
critical supplement along with the drug to reduce poten-
tially life-threatening toxicities, Eli Lilly & Co. v. Teva Par-
enteral Medicines, Inc., 845 F.3d 1357, 1365, 1368–69 (Fed.
Cir. 2017). This is not such a case. Here, there is no new
discovery requiring instructing how to safely take the drug,
or identifying a class of patients who should not take the
drug at all.
6 The original brand named of Trintellix was Brin-
tellix®.
7 This case is thus unlike GlaxoSmithKline, where
the portion of the label relied on to support a finding of in-
duced infringement, the post-MI LVD indication, did not
describe or relate to a use claimed in an expired patent. 7
F.4th at 1327–29.
Case: 22-1194 Document: 95 Page: 16 Filed: 12/07/2023
16 H. LUNDBECK A/S v. LUPIN LTD.
This is also not a situation in which there is an “ex-
press[] direct[ion]” in the label to review data about “the
class of patients for whom the drug is indicated to achieve
the stated objective” of a new patent. Sanofi v. Watson
Lab’ys Inc., 875 F.3d 636, 645 (Fed. Cir. 2017). With FDA
approval, defendants have “carved out” the portions of the
NDA labels relating to the ’096 patent and identifying
those individuals who would particularly benefit from tak-
ing the drug (because of the low incidence of TESD). 8
Under section 355(j)(4), which is part of the Hatch-
Waxman Act, the FDA is instructed “to approve an ANDA
filed with a section viii statement when it proposes to mar-
ket a drug for only unpatented methods of use” in order to
facilitate the approval of noninfringing generic drugs. See
Caraco, 566 U.S. at 419. FDA regulations permit an ANDA
filer to omit “an indication or other aspect of labeling pro-
tected by patent” as an exception to the general rule that
an ANDA label must be the same as the branded drug’s.
21 C.F.R. § 314.94(a)(8)(iv). Here, defendants’ ANDA la-
bels “carved out” the superiority data in the clinical studies
portion of the label and the cross-reference to that data.
The label itself does not even reference the patient class
8 The ’096 patent and the corresponding portions of
the label followed after the plaintiffs conducted two supe-
riority studies, which were successful in demonstrating
clinically meaningful improvement in sexual functioning
when patients switched to Trintellix as compared to other
drugs. Based on these further studies, at plaintiffs’ re-
quest, on October 19, 2018, FDA approved additions to the
Trintellix label in a section entitled “Clinical Studies,” to
present data from the two superiority studies. FDA also
approved adding a new sentence at the beginning of the
section describing the adverse reactions of sexual dysfunc-
tion that cross-references the superiority studies presented
elsewhere in the new label.
Case: 22-1194 Document: 95 Page: 17 Filed: 12/07/2023
H. LUNDBECK A/S v. LUPIN LTD. 17
recited in claim 7 of the ’096 patent and instructs physi-
cians not to compare rates of adverse reactions of sexual
dysfunction between vortioxetine and other drugs. The dis-
trict court correctly determined that, under these circum-
stances and consistent with our cases, 9 the proposed ANDA
labels “will not encourage, recommend, or promote an in-
fringing use.” J.A. 227.
It remains only to consider two additional arguments
offered by plaintiffs. First, they contend that an ANDA la-
bel induces infringement if physicians will prescribe the
drug for uses claimed by the ’096 patent based on their
background knowledge together with information in the
carved-out label. In the Hatch-Waxman context, we have
9 See, e.g., Grunenthal GmbH v. Alkem Lab’ys Ltd.,
919 F.3d 1333, 1339–40 (Fed. Cir. 2019) (affirming that a
generic label can avoid inducing infringement by carving
out the inducing material from the label); HZNP Meds.
LLC v. Actavis Lab’ys UT, Inc., 940 F.3d 680, 702 (Fed. Cir.
2019) (affirming that a label did not induce infringement
when it did not instruct carrying out all of the claimed
method’s steps); Takeda, 785 F.3d at 632 (“[V]ague label
language cannot be combined with speculation about how
physicians may act to find inducement.”); Bayer Schering
Pharma AG v. Lupin, Ltd., 676 F.3d 1316, 1324 (Fed. Cir.
