United States Court of Appeals 

for the Federal Circuit ______________________ 

ALLERGAN, INC.,

Plaintiff-Appellee

v.

SANDOZ INC., LUPIN LTD., LUPIN 

PHARMACEUTICALS, INC., HI-TECH 

PHARMACAL CO., INC.,

Defendants-Appellants

______________________ 

2014-1275

______________________ 

Appeal from the United States District Court for the 

Eastern District of Texas in No. 6:11-cv-00441-MHS, 

Judge Michael H. Schneider.

______________________ 

Decided: August 4, 2015

______________________ 

JUANITA ROSE BROOKS, Fish & Richardson, P.C., San 

Diego, CA, argued for plaintiff-appellee. Also represented 

by CRAIG E. COUNTRYMAN; JONATHAN ELLIOT SINGER,

DEANNA JEAN REICHEL, Minneapolis, MN; DOUGLAS E.

MCCANN, SUSAN M. COLETTI, Wilmington, DE. 

DEANNE MAYNARD, Morrison & Foerster LLP, Washington, DC, argued for defendant-appellant Sandoz Inc. 

Also represented by BRIAN ROBERT MATSUI; DAVID 
2 ALLERGAN, INC. v. SANDOZ INC. 

CLARENCE DOYLE, ANDERS T. AANNESTAD, JAMES CEKOLA, 

San Diego, CA.

WILLIAM A. RAKOCZY, Rakoczy Molino Mazzochi, 

Siwik LLP, Chicago, IL, argued for defendants-appellants 

Lupin Ltd., Lupin Pharmaceuticals, Inc. Also represented 

by PAUL J. MOLINO, DEANNE M. MAZZOCHI, THEODORE 

JOSEPH CHIACCHIO, JOHN POLIVICK. 

STEVEN D. ROTH, Locke Lord, LLP, New York, NY, argued for defendant-appellant Hi-Tech Pharmacal Co., Inc. 

Also represented by THOMAS J. VETTER, Lucas & Mercanti, LLP, New York, NY. 

______________________ 

Before LOURIE, LINN, and HUGHES, Circuit Judges.

LOURIE, Circuit Judge. 

Sandoz Inc. (“Sandoz”), Lupin Ltd. and Lupin Pharmaceuticals, Inc. (collectively, “Lupin”), and Hi-Tech 

Pharmacal Co., Inc. (“Hi-Tech”) (collectively, “the Appellants”)1 appeal from the decision of the United States 

District Court for the Eastern District of Texas, following 

a bench trial, which held that the claims of U.S. Patents 

7,851,504 (the “ ’504 patent”), 8,278,353 (the “ ’353 patent”), 8,299,118 (the “ ’118 patent”), 8,309,605 (the “ ’605 

patent”), and 8,338,479 (the “ ’479 patent”), asserted by 

Allergan, Inc. (“Allergan”), were not shown to be invalid 

for obviousness under 35 U.S.C. § 103, and that the 

1 Watson Laboratories, Inc., Watson Pharmaceuticals, Inc., and Watson Pharm, Inc. (collectively, “Watson”) 

were also defendants-appellants initially. But Watson 

has since been dismissed from this appeal on a joint 

motion filed by Watson and Allergan. See Allergan, Inc. v. 

Sandoz Inc., No. 14-1275, ECF No. 121 (Fed. Cir. Apr. 17, 

2015).

 
ALLERGAN, INC. v. SANDOZ INC. 3

claims of the ’353 and ’118 patents were not shown to be 

invalid for lack of an adequate written description under 

35 U.S.C. § 112, ¶ 1.2 Allergan, Inc. v. Sandoz Inc., No. 

6:11-cv-00441, ECF No. 303, slip op. at 77, 79 (E.D. Tex. 

Jan. 13, 2014) (“Opinion”). Additionally, Lupin challenges

the district court’s determination that the claims of Allergan’s patents were not shown to be invalid for lack of 

enablement under § 112, ¶ 1. Id. at 80–81. Hi-Tech also 

challenges the district court’s finding that it infringed the 

claims of the ’504, ’605, and ’479 patents literally and 

under the doctrine of equivalents. Id. at 64–66. For the 

reasons that follow, we affirm in all respects.

