Source: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-15-01139/USCOURTS-ca13-15-01139-0/pdf.json

Nature of Suit Code: 830
Nature of Suit: Patent
Cause of Action: 

---

United States Court of Appeals 

for the Federal Circuit ______________________ 

TAKEDA PHARMACEUTICALS U.S.A., INC.,

Plaintiff-Appellant

v.

WEST-WARD PHARMACEUTICAL CORPORATION, 

HIKMA AMERICAS INC., HIKMA 

PHARMACEUTICALS PLC,

Defendants-Cross-Appellants

______________________ 

2015-1139, 2015-1142

______________________ 

Appeals from the United States District Court for the 

District of Delaware in No. 1:14-cv-01268-SLR, Judge Sue 

L. Robinson.

______________________ 

Decided: May 6, 2015 

______________________ 

JEFFREY I. WEINBERGER, Munger, Tolles & Olson LLP, 

Los Angeles, CA, argued for plaintiff-appellant. Also 

represented by TED G. DANE, ELIZABETH LAUGHTON; ERIC 

KELVIN CHIU, AMY GREYWITT, San Francisco, CA; MARY 

W. BOURKE, Womble, Carlyle, Sandridge & Rice, PLLC, 

Wilmington, DE; TRYN T. STIMART, Tysons Corner, VA . 

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2 TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 

CHARLES B. KLEIN, Winston & Strawn LLP, Washington, DC, argued for defendants-cross appellants. Also 

represented by JOVIAL WONG, STEFFEN NATHANAEL 

JOHNSON; SAMUEL S. PARK, Chicago, IL; WILLIAM G.

JAMES, II, WILLIAM M. JAY, Goodwin Procter LLP, Washington, DC.

EDWARD A. MARSHALL, Arnall Golden Gregory LLP, 

Atlanta, GA, for amicus curiae The American College of 

Rheumatology. 

MELISSA ARBUS SHERRY, Latham & Watkins LLP, 

Washington, DC, for amicus curiae Generic Pharmaceutical Association. 

______________________ 

Before NEWMAN, DYK, and HUGHES, Circuit Judges.

Opinion for the court filed by Circuit Judge DYK. 

Dissenting opinion filed by Circuit Judge NEWMAN. 

DYK, Circuit Judge. 

Takeda Pharmaceuticals U.S.A., Inc. (“Takeda”) appeals the order of the United States District Court for the 

District of Delaware denying its motion for preliminary 

injunction. Takeda sought to enjoin West-Ward Pharmaceutical Corporation, Hikma Americas Inc., and Hikma 

Pharmaceuticals PLC (collectively “Hikma”) from continuing its launch of Mitigare, a colchicine product for prophylactic treatment of gout, and from launching an 

authorized generic version of Mitigare. We affirm.

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TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 3

BACKGROUND

Takeda owns several asserted patents1 that cover 

several methods of administering colchicine products to 

treat gout. Colchicine itself, which has been used for 

centuries, is not covered by Takeda’s patents. The ’647 

and ’938 patents (the “acute gout patents”) are directed to 

methods of treating acute gout flares. The ’655, ’648 and 

’722 patents (the “drug-drug-interaction (DDI) patents”) 

are directed to methods for administering colchicine for 

prophylaxis of gout in patients who are concomitantly 

taking certain drug inhibitors known as “CYP3A4” and 

“P-gp” inhibitors. 

The acute gout patents recite methods of treating 

acute gout by administering 1.2 mg of oral colchicine at 

the onset of the flare, followed by 0.6 mg of colchicine 

about one hour later.

DDI patent ’655 recites administering colchicine concomitantly with clarithromycin by reducing the typical 

prophylactic dosage of colchicine by 75%, including a dose 

of 0.3 mg once a day. DDI patent ’648 recites concomitant 

administration with ketoconazole, where the reduced 

daily dose of colchicine is 25% to 50% of the daily dose, 

including a dose of 0.3 mg once a day. DDI patent ’722 

recites concomitant administration with 240 ml of verapamil, where the reduced daily dose of colchicine is 50% to 

75% of the daily dose. 

In 2009, Mutual was the first drug manufacturer to 

receive approval from the Food and Drug Administration 

(“FDA”) to market colchicine for treatment and prophylax1 The asserted patents are U.S. Patent Nos. 

7,964,648 (“the ’648 patent”), 7,981,938 (“the ’938 patent”), 8,097,655 (“the ’655 patent”), 8,440,722 (“the ’722 

patent”), and 7,964,647 (“the ’647 patent”).

 

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is of gout flares. Takeda acquired Mutual and the approved New Drug Application (“NDA”). Takeda sells the 

colchicine product under the brand name Colcrys. 

In 2010, Hikma sought FDA approval of a colchicine 

product for prophylaxis of gout flares. It submitted an 

NDA under § 505(b)(2) of the Drug Price Competition and 

Patent Term Restoration Act of 1984 (the “HatchWaxman Act”), codified at 21 U.S.C. § 355(b)(2). On 

September 26, 2014, the FDA granted Hikma approval to 

market its Mitigare colchicine capsule.

