United States Court of Appeals 

for the Federal Circuit 

__________________________ 

ASTRAZENECA LP 

AND ASTRAZENECA AB, 

Plaintiffs-Cross Appellants, 

v. 

APOTEX, INC. 

AND APOTEX CORP., 

Defendants-Appellants. 

__________________________ 

2009-1381, -1424 

__________________________ 

Appeal from the United States District Court for the 

District of New Jersey in case no. 09-CV-1518, Judge 

Renee Marie Bumb. 

__________________________ 

Decided: November 1, 2010 

__________________________ 

DENISE L. LORING, Ropes & Gray LLP, of New York, 

New York, argued for plaintiffs-appellees. With her on 

the brief were CHRISTOPHER J. HARNETT, PABLO D.

HENDLER and DEREK M. KATO. 

RICHARD J. BASILE, St. Onge Steward Johnston & 

Reens LLC, of Stamford, Connecticut, argued for defendants-appellants. With him on the brief were DAVID W.

ALDRICH and ROY D. GROSS. Of counsel on the brief was 
ASTRAZENECA LP v. APOTEX 2

SHASHANK UPADHYE, Intellectual Property Law Apotex, 

Inc., of Toronto, Ontario, Canada. 

WILLIAM A. RAKOCZY, Rackoczy Molino Mazzochi Siwik LLP, of Chicago, Illinois, for amicus curiae Breath 

Limited. With him on the brief were DEANNE M.

MAZZOCHI and AMY D. BRODY. 

RICHARD T. RUZICH, Duane Morris LLP, of Chicago, 

Illinois, for amicus curiae Xttrium Laboratories, Inc. 

With him on the brief were JOSEPH M. BENNETT-PARIS, of 

Atlanta, Georgia; ANTHONY J. FITZPATRICK and 

CHRISTOPHER S. KROON, of Boston, Massachusetts; 

MATTHEW C. MOUSLEY, of Philadelphia, Pennsylvania; 

and KERRY B. MCTIGUE, of Washington, DC. 

__________________________ 

Before RADER, Chief Judge,* BRYSON and LINN, Circuit 

Judges. 

Opinion for the court filed by Circuit Judge LINN. 

Opinion concurring-in-part and dissenting-in-part filed by 

Circuit Judge BRYSON. 

LINN, Circuit Judge. 

Apotex, Inc. and Apotex Corp. (collectively “Apotex”) 

appeal from the grant by the United States District Court 

for the District of New Jersey of a preliminary injunction 

barring Apotex from launching a generic version of a 

budesonide drug made and distributed under the approval of the United States Food and Drug Administration (“FDA”) by AstraZeneca LP and AstraZeneca AB 

(collectively “AstraZeneca”) and covered under method 

 * Randall R. Rader assumed the position of 

Chief Judge on June 1, 2010. 
3 ASTRAZENECA LP v. APOTEX

and kit claims in AstraZeneca’s U.S. Patents No. 

6,598,603 (“the ’603 Patent”) and No. 6,899,099 (“the ’099 

Patent”). AstraZeneca cross-appeals the district court’s 

ruling that the asserted kit claims in both patents are 

invalid. Because the district court did not abuse its 

discretion by granting the preliminary injunction and did 

not err in determining that the kit claims are invalid, this 

court affirms. 

BACKGROUND

I. The Drug Approval Process 

In part, this appeal concerns the procedures for obtaining permission to sell either a “new” or generic drug 

under the Federal Food, Drug, and Cosmetic Act, ch. 675, 

52 Stat. 1040 (1938) (codified as amended in scattered 

sections of 21 U.S.C.). Under the Act, the FDA must 

approve all new drugs before such drugs may be distributed in interstate commerce. 21 U.S.C. § 355(a). To 

obtain approval for a new drug, an applicant may file a 

New Drug Application (“NDA”) that includes examples of 

the proposed label for the drug and clinical data demonstrating that the drug is safe and effective for use. Id.

§ 355(b)(1)(A), (b)(1)(F). The NDA must contain the 

patent number and expiration date of any patent that 

claims either the drug or a method of using the drug if “a 

claim of patent infringement could reasonably be asserted.” Id. § 355(b)(1). The FDA publishes the names of 

approved drugs and their associated patent information 

in the Approved Drug Products with Therapeutic Equivalence Evaluations list, commonly referred to as the “Orange Book.” 

An applicant seeking approval to market a generic 

version of a drug may file either an Abbreviated New 

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

which is also known as a “paper NDA.” Id. § 355(b)(2), (j). 
ASTRAZENECA LP v. APOTEX 4

An ANDA allows an applicant to rely on the safety and 

efficacy information for the listed drug if the applicant 

can show that the generic drug is “bioequivalent” to the 

listed drug. 

An ANDA has three requirements that are particularly relevant here. First, the applicant must demonstrate that “the route of administration, the dosage form, 

and the strength of the new drug are the same as those of 

the listed drug,” unless the FDA has approved a “suitability petition” requesting permission to file an ANDA that 

differs from the listed drug in one or more of these respects. Id. § 355(j)(2)(A)(iii), (j)(2)(C). Second, subject to 

changes required by FDA regulations or a successful 

suitability petition, the applicant must also show that 

“the labeling proposed for the new drug is the same as the 

labeling approved for the listed drug.” Id.

§ 355(j)(2)(A)(v). Third, for each patent listed in the 

Orange Book that claims either the listed drug or a use of 

the listed drug for which the applicant is requesting 

approval, an ANDA must include either one of four certifications or a “section viii statement.” 

If an applicant chooses to submit a certification, the 

applicant must certify “(I) that . . . patent information has 

not been filed, (II) that such patent has expired, (III) . . . 

the date on which such patent will expire, or (IV) that 

such patent is invalid or will not be infringed by the 

manufacture, use, or sale of the new drug.” Id.

§ 355(j)(2)(A)(vii)(I)-(IV). These certifications are referred 

to as Paragraph I, II, III, and IV certifications, respectively. 

Assuming all regulatory requirements are satisfied, 

the FDA may immediately make effective the approval of 

an ANDA that includes either a Paragraph I or II certification. Id. § 355(j)(5)(B)(i). By contrast, the filing of a 
5 ASTRAZENECA LP v. APOTEX

Paragraph III or IV certification may delay the effective 

date of an ANDA approval, and, in the case of a Paragraph IV certification, invite a patent infringement suit. 

See 35 U.S.C. § 271(e)(2), 21 U.S.C. § 355(j)(5)(B)(ii)-(iii). 

If, however, an applicant is seeking approval for a 

method of use not claimed in a “method of use patent” 

associated with the listed drug, the applicant must submit 

a section viii statement declaring that the patent does not 

claim such a use. 21 U.S.C. § 355(j)(2)(A)(viii). The 

applicant must also remove or “carve out” any mention of 

the patented method of use from the proposed label for 

the generic drug. See 21 C.F.R. § 314.92(a)(1); Novo 

Nordisk A/S v. Caraco Pharm. Labs., Ltd., 601 F.3d 1359, 

1361 (Fed. Cir. 2010) (“Along with the section viii statement, the generic manufacturer must submit a proposed 

label to the FDA that does not contain the patented 

method of using the listed drug.”). Unlike a Paragraph III 

or IV certification, the filing of a section viii statement 

will not by itself delay approval of an ANDA. 

Finally, in contrast to an ANDA, a paper NDA must 

include safety and effectiveness data. 21 U.S.C. 

§ 355(b)(2). However, a paper NDA may rely on safety 

and effectiveness data not developed by the applicant. Id. 

As with an ANDA, a paper NDA requires the applicant to 

submit either a patent certification or a statement declaring that the patent does not claim the method of use for 

which the applicant is seeking approval. Id.

§ 355(b)(2)(A)-(B). 

II. AstraZeneca’s Budesonide Drug and Patents 

In 2000, the FDA approved AstraZeneca’s NDA for a 

budesonide inhalation suspension that AstraZeneca now 

markets under the name “PULMICORT RESPULES®.” 

Each “respule” is a plastic vial containing a single dose of 

budesonide, an anti-inflammatory corticosteroid, sus-
ASTRAZENECA LP v. APOTEX 6

pended in a sterile liquid. The drug is administered by 

squeezing the entire contents of a vial into a jet nebulizer 

and inhaling the resulting mist through a mask attached 

to the nebulizer. 

The Orange Book entry for AstraZeneca’s budesonide 

product includes the ’099 Patent and its parent, the ’603 

Patent. Both patents are owned by AstraZeneca and have 

specifications that are nearly identical in all relevant 

respects. The patents explain that “[t]he invention provides a new method of treating respiratory diseases such 

as asthma that involves administering a budesonide 

composition with a nebulizer not more than once per day.” 

’603 Patent col.1 ll.20-23; ’099 Patent col.1 ll.26-29. “The 

invention also features a kit for treating respiratory 

diseases, the kit including a budesonide composition in a 

sealed container . . . and a label indicating administration 

by nebulization in a continuing regimen at a frequency of 

not more than once per day.” ’603 Patent col.2 ll.1-6; ’099 

Patent col.2 ll.7-12. Both patents include method claims 

directed to administering a budesonide composition once 

daily and product claims directed to the described kit 

containing either a budesonide composition or suspension 

and a label indicating once-daily administration by nebulization. 