BACKGROUND

I 

Glaucoma is an eye disease associated with elevated 

intraocular pressure (“IOP”). Treatments that effectively 

reduce IOP can slow the progression of the disease. If left 

untreated, however, elevated IOP can damage the optic 

nerve and lead to permanent vision loss and blindness. In 

2001, the U.S. Food and Drug Administration (the “FDA”) 

approved Lumigan® 0.03% (“Lumigan 0.03%”), a oncedaily topical solution developed by Allergan, for treating

open angle glaucoma and ocular hypertension. Lumigan 

0.03% contains 0.03% by weight of bimatoprost and 50 

parts per million (“ppm”) benzalkonium chloride (“BAK”), 

among other ingredients. 

Bimatoprost, the active ingredient in Lumigan 0.03%,

is a prostaglandin analog that effectively lowers IOP, but 

can cause hyperemia, i.e., red eye, when administered to 

2 Because the applications resulting in the patents 

asserted in this case were filed before the enactment of 

the Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 

112-29, 125 Stat. 284 (2011), we apply the pre-AIA version of 35 U.S.C. § 103 and § 112.

 
4 ALLERGAN, INC. v. SANDOZ INC. 

the ocular surface. One structural difference between 

bimatoprost and two other prostaglandin analogs that 

were approved for treating glaucoma at the time of its 

approval, Xalatan® (latanoprost) and Travatan®

(travoprost), is that bimatoprost contains an amide, 

instead of an ester as in latanoprost and travoprost. 

Opinion at 7–8. It was understood that both latanoprost 

and travoprost, but not bimatoprost, act as prodrugs of 

the corresponding acids. Id.

BAK is a preservative for inhibiting bacterial growth

in ophthalmic solutions. It was known, however, that 

BAK is cytotoxic and that it can damage the cells on the 

ocular surface and cause undesirable side effects. 

Although Lumigan 0.03% was effective at lowering 

IOP, it also caused frequent and severe hyperemia. Many 

patients thus stopped using it without consulting their 

physicians, which led to gradual vision loss. To address 

that problem, Allergan explored a number of alternative 

formulations of bimatoprost and surprisingly discovered 

that increasing the concentration of BAK from 50 ppm to 

200 ppm significantly increased the corneal permeability 

of bimatoprost. Id. at 12–13. After further research, 

Allergan developed Lumigan® 0.01% (“Lumigan 0.01%”). 

Lumigan 0.01% is a topical solution containing 0.01%

bimatoprost and 200 ppm BAK; otherwise, it has the 

same ingredients as Lumigan 0.03%. Thus, as compared 

with Lumigan 0.03%, Lumigan 0.01% has a three-fold 

lower bimatoprost concentration and a four-fold higher 

BAK concentration. Clinical studies showed that Lumigan 0.01% has similar efficacy to Lumigan 0.03%, viz., 

IOP-lowering within 0.5 mmHg of that of Lumigan 0.03%, 

but it causes less frequent and severe hyperemia than 

Lumigan 0.03%. Id. at 20–21. In 2010, the FDA approved Allergan’s New Drug Application for Lumigan 

0.01% for the same approved uses as Lumigan 0.03%. 
ALLERGAN, INC. v. SANDOZ INC. 5

II

Allergan owns the ’504, ’353, ’118, ’605, and ’479 patents, which are all listed in the FDA’s Approved Drug 

Products with Therapeutic Equivalence Evaluations

(commonly known as the “Orange Book”) as claiming 

Lumigan 0.01% and its approved uses. After Allergan 

received FDA-approval of Lumigan 0.01%, Sandoz, Lupin, 

Hi-Tech, and Watson each submitted an Abbreviated New 

Drug Application (“ANDA”) to the FDA, seeking approval 

to engage in the commercial manufacture, use, importation, sale, or offer for sale of generic versions of Lumigan 

0.01% prior to the expiration of the ’504, ’353, ’118, ’605, 

and ’479 patents. In response, Allergan sued each of the 

ANDA applicants in the United States District Court for 

the Eastern District of Texas, asserting that their ANDA 

filings infringed those patents. The district court consolidated those actions into one case. 