On October 3, 2014, Hikma launched Mitigare, and 

Takeda filed suit against Hikma, asserting induced 

infringement under 35 U.S.C. § 271(b) based on Hikma’s 

labeling of the Mitigare product. Hikma planned on 

launching an authorized generic version of Mitigare as 

early as October 10, 2014. However, the district court 

granted Takeda’s request for a temporary restraining 

order (“TRO”) on October 9, 2014, restraining Hikma from 

selling Mitigare and from launching a generic colchicine 

product. The district court also restrained Takeda from 

launching an authorized generic version of its branded 

Colcrys product during the TRO and required that

Takeda “provide notice to Hikma at least 10 business 

days before the launch of any authorized generic of Colcrys.” J.A. 20.

On November 4, 2014, the district court denied 

Takeda’s motion for preliminary injunction on the 

grounds that Takeda did not meet its burden of showing a 

likelihood of success on the merits for its induced infringement claims or irreparable injury. On the issue of 

the likelihood of success on the merits, the district court 

concluded that, although Hikma failed to raise a substantial question regarding the validity of the patents, Takeda 

had not met its burden of showing likelihood of proving 

induced infringement. On the issue of irreparable harm, 

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the district court concluded that Takeda had not shown a 

causal nexus between Hikma’s infringement and Takeda’s 

alleged harm.

In the order denying a preliminary injunction, the 

court also ordered that, if Takeda took an immediate 

appeal (the next day), “the status quo [would] be maintained pending appeal” by extending the TRO, including 

its 10-day notice provision. J.A. 16–17. 

Takeda timely appealed the denial of preliminary injunction, and Hikma cross-appealed. In its cross-appeal, 

Hikma argues that the extension of the TRO was based 

solely on its “consent,” and it should not have been extended past oral argument in this appeal. After oral 

argument on January 9, 2015, we issued, without dissent,

an order affirming the district court’s denial of preliminary injunction and vacating the TRO, including its 10-

day notice provision.2 Our order mooted Hikma’s crossappeal and Takeda’s argument that the 10-day notice 

provision in the TRO was improper. Our vacating of the 

order did not affect Takeda’s liability under the bond. We 

have jurisdiction pursuant to 28 U.S.C. § 1292(c). 

2 The order stated:

The district court’s order denying Takeda 

Pharmaceuticals U.S.A., Inc.’s motion for preliminary injunction is affirmed, opinion to follow.

The injunction pending appeal ordered by the 

district court is vacated effective immediately. 

The consequence of vacating the injunction pending appeal is that both parties are free to immediately offer colchicine products for prophylactic 

use, without regard to the 10-day provision of the 

district court’s order.

 

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DISCUSSION

We review a denial of a preliminary injunction for 

abuse of discretion. Abbott Labs. v. Sandoz, Inc., 544 F.3d 

1341, 1345 (Fed. Cir. 2008) (citing Doran v. Salem Inn, 

422 U.S. 922, 932 (1975)). A court abuses its discretion if 

it “ma[kes] a clear error of judgment in weighing relevant 

factors or exercise[s] its discretion based upon an error of 

law or clearly erroneous factual findings.” Id. (quoting 

Novo Nordisk of N. Am., Inc. v. Genentech, Inc., 77 F.3d 

1364, 1367 (Fed. Cir. 1996)).

In general, a party seeking a preliminary injunction 

must establish that it is likely to succeed on the merits, 

that it is likely to suffer irreparable harm in the absence 

of relief, that the balance of equities is in its favor, and 

that an injunction is in the public interest. See Titan Tire 

Corp. v. Case New Holland, Inc., 566 F.3d 1372, 1375–76

(Fed. Cir. 2009).

I 

The relevant statutory provisions here are in the 

Hatch-Waxman Act. The Hatch-Waxman Act allows 

generic manufacturers to rely on certain streamlined FDA 

approval processes by which generic drug manufacturers 

can bring their products to market without submitting all 

of the extensive drug and clinical data ordinarily required 

of an NDA under 21 U.S.C. § 355(b)(1). In particular, an 

applicant seeking approval to market a generic version or 

variant of a drug may file either an Abbreviated New 

Drug Application (“ANDA”) or a “505(b)(2) application,” 

sometimes called a “paper NDA.” Id. §§ 355(b)(2), (j). An 

ANDA allows applicants seeking approval for generic 

versions of existing drugs to rely on the safety and efficacy information for an approved drug listed in the Approved Drug Products with Therapeutic Equivalence 

Evaluations, or the “Orange Book.” A paper NDA allows 

applicants seeking approval for a new drug or a change to 

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an approved drug to rely on existing FDA findings of 

safety and effectiveness or studies not performed by the 

NDA applicant. 

Both the ANDA and paper NDA pathways generally 

require applicants to submit one of several kinds of patent 

certifications, see id. §§ 355(j)(2)(A)(vii)(I)-(IV), 

355(b)(2)(A)–(B), including a “Paragraph IV” certification 

that the relevant patents are either invalid or not infringed, which may in turn trigger patent litigation under

the artificial act of infringement created by 35 U.S.C. 