2012) (affirming that a label did not induce infringement
when, despite presenting data suggesting that a claimed
combination of effects could occur, the label as a whole did
not “recommend or suggest to a physician that [the drug]
is safe and effective for inducing the claimed combination
of effects in patients in need thereof”); AstraZeneca, 669
F.3d at 1380 (affirming no infringement when, despite
“market realities” that doctors will substitute the generic
for all indications, “[s]ection viii statements and corre-
sponding proposed labeling explicitly and undisputedly
carve out all patented indications”).
Case: 22-1194 Document: 95 Page: 18 Filed: 12/07/2023
18 H. LUNDBECK A/S v. LUPIN LTD.
held that “mere knowledge of possible infringement by oth-
ers does not amount to inducement; specific intent and ac-
tion to induce infringement must be proven.” Warner-
Lambert, 316 F.3d at 1364. This is so because a central
purpose of the Hatch-Waxman Act is to allow, through the
section viii carve out process, the sale of drugs for unpat-
ented uses even though those sales result in some infring-
ing uses. Takeda, 785 F.3d at 631–32. So too, the fact that
some individuals may have been influenced by one piece of
information from a label required to sell the drug for other
purposes does not amount to inducement. Plaintiffs’ argu-
ment is nothing more than an attempt to impose contribu-
tory infringement liability on the sale of a product knowing
it will be put to infringing uses without recognition of the
additional requirement that there be no substantial nonin-
fringing use.
Second, plaintiffs argue that the district court’s in-
duced infringement analysis “ignored [the] 5 mg, 10 mg,
and 15 mg doses” and “failed to cite any record evidence”
for them. Appellants’ Brief at 53. We disagree. The dis-
trict court relied on multiple sources of evidence that ap-
plied equally to all dosage forms, including the label’s
instruction against comparing TESD rates between vorti-
oxetine and other drugs and a survey of clinicians regard-
ing how they understand the label. The district court
explicitly noted that clinicians would not be encouraged to
prescribe vortioxetine to the implicated patient class “par-
ticularly for the recommended 20 mg dose.” J.A. 146 (em-
phasis added). There is no error in relying on evidence
about the recommended dose in addition to evidence that
applies equally to all approved doses. Notably, plaintiffs
argued in their post-trial brief on validity that “a POSA
would have understood all therapeutic doses to have simi-
larly low levels of [sexually related adverse events].” J.A.
236 (quoting D.I. 1059 at 28). Plaintiffs cannot now fault
the district court for crediting their own argument.
Case: 22-1194 Document: 95 Page: 19 Filed: 12/07/2023
H. LUNDBECK A/S v. LUPIN LTD. 19
The district court did not err in finding that plaintiffs
failed to establish induced infringement under 35 U.S.C.
§ 271(b).
C
Plaintiffs next argue that the district court erred by
concluding that the plaintiffs had not established contrib-
utory infringement of the ’096 and ’910 patents. The plain-
tiffs’ theory is that defendants will contributorily infringe
by selling their ANDA products because physicians will
prescribe them in accordance with the methods claimed in
the ’096 and ’910 patents. Under 35 U.S.C. § 271(c), there
is no liability for contributory infringement for selling an
article that is “suitable for substantial noninfringing use.”
The district court concluded that there was no contrib-
utory infringement because there are substantial nonin-
fringing uses of vortioxetine. With respect to the ’096
patent, the district court found that there will be substan-
tial noninfringing uses including prescribing vortioxetine
to patients with no prior treatment, patients with prior
treatment other than with the drugs referenced in the ’096
patent, and in cases where the prior antidepressant was
ceased or reduced for reasons other than sexually related
adverse events (for example, due to poor efficacy). Simi-
larly, with respect to the ’910 patent, there will be substan-
tial noninfringing uses including prescription for treating
MDD, prescription to patients without cognitive impair-
ment, and prescription for purposes unrelated to cognition.