The asserted patents all derive from an application 

filed on March 16, 2005 and share a common specification. The patents are entitled “Enhanced Bimatoprost 

Ophthalmic Solution,” ’504 patent col. 1 ll. 1–2,3 and refer 

to what is Lumigan 0.03% in the background section, id.

col. 1 ll. 34–36. The specifications of the patents describe 

a composition comprising 0.005% to 0.02% bimatoprost 

and 100 ppm to 250 ppm BAK, which is an aqueous liquid

“formulated for ophthalmic administration” and “useful in 

treating glaucoma or ocular hypertension.” Id. col. 1 

ll. 61–67. The specifications also specifically describe a 

formulation comprising 0.01% bimatoprost and 200 ppm

BAK, among other formulations, as a “best mode” of the 

invention. Id. col. 2 ll. 59, 64–67.

3 Because the asserted patents share an identical 

specification in relevant part, we refer only to the ’504 

patent when discussing the specifications of those patents.

 
6 ALLERGAN, INC. v. SANDOZ INC. 

Additionally, the specifications disclose in vitro and in 

vivo experimental data in rabbits, showing that increasing the concentration of BAK from 50 ppm to 200 ppm

significantly increased the permeability of bimatoprost 

across ocular membranes. Id. col. 4 ll. 10–58, col. 5 l. 19–

col. 6 l. 5, Figs. 1 & 2. Finally, in a constructive example, 

the specifications describe the once-daily ophthalmic 

administration to a glaucoma patient of a formulation 

containing 0.015% bimatoprost, 125 ppm BAK, and 

0.015% EDTA, stating that “intraocular pressure drops 

more and less hyperemia is observed than would be 

observed for [a formulation containing 0.03% bimatoprost 

and 50 ppm BAK,]” and “[l]owered intraocular pressure 

persists for as long as the treatment continues.” Id. col. 6 

ll. 7–14. 

Allergan asserted the following claims against each of 

the ANDA applicants: claim 2 of the ’504 patent; claim 15 

of the ’479 patent; claims 1, 6, 10, and 12 of the ’605 

patent; claims 1, 7, and 8 of the ’353 patent; and claims 1, 

7, and 8 of the ’118 patent (collectively, “the asserted 

claims”). Those claims collectively are directed to compositions comprising bimatoprost and BAK and methods of 

using them to treat glaucoma or to lower IOP. 

Each of the asserted claims requires a composition 

comprising 0.01% bimatoprost and 200 ppm BAK. Claim 

2 of the ’504 patent, claim 15 of the ’479 patent, and 

claims 1, 6, 10, and 12 of the ’605 patent (collectively, “the 

Group I claims”) further require the composition to have a 

pH of “about 7.3.” Claims 1, 7, and 8 of the ’353 patent 

and claims 1, 7, and 8 of the ’118 patent (collectively, “the 

Group II claims”) do not contain such a pH limitation, but 

they require a particular clinical profile of the claimed

composition as compared to a composition comprising 

0.03% bimatoprost and 50 ppm BAK. 

Claim 2 of the ’504 patent is representative of the 

Group I composition claims and reads as follows: 
ALLERGAN, INC. v. SANDOZ INC. 7

2. A composition having a pH of about 7.3 which 

comprises about 0.01% bimatoprost, about 200 

ppm benzalkonium chloride, citric acid monohydrate, a phosphate buffer, and NaCl wherein said 

composition is an aqueous liquid which is formulated for ophthalmic administration. 

Id. col. 6 ll. 21–25 (emphases added). 

Claim 1 of the ’605 patent is representative of the 

Group I method claims and reads as follows:

1. A method of lowering elevated intraocular 

pressure in a patient with open-angle glaucoma or 

ocular hypertension which comprises applying to 

the eyes of the patient an aqueous solution comprised of: about 0.01% w/v bimatoprost; about 200 

ppm benzalkonium chloride; the solution 

having a pH of about 7.3; a phosphate buffer; and

water.

’605 patent col. 5 ll. 47–55 (emphases added). 

As indicated, the Group II claims all contain clinical 

profile limitations. Claims 1, 7, and 8 of the ’353 patent 

are directed to compositions and read as follows:

1. A first composition administered once daily for 

lowering intraocular pressure in a person with 

glaucoma or ocular hypertension, the first composition comprising about 0.01% w/v bimatoprost 

and about 0.02% w/v benzalkonium chloride,

wherein the first composition lowers intraocular 

pressure and results in less hyperemia as compared to the once daily administration of a second 

composition comprising 0.03% w/v bimatoprost 

and 0.005% w/v benzalkonium chloride. 