§ 271(e)(2)(A). See §§ 355(j)(2)(A)(vii)(IV), 

355(b)(2)(A)(iv); Eli Lilly & Co. v. Medtronic, Inc., 496 

U.S. 661, 675 (1990).

Here Colcrys was an FDA-approved drug, and Hikma 

elected to file a paper NDA pursuant to 21 U.S.C. 

§ 355(b)(2). Hikma did not, however, file a Paragraph IV 

certification with respect to Takeda’s patents because it 

relied on prior FDA findings of safety and efficacy concerning colchicine, and did not seek FDA approval for a 

use covered by Takeda’s patents. As Takeda concedes, 

“[a]dministering colchicine for prophylaxis of gout flares is 

not covered by Takeda’s asserted patents, except when it 

involves concomitant administration with certain other 

drugs.” Appellant’s Br. 4 n.1.

As we explained in Warner-Lambert Co. v. Apotex 

Corp., 316 F.3d 1348 (Fed. Cir. 2003), Congress intended

“that a single drug could have more than one indication 

and yet that [an] ANDA applicant could seek approval for 

less than all of those indications.” Id. at 1360. A patent 

certification such as a Paragraph IV certification need not 

be provided “for a patent claiming a use for which the 

ANDA applicant is not seeking approval.” Id. at 1361; see 

21 U.S.C. § 355(j)(2)(A)(viii); Caraco Pharm. Labs. v. Novo 

Nordisk A/S, 132 S. Ct. 1670, 1677 (2012); see also 21 

U.S.C. §§ 355(b)(2)(A)(i)–(iv), (b)(2)(B) (parallel provisions 

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8 TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 

in the paper NDA process). In such a situation, a generic 

manufacturer may avoid infringement by proposing a 

label that does not claim a patented method of use, Caraco, 132 S. Ct. at 1676–77, ensuring that “one patented use 

will not foreclose marketing a generic drug for other 

unpatented ones,” id. at 1682. 

II

With this statutory scheme in mind, we address the 

question of whether Takeda showed a likelihood of success on the merits of the induced infringement claim.

Such likelihood is not shown if an alleged infringer raises 

a substantial question regarding either infringement or 

validity of the asserted patents. See Genentech, Inc. v. 

Novo Nordisk A/S, 108 F.3d 1361, 1364 (Fed. Cir. 1997). 

A 

We first consider induced infringement with respect to 

the acute gout patents. Since Hikma did not seek FDA 

approval to market Mitigare for treatment of acute gout 

flares, Mitigare’s label stated that Mitigare is “indicated 

for prophylaxis” and that the “safety and effectiveness of 

[it] for acute treatment of gout flares during prophylaxis 

has not been studied.” J.A. 138. The label also said that 

“[i]f you have a gout flare while taking [Mitigare], tell 

your healthcare provider.” J.A. 148. Takeda argued that 

this latter statement induced infringement because, in 

the case of the patient taking Mitigare for prophylaxis, 

the physician would likely tell the patient to use the 

Mitigare product to treat the acute flare. The district 

court concluded that the latter instruction was not sufficient to establish induced infringement. We agree.

“Whoever actively induces infringement of a patent 

shall be liable as an infringer.” 35 U.S.C. § 271(b). “[The] 

sale of a lawful product by lawful means, with the 

knowledge that an unaffiliated, third party may infringe, 

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cannot, in and of itself, constitute inducement of infringement.” Dynacore Holdings Corp. v. U.S. Philips 

Corp., 363 F.3d 1263, 1276 n.6 (Fed. Cir. 2004) (internal 

quotation marks and citation omitted). The accused 

infringer must have “knowingly aided and abetted” direct 

infringement. Warner-Lambert, 316 F.3d at 1363 (citations omitted).

As the Supreme Court held in the analogous context 

of copyright infringement, there is no indirect infringement “when a defendant merely sells a commercial product suitable for some lawful use.” Metro-Goldwyn-Mayer 

Studios Inc. v. Grokster, Ltd., 545 U.S. 913, 936 (2005) 

(citing Water Techs. Corp. v. Calco, Ltd., 850 F.2d 660, 

668 (Fed. Cir. 1988)). Infringement only exists where 

there is evidence that “goes beyond a product’s characteristics or the knowledge that it may be put to infringing 

uses.” Id. at 935. Inducement can be found where there is 

“[e]vidence of active steps taken to encourage direct 

infringement,” which can in turn be found in “advertising 

an infringing use or instructing how to engage in an 

infringing use.” Id. at 936 (citations and internal quotation marks omitted).3 But such instructions need to 

3 We have specifically approved Grokster’s definition in the patent context. See Ricoh Co., Ltd. v. Quanta 

Computer Inc., 550 F.3d 1325, 1341 (Fed. Cir. 2008) 

(noting that “we turn to Grokster and its analysis of the 

law of active inducement,” quoting Grokster, and stating 

that inducement requires evidence of promotion, active 

steps, or encouragement). Well before Grokster, we had 

adopted a virtually identical test. For example, in Water 

Technologies (a patent case cited approvingly by the 

Supreme Court in Grokster in its analysis of inducement, 

see 545 U.S. at 936), we noted that inducement requires 

“actively . . . aiding and abetting another’s direct in-

 

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evidence “intent to encourage infringement.” Vita-Mix 

Corp. v. Basic Holding, Inc., 581 F.3d 1317, 1329 (Fed. 