While AstraZeneca’s patents are directed to once-daily 

treatment, the label that accompanies AstraZeneca’s 

budesonide product indicates that the drug may be administered once or twice daily. The label states that the 

drug is available in three strengths—0.25 mg, 0.5 mg, and 

1.0 mg per 2 mL vial—and provides a table of recommended starting doses based on a patient’s history of 

therapy. The label repeatedly warns that patients should 

“titrate down” to the lowest effective dose of the medication to avoid any adverse effects from excessive use of the 

medication. For example, in its DOSAGE AND 
7 ASTRAZENECA LP v. APOTEX

ADMINISTRATION section, the label states that “[i]n all 

patients, it is desirable to downward-titrate to the lowest 

effective dose once asthma stability is achieved” and 

“[o]nce the desired clinical effect is achieved, consideration should be given to tapering to the lowest effective 

dose.” The PRECAUTIONS section also warns that 

“suppression of HPA function may be associated . . . when 

the dose is not titrated to the lowest effective dose” and 

“[t]o minimize the systemic effects of orally inhaled corticosteroids . . . each patient should be titrated to his/her 

lowest effective dose.” It is undisputed that the FDA 

requires all manufacturers of inhaled corticosteroids such 

as budesonide to include this downward titration language in the labels of their inhaled corticosteroid products. 

III. Apotex’s ANDA 

Apotex submitted an ANDA seeking FDA approval to 

manufacture and sell a generic version of budesonide for 

twice-daily use, a use not claimed in either the ’603 or 

’099 patents. The ANDA included a proposed label for the 

generic drug that, with certain exceptions, is identical to 

the label included with AstraZeneca’s budesonide product. 

Specifically, in its label, Apotex replaced the 

“PULMICORT RESPULES®” brand name on AstraZeneca’s product with the generic name “budesonide 

inhalation suspension.” Apotex also submitted a section 

viii statement asserting that it was not seeking approval 

for the once-daily method of use claimed in the ’603 and 

’099 patents and that its proposed generic label would 

contain no explicit mention of once-daily administration. 

However, the proposed label retained the FDA-mandated 

downward-titration language found in AstraZeneca’s 

PULMICORT RESPULES® product label. Apotex further 

represented that the proposed label would indicate that 

the generic drug is available in only two strengths: 0.25 
ASTRAZENECA LP v. APOTEX 8

mg and 0.5 mg per 2 mL vial. The FDA approved Apotex’s ANDA on March 30, 2009. 

IV. Proceedings Before the District Court 

On March 31, 2009, the day after Apotex’s ANDA was 

approved, AstraZeneca initiated the declaratory judgment 

action underlying this appeal and moved for a preliminary injunction barring Apotex from distributing its 

generic budesonide drug. In that action, AstraZeneca 

argued that Apotex would directly infringe certain kit 

claims in both patents (claims 29 and 30 of the ’603 Patent and claims 17, 18, 20, 21, and 24-27 of the ’099 Patent) and would induce infringement of specified method 

claims in the ’603 Patent (claims 1-3, 6-8, 11-18, and 21-

28) by including the downward-titration statements in the 

proposed label. AstraZeneca asserted that the downwardtitration statements effectively instructed consumers to 

use the drug once daily. Claims 1 and 29, respectively, 

are representative of the asserted method and kit claims 

in the ’603 Patent: 

1. A method of treating a patient suffering from a 

respiratory disease, the method comprising administering to the patient a nebulized dose of a 

budesonide composition in a continuing regimen 

at a frequency of not more than once per day. 

’603 Patent col.10 ll.18-22. 

29. A kit for treating respiratory diseases, the kit 

comprising (a) a budesonide composition in a 

sealed container, the composition containing 0.05 

mg to 15 mg budesonide and a solvent, and (b) a 

label indicating administration by nebulization in 

a continuing regimen at a frequency of not more 

than once per day. 
9 ASTRAZENECA LP v. APOTEX

Id. col.12 ll.3-8. 

Claim 17 is representative of the asserted kit claims in 

the ’099 Patent: 

17. A kit for treating a respiratory disease, the kit 

comprising (a) a budesonide suspension in a 

sealed container, the suspension containing 0.05 

mg to 15 mg budesonide and a solvent, and (b) a 

label indicating administration by nebulization in 

a continuing regimen at a frequency of not more 

than once per day. 

’099 Patent col.11 ll.9-14. 

The court held a five-day hearing on AstraZeneca’s 

request for a preliminary injunction. At the hearing, 

Apotex argued that U.S. Patent No. 5,192,528 (“the ’528 

Patent”) anticipates all but three of the asserted method 

claims (claims 12, 14, and 16). Apotex also argued that a 

1994 advertisement for AstraZeneca’s PULMICORT 

RESPULES® drug in the British medical journal Thorax

(“the Thorax advertisement”) anticipates each of the 

asserted method claims. Apotex contended that the 

asserted kit claims of both patents were invalid because 

the claimed budesonide composition and suspension were 

known in the prior art and the recited label could not 

render a known product patentable. 

Apotex further argued that it would not induce infringement of the asserted method claims. Apotex contended that the proposed label would not lead consumers 

to directly infringe the claims because the downwardtitration statements included in the label did not instruct 

users to take the generic drug once daily. In support of 

this argument, Apotex pointed out that the FDA had 

previously issued a letter agreeing that the downward-
ASTRAZENECA LP v. APOTEX 10

titration language did not “teach” once-daily usage and 

was not protected by the ’603 and ’099 patents. Apotex 

also contended that it lacked the requisite specific intent 

to induce infringement because it was the FDA that had 

required Apotex to include the downward-titration statements in the label. Moreover, because the generic drug 

allegedly has substantial noninfringing uses (e.g., twicedaily administration to treat asthma), Apotex argued that 

the district court could not infer that Apotex intended to 

induce infringement. 

In the first of two opinions, the district court agreed 

that Apotex had shown a likelihood of success in its 

contention that all of the asserted kit claims were invalid, 

concluding that the “addition of the instruction does not 

functionally alter the known product so as to create a new 

patentable product.” AstraZeneca LP v. Apotex, Inc.

(“Opinion”), 623 F. Supp. 2d 579, 591 (D.N.J. 2009). With 

respect to the asserted method claims, the court determined that under its construction of the term “budesonide 

composition” Apotex had not shown the asserted method 

claims likely to be anticipated by the ’528 Patent. Id. at 

595. The court likewise was not convinced that the Thorax advertisement anticipated these claims, finding 

persuasive evidence that one of ordinary skill in the art at 

the time of the invention would not have understood the 

advertisement to instruct once-daily usage of AstraZeneca’s PULMICORT RESPULES® drug. Id. at 596. 

Regarding inducement, the district court concluded 

that the downward-titration language would lead many 

users to directly infringe the asserted method claims 

because titrating down from the recommended starting 

doses would necessarily lead to once-daily usage. Id. at 

601-02. The court found that the proposed label provided 

evidence of Apotex’s affirmative intent to induce infringement and that there was no evidence in the record 
11 ASTRAZENECA LP v. APOTEX

that Apotex had attempted to craft a noninfringing label. 

Id. at 605, 607. 

The district court also found that AstraZeneca would 

suffer irreparable harm if the court did not issue a preliminary injunction, as the damage caused by layoffs and 

loss of consumer goodwill would be unquantifiable, and a 

confidential settlement agreement between AstraZeneca 

and Teva Pharmaceuticals (“Teva”) made determining 

economic harm speculative. Id. at 611-14. The court 

found that the public interest did not favor either party. 

Id. at 614. Before deciding whether to issue the requested 

preliminary injunction, the court offered Apotex the 

opportunity to present additional evidence addressing 

whether Apotex had the necessary specific intent to 

induce infringement of the asserted method claims. 

Apotex accepted and presented testimony regarding 

Apotex’s efforts to develop a non-infringing label. After 

considering this testimony, the court issued a supplemental opinion in which it concluded that AstraZeneca had 

shown that Apotex had the requisite specific intent to 

induce infringement. AstraZeneca LP v. Apotex, Inc.

(“Supplemental Opinion”), 623 F. Supp. 2d 615 (D.N.J. 

2009). The district court then issued its preliminary 

injunction. Apotex filed a timely appeal and AstraZeneca 

timely filed a cross-appeal. This court has jurisdiction 

under 28 U.S.C. § 1292(c)(1). 

DISCUSSION

I. The Preliminary Injunction 

This court reviews a decision to grant a preliminary 

injunction for abuse of discretion. Abbott Labs. v. Sandoz, 

Inc., 566 F.3d 1282, 1298 (Fed. Cir. 2009) (citing Amazon.com, Inc. v. Barnesandnoble.com, Inc., 239 F.3d 1343, 

1350 (Fed. Cir. 2001)). “An abuse of discretion may be 

established by showing that the court made a clear error 
ASTRAZENECA LP v. APOTEX 12

of judgment in weighing relevant factors or exercised its 

discretion based upon an error of law or clearly erroneous 

factual findings.” Amazon.com, 239 F.3d at 1350 (quoting 

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

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

“A plaintiff 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 

preliminary relief, that the balance of equities tips in [its] 

favor, and that an injunction is in the public interest.” 

Winter v. Natural Res. Def. Council, Inc., 129 S. Ct. 365, 

374 (2008); see also Titan Tire Corp. v. Case New Holland, 

Inc., 566 F.3d 1372, 1375 (Fed. Cir. 2009). Apotex appeals 

only the district court’s findings that AstraZeneca is likely 

to succeed on the merits with respect to the asserted 

method claims and is likely to suffer irreparable harm in 

the absence of a preliminary injunction. 