7. A first composition administered once daily for 

lowering intraocular pressure in a person with 

glaucoma or ocular hypertension, the first compo-
8 ALLERGAN, INC. v. SANDOZ INC. 

sition comprising about 0.01% w/v bimatoprost 

and about 0.02% w/v benzalkonium chloride, 

wherein the first composition lowers intraocular 

pressure without a substantial reduction in the intraocular pressure lowering benefit provided by 

the once daily administration of a second composition comprising 0.03% w/v bimatoprost and 

0.005% w/v benzalkonium chloride. 

8. The composition of claim 7 wherein the once 

daily administration of the first composition results in less hyperemia as compared to the once 

daily administration of the second composition. 

’353 patent col. 5 ll. 48–56, col. 6 ll. 3–15 (emphases 

added).4 Claims 1, 7, and 8 of the ’118 patent are directed 

to methods of treatment; they contain the same clinical 

profile limitations as those in claims 1, 7, and 8 of the ’353 

patent. ’118 patent col. 5 ll. 48–56, col. 6 ll. 3–16.

III

The district court held a five-day bench trial in July 

2013 on the issues of obviousness and infringement. The 

defendants also argued that the claims were invalid for 

lack of written description and enablement in pre- and 

post-trial briefings. In January 2014, the court rendered 

its findings of fact and conclusions of law on all of those 

issues.

a.

The district court concluded that the asserted claims 

would not have been obvious in view of the cited prior art, 

which included: (1) U.S. Patent 5,688,819 (“Woodward”); 

(2) U.S. Patent 6,933,289 (“Lyons”); (3) Laibovitz et al., 

Comparison of the Ocular Hypotensive Lipid AGN 192024 

4 The parties agree that 0.02% w/v corresponds to

200 ppm, and 0.005% w/v corresponds to 50 ppm.

 
ALLERGAN, INC. v. SANDOZ INC. 9

with Timolol, 119 Archives of Ophthalmology 994 (2001) 

(“Laibovitz”); (4) Abelson et al., How to Handle BAK Talk, 

Rev. of Ophthalmology, Dec. 2002, at 52–54 (“Abelson”); 

(5) Lee et al., Review: Topical Ocular Drug Delivery: 

Recent Developments and Future Challenges, 2 J. Ocular 

Pharmacology 67 (1986) (“Lee”); (6) Camber et al., Factors 

Influencing the Corneal Permeability of Prostaglandin F2α

and Its Isopropyl Ester In Vitro, 37 Int’l J. Pharmaceutics 

27 (1987) (“Camber”); (7) Higaki et al., Estimation and 

Enhancement of In Vitro Corneal Transport of S-1033, a 

Novel Antiglaucoma Medication, 132 Int’l J. Pharmaceutics 165 (1996) (“Higaki”); and (8) Keller et al., Increased 

Corneal Permeability Induced by the Dual Effects of 

Transient Tear Film Acidification and Exposure to Benzalkonium Chloride, 30 Experimental Eye Res. 203 (1980) 

(“Keller”). 

Specifically, with respect to the scope and content of 

the prior art, the district court found that: (1) ophthalmic 

formulation was unpredictable, and it was not a field with 

a finite number of identified and predictable solutions, 

Opinion at 29–31; (2) Laibovitz and Lyons both taught 

that reducing bimatoprost from 0.03% to 0.01% would 

result in less IOP-lowering efficacy, id. at 31–34; 

(3) Laibovitz also taught that reducing bimatoprost from 

0.03% to 0.01% would not result in less hyperemia, and 

Lyons did not suggest the contrary, id. at 34–35; (4) the 

cited prior art, including Higaki, Camber, Lee, Keller, and 

Abelson, as well as Xalatan® (latanoprost), which contains 

200 ppm BAK, did not teach that high concentrations of 

BAK would enhance the corneal permeability of bimatoprost, a neutral prostaglandin amide analog; instead, the 

prior art suggested that BAK would decrease the permeability of a neutral prostaglandin analog, id. at 35, 38–47; 

and (5) the prior art taught that BAK should be minimized in ophthalmic formulations due to its toxicity, and, 

in particular, taught away from using 200 ppm BAK in a 

bimatoprost formulation because BAK was known to 
10 ALLERGAN, INC. v. SANDOZ INC. 

cause side effects, including increased IOP, hyperemia,

and dry eye, making it unsuitable for chronic use at high 

concentrations, id. at 47–54.