Cir. 2009) (emphasis added). The question is not just 

whether instructions “describ[e] the infringing mode,” 

Toshiba Corp. v. Imation Corp., 681 F.3d 1358, 1365 (Fed. 

Cir. 2012) (distinguishing Fujitsu Ltd. v. Netgear Inc., 620 

F.3d 1321 (Fed. Cir. 2010)), but whether the “instructions 

teach an infringing use of the device such that we are 

willing to infer from those instructions an affirmative 

intent to infringe the patent,” Vita-Mix, 581 F.3d at 1329

n.2 (emphasis added). Merely “describ[ing],” Toshiba, 681 

F.3d at 1365, an infringing mode is not the same as 

“recommend[ing],” id., “encourag[ing],” Grokster, 545 U.S. 

at 930, or “promot[ing],” Metabolite Labs., Inc. v. Lab.

Corp. of Am. Holdings, 370 F.3d 1354, 1365 (Fed. Cir. 

2004), an infringing use, or suggesting that an infringing 

use “should” be performed, see Arthrocare Corp. v. Smith 

& Nephew, Inc., 406 F.3d 1365, 1377 (Fed. Cir. 2005) 

(finding inducement where instruction manuals indicated 

product should be used in infringing manner).

fringement.” Water Techs., 850 F.2d at 668 (emphasis 

added); see also Warner-Lambert, 316 F.3d at 1364 (“In 

the absence of any evidence that Apotex has or will promote or encourage doctors to infringe the neurodegenerative method patent, there has been raised no genuine 

issue of material fact [as to inducement]” (emphases 

added)); Tegal Corp. v. Tokyo Electron Co., 248 F.3d 1376, 

1378–79 (Fed. Cir. 2001) (explaining that inducement 

requires an “affirmative act,” including that which “causes, or urges, or encourages, or aids another to infringe a 

patent” (citation omitted)); Manville Sales Corp. v. Paramount Sys., Inc., 917 F.2d 544, 553 (Fed. Cir. 1990) (inducement requires “intent to encourage another’s 

infringement”).

 

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The principles that can be distilled from these cases 

are applicable in the Hatch-Waxman Act context where, 

as here, it is alleged that the drug label induces infringement by physicians. The label must encourage, recommend, or promote infringement. See Grokster, 545 U.S. at 

936; Toshiba, 681 F.3d at 1365; Metabolite, 370 F.3d at 

1365. The mere existence of direct infringement by physicians, while necessary to find liability for induced infringement, is not sufficient for inducement. As we stated 

in Warner-Lambert in the ANDA context, it is wellestablished that “mere knowledge of possible infringement by others does not amount to inducement; specific 

intent and action to induce infringement must be proven.” 

316 F.3d at 1364 (citation omitted).

This requirement of inducing acts is particularly important in the Hatch-Waxman Act context because the 

statute was designed to enable the sale of drugs for nonpatented uses even though this would result in some offlabel infringing uses. See Caraco, 132 S. Ct. at 1681–82

(“Congress understood [that] a single drug may have 

multiple methods of use, only one or some of which a 

patent covers” and that the statute “contemplates that 

one patented use will not foreclose marketing a generic 

drug for other unpatented ones.”); Warner-Lambert, 316 

F.3d at 1359 (the Hatch-Waxman Act was not intended 

“as a sword against any competitor’s ANDA seeking 

approval to market an off-patent drug for an approved use 

not covered by the patent”).

Takeda concedes that mere knowledge of off-label infringing uses of Mitigare’s product would not establish 

inducement. Similarly insufficient is Hikma’s knowledge, 

acquired from the FDA, that colchicine is used to treat 

acute gout flares. The FDA has previously told healthcare 

providers to prescribe Colcrys for acute gout flares, and 

the FDA told Hikma that “it may be natural for the 

provider to use [Mitigare] for acute treatment.” AppelCase: 15-1139 Document: 75-2 Page: 11 Filed: 05/06/2015
12 TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 

lant’s Br. 37. So too the guidelines from the American 

College of Rheumatology (“ACR”) that recommend prescribing Colcrys for acute gout flares are irrelevant to the 

question of inducement. All of this, without more, is mere 

knowledge of infringing uses and does not establish 

inducement.