A. Likelihood of Success on the Merits 

For a patentee to establish that it is likely to succeed 

on the merits, it “must demonstrate that it will likely 

prove infringement of one or more claims of the patentsin-suit, and that at least one of those same allegedly 

infringed claims will also likely withstand the validity 

challenges presented by the accused infringer.” Amazon.com, 239 F.3d at 1351. When reviewing the grant of a 

preliminary injunction, this court “views the matter in 

light of the burdens and presumptions that will inhere at 

trial.” Titan Tire Corp., 566 F.3d at 1376 (citation omitted). A preliminary injunction should not issue if an 

alleged infringer raises a substantial question regarding 

either infringement or validity, i.e., the alleged infringer 

asserts an infringement or invalidity defense that the 

patentee has not shown lacks substantial merit. Genen-
13 ASTRAZENECA LP v. APOTEX

tech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1364 (Fed. 

Cir. 1997). 

Apotex contends that AstraZeneca has failed on both 

validity and infringement. Regarding validity, Apotex 

repeats its argument that the ’528 Patent and the Thorax

advertisement anticipate the asserted method claims. 

With respect to infringement, Apotex renews its contention that the distribution of its generic version of AstraZeneca’s budesonide product would not induce 

infringement because such distribution fails to show that 

Apotex possessed the requisite specific intent to infringe. 

These contentions are addressed in turn. 

i. The ’528 Patent 

The ’528 Patent, entitled “Corticosteroid Inhalation 

Treatment Method,” issued in 1993, several years before 

the filing of the application that matured into the ’603 

Patent. The ’528 Patent discloses a method for treating 

lung conditions such as asthma by administering a suspension of budesonide “entrapped” within a liposome (i.e., 

a spherical vesicle) once daily. Col.7 ll.57-63, col.8 ll.4-11. 

Before addressing validity, the district court construed the term “budesonide composition” in the asserted 

method claims. The court concluded that the term means 

“budesonide dispersed in a solvent in the form of a solution or suspension” and excludes “the involvement of 

liposomes as described in the ’528 Patent.” Opinion at 

595. In support of this construction, the district court 

noted that the ’603 Patent consistently describes the 

compositions used in the claimed method as either suspensions or solutions of budesonide dispersed in a solvent. 

Id. The court also cited the testimony of Dr. Robert O. 

Williams III, an expert witness presented by AstraZeneca. 

Dr. Williams testified that the ’603 Patent discloses a 

“depot effect” associated with budesonide that enables the 
ASTRAZENECA LP v. APOTEX 14

drug to be effective when administered only once per day. 

Prelim. Inj. Hr’g Tr. 16-17, May 4, 2009. Dr. Williams 

explained that the ’603 Patent teaches dispersing 

budesonide in a solvent as either a solution (i.e., budesonide dissolved in the solvent) or as a suspension (i.e., 

budesonide particles floating in the solvent). Id. at 16-19. 

According to Dr. Williams, dispersing budesonide in the 

solvent in either form places the budesonide in direct 

contact with the solvent, which allows the budesonide to 

be absorbed by lung cells where the drug binds with fatty 

acids and is rendered inactive. Id. at 16-18. This inactive 

budesonide acts as a “depot” or reservoir of budesonide 

that replaces free budesonide as the free budesonide is 

used. Id. at 16-17. He explained that, unlike the liposome-entrapped budesonide disclosed in the ’528 Patent, 

“the budesonide is provided . . . in . . . immediate contact 

with the solvent[] such that . . . the budesonide molecules 

. . . are available to be absorbed by the airway cells . . . 

and act as a depot effect.” Id. at 26-27. Dr. Williams 

testified that the ’603 Patent “tells one of skill in the art 

that it’s important to provide budesonide immediately in 

contact with the solvent either dissolved as a solution or 

suspended in a suspension” and later opined that providing budesonide in direct contact with the solvent was 

critical to the depot effect. Id. at 17-18. Based on the 

testimony of Dr. Williams, the court found that the “‘depot 

effect’ is at the heart of AstraZeneca’s revolutionary 

method and it could not occur if the liposomes involved in 

the ’528 Patent were present.” Opinion at 595. Accordingly, the district court concluded that the ’528 Patent 

does not anticipate the asserted method claims because 

the patent does not disclose the claimed “budesonide 

composition.” Id. 

On appeal, Apotex points out that the ’603 Patent discloses budesonide formulations that include liposomes: 
15 ASTRAZENECA LP v. APOTEX

“[T]herapeutic suspensions can also contain one or more 

excipients. Excipients are well known in the art and 

include . . . liposomes . . . . Solutions or suspensions can 

be encapsulated in liposomes or biodegradable microspheres.” ’603 Patent col.3 ll.32-39 (emphases added). 

Apotex argues that the district court improperly relied on 

expert testimony to arrive at a construction of “budesonide composition” that excludes these formulations, violating this court’s warnings that claims should generally not 

be interpreted in a manner that excludes embodiments 

disclosed in the specification. 

In response, AstraZeneca argues that the district 

court correctly construed the “budesonide composition” 

term based on the intrinsic evidence and expert testimony 

in the record. AstraZeneca contends that the district 

court’s reliance on the testimony of Dr. Williams was 

entirely proper, as his testimony simply explained the 

meaning of the term “budesonide composition” in the 

context of the ’603 Patent. 

There is no serious dispute that the ’528 Patent would 

anticipate the majority of the asserted method claims if 

the term “budesonide composition” is interpreted to 

include the liposome embodiments disclosed in the ’528 

Patent and would not anticipate the method claims if the 

district court’s construction was correct. Thus, the question before us is whether the district court correctly 

construed the term to exclude these embodiments. This 

court reviews the district court’s claim construction de 

novo. Cybor Corp. v. Fas Techs., Inc., 138 F.3d 1448, 1456 

(Fed. Cir. 1998) (en banc). 

This court agrees with AstraZeneca and concludes 

that the district court was correct in its claim construction. A claim term is generally given its “ordinary and 

customary meaning,” that is, “the meaning that the term 
ASTRAZENECA LP v. APOTEX 16

would have to a person of ordinary skill in the art in 

question at the time of the invention.” Phillips v. AWH 

Corp., 415 F.3d 1303, 1312-13 (Fed. Cir. 2005) (en banc). 

“[T]he person of ordinary skill in the art is deemed to read 

the claim term not only in the context of the particular 

claim in which the disputed term appears, but in the 

context of the entire patent, including the specification.” 

Id. at 1313. “[T]he specification may reveal a special 

definition given to a claim term by the patentee that 

differs from the meaning it would otherwise possess. In 

such cases, the inventor’s lexicography governs.” Id. at 

1316. The specification need not reveal such a definition 

explicitly. See Bell Atl. Network Servs., Inc. v. Covad 

Commc’ns Group, Inc., 262 F.3d 1258, 1268 (Fed. Cir. 

2001) (“[A] claim term may be clearly redefined without 

an explicit statement of redefinition.”). “[W]hen a patentee uses a claim term throughout the entire patent 

specification, in a manner consistent with only a single 

meaning, he has defined that term ‘by implication.’” Id.

at 1271 (quoting Vitronics Corp. v. Conceptronic, Inc., 90 

F.3d 1576, 1582 (Fed. Cir. 1996)). 

Here, the specification of the ’603 Patent supports the 

conclusion that one of ordinary skill in the art would have 

understood the term “budesonide composition” to mean 

“budesonide dispersed in a solvent in the form of a solution or suspension” as construed by the district court. The 

specification consistently describes the budesonide compositions in that way. The SUMMARY OF THE 

INVENTION states that “the invention features a method 

of treating a patient suffering from a respiratory disease 

in which a composition, e.g., a suspension, of budesonide 

is administered by nebulization,” ’603 Patent col.1 ll.29-

31, and explains a few sentences later that “[t]he drug can 

be provided as an aqueous suspension in which the 

budesonide is suspended in a solvent,” id. col.1 ll.37-39. 
17 ASTRAZENECA LP v. APOTEX

The SUMMARY OF THE INVENTION notes that “the 

invention also features a kit . . . including a budesonide 

composition in a sealed container, the composition including 0.05 mg to 15 mg budesonide and a solvent.” Id. col.2 

ll.1-6. Similarly, the DETAILED DESCRIPTION states 

that “[t]he drug can be delivered in a solvent, e.g., in the 

form of a solution or a suspension.” Id. col.3 ll.22-23. The 

DETAILED DESCRIPTION goes on to note that nebulizable budesonide is packaged in vials containing “micronized budesonide suspended in a volume, e.g., 2 ml, of 

solvent.” Id. col.4 ll.12-14. The EXAMPLES section 

describes two clinical studies performed to determine the 

safety and efficacy of administering budesonide once 

daily. The patent discloses that in each study 

“[b]udesonide was administered once per day as a nebulized suspension.” Id. col.4 ll.65-67, col.7 ll.57-60. 

As noted above, the specification does mention liposome formulations in two places. Id. col.3 ll.32-39 

(“[T]herapeutic suspensions can also contain one or more 

excipients. Excipients are well known in the art and 

include . . . liposomes . . . . Solutions or suspensions can 

be encapsulated in liposomes or biodegradable microspheres.” (emphases added)). Contrary to Apotex’s contention, however, the district court’s construction does not 

exclude either of these formulations. The district court’s 

construction excludes “the involvement of liposomes as 

described in the ’528 Patent.” Neither of the liposome 

formulations discussed in the specification use liposomes 

in the manner described in the ’528 Patent. The ’528 

Patent describes entrapping budesonide in a liposome. 