The district court then found that there would not 

have been a reason to pursue the claimed invention or a 

reasonable expectation of success if it were pursued. Id.

at 55–56. The court also found evidence of long-felt need, 

unexpected results, and commercial success supporting a 

conclusion of nonobviousness. Id. at 56–59. The court 

specifically found that it was unexpected that Lumigan

0.01% would reduce the incidence and severity of hyperemia, as compared to Lumigan 0.03%, while maintaining 

IOP-lowering efficacy, and that it was also unexpected 

that 200 ppm BAK would enhance the permeability of 

bimatoprost to such an extent so as to allow the reduction 

of the bimatoprost concentration from 0.03% to 0.01%

without loss of efficacy. Id. at 57–58.

In view of those factual findings, the district court 

concluded that the asserted claims would not have been 

obvious. Id. at 74. In reaching that conclusion, the court 

emphasized that the prior art taught away from the 

claimed invention because it taught “(1) that bimatoprost 

lost efficacy as its concentration decreased; (2) that BAK 

had no impact on bimatoprost’s permeability; and (3) that 

BAK was cytotoxic and could cause corneal disorders, 

therefore encouraging the elimination or reduction in the 

concentration of BAK.” Id. at 74–75.

The district court also rejected the defendants’ argument raised in post-trial briefings that our decision in 

Galderma Laboratories, L.P. v. Tolmar, Inc., 737 F.3d 731 

(Fed. Cir. 2013), compels a conclusion of obviousness in 

this case. The defendants argued that Woodward disclosed a formulation comprising 0.001%–1% bimatoprost 

and 0–1000 ppm BAK for treating glaucoma, and that the 

amounts of bimatoprost and BAK in the claimed formulation fall within those prior art ranges, thus rendering the 
ALLERGAN, INC. v. SANDOZ INC. 11

claims obvious. The district court reasoned that “Allergan 

has met its burden of producing rebuttal evidence, i.e., 

‘that (1) the prior art taught away from the claimed 

invention; (2) there were new and unexpected results 

relative to the prior art; or (3) there are other pertinent 

secondary considerations.’” Opinion at 75 (quoting Galderma, 737 F.3d at 738). The court again emphasized

that the prior art taught away from 200 ppm BAK, noting

that the defendants’ own expert, Dr. Samples, had serious 

concerns about BAK and strongly warned against its use. 

Id. at 75–76. The court also emphasized that the unexpected results were “of a different kind, not just of different degree.” Id. at 76 (emphases in original).

The district court thus concluded that the defendants 

failed to prove by clear and convincing evidence that the 

asserted claims would have been obvious. Id. at 77.

b.

The district court also rejected the defendants’ invalidity challenges based on the written description and 

enablement requirements, which they raised only in preand post-trial briefings. Id. at 77–81. The court noted 

that the defendants “did not present any evidence or 

argument” on those issues at trial. Id. at 77, 79.

Specifically, the defendants alleged that the Group II 

claims, which recite clinical profile limitations, were 

invalid for lack of an adequate written description. The 

district court found, however, that the patents explicitly 

describe the formulation of Lumigan 0.01%, and that 

Lumigan 0.01% has the clinical profile recited in the 

Group II claims. Id. at 78. The court also found additional support in the titles of the patents, the disclosed in 

vitro and in vivo permeability data of bimatoprost, as well 

as the constructive example comparing the IOP-lowering 

efficacy and hyperemia profile of a test formulation to 

that of Lumigan 0.03%. The court therefore found that 

the Group II claims have adequate written description 
12 ALLERGAN, INC. v. SANDOZ INC. 

support, “especially given the express disclosure that 

Lumigan 0.01% is an example of the best mode of the 

invention.” Id. The court additionally reasoned that the 

inventors had possession of the claimed invention because

a clinical protocol prepared in November 2004, before the 

March 2005 application filing date, describes the formulation of Lumigan 0.01% and the later-claimed clinical 

profile. Id. at 79.

Lupin also alleged that the asserted claims were invalid for lack of enablement. The district court rejected that 

argument, reasoning that Allergan’s patents disclose the 

formulation of Lumigan 0.01% and that the patents’ 

disclosure would enable one of ordinary skill in the art to 

make and use the claimed invention without undue 

experimentation. Id. at 80–81.

c.