But Takeda argues that Mitigare’s label, though indicated only for prophylaxis of gout, induces infringement 

by stating that “[i]f you have a gout flare while taking 

Mitigare, tell your healthcare provider,” J.A. 148. Although this is neither an explicit nor implicit instruction to 

take Mitigare for acute gout treatment, Takeda argues 

that the instruction to “tell your healthcare provider” will 

“inevitably” lead to physicians who are consulted to advise 

patients taking Mitigare for prophylaxis to simply increase their dose of Mitigare to treat acute gout flares, 

and that Hikma was aware of or willfully blind to this 

possibility. Hikma argues that the label’s statement that 

the “safety and effectiveness” of Mitigare “for acute 

treatment of gout flares during prophylaxis has not been 

studied” bars a finding of inducement, relying on Bayer 

Schering Pharma AG v. Lupin, Ltd., 676 F.3d 1324 (Fed. 

Cir. 2012). We need not address whether or not lack of 

approval language precludes a finding of inducement. 

Given the statutory scheme explained above, vague 

label language cannot be combined with speculation about 

how physicians may act to find inducement. This would 

seem to too easily transform that which we have held is 

“legally irrelevant,” Warner-Lambert, 316 F.3d at 1364—

mere knowledge of infringing uses—into induced infringement.4

4 Takeda even goes so far as to suggest that the label needs to contain a “clear statement” to show that it 

 

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But we need not decide whether evidence as to the invariable response of physicians could ever transform a 

vague label into active encouragement. Here, even if we 

do look outside the label, there is no evidence that the 

label would necessarily lead doctors who are consulted by 

patients taking Mitigare to prescribe an off-label use of it 

to treat acute gout flares.

First, Takeda does not dispute that there are a host of 

alternatives for treating gout flares. These alternatives 

include non-steroidal anti-inflammatory drugs such as 

indomethacin or naproxen and systemic and intraarticular corticosteroids. As the 2012 ACR Guidelines for 

Gout Management explain, “it is at the discretion of the 

prescribing physicians to choose the most appropriate 

monotherapy based on the patient’s preference, prior 

response to pharmacologic therapy for an acute gout 

attack, and associated comorbidities.” J.A. 387. Takeda 

points to no record evidence that physicians would forego 

these alternatives and simply increase the dose of Mitigare when it failed to work as a prophylactic. Indeed, the 

ACR says that because colchicine can cause various 

adverse side effects, “[r]heumatologists rarely use colchicine for acute gout flares but utilize colchicine frequently 

for chronic gout prophylaxis.” J.A. 1505. Instead, nonsteroidal anti-inflammatory drugs have become the 

“treatment choice for most acute attacks of gout.” Appellee’s Br. 32.

was avoiding gout flare indication, and that Hikma needs 

to “believe[] Mitigare will be used for prophylaxis only.” 

Appellant’s Reply Br. 12. This turns the legal test on its 

head. Takeda needs to show that Hikma took affirmative 

steps to induce, not affirmative steps to make sure others 

avoid infringement.

 

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Second, even with respect to physicians who would 

prescribe colchicine for the acute gout flares, there is 

insufficient evidence that doctors would inevitably prescribe Mitigare. Evidence that colchicine is prescribed for 

acute gout flares says nothing about whether Mitigare 

would be so prescribed. Takeda argues that, where the 

physician prescribes colchicine for an acute gout flare, it 

would be “impractical” for a patient already taking colchicine for prophylaxis not to “reach for the colchicine they 

have on hand” and follow Takeda’s patented methods. 

Appellant’s Reply Br. at 5. Takeda also suggested that it 

is “common sense” that doctors would prescribe Mitigare 

for an infringing use because it is already available on the 

shelf of the patient taking it for prophylaxis. But in 

Warner-Lambert, we already rejected the argument that 

it was “common knowledge” in the field that physicians 

routinely prescribe approved drugs for off-label uses, that 

information regarding the off-label prescriptions was 

“readily available” to the public, and that generic drugs 

are “commonly substitute[d]” for branded drugs. 316 F.3d 

at 1364; see also ACCO Brands, Inc. v. ABA Locks Mfr.

Co., 501 F.3d 1307, 1312–13 (Fed. Cir. 2007) (rejecting the 

argument that infringement can be found because a 

“natural and intuitive way to employ” the accused product 

was infringing).

Attempting to bridge this evidentiary deficit, Takeda 

also submitted physicians’ declarations allegedly showing 

what physicians would do when patients consult them 

about acute gout flares. One of Takeda’s physician 

declarations stated that “[e]ven though the [Mitigare] 

label states that the product has not been tested for use in 

treating gout flares, [he] believe[s] treating physicians 

would encourage patients to use Mitigare for this purpose” anyway because “in [his] experience, physicians will 

not recommend that a patient suffering a gout flare have 

two very similar colchicine products, i.e., Colcrys and 

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Mitigare, on hand.” J.A. 2658–59 (emphasis added). The 

other declarant stated that he would “understand” that 

either Colcrys or Mitigare “could be used with equal 

effectiveness for the indications for which the other drug 

is approved,” and that “[b]ecause the Mitigare product 

label does not provide a low-dose regimen for treating 

acute flares . . . [he] expect[s] that some doctors would 

consult the Colcrys product label to inform a patient using 

Mitigare to take colchicine according to the low-dose 

regimen specified in the Colcrys label.” J.A. 99. Takeda 

contends that these declarations establish a “likelihood 

that some prescribers would practice the claimed method.” 