Such entrapment separates the budesonide from the 

surrounding solvent. By contrast, the reference in the 

specification to placing liposomes in a suspension as an 

excipient indicates a formulation where budesonide and 

liposomes are in the same suspension, with the liposomes 
ASTRAZENECA LP v. APOTEX 18

independent of and apart from the budesonide, which 

remains in contact with the solvent. The statement that 

“[s]olutions or suspensions can be encapsulated in liposomes or biodegradable microspheres” indicates that 

budesonide either dissolved or floating in a solvent may be 

placed within a liposome, not that the term “budesonide 

composition” includes budesonide separated from a solvent by a liposome as described in the ’528 Patent. 

The specification and the claims are not the only 

sources that a court may consider when determining the 

meaning of a claim term. A court may look to “those 

sources available to the public that show what a person of 

skill in the art would have understood disputed claim 

language to mean,” which, in addition to the claims and 

the rest of the specification, may include “the prosecution 

history[] and extrinsic evidence concerning relevant 

scientific principles, the meaning of technical terms, and 

the state of the art.” Phillips, 415 F.3d at 1314 (quoting 

Innova/Pure Water, Inc. v. Safari Water Filtration Sys., 

Inc., 381 F.3d 1111, 1116 (Fed. Cir. 2004)). Extrinsic 

evidence “consists of all evidence external to the patent 

and prosecution history, including expert and inventor 

testimony, dictionaries, and learned treatises.” Id. at 

1317 (quoting Markman v. Westview Instruments, Inc., 52 

F.3d 967, 980 (Fed. Cir. 1995)). 

Here, the record includes the testimony of AstraZeneca’s expert, Dr. Williams. This court generally views 

expert testimony “as less reliable than the patent and its 

prosecution history in determining how to read claim 

terms.” Id. at 1318. However, expert testimony can be 

useful “for a variety of purposes, such as to provide background on the technology at issue, to explain how an 

invention works, [or] to ensure that the court's understanding of the technical aspects of the patent is consistent with that of a person of skill in the art . . . .” Id. at 
19 ASTRAZENECA LP v. APOTEX

1318. In this case, the district court properly relied on the 

testimony of Dr. Williams to understand how the claimed 

invention works and construed the disputed term in a 

manner consistent with that understanding. As described 

above, Dr. Williams explained that the ’603 Patent discloses that the depot effect permits budesonide to be 

effective when administered once daily and opined that 

for the depot effect to occur budesonide must be in direct 

contact with the solvent. He also testified that one of skill 

in the art would have understood the ’603 Patent to 

disclose budesonide in immediate contact with the solvent 

as either a solution or suspension. This would exclude the 

liposome-entrapped embodiments disclosed in the ’528 

Patent. Although Apotex takes issue with the district 

court’s reliance on Dr. Williams’s testimony, Apotex does 

not seriously dispute his explanation of how the claimed 

invention works and provided no testimony to the contrary at the preliminary injunction hearing. This court 

sees no error in relying on uncontested expert testimony 

to explain how the invention described in the intrinsic 

record functions. See Netword, LLC v. Centraal Corp., 

242 F.3d 1347, 1356 (Fed. Cir. 2001) (“[A] district court 

can not be faulted for relying on the only expert explanation of the technology that was presented.”). 

Considered together, the intrinsic evidence and expert 

testimony support the conclusion that a person skilled in 

the art would have understood the term “budesonide 

composition” to mean “budesonide dispersed in a solvent 

in the form of a solution or suspension” and excludes “the 

involvement of liposomes as described in the ’528 Patent.”1 Accordingly, this court concludes that, based on the 

 1 The dissent notes that after discussing the 

depot effect, the ’603 Patent states that “[t]his proposed 

mechanism of action is exemplary; the invention is not 

limited by any particular mechanism of action,” ’603 
ASTRAZENECA LP v. APOTEX 20

evidence of record at this point, the district court correctly 

construed this term, and thus correctly found that the 

asserted method claims are likely to withstand the validity challenge posed by the ’528 Patent. 

ii. The Thorax Advertisement 

As discussed above, a British medical journal published the Thorax advertisement in 1994, more than one 

year before the filing of the application that issued as the 

’603 Patent. The advertisement touts AstraZeneca’s 

PULMICORT RESPULES® drug as “[a] high-dose nebulised steroid that’s low on side effects” and notes that the 

drug can be used to treat bronchial asthma in children. 

The advertisement indicates that the drug was available 

in 2 mL single dose vials, each vial containing either 0.25 

mg/mL or 0.5 mg/mL of budesonide. The advertisement 

includes the following statement regarding dosing: 

 

Patent col.3 ll.11-12, and concludes that the testimony of 

Dr. Williams regarding the necessity of the depot effect is 

therefore contrary to the specification. But no other 

“mechanism of action” is disclosed in the patent, and the 

undisputed testimony of Dr. Williams—the only expert 

testimony provided to the court on this issue—is that 

after reading the ’603 Patent a person of skill in the art 

would have understood that the claimed invention simply 

would not work without the depot effect. Therefore this 

court sees no error in the district court’s construction, as 

the evidence of record leaves no doubt that the claimed 

invention would be inoperable if the claims are construed 

in the manner suggested by Apotex. See Talbert Fuel Sys. 

Patents Co. v. Unocal Corp., 275 F.3d 1371, 1376 (Fed. 

Cir. 2002), vacated and remanded on other grounds, 537 

U.S. 802 (2002) (“[A] construction that renders the 

claimed invention inoperable should be viewed with 

extreme skepticism.” (citation omitted)). 
21 ASTRAZENECA LP v. APOTEX

Initially . . . the recommended dose in adults . . . is 

usually 1-2 mg twice daily. . . . Children . . . 0.5-1 

mg twice daily. The maintenance dose should be 

the lowest dose which keeps the patient symptomfree. Recommended doses are Adults . . . 0.5-1 mg 

twice daily. Children . . . 0.25-0.5 mg twice daily. 

When the advertisement was published, AstraZeneca’s 

budesonide product was not approved for any use in the 

United States and was approved for only twice-daily use 

in Europe. 

Because it is undisputed that the asserted method 

claims cover the use of budesonide solution, the only 

question before the district court was whether the advertisement disclosed administering that solution “in a 

continuing regimen at a frequency of not more than once 

per day” as recited in the claims. The district court found 

that the advertisement does not anticipate the asserted 

method claims, finding persuasive the explanation of 

AstraZeneca’s expert, Dr. Bradley Chipps, that the advertisement does not explicitly or inherently disclose oncedaily dosing because the advertisement was published 

“before we had any information or historical perspective 

that once a day therapy worked for anyone.” Opinion at 

596. The district court reached that conclusion with the 

understanding of Dr. Chipps, who also testified that, if 

made today, the statement “[t]he maintenance dose 

should be the lowest dose which keeps the patient symptom-free” would be equivalent to the downward-titration 

language included in the proposed label that AstraZeneca 

claimed would induce infringement of the asserted 

method claims. Prelim. Inj. Hr’g Tr. 186, May 4, 2009. 

On appeal, Apotex asserts that if the language in the 

Thorax advertisement would today suggest to those in the 

art the possibility of administering the drug once daily, it 
ASTRAZENECA LP v. APOTEX 22

would also have suggested this possibility when the 

advertisement was published, regardless of whether 

anyone had proven that the drug could be effective when 

administered once per day. Apotex argues that in concluding otherwise the district court improperly imposed a 

temporal limitation on the anticipation inquiry, violating 

the oft-repeated axiom “that which would literally infringe if later in time anticipates if earlier.” AstraZeneca 

responds that because the drug was only approved for 

twice-daily use and was not known to be safe or effective 

when administered once daily, there is nothing to show 

that one of skill in the art at the time the patent application was filed would have understood the advertisement 

to disclose once-daily dosing. AstraZeneca thus argues 

that the Thorax advertisement was not enabling and for 

that reason cannot be considered anticipatory. In any 

event, AstraZeneca argues that the reference simply does 

not disclose once-daily dosing. 

Anticipation is a question of fact, Sanofi-Synthelabo v. 

Apotex, Inc., 550 F.3d 1075, 1082 (Fed. Cir. 2008) (citation 

omitted), that must be established at trial by clear and 

convincing evidence, Purdue Pharma L.P. v. Boehringer 

Ingelheim GmbH, 237 F.3d 1359, 1365 (Fed. Cir. 2001). 

This court reviews for clear error the district court’s 

determination that AstraZeneca has demonstrated that 

the asserted method claims will likely survive the validity 

challenge posed by the Thorax advertisement. See Amazon.com, 239 F.3d at 1350. 

While the question is close, this court agrees with AstraZeneca that the district court correctly determined that 

AstraZeneca has demonstrated that the asserted method 

claims will likely withstand the validity challenge presented by the Thorax advertisement. In the context of 

anticipation, the question is not whether a prior art 

reference “suggests” the claimed subject matter as posited 
23 ASTRAZENECA LP v. APOTEX

by Apotex. Rather, “the dispositive question regarding 

anticipation [is] whether one skilled in the art would 

reasonably understand or infer from a [prior art reference]” that every claim element is disclosed in that reference. In re Baxter Travenol Labs, 952 F.2d 388, 390 (Fed. 

Cir. 1991). And although a reference must be enabling to 

be anticipatory, see Sanofi-Synthelabo, 550 F.3d at 1082, 

unlike enablement under § 112, a reference need not, as 

AstraZeneca suggests, demonstrate utility or efficacy to 

be enabling in the context of § 102, see In re Gleave, 560 

F.3d 1331, 1335-36 (Fed. Cir. 2009) (“[A] reference need 

disclose no independent use or utility to anticipate a claim 

under § 102.”); Bristol-Myers Squibb Co. v. Ben Venue 

Labs., Inc., 246 F.3d 1368, 1379 (Fed. Cir. 2001). As 

explained in Rasmusson v. SmithKline Beecham Corp., 

413 F.3d 1318, 1325 (Fed. Cir. 2005), the reason for this 

distinction “is that [§] 112 ‘provides that the specification 

must enable one skilled in the art to ‘use’ the invention 

whereas [§] 102 makes no such requirement as to an 

anticipatory disclosure.’" Id. (quoting In re Hafner, 410 

F.2d 1403, 1405 (CCPA 1969 )). 