The district court also found that each of the ANDA 

products infringed each of the asserted claims. Relevant 

to this appeal, the court found that Hi-Tech’s ANDA 

product infringed the Group I claims, which require the 

claimed composition to have a pH of “about 7.3.” Before 

trial, the parties agreed to construe a “pH of about 7.3” as 

a “pH of approximately 7.3,” and the court adopted that 

construction. Allergan, Inc. v. Sandoz Inc., No. 6:11-cv00441, 2013 WL 139350, at *9 (E.D. Tex. Jan. 10, 2013). 

Hi-Tech’s ANDA specified that its proposed product has a

pH of 6.8–7.2 during the product’s shelf life. Opinion at 

27. After considering the evidence presented at trial, the 

court found that Hi-Tech’s ANDA product literally infringed the Group I claims. Id. at 64. The court also 

found, in the alternative, that Hi-Tech’s ANDA product

infringed the Group I claims under the doctrine of equivalents. Id. at 64–66.

Accordingly, the district court entered final judgment

of infringement and no invalidity. The Appellants timely 
ALLERGAN, INC. v. SANDOZ INC. 13

appealed to this court; we have jurisdiction under 28 

U.S.C. § 1295(a)(1).

DISCUSSION

Following a bench trial, we review a district court’s 

conclusions of law de novo and its findings of fact for clear 

error. Golden Blount, Inc. v. Robert H. Peterson Co., 365 

F.3d 1054, 1058 (Fed. Cir. 2004). A factual finding is 

clearly erroneous if, despite some supporting evidence, we 

are left with a definite and firm conviction that a mistake 

has been made. United States v. U.S. Gypsum Co., 333 

U.S. 364, 395 (1948); Alza Corp. v. Mylan Labs., Inc., 464 

F.3d 1286, 1289 (Fed. Cir. 2006).

Furthermore, patents are presumed to be valid and 

overcoming that presumption requires clear and convincing evidence. 35 U.S.C. § 282; Microsoft Corp. v. i4i Ltd.

P’ship, 564 U.S. __, 131 S. Ct. 2238, 2242 (2011).

I 

We first consider the Appellants’ arguments contending that the district court erred in concluding that the 

asserted claims would not have been obvious. 

A patent claim is invalid as obvious if an alleged infringer proves that the differences between the claimed 

subject matter and the prior art are such that the subject 

matter as a whole would have been obvious at the time of 

invention to a person having ordinary skill in the art. 35 

U.S.C. § 103(a) (2006). Obviousness is ultimately a 

question of law premised on underlying issues of fact, 

including: (1) the scope and content of the prior art; 

(2) the level of ordinary skill in the pertinent art; (3) the 

differences between the claimed invention and the prior 

art; and (4) objective evidence, such as commercial success, long-felt need, and the failure of others. KSR Int’l 

Co. v. Teleflex Inc., 550 U.S. 398, 427 (2007); Graham v. 

John Deere Co., 383 U.S. 1, 17–18 (1966); Monarch Knit-
14 ALLERGAN, INC. v. SANDOZ INC. 

ting Mach. Corp. v. Sulzer Morat GmbH, 139 F.3d 877, 

881 (Fed. Cir. 1998). 

The Appellants argue that the district court erred as a 

matter of law by requiring them to establish a motivation 

to pursue the claimed formulation by modifying Lumigan 

0.03% and a reasonable expectation of success in doing so. 

According to the Appellants, because the claimed amounts 

of bimatoprost and BAK fall within prior art ranges, the 

proper obviousness inquiry should focus only on teaching 

away, unexpected results, and other objective indicia. 

The Appellants also assert that the district court applied 

an incorrect standard for teaching away because it merely 

found that the prior art taught that the claimed formulation would be inferior, rather than that it would not work. 

And they argue that the prior art does not teach away 

from 0.01% bimatoprost or 200 ppm BAK. They assert, 

moreover, that there are no unexpected results because

the observed results of similar efficacy and less hyperemia 

are only a difference in degree, not a difference in kind. 

They also argue that those results are the inherent properties of an otherwise obvious formulation. Finally, they 

argue that the district court erred in finding other objective indicia as supporting nonobviousness.