Appellant’s Br. 36.

Speculation or even proof that some, or even many,

doctors would prescribe Mitigare for acute flares is hardly 

evidence of inevitability. This evidence does not show 

anything more than that there may be some infringing 

uses of Mitigare.5

Finally, Takeda relies heavily on Astrazeneca LP v. 

Apotex, Inc., 633 F.3d 1042 (Fed. Cir. 2010), to argue that 

the label induces infringement. The asserted method 

claims there covered treating respiratory diseases such as 

asthma by administering “a nebulized dose” of 

budesonide, i.e., an anti-inflammatory corticosteroid 

5 One declaration also stated that, “for a patient 

suffering a new or recurring acute gout attack, the patient 

will reach for his colchicine and follow the Colcrys lowdose regimen.” J.A. 2659. This evidence does not suggest 

physicians would prescribe Mitigare in accordance with 

Colcrys’ product label when consulted by patients. In fact, 

it seems to indicate something that undermines Takeda’s 

argument: that a physician believes that patients will 

simply ignore Mitigare’s label instructing them to consult 

their physician and use the drug off-label themselves. 

 

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suspended in a liquid to be inhaled, at a frequency of “not 

more than once per day.” Id. at 1048. An accused infringer’s label for a generic version of such an asthma inhaler 

instructed patients to take the drug “twice daily in divided doses” for a total daily dose of 0.5 mg, and that patients should “downward-titrate to the lowest effective 

dose.” Id. at 1057. Because the label stated that the 

lowest available dose was a 0.25 mg vial, titrating down 

required going down from taking 0.25 mg twice a day to 

taking it once a day. Id. Thus the patient did not have to 

consult anything outside of the label to infringe. The 

instruction would “necessarily lead” to infringement. Id.

This, we explained, was enough for “active steps” taken to 

“encourage” direct infringement. Id. at 1059. Here, in 

contrast, Takeda asks us to look outside the label to 

understand the alleged implicit encouragement in the 

label, even while it admits that evidence of mere 

knowledge of infringing uses is not sufficient.

The district court correctly concluded that Takeda did 

not establish a probability of success on the issue of 

infringement.

B 

Takeda’s arguments with respect to the DDI patents 

are similarly insufficient to support a finding of inducement. The Mitigare label warns patients that coadministration of colchicine and certain inhibitors “have 

been reported to lead to colchicine toxicity,” that drugdrug interactions must thus “be considered prior to and 

during therapy,” and that concomitant use “should be 

avoided if possible.” J.A. 137. The label also warns that if 

co-administration “is necessary, the dose of Mitigare 

should be reduced and the patient should be monitored 

carefully for colchicine toxicity.” Id. At one point the label 

also suggests that if co-administration is necessary, “the 

dose . . . should be adjusted by either reducing the daily 

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TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 17

dose or reducing the dose frequency.” J.A. 140. Takeda 

argues that this language constitutes inducement because 

a healthcare provider will have to determine whether coadministration is “necessary,” and the physician would 

then follow the patented methods. Takeda submitted 

declarations in which a physician hypothesized that he 

would “typically” follow Takeda’s patented methods if it 

was necessary to co-administer colchicine and medications 

“such as” the relevant inhibitors. J.A. 100.

Noting that this label language failed to recommend 

or suggest to physicians that the patented DDI methods 

should be followed, the district court found that, in any 

case, there was insufficient evidence “that any healthcare 

provider has actually practiced the methods of the DDI 

patents,” J.A. 13. The district court concluded that 

Takeda did not even meet its burden to show likelihood of 

direct infringement, which is a prerequisite for indirect 

infringement. See Ricoh, 550 F.3d at 1341.

With respect to the ’655 and ’648 patents requiring a 

0.3 mg dose of colchicine, the district court found that 

Mitigare would not likely be used to directly infringe 

because it comes in 0.6 mg capsules that cannot feasibly 

be split to reach a 0.3 mg dose of colchicine per day. 

Takeda argues that the capsules can be taken every other 

day to reach an average of 0.3 mg per day, citing in particular the language in Mitigare’s label that warned 

patients to “either reduc[e] the daily dose or reduc[e] the 

dose frequency” if concomitant administration is necessary. But the district court found that, given that colchicine has a “narrow therapeutic index” whereby the 

margin between an effective dose and a toxic dose is 

narrow, this possibility was not likely. In any case, as 

Hikma argues, given that Mitigare’s label recites a 0.6 mg 

“once or twice daily” recommendation and a “maximum 

dose” recommendation, J.A. 137, it is natural to read 

“reducing the dose frequency” as just instructing reducing

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18 TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 

0.6 mg from twice daily to once daily and not to achieve 

the 0.3 mg dose by administering 0.6 mg every other day. 

The district court’s findings on this issue were not clearly 

erroneous. 