Apotex’s argument that the Thorax advertisement is 

anticipatory because the advertisement and the proposed 

label are essentially the same ignores a key difference 

between the advertisement and the proposed label. As 

discussed in greater detail in the next section, depending 

on a patient’s previous therapy, the proposed label recommends initially administering 0.25 mg of budesonide 

twice daily. The district court concluded that the proposed label would induce infringement because, absent 

instructions to the contrary, titrating down to the lowest 

effective dose from the recommended starting dose of 0.25 

mg of budesonide twice daily would necessarily lead some 

users to take 0.25 mg of budesonide once daily as a maintenance dose, as there would be no way to properly ad-
ASTRAZENECA LP v. APOTEX 24

minister less than 0.25 mg of the drug. By contrast, the 

Thorax advertisement explicitly discloses that such maintenance doses should be administered twice daily. Immediately after the advertisement warns that “[t]he 

maintenance dose should be the lowest dose which keeps 

the patient symptom-free,” the advertisement sets out 

recommended doses for adults and children: 0.5-1 mg 

twice daily for adults, and 0.25-0.5 mg twice daily for 

children. The most natural reading of this passage is that 

the recommended doses are recommended maintenance

doses, which the advertisement explicitly states should be 

administered twice daily. Thus, although Dr. Chipps 

testified that the statement “[t]he maintenance dose 

should be the lowest dose which keeps the patient symptom-free” would, if made today, be equivalent to the 

downward-titration language included in the proposed 

label, the advertisement—unlike the proposed label—

clearly states how often a maintenance dose should be 

given: twice per day. 

Dr. Chipps confirmed that one of ordinary skill in the 

art would have understood the advertisement to disclose 

administering budesonide twice-daily, not once per day as 

argued by Apotex. He testified that “there’s nothing in 

[the Thorax advertisement] that talks about or alludes to 

once a day dosage,” and noted that the advertisement 

instructs that the recommended starting and maintenance doses are to be administered twice daily. Prelim. 

Inj. Hr’g Tr. 144, May 4, 2009. Dr. Chipps opined that 

when the Thorax advertisement was published in 1994 a 

physician reading the dosing recommendations set forth 

in the advertisement would not have understood the 

dosing recommendations to teach once-daily dosing. Id.

at 144. He explained that until AstraZeneca conducted 

clinical studies on its budesonide product in 1997 there 

was no evidence that administering budesonide once-daily 
25 ASTRAZENECA LP v. APOTEX

would be safe and effective. Indeed, he noted that prior to 

1997, the lowest dose of budesonide known to be effective 

was 0.25 mg taken twice a day. Id. at 147-48. Apotex 

presented no testimony or evidence to the contrary. 

After considering the reference and appreciating how 

that reference would have been understood by persons of 

ordinary skill in the art at that time, this court is not left 

with a definite and firm conviction that the district court 

clearly erred by concluding that at trial Apotex will likely 

not be able to demonstrate by clear and convincing evidence that the Thorax advertisement anticipates the 

asserted method claims.2 Accordingly, the district court’s 

determination is affirmed. 

iii. Inducement 

“Whoever actively induces infringement of a patent 

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

“[I]nducement requires that the alleged infringer knowingly induced infringement and possessed specific intent 

to encourage another’s infringement.” DSU Med. Corp. v. 

JMS Co., 471 F.3d 1293, 1306 (Fed. Cir. 2006) (en banc in 

 2 By rearranging the language of the Thorax

advertisement, the dissent makes it appear that the 

advertisement and the proposed label both recommend 

administering a starting dose of 0.25 to 0.5 mg twice daily 

followed by eventual reduction to the lowest effective 

dose. But the facts do not support that suggestion. The 

Thorax advertisement actually specifies higher levels of 

initial recommended twice daily dosing and then goes on 

to state that “[t]he maintenance dose should be the lowest 

dose which keeps the patient symptom-free. Recommended doses are: . . . 0.25-0.5 mg twice daily.” The 

Thorax advertisement thus recommends reducing a 

higher dose to the twice daily dose of 0.25-0.5 mg, not first 

administering 0.25-0.5 mg twice daily and then reducing 

the dosage to either once daily or twice daily doses as 

suggested by the dissent. 
ASTRAZENECA LP v. APOTEX 26

relevant part) (citation omitted) (internal quotation 

marks omitted). “Infringement is a question of fact reviewed for clear error.” Golden Blount, Inc. v. Robert H. 

Peterson, Co., 438 F.3d 1354, 1361 (Fed. Cir. 2006) (citation omitted). “A factual finding is clearly erroneous 

when, despite some supporting evidence, the reviewing 

court is left with the definite and firm conviction that a 

mistake has been made.” Id. at 1361 (citation omitted). 

Before the district court, AstraZeneca contended that 

Apotex’s proposed label would induce consumers to infringe the asserted method claims because the label 

implicitly instructed users to administer the generic drug 

once daily. As in AstraZeneca’s PULMICORT 

RESPULES® drug label, the DOSAGE AND 

ADMINISTRATION section of the proposed generic label 

explains that “[i]n all patients, it is desirable to downward-titrate to the lowest effective dose once asthma 

stability is achieved.” The section also includes the following table of recommended starting doses and highest 

recommended doses, which differs from AstraZeneca’s 

label in the removal of all mention of once-daily dosing: 
27 ASTRAZENECA LP v. APOTEX

Previous 

Therapy 

Recommended 

Starting Dose 

Highest 

Recommended 

Dose 

Bronchodilators 

alone 

0.5 mg total daily 

dose administered 

twice daily in divided doses 

0.5 mg total 

daily dose 

Inhaled 

Corticosteroids 

0.5 mg total daily 

dose administered 

twice daily in divided doses 

1 mg total daily 

dose 

Oral 

Corticosteroids 

1 mg total daily dose 

administered as 0.5 

mg twice daily 

1 mg total daily 

dose 

In the paragraph following the table, the label again 

warns that “[o]nce the desired clinical effect is achieved, 

consideration should be given to tapering to the lowest 

effective dose.” 

The district court agreed with AstraZeneca that the 

proposed label would cause some users to infringe the 

asserted method claims. The proposed label indicates 

that the generic drug will be available in only two 

strengths: 0.25 mg and 0.5 mg per 2 mL vial. The court 

noted that, once opened, each vial of the generic drug 

must immediately be administered in its entirety because 

dividing the contents of a vial for use at different times 

would compromise the drug’s sterility. Opinion at 600 

n.17. Because the recommended starting dose for patients in the first two rows of the dosing table is “0.5 mg 
ASTRAZENECA LP v. APOTEX 28

total daily dose administered twice daily in divided doses” 

(i.e., 0.25 mg administered twice a day), the court reasoned that the first step in titrating down from this dose 

would have to be 0.25 mg once daily, as there was no way 

of decreasing the amount of each dose below 0.25 mg. Id.

at 602. Accordingly, the court concluded that, for patients 

whose previous treatments fell within the first two rows 

of the dosage table, the downward-titration language 

would necessarily lead patients to use a 0.25 mg vial of 

the drug once-daily. 

The district court found that a letter issued by the 

FDA supported this conclusion. In 2008, AstraZeneca 

filed a citizen petition with the FDA concerning an ANDA 

submitted by IVAX Pharmaceuticals, Inc. (“IVAX”) that is 

virtually identical to the ANDA submitted by Apotex. In 

the petition, AstraZeneca asked the FDA to determine 

that labeling for a generic budesonide inhalation suspension must include once-daily dosing language. AstraZeneca also questioned the propriety of including 

downward-titration language in a proposed label for a 

generic budesonide inhalation suspension. In response, 

the FDA issued a letter explaining that the labeling for a 

generic budesonide inhalation suspension could omit 

references to once-daily dosing “[b]ecause the weight of 

the evidence is stronger in support of efficacy for twicedaily dosing as opposed to once-daily dosing . . . omission 

of once-daily dosing in the generic BIS labeling would not 

render the generic drug less safe or effective than 

PULMICORT RESPULES®.” Letter from the FDA to 

AstraZeneca 16 (Nov. 18, 2008). The letter also stated 

that the FDA found it appropriate to include the downward-titration language in proposed labeling for generic 

budesonide inhalation suspensions because the FDA 

believed that the language did not “teach” once-daily 

dosing: 
29 ASTRAZENECA LP v. APOTEX

Titration to the lowest effective dose may involve, 

for example, a twice-daily regimen, once-daily dosing, or even alternate day dosing . . . . The labeling does not state the lowest effective dose is 0.25 

mg once daily. As such, contrary to your assertion, the downward titration statement does not 

“teach” once-daily dosing. 

. . . . 

. . . . The downward titration statement does not 

specify or instruct that the dosing frequency must 

be once daily and need not be carved out as protected by the 6,598,603 and 6,899,099 patents. 

Id. at 18. The district court concluded that the letter 

supported the court’s finding of direct infringement because the letter explicitly stated (and therefore put Apotex on notice) that downward titration may involve oncedaily dosing. Opinion at 601. 