Plaintiffs contend nonetheless that the district court
erred as a matter of law in finding substantial noninfring-
ing uses when those uses purportedly infringe other pa-
tents owned by Lundbeck, specifically patents on the drug
compound. However, substantial noninfringing use in sec-
tion 271(c) refers to uses that do not infringe the patent in
question, not other patents. The text is clear: to support
liability, the accused infringer must sell a material part of
an invention or an article for use in practicing a patented
Case: 22-1194 Document: 95 Page: 20 Filed: 12/07/2023
20 H. LUNDBECK A/S v. LUPIN LTD.
process “knowing the same to be especially made or espe-
cially adapted for use in an infringement of such patent.”
35 U.S.C. § 271(c) (emphasis added). “Such patent” is in
the singular and refers to a specific patent—the asserted
patent. In Sony v. Universal City Studios, describing the
scope of the patent laws, the Supreme Court noted that
“[t]here is no suggestion in the statute [section 271(c)] that
one patentee may object to the sale of a product that might
be used in connection with other patents” and stated that
“the Court has always recognized the critical importance of
not allowing the patentee to extend his monopoly beyond
the limits of his specific grant.” 464 U.S. 417, 440–41
(1984). To consider patents other than those asserted
against a defendant, as urged by plaintiffs, would imper-
missibly expand the exclusive grant Congress provided.
Plaintiffs also argue that the district court legally erred
in its factual finding that “Plaintiffs have not shown that
Defendants possess the intent required to prove contribu-
tory infringement” because intent is not an element of con-
tributory infringement. J.A. 151. While section 271(c)
does not use the word “intent,” the statute still imposes a
scienter requirement—that the accused infringer sells ar-
ticles “knowing the same to be especially made or especially
adapted for use in an infringement of such patent.” The
Supreme Court has characterized this as “§ 271(c)’s intent
requirement.” Global-Tech Appliances, Inc. v. SEB S.A.,
563 U.S. 754, 765 (2011); see also Grokster, 545 U.S. at 932(“The [contributory infringement] doctrine was devised to
identify instances in which it may be presumed from dis-
tribution of an article in commerce that the distributor in-
tended the article to be used to infringe another’s
patent . . . .”). The district court using similar language
was not error. In any event, the district court did not cite
a lack of intent in its legal analysis of contributory infringe-
ment. Rather, the district court relied on the existence of
substantial noninfringing uses to find no contributory in-
fringement. We see no error in this analysis.
Case: 22-1194 Document: 95 Page: 21 Filed: 12/07/2023
H. LUNDBECK A/S v. LUPIN LTD. 21
The district court did not err finding that plaintiffs
failed to establish contributory infringement under 35
U.S.C. § 271(c).
II
Lupin on its cross appeal argues that the district court
erred in construing “reacting” in the ’626 patent to mean
“the changing of a reactant(s) to product(s)” and in finding
infringement under that construction. We see no error.
“Claim construction is a matter of law and is reviewed
de novo.” Allen Eng’g Corp., 299 F.3d at 1344. “[T]he
words of a claim are generally given their ordinary and cus-
tomary meaning,” which is “the meaning that the term
would have to a person of ordinary skill in the art” deter-
mined “in the context of the entire patent.” Phillips v.
AWH Corp., 415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en
banc) (citations and internal quotation marks omitted).
Claim 12 depends from claim 1, which recites “a pro-
cess for the preparation of [compound I] . . . the process
comprising reacting compound II . . ., with a compound of
formula III . . ., and a compound [IV] . . .” (emphasis
added). The parties disagree on the construction of “react-
ing” in claim 1. Plaintiffs argued for the purported plain
and ordinary meaning, “the changing of a reactant(s) to
product(s).” J.A. 222. Lupin contended that “reacting”
means “the specified chemicals are added to the reaction
vessel at the beginning of the process as starting material.”
Id. The district court adopted plaintiffs’ construction. Lu-
pin, on cross appeal, contends the district court erred in
that construction and in finding infringement because Lu-
pin’s process does not use compound II as a starting mate-
rial. While it is true that the specification only refers to
using compound II as a starting material, nothing in the
claims, specification, or file history requires Lupin’s nar-
rower reading.
Case: 22-1194 Document: 95 Page: 22 Filed: 12/07/2023
22 H. LUNDBECK A/S v. LUPIN LTD.
The ’626 patent’s specification does not define the word
“reacting.” The 2004 Fifth Edition of the Oxford Dictionary
of Chemistry defines “chemical reaction” as “[a] change in
which one or more chemical elements or compounds (the
reactants) form new compounds (the products).” J.A. 124.
Plaintiffs’ expert agreed with this definition, as did defend-
ants’ invalidity expert. The district court noted that the
“claims of the ’626 Patent do not expressly recite ‘added,’
‘reaction vessel,’ ‘beginning of the process,’ or ‘starting ma-
terial,’ and they do not otherwise limit Claim 12 to a pro-
cess in which ‘the specified chemicals are added to the
reaction vessel at the beginning of the process as starting
material.’” J.A. 223.
Lupin primarily argues on appeal that the district
court erred by discounting evidence from the prosecution
history. In the referenced office action, the examiner used
the phrase “starting compound” to refer to the materials
that are reacted together. The examiner here appears to
have used “starting compound” to distinguish between
claimed reactants and the claimed products. See J.A.
18671 (“The level of skill and knowledge in the art would
not allow the Examiner to predict the use of a [particular]
starting compound in the production of the product of the
instant claims.”). But the examiner said nothing about the
scope of “reacting,” and the examiner’s use of the word
“starting compound” in isolation does not suggest that he
defined reacting as referring only to starting materials. In
any event, there are no statements by the patentee during
prosecution that limited the scope of “reacting,” and “the
examiner’s unilateral remarks alone do not affect the scope
of the claim.” Salazar v. Procter & Gamble Co., 414 F.3d
1342, 1347 (Fed. Cir. 2005).
Lupin also argues that the claims must be read to re-
strict the construction of “reacting” because claim 2, which
depends from claim 1, involves a two-reaction sequence
that first reacts compounds II and III and then reacts the
product of that reaction with compound IV in a subsequent
Case: 22-1194 Document: 95 Page: 23 Filed: 12/07/2023
H. LUNDBECK A/S v. LUPIN LTD. 23
reaction. Lupin failed to explain how claim 2 is incon-
sistent with the district court’s construction, which re-
quires only the changing of reactants to products.
Moreover, Lupin’s construction is in tension with depend-
ent claim 3, which recites “[t]he process according to claim
1, wherein compound II, compound III and compound IV
are mixed together at the start of the process.” Lupin’s con-
struction requires that the compounds be added “at the be-
ginning of the process as starting material,” rendering
claim 3 superfluous.
The district court did not err in its construction of “re-
acting” or in its determination of infringement.
CONCLUSION
We conclude that the district court did not err in find-
ing no infringement of the ’096 or ’910 patents. Lupin’s
cross appeal challenging the district court’s determination
that Lupin infringed the ’626 patent is similarly without
merit. We do not reach the conditional cross appeal as to
invalidity.
AFFIRMED
COSTS
Costs in the 22-1194 appeal to defendants Lupin Ltd.,
Lupin Pharmaceuticals, Inc., Macleods Pharma USA, Inc.,
Macleods Pharmaceuticals Ltd., Sandoz Inc., Sigmapharm
Laboratories, LLC, Zydus Pharmaceuticals (USA) Inc.,
Alembic Global Holding S.A., Alembic Pharmaceuticals
Inc., Alembic Pharmaceuticals Ltd., Cadila Healthcare
Ltd., and Lek Pharmaceuticals, d.d.
No costs in the 22-1246 cross appeal. Costs in the 22-
1208 cross appeal to plaintiffs H. Lundbeck A/S, Takeda
Pharmaceutical Company Ltd., Takeda Pharmaceuticals
U.S.A., Inc., Takeda Pharmaceuticals International AG,
and Takeda Pharmaceuticals America, Inc., and against
defendants Lupin Ltd. and Lupin Pharmaceuticals, Inc.