With respect to the ’722 patent, which requires 0.6 mg 

of colchicine concomitantly administered with 240 ml of 

verapamil, the district court found that Takeda cited 

insufficient evidence this method would actually be practiced. While Takeda points out that it submitted evidence 

that 240 ml was the “usual” dose of verapamil, we see no 

clear error in the district court’s finding that this was 

insufficient, especially since the issue is whether the 

concomitant administration occurs, and Hikma’s physician experts declared that they try to and can easily avoid 

concomitant administration of the drugs.6 Since there was 

insufficient proof of direct infringement here, we need not 

reach the question of whether there was evidence of 

inducement.

CONCLUSION

We conclude that the district court did not abuse its 

discretion in denying a preliminary injunction on the 

ground that Takeda had failed to meet its burden to show 

a likelihood of success on the merits. Because of our 

disposition, we need not reach Takeda’s other arguments.

The main appeal is:

AFFIRMED

The cross-appeal is:

6 The fact that one doctor said that he has prescribed colchicine concomitantly with the inhibitors is not 

evidence that other doctors would do the same, nor is it 

evidence of direct infringement since he did not speak of 

using Mitigare.

 

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TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 19

DISMISSED AS MOOT

COSTS

Costs to Hikma. 

Case: 15-1139 Document: 75-2 Page: 19 Filed: 05/06/2015
United States Court of Appeals 

for the Federal Circuit ______________________ 

TAKEDA PHARMACEUTICALS U.S.A., INC.,

Plaintiff-Appellant

v.

WEST-WARD PHARMACEUTICAL CORPORATION, 

HIKMA AMERICAS INC., HIKMA 

PHARMACEUTICALS PLC,

Defendants-Cross-Appellants

______________________ 

2015-1139, 2015-1142

______________________ 

Appeals from the United States District Court for the 

District of Delaware in No. 1:14-cv-01268-SLR, Judge Sue 

L. Robinson.

______________________ 

NEWMAN, Circuit Judge, dissenting.

This is not a simple question of the legal status of patented uses of unpatented drugs. This is a legal policy 

issue, for the patent law implements a complex balance 

between the incentive to develop new medicinal treatments in the public interest, while facilitating competition 

after patent expiration.

The product colchicine has been used to treat gout for 

centuries, but was known to have highly toxic side effects. 

Takeda discovered and developed modes of treatment at 

reduced toxicity. Takeda took these methods and products through clinical trials and FDA approval, and obCase: 15-1139 Document: 75-2 Page: 20 Filed: 05/06/2015
2 TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 

tained patents on the treatment methods. My colleagues 

hold that none of these patents is enforceable against 

Hikma, a new provider of colchicine. 

It is agreed that Hikma is not a direct infringer of the 

Takeda patents, and my colleagues hold that Hikma does 

not induce infringement because the official Hikma “label” does not contain directions to use colchicine in accordance with the Takeda patented uses. Takeda argued 

that it suffices that the Hikma label directs patients to 

tell a health care provider if the affliction of acute gout 

flares arises, because the health care provider will prescribe the Takeda method of use. My colleagues hold that 

such circumstance cannot produce induced infringement.

In my view, these events do not produce a simple, 

bright line rule of law. In this preliminary injunction 

proceeding, the parties produced conflicting evidence as to 

the prevalence of gout flares and the likelihood that a 

doctor would prescribe the patented Takeda treatments. 

Precedent is also conflicting if generalized to all circumstances. In Toshiba Corp. v. Imation Corp., 681 F.3d 

1358, 1364 (Fed, Cir. 2012), this court held that “[t]he 

existence of a substantial non-infringing use does not 

preclude a finding of inducement.” But in WarnerLambert Co. v. Apotex Corp., 316 F.3d 1348, 1366 (Fed. 

Cir 2002) this court said that “[w]here a product has 

substantial noninfringing uses, intent to induce infringement cannot be inferred even when [the accused infringer] has actual knowledge that some users of its product 

may be infringing the patent.”

The panel majority today adopts a rule that inducement cannot be found, whatever the facts of the particular

medicament and use. That is seriously flawed, for the 

variety of medicinal situations is unlimited. In turn, the 

public interest in new uses, new methods, and new combination treatments is disserved by a rule that is a disinCase: 15-1139 Document: 75-2 Page: 21 Filed: 05/06/2015
TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 3

centive to the development of new uses of unpatented 

medicinal products.

Thus I dissent from the court’s ruling that the provider of a known drug product, with knowledge that it is 

likely to be used in direct infringement, can never be 

liable for induced infringement. These are fact-specific 

circumstances, and are not amenable to final disposition 

at a preliminary injunction hearing. The question requires trial on the facts of this case.

DISCUSSION

The panel majority presents an incomplete picture of 

the facts and the law and ignores the public interest in 

the development of improved methods of treatment.

Although colchicine is a known gout treatment, 

Takeda, through its predecessor Mutual, developed new 

treatment protocols for acute gout flares, conducted 

clinical trials, including treatment for patients concomitantly taking other drugs, and secured FDA approval for 

safety and efficacy of specified dosages and combinations 

and schedule of administration. This information is 

included on the FDA-approved Takeda label, and omitted 

from the Hikma label. 