Regarding specific intent to induce infringement, the 

district court found that AstraZeneca had submitted 

evidence of Apotex’s affirmative intent that consumers 

use the generic drug in an infringing manner: Apotex’s 

inclusion of the downward-titration language in the 

proposed label. Id. at 605. The court also noted that 

Apotex had presented no evidence that the company had 

attempted to draft a non-infringing label. Id. at 606-07. 

Because the question of Apotex’s efforts to draft a noninfringing label had arisen late in the proceedings, the 

court offered Apotex the opportunity to continue the 

hearing and present evidence on this issue. 

Apotex accepted the court’s offer and presented Bernice Tau, the Director of Regulatory Affairs at Apotex, to 
ASTRAZENECA LP v. APOTEX 30

testify at the hearing. Tau testified that, in addition to 

removing all explicit references to once-daily dosing, at 

the advice of counsel, Apotex had also inserted the phrase 

“by administration twice-daily” in sections of the proposed 

label that Apotex included with its ANDA. Prelim. Inj. 

Hr’g Tr. 19, 21-22, May 20, 2009. She explained that the 

FDA responded by instructing Apotex to delete this 

phrase and sending Apotex a template containing the 

language Apotex was to include in the proposed label. Id.

at 22-23. 

Tau stated that Apotex never intended to instruct or 

encourage either physicians or patients to use its generic 

drug once-daily. Id. at 32. She also testified that it never 

occurred to Apotex that the downward-titration statements in the proposed label would suggest once-daily use 

of Apotex’s generic version of the drug. Id. at 27. She 

explained that she became aware that the language was 

problematic after Apotex obtained approval of its ANDA, 

when Apotex’s counsel notified her that AstraZeneca was 

objecting to use of the language. Id. at 27, 37. She stated 

that after learning of the issue, she made two calls to the 

FDA to address AstraZeneca’s concerns and proposed the 

following three amendments to the label: (1) adding the 

words “twice daily” to the downward-titration language; 

(2) adding language stating the drug is not approved for 

less than twice-daily use; and (3) removing the downwardtitration language Id. at 27-31. She testified that she did 

so despite believing, based on her experience with the 

FDA, that the FDA would not allow Apotex to alter the 

label. Id. at 27-28. She stated that during these calls the 

FDA informed her of the letter it issued in response to 

AstraZeneca’s petition. Id. at 37-38. As she expected, the 

FDA did not permit Apotex to make any of the suggested 

changes. She explained that Apotex did not submit a 

formal labeling amendment because, based on her conver-
31 ASTRAZENECA LP v. APOTEX

sations with the FDA, she believed doing so would have 

been futile. Id. at 33-34. 

Tau acknowledged that she knew that FDA decisions 

could be appealed, but stated that she was not familiar 

with the process, as she had never had to appeal an FDA 

decision regarding an ANDA. Id. at 37, 40. Tau also 

admitted that had Apotex wanted to seek approval to 

distribute a different strength of the generic drug, Apotex 

could have submitted a suitability petition, but she explained that she thought this was unnecessary because 

Apotex’s ANDA satisfied all of the applicable requirements. Id. at 11-12, 52-53. 

Based on the evidence presented on the hearing, the 

district court found that Apotex “was aware of and certainly concerned about the potential infringement problem posed by its label,” but nevertheless decided to 

proceed with the label. Opinion at 618. The district court 

noted that Apotex had other options at its disposal that it 

chose not to pursue. The court pointed out that Apotex 

could have formally appealed the FDA’s decision. Id. The 

court also noted that Apotex could have filed a suitability 

petition or a paper NDA that sought approval to produce 

the generic drug at a strength of 0.125 mg per 2 mL. At 

that strength, AstraZeneca conceded that the downwardtitration language would not teach an infringing use. Id.

at 619 & n.3. The court found that this conduct showed 

that Apotex had the requisite specific intent to induce 

infringement and granted AstraZeneca’s request for a 

preliminary injunction. Id. at 618-19. 

Apotex, joined by two amici, mounts multiple challenges to the district court’s finding that Apotex had the 

necessary specific intent to induce infringement. Apotex 

first contends that the district court inferred specific 

intent to induce infringement from Apotex’s planned 
ASTRAZENECA LP v. APOTEX 32

distribution of the generic drug. Apotex argues that 

drawing such an inference is improper where the product 

in question has substantial non-infringing uses. AstraZeneca responds that the district court based its specific 

intent finding not on an improper inference but rather on 

the circumstances surrounding Apotex’s decision to proceed with its planned distribution of the generic drug and 

the affirmative evidence of intent provided by the proposed label. 

This court agrees with AstraZeneca. Apotex is correct 

that “where a product has substantial noninfringing uses, 

intent to induce infringement cannot be inferred even 

when the [alleged inducer] has actual knowledge that 

some users of its product may be infringing the patent.” 

Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365 

(Fed. Cir. 2003). However, “liability for active inducement may be found ‘where evidence goes beyond a product’s characteristics or the knowledge that it may be put 

to infringing uses, and shows statements or actions directed to promoting infringement.’” Ricoh Co. v. Quanta 

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

(quoting Metro-Goldwyn-Mayer Studios Inc. v. Grokster, 

Ltd. (“Grokster”), 545 U.S. 913, 935 (2005)). As the Supreme Court explained in Grokster in the context of 

infringement under the copyright laws, “[e]vidence of 

active steps . . . taken to encourage direct infringement, 

such as advertising an infringing use or instructing how 

to engage in an infringing use, show an affirmative intent 

that the product be used to infringe.” 545 U.S. at 936 

(internal quotation marks and citations omitted). 

The district court correctly concluded that such evidence exists here. As an initial matter, the district court 

suggested that there was insufficient evidence to establish 

that any noninfringing use of the generic drug was substantial, calling into question the applicability of the 
33 ASTRAZENECA LP v. APOTEX

“substantial non-infringing use” doctrine in this case. 

Opinion at 605 n.25. Be that as it may, the district court 

found that Apotex had the requisite specific intent to 

induce infringement because Apotex included instructions 

in its proposed label that will cause at least some users to 

infringe the asserted method claims. Id. at 605. The 

district court also found that, despite being aware of the 

infringement problem presented by the proposed label, 

Apotex nonetheless proceeded with its plans to distribute 

its generic drug product. Supplemental Opinion at 618. 

This conduct, not merely the planned distribution of the 

generic drug, formed the basis of the district court’s 

specific intent finding. See id. at 618-19. To the extent 

that Apotex contends that such circumstantial evidence 

cannot support a finding of specific intent, this court has 

explicitly stated otherwise. Water Techs. Corp. v. Calco, 

Ltd., 850 F.2d 660, 668 (Fed. Cir. 1988) (“While proof of 

intent is necessary, direct evidence is not required; rather, 

circumstantial evidence may suffice.” (citation omitted)). 

Apotex next contends that the proposed label is not 

evidence of specific intent because warnings on drug 

labels do not influence how a drug is used. Apotex further 

argues that even if labels did affect how drugs are used, 

the district court erroneously determined that the downward-titration language would lead the generic drug to be 

used in an infringing manner. Apotex asserts that the 

label does not instruct users to titrate down from a specific starting dose; instead, the label contains a general 

recommendation that is applicable to any dosing regimen. 

This court disagrees. In the context of specific intent, 

it is irrelevant that some users may ignore the warnings 

in the proposed label. The pertinent question is whether 

the proposed label instructs users to perform the patented 

method. If so, the proposed label may provide evidence of 

Apotex’s affirmative intent to induce infringement. See
ASTRAZENECA LP v. APOTEX 34

Vita-Mix Corp. v. Basic Holding, Inc., 581 F.3d 1317, 1329 

n.2 (Fed. Cir. 2009) (“The question is not . . . whether a 

user following the instructions may end up using the 

device in an infringing way. Rather, it is 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.”). Even if Apotex were correct that the downward-titration language 

may be applied to other dosing regimens, the language is 

still applicable to the recommended starting doses and, as 

correctly determined by the district court, would inevitably lead some consumers to practice the claimed method. 

Apotex and the amici also argue that the proposed label alone is not sufficient evidence of specific intent because the FDA required Apotex to include the downwardtitration language in the label and stated that the language does not teach the patented method. Apotex asserts that it agrees with the FDA and has never believed 

that the downward-titration language teaches the claimed 

once-daily method of administration. In response, AstraZeneca contends that Apotex’s compliance with FDA 

requirements and agreement with the FDA’s opinion 

regarding the downward-titration is immaterial. AstraZeneca argues that if Apotex could not create a noninfringing label, Apotex should have waited for the ’603 

Patent to expire before attempting to market its generic 

drug. 

This court again agrees with AstraZeneca. As explained above, the district court’s specific intent finding 

was not based solely on the proposed label, but also on 

Apotex’s decision to proceed with its plan to distribute the 

drug despite being aware that the label presented infringement problems. Apotex and the amici make much 

of the Hobson’s choice they contend that Apotex faced: 

either comply with FDA requirements and risk a patent 
35 ASTRAZENECA LP v. APOTEX

infringement suit or remove the downward-titration 

language and ensure that the ANDA would not be approved. This court sees no such dilemma. Apotex was 

free to submit a Paragraph III certification and wait until 

the patents expired before distributing its generic drug or 

file a Paragraph IV certification and challenge infringement and validity of the asserted claims. Or, as observed 

by the district court, Apotex could have formally appealed 

the FDA’s denial of Apotex’s proposed labeling amendments or filed either a suitability petition or a paper NDA 

seeking approval for a 0.125 mg per 2 mL strength of the 

drug. 