Allergan responds that this appeal turns on disputed 

facts and that the district court did not clearly err in 

finding those facts in Allergan’s favor, including finding 

that the prior art taught that (1) 0.01% bimatoprost 

would be less efficacious than 0.03% bimatoprost; (2) BAK 

would decrease the permeability of bimatoprost; and 

(3) 200 ppm BAK would be unsafe for chronic use with 

bimatoprost. Allergan contends that the Appellants 

should not, on appeal, fault the district court for approaching the issue of obviousness in the way they argued 

it during trial. Allergan maintains that it would not have 

been obvious to modify Lumigan 0.03% to make the 

claimed formulation or to select the claimed amounts of 

bimatoprost and BAK from two very broad prior art 
ALLERGAN, INC. v. SANDOZ INC. 15

ranges. Allergan also responds that, in any event, the 

district court did not err in finding teaching away, unexpected results, and other objective indicia, which fully 

supported the court’s conclusion of nonobviousness.

We agree with Allergan that the district court did not 

err in concluding that the asserted claims would not have 

been obvious. That conclusion is supported by underlying 

factual findings, which are not clearly erroneous on this 

record. In particular, the district court did not clearly err 

in finding that the prior art taught away from a formulation comprising 0.01% bimatoprost and 200 ppm BAK, 

and that such a formulation exhibited unexpected results. 

It is undisputed that the asserted claims all require a 

formulation comprising 0.01% bimatoprost and 200 ppm 

BAK. Although the prior art does not teach that particular combination of amounts of bimatoprost and BAK, 

those amounts do fall within the ranges disclosed in a

single reference: Woodward discloses a composition comprising 0.001%–1% bimatoprost and 0–1000 ppm of a 

preservative, including BAK. Those disclosed ranges also 

encompass Lumigan 0.03%, a prior art commercial embodiment, which contains 0.03% bimatoprost and 50 ppm 

BAK.

As we explained in Galderma, where there is a range 

disclosed in the prior art, and the claimed invention falls 

within that range, a relevant inquiry is whether there 

would have been a motivation to select the claimed composition from the prior art ranges. Galderma, 737 F.3d at 

737–38 (prior art disclosing 0.01%–1% adapalene encompassing the claimed composition comprising 0.3% adapalene). In those circumstances, “the burden of production 

falls upon the patentee to come forward with evidence 

that (1) the prior art taught away from the claimed invention; (2) there were new and unexpected results relative to 

the prior art; or (3) there are other pertinent secondary

considerations.” Id. at 738.
16 ALLERGAN, INC. v. SANDOZ INC. 

Here in this case, the prior art ranges are broader 

than the range in Galderma, and the record shows that 

the claimed amounts of the two different ingredients 

could and did materially and unpredictably alter the 

property of the claimed formulation. Thus, Galderma

does not compel a conclusion of obviousness in this case. 

It may also be true here that “the disclosed range[s are] so 

broad as to encompass a very large number of possible 

distinct compositions,” In re Peterson, 315 F.3d 1325, 1330 

n.1 (Fed. Cir. 2003), such that they do not teach any 

specific amounts or combinations and that the burden of 

producing evidence of teaching away, unexpected results, 

and other pertinent secondary considerations did not shift 

to Allergan. But we need not decide that issue, as it 

would not affect our affirmance of the district court’s 

conclusion of nonobviousness, because, as indicated infra, 

we conclude that the district court did not clearly err in 

finding that Allergan had produced ample evidence of 

teaching away and unexpected results, and that such 

evidence fully supports a conclusion of nonobviousness.

“Whether the prior art teaches away from the claimed 

invention is a question of fact.” Spectralytics, Inc. v. 

Cordis Corp., 649 F.3d 1336, 1343 (Fed. Cir. 2011). “A 

reference may be said to teach away when a person of 

ordinary skill, upon reading the reference, would be 

discouraged from following the path set out in the reference, or would be led in a direction divergent from the 

path that was taken by the applicant.” In re Gurley, 27 

F.3d 551, 553 (Fed. Cir. 1994). 

The district court did not clearly err in finding that 

the prior art taught away from using 200 ppm BAK in a 

bimatoprost formulation. As the district court found, the 

prior art taught that BAK should be minimized in ophthalmic formulations to avoid safety problems. Opinion

at 49. Indeed, the Appellants’ own expert summarized 

the prior art’s widespread concern by describing BAK as 

“a natural-born killer” that was “from Satan.” Id. at 75–
ALLERGAN, INC. v. SANDOZ INC. 17

76. Specifically, as the district court found in great detail, 

BAK was known to cause increased IOP, hyperemia, dry 