Hikma provides colchicine capsules in the same 0.6 

mg dosage as the Takeda approved product, but the FDA 

permitted Hikma to omit from its label the combinations 

and acute flare treatment method patented by Takeda. 

Instead, the Hikma label instructs users that if acute gout 

flares arise, “tell your healthcare provider.”1

1 The FDA initially objected to this omission from 

the Hikma label, stating that “If Mitigare is being used 

for prophylaxis, it may be natural for the provider to use 

it for acute treatment as well.” Hikma then added to its 

label that Mitigare was not “studied” for “safety and 

 

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4 TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 

Takeda argues that the Hikma label statement is an 

inducement to infringe, providing testimony from physicians that they would tell the patient to use the Takeda 

protocol. Hikma provided contrary testimony. My colleagues on this panel hold that it is “not sufficient for 

inducement” that physicians and patients would directly 

infringe the Takeda patents. Maj. Op. at 11. To the 

contrary, it is highly relevant, for this situation does not 

lend itself to a rigid, all-purpose rule of law. This should 

be a fact-dependent, case-by-case determination based on 

evidence of likelihood and intent for the particular unpatented drug and patented new use. 

The panel majority goes too far, and states a general 

rule that provides easy avoidance of patents on new uses 

and improvements. The Hatch-Waxman Act is intended 

to encourage drug research and development, not to

provide a disincentive by negating enforcement of improvement patents by the simple expedient of omitting 

the improvement from the label. With the removal of the 

patent incentive for improvements, the loser is the afflicted public.

The panel majority is incorrect in stating that “in the 

Hatch-Waxman Act context . . . . [t]he label must encourage, recommend, or promote infringement.” Maj. Op. at 

11 (citing Metro-Goldwyn-Mayer Studios Inc. v. Grokster, 

Ltd., 545 U.S. 913, 936 (2005). The FDA label is not a 

vehicle of promotion of any use; it is a record of approved 

safety and efficacy of the product as used in accordance 

with the label. Nor does the FDA “aid and abet” infringement by including approved uses on the label. 

Grokster is a copyright case, and although there is common law commonality in the word “inducement,” questions of intent and scienter are as fact-specific in the 

effectiveness” of treatment of acute gout flares. On this 

statement, the FDA withdrew its objection. 

 

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copyright field as in connection with patents. An oversimplified analogy between copyright and patent causes 

does not aid understanding of these complex issues.

The panel majority also appears to misunderstand the 

Hatch-Waxman Act. The majority says “the statute was 

designed to enable the sale of drugs for non-patented uses 

even though this would result in some off-label infringing 

uses,” Maj. Op. at 11, citing purported authority in Caraco Pharm. Labs., Ltd. v. Novo Nordisk A/S, 132 S. Ct. 

1670, 1681-82 (2012); Warner-Lambert, 316 F.3d at 1359. 

That is a misreading of statute and precedent. The 

Hatch-Waxman Act is not designed to enable off-label 

uses, whether or not they are infringing.

The cited cases do not hold otherwise. To the contrary, Warner-Lambert states that “‘[I]f there are indications 

which are claimed by any use patent and for which the 

[ANDA] applicant is not seeking approval, then an ANDA 

must state that the applicant is not seeking approval for 

those indications which are claimed by such use patent.’” 

316 F.3d at 1359 (quoting House Report No. 98-857). 

Takeda argues that the Hikma label, which mentions 

acute gout flares but advises afflicted persons to see a 

physician instead of reciting the FDA-approved protocol, 

suffices to induce infringement. Unlike the facts of Warner-Lambert, Takeda is not “asserting patents on unapproved uses,” 316 F.3d at 1359. It is infringement of the 

approved patented uses that Takeda states is induced by 

instructing the patient to tell a doctor in the event of 

acute flares. Takeda offered evidence that the physician 

is likely to prescribe the Takeda protocol and dosage for 

treatment of acute flares. Resolution of the question of 

inducement depends on the facts of the case. However, 

the panel majority rejects even the need for such resolution, stating that “we need not decide whether evidence as 

to the invariable response of physicians could ever transCase: 15-1139 Document: 75-2 Page: 24 Filed: 05/06/2015
6 TAKEDA PHARMACEUTICALS U.S.A. v. HIKMA AMERICAS INC. 

form a vague label into active encouragement.” Maj. Op. 

13. To the contrary: that is the issue of this case.

The trier of fact must have the opportunity to consider 

the evidence of how particular uses are made known and 

implemented for the Hikma product. The panel majority 

misstates my argument, for I do not propose that liability 

for inducement is automatic. Here, Hikma instructs that 

if acute flares arise, “tell your healthcare provider”; and 

Takeda presented evidence that the doctor is likely to 

prescribe the Takeda protocol, for that protocol is approved by the FDA and is known to physicians who treat 

gout. The panel majority errs in discarding all this as 

irrelevant, for the knowledge and extent and likelihood of 

infringement are highly relevant to whether infringement 

is deemed induced. 

These aspects warrant full development of fact and 

law, and thoughtful application to this case. 

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