Apotex’s reliance on the FDA’s statements that the 

downward-titration language does not “teach” once-daily 

dosing and is not protected by the ’603 and ’099 patents is 

misplaced. As acknowledged by both the parties and the 

district court, the FDA is not the arbiter of patent infringement issues. See Applications for FDA Approval To 

Market a New Drug: Patent Submission and Listing 

Requirements and Application of 30-Month Stays on 

Approval of Abbreviated New Drug Applications Certifying That a Patent Claiming a Drug Is Invalid or Will Not 

Be Infringed, Fed. Reg. 36,676, 36,683 (June 18, 2003) 

(“[W]e lack expertise in patent matters. An administrative process for reviewing patents, assessing patent 

challenges, and de-listing patents would involve patent 

law issues that are outside both our expertise and our 

authority.”). 

In light of the evidence presented to the district court, 

this court is not left with a definite and firm conviction 

that a mistake has been made. Thus, this court affirms 

the district court’s finding that AstraZeneca will likely 

prove induced infringement at trial. 
ASTRAZENECA LP v. APOTEX 36

B. Irreparable Harm 

The district court found that AstraZeneca would suffer three types of irreparable harm if the court did not 

grant the requested preliminary injunction. First, the 

court determined that a confidential settlement agreement between AstraZeneca and Teva would make calculating the economic harm from a premature launch of 

Apotex’s generic budesonide impossible. Second, the court 

concluded that AstraZeneca would incur unquantifiable 

damage to its reputation and goodwill if Apotex were 

allowed to launch its generic drug and was subsequently 

forced to remove the drug from the market. Third, the 

court found that the damage caused by layoffs stemming 

from entry of the generic drug into the market would also 

be significant and unquantifiable. Apotex challenges each 

of these findings, and each finding is considered in turn. 

i. The Settlement Agreement 

On November 18, 2008, Teva received FDA approval 

to distribute a generic version of AstraZeneca’s budesonide drug and immediately began its distribution. Later 

that day, AstraZeneca initiated a patent infringement 

suit in the district court against Teva and successfully 

moved the court for a temporary restraining order enjoining Teva from selling the generic drug. AstraZeneca and 

Teva subsequently entered into a settlement agreement 

that granted Teva an exclusive license to sell its generic 

drug beginning December 15, 2009, with Teva agreeing to 

pay AstraZeneca a significant royalty. The agreement 

also included a “step down” provision that reduced the 

amount Teva was obligated to pay AstraZeneca if unlicensed drug manufacturers launched generic versions of 

the drug and certain conditions were met. In addition, 

Teva agreed to pay AstraZeneca a specified amount for 
37 ASTRAZENECA LP v. APOTEX

damages caused by Teva’s unauthorized launch of its 

generic drug. 

The district court observed that under the settlement 

agreement AstraZeneca would continue to have market 

exclusivity until December 15, 2009, and that after that 

date AstraZeneca and Teva would share the market. 

Based on expert testimony, the court concluded that to 

reliably calculate the economic harm AstraZeneca would 

suffer after December 15, 2009, the court would need data 

reflecting a market including only AstraZeneca and Teva. 

Because Apotex’s planned launch would prevent a market 

with only AstraZeneca and Teva from ever occurring, the 

district court determined that it would be “complete 

speculation to put a number on what this market would 

have been worth to AstraZeneca.” Opinion at 611. The 

court dismissed Apotex’s argument that “the parties 

expectations when they entered into the licensing agreement” would be sufficient to calculate damages, explaining that “there is a distinction between what the parties 

expect and what actually would have occurred” and 

concluding that it would be impossible to calculate with 

reasonable certainty the economic damage that AstraZeneca would suffer under the settlement agreement if 

Apotex began distributing its generic drug. Id.

Apotex argues on appeal that testimony during the 

hearing established that during the settlement negotiations AstraZeneca and Teva had estimated the required 

market data. Because this information would be subject 

to discovery, Apotex contends that that district court 

clearly erred when the court concluded that the damages 

AstraZeneca would suffer would be incalculable. 

In response, AstraZeneca suggests that the data generated during the settlement negotiations was influenced 

by the relative bargaining power of the parties and is not 
ASTRAZENECA LP v. APOTEX 38

an accurate reflection of a market with only AstraZeneca 

and Teva. AstraZeneca argues that without the benefit of 

actual data from such a market, any damages calculation 

would be based on speculation. 

This court agrees with AstraZeneca. Both AstraZeneca and Apotex rely on the testimony of Richard 

Fante, the president of AstraZeneca. Fante admitted that 

AstraZeneca and Teva did forecast certain market data 

during the settlement negotiation, but characterized the 

negotiation as a “gun-to-head moment” and explained 

that the companies relied mostly on “the experience we’d 

had as executives” when generating the forecast. Prelim. 

Inj. Hr’g Tr. 63-64, Apr. 30, 2009. Given the lack of 

reliable data regarding a market with only AstraZeneca 

and Teva, this court is not left with a definite and firm 

conviction that the district court erred by concluding that 

the damages AstraZeneca would incur under the settlement agreement would be incalculable. 

ii. Goodwill 

The district court found that if Apotex began distributing its generic drug and was subsequently forced to 

remove the drug from the market, the resulting confusion 

among physicians and patients, as well as price changes, 

would cause unquantifiable harm to AstraZeneca’s goodwill. Apotex asserts that this finding is speculative, as 

certain provisions of the settlement agreement would 

mitigate, if not eliminate, any adverse effects of Apotex 

launching and then removing its generic drug from the 

market. Although this court agrees with Apotex that 

there has not been a particularly strong showing regarding this finding, after reviewing the record, this court 

concludes that the district court did not clearly err by 

determining that AstraZeneca will suffer incalculable 

harm to its goodwill. 
39 ASTRAZENECA LP v. APOTEX

iii. Layoffs 

Based on the testimony of Fante, the district court 

concluded that AstraZeneca would have to lay off some of 

its employees if Apotex launched its generic drug and the 

resulting noneconomic loss would be significant and 

unquantifiable. Opinion at 612. The parties’ dispute 

regarding this finding largely concerns whether Fante 

testified that he would have to lay off employees if Apotex 

launched its generic drug or merely testified that layoffs 

might occur in that situation. Apotex points out that 

when asked whether Apotex’s entry would force him to lay 

off employees at AstraZeneca’s manufacturing facility, 

Fante responded, “It could.” Prelim. Inj. Hr’g Tr. 100, 

Apr. 30, 2009. However, as noted by AstraZeneca, Fante 

later clarified that if Apotex and Teva were both in the 

market that “in that scenario we would have to have a 

layoff [in the manufacturing facility].” Id. Moreover, 

when asked what effect Apotex’s launch would have on 

AstraZeneca employees, Fante explained that 

“[u]ndoubtedly . . . I would have to have a further reduction in the size of the U.S. workforce.” Id. at 47. Similarly, when asked whether this reduction would occur if 

Apotex launched its product after December 15, he stated, 

“Absolutely.” Id. Given this undisputed testimony, this 

court discerns no clear error in the district court’s finding. 

This court has reviewed the other arguments raised by 

Apotex concerning this finding and conclude that they too 

lack merit. 

* * * * 

Because Apotex has not demonstrated that that any of 

the district court’s findings regarding irreparable harm 

are clearly erroneous, this court sees no reason to disturb 

the district court’s determination that AstraZeneca would 

suffer irreparable harm. 
ASTRAZENECA LP v. APOTEX 40

II. The Kit Claims 

The asserted kit claims recite two elements: (1) a 

budesonide composition or suspension in a sealed container containing 0.05 mg to 15 mg budesonide and a 

solvent, and (2) a label indicating administration by 

nebulization in a continuing regimen at a frequency of not 

more than once per day. See, e g., ’603 Patent col.12 ll.3-8; 

’099 Patent col.11 ll.9-14. The district court concluded 

that the kit claims are invalid, finding the claimed 

budesonide composition and suspension were known in 

the prior art and that the instructions in the claimed label 

are non-statutory subject matter and therefore not entitled to patentable weight. Opinion at 589-92. Regarding 

the instructions in the label, the district court explained 

that under Federal Circuit precedent “[w]here . . . printed 

matter is not functionally related to the substrate, the 

printed matter will not distinguish the invention from the 

prior art in terms of patentability.” Id. at 590 (citation 

omitted). This court noted that here the parties disputed 

what constitutes the substrate, with Apotex contending 

that the label is the substrate and AstraZeneca asserting 

that the substrate is the drug. Id. at 592. After considering our precedent, the district court concluded that this 

dispute was immaterial because regardless of how the 

substrate was defined, “the instructions simply explain 

how to use the known product. This type of relationship 

does not qualify as a functional one . . . .” Id. at 591. 

AstraZeneca argues that a drug label and its associated drug are “inextricably interrelated,” as a drug cannot 

be approved unless and until the FDA approves its label. 

AstraZeneca notes that FDA regulations require the label 

for a drug to include information needed for proper use of 

the drug and argues that without the label a physician 

would be unable to safely and effectively treat patients. 

In light of this, AstraZeneca contends that a drug label is 
41 ASTRAZENECA LP v. APOTEX

essential to physicians when prescribing a drug and, 

therefore, is functionally related to the drug. 

Apotex counters that, for the purposes of determining 

whether the claimed label is entitled to patentable 

weight, the relationship between the drug and the label is 

irrelevant. According to Apotex, the proper inquiry is 

whether there is a functional relationship between the 

printed matter and its substrate, i.e., the object the 

printed matter is printed on. Apotex contends that here 

the printed matter is the instruction for once-daily use 

and the substrate is the paper label. Citing In re Ngai, 

367 F.3d 1336 (Fed. Cir. 2004), Apotex argues that the 

instructions are not functionally related to the label on 

which they are printed because they do not function 

together in any way. 

There is no dispute that the budesonide suspension 

recited in the claims is known in the prior art. The question before us is whether the district court correctly 

determined that the recitation in the claims of a label 

instructing not more than once-a-day dosing is of no 

patentable consequence. This court reviews de novo the 

district court’s determination that the asserted claims 

recite non-statutory subject matter. See In re Comiskey, 

554 F.3d 967, 975 (Fed. Cir. 2009) (explaining that 

“whether the asserted claims . . . are invalid for failure to 

claim statutory subject matter under 35 U.S.C. § 101[] is 

a question of law which we review without deference.” 

(quoting AT&T Corp. v. Excel Commc’ns, Inc., 172 F.3d 

1352, 1355 (Fed. Cir. 1999))). 

The categories of patentable subject matter are set 

forth in 35 U.S.C. § 101: 

Whoever invents or discovers any new and useful 

process, machine, manufacture, or composition of 

matter, or any new and useful improvement 
ASTRAZENECA LP v. APOTEX 42

thereof, may obtain a patent therefor, subject to 

the conditions and requirements of this title. 

This court has generally found printed matter to fall 

outside the scope of § 101. See In re Chatfield, 545 F.2d 

152, 157 (CCPA 1976) (“Some inventions, however meritorious, do not constitute patentable subject matter, e.g., 

printed matter . . . .” (citation omitted)). However, as 

observed by the district court, this court has long recognized an exception to this general rule: If there is a “functional relationship” between the printed matter and its 

substrate, the printed matter may serve to distinguish the 

invention from the prior art. See In re Miller, 418 F.2d 

1392, 1396 (CCPA 1969); In re Gulack, 703 F.2d 1381, 

1385-87 (Fed. Cir. 1983). 

This court considered the printed matter exception in 

Ngai, a case similar to the one now before us. In Ngai, 

the Board affirmed the rejection of a claim reciting a kit 

comprising instructions to amplify ribonucleic acids. The 

Board found that the only difference between the claimed 

kit and the prior art was the content of the claimed instructions. Concluding that this content was not functionally related to the kit, the Board found that the claim 

was anticipated by the prior art. This court affirmed, 

rejecting the argument that the addition of new printed 

matter to a known product makes the product patentable. 

This court reasoned that “the printed matter in no way 

depends on the kit, and the kit does not depend on the 

printed matter. All that the printed matter does is teach 

a new use for an existing product.” Ngai, 367 F.3d at 

1339. 

This court agrees with Apotex that as in Ngai the 

claimed instructions here are not entitled to patentable 

weight. The instructions in no way function with the drug 

to create a new, unobvious product. Removing the in-
43 ASTRAZENECA LP v. APOTEX

structions from the claimed kit does not change the ability 

of the drug to treat respiratory diseases. Although AstraZeneca is correct that FDA regulations require a label 

containing information needed for the safe and effective 

use of any drug, this is a requirement for FDA approval, 

not patentability. 

This court also agrees with the district court that the 

dispute over whether the “substrate” is the label or the 

drug is immaterial, for in both cases the instructions do 

nothing more than explain how to use the known drug. 

Our decision in Ngai foreclosed the argument that simply 

adding new instructions to a known product creates the 

functional relationship necessary to distinguish the 

product from the prior art. As explained in Ngai, if this 

court concluded otherwise “anyone could continue patenting a product indefinitely provided that they add a new 

instruction sheet to the product.” 367 F.3d at 1339. 

Neither the Patent Act nor our precedent countenances 

such an outcome. The district court’s determination that 

the kit claims are invalid is affirmed. 

CONCLUSION

For the foregoing reasons, this court concludes that 

the district court did not abuse its discretion by granting 

the preliminary injunction and did not err in determining 

that the kit claims are invalid. 

AFFIRMED 
United States Court of Appeals 

for the Federal Circuit 

__________________________ 

ASTRAZENECA LP 

AND ASTRAZENECA AB, 

Plaintiffs-Cross Appellants, 

v. 

APOTEX, INC. 

AND APOTEX CORP., 

Defendants-Appellants. 

__________________________ 

2009-1381, -1424 

__________________________ 

Appeal from the United States District Court for the 

District of New Jersey in case No. 09-CV-1518, Judge 

Renee Marie Bumb. 

__________________________ 

BRYSON, Circuit Judge, concurring in part and dissenting 

in part. 

I concur in the portion of the court’s opinion sustaining the district court’s ruling that the “kit” claims of 

AstraZeneca’s ’603 and ’099 patents are invalid. Because 

I believe Apotex has raised a substantial question of 

invalidity as to the other claims of the ’603 patent, see

Amazon.com, Inc. v. Barnesandnoble.com, Inc., 239 F.3d 

1343, 1359 (Fed. Cir. 2001), I would reverse the district 

court’s grant of a preliminary injunction. 
ASTRAZENECA LP v. APOTEX 2

Apotex has asserted that two prior art references anticipate the claims in dispute, the ’528 patent and the 

Thorax advertisement. 

1. The district court’s ruling that the ’528 patent does 

not anticipate the ’603 claims was predicated on an unduly narrow claim construction of the term “budesonide 

composition” in the ’603 claims. The court’s construction 

required the budesonide to be “dispersed in a solvent in 

the form of a solution or a suspension,” and it excluded 

“the involvement of liposomes as described in the ’528 

[reference.]” The claims of the ’603 patent, however, are 

broader than that. 

Claim 1, the only independent method claim of the 

’603 patent, recites the administration of a “nebulized 

dose of a budesonide composition in a continuing regimen 

at a frequency of not more than once per day.” Even 

assuming that the reference to a “nebulized” dose requires 

dispersion in a solvent, nothing in the patent mandates a 

particular manner in which the budesonide and the 

solvent are to be combined. 

More specifically, contrary to the testimony of AstraZeneca’s expert Dr. Williams, the ’603 patent does not 

require that the budesonide of the “budesonide composition” be directly suspended or dissolved in a solvent, free 

from encapsulation or entrapment within liposomes. In 

fact, the language of the patent undercuts Dr. Williams’s 

rationale for that interpretation. While Dr. Williams 

assumed that use of the “depot effect,” with which liposome involvement may interfere, is a critical aspect of the 

invention of the ’603 patent, the specification explicitly 

disavows any need for the depot effect to occur. Thus, 

after describing the depot effect, the specification states: 

“This proposed mechanism of action is exemplary; the 
3 ASTRAZENECA LP v. APOTEX

invention is not limited by any particular mechanism of 

action.” ’603 patent, col. 3, ll. 12-13. That language 

indicates that the patentees did not consider the depot 

effect to be essential to the effectiveness of once-daily-orless dosing, as Dr. Williams claimed. Because the patented method of treatment encompasses mechanisms of 

action other than the depot effect, the term “budesonide 

composition” need not consist of budesonide directly 

dispersed in solvent, and it need not exclude the involvement of liposomes as described in the ’528 reference. The 

’528 reference therefore appears to anticipate (or render 

obvious) the asserted claims under the proper construction of the term “budesonide composition.” 

2. With respect to the 1994 advertisement for Pulmicort Respules® in the journal Thorax, AstraZeneca concedes that the advertisement discloses every limitation of 

the asserted method claims except for the frequency of 

drug administration: “not more than once per day.” On 

that issue, the district court stated: 

[a]lthough the Thorax advertisement states that 

“[t]he maintenance dose should be the lowest dose 

which keeps the patient symptom-free[,]” Dr. 

Chipps testified that this statement does not instruct once-daily dosing because the ad was published “back in 1994 . . . before we had any 

information or historical perspective that once a 

day therapy worked for anybody.” The Court 

finds this answer persuasive. 

AstraZeneca LP v. Apotex, Inc., 623 F. Supp. 2d 579, 596 

(D.N.J. 2009). The district court concluded that at the 

time of its publication the Thorax advertisement did not 

enable once-daily dosing, because a person of skill in the 

art in 1994 would not have believed that once-daily ad-
ASTRAZENECA LP v. APOTEX 4

ministration of Pulmicort Respules® would be effective. 

As the majority acknowledges, however, a prior art reference need not demonstrate utility in order to serve as an 

anticipating reference under section 102. Rasmusson v. 

SmithKline Beecham Corp., 413 F.3d 1318, 1326 (Fed. 

Cir. 2005). 

The Thorax advertisement contains a list of recommended dosing regimens as low as “0.25-0.5 mg twice 

daily”; it also suggests that “the maintenance dosage 

should be the lowest dosage which keeps the patient 

symptom-free.” The Apotex label similarly recommends 

dosages of 0.25 mg to 0.5 mg administered twice daily and 

states that “[o]nce the desired clinical effect is achieved, 

consideration should be given to tapering to the lowest 

effective dose.” The district court concluded that Apotex’s 

label induced infringement by suggesting the administration of the drug once a day. There is no reason to treat 

the similar recitation in the Thorax advertisement differently. The district court’s rationale for distinguishing 

between the Apotex label and the Thorax advertisement—

that in 1994 the scientific community had yet to confirm 

that once-daily dosing was effective in large patient 

populations—does not undermine the effect of the advertisement in suggesting a reduction in dosage for particular patients, which would necessarily be achieved either 

by reducing the amount administered on each occasion or 

the frequency of administration. 

Because Apotex has presented a substantial question 

concerning the validity of the ’603 patent’s method claims, 

I would vacate the preliminary injunction.