H. Lundbeck A/S v. Lupin Ltd.

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
                 ______________________
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 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
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 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.
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 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.
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 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”).
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 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.
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 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
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 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.
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 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.
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 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
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 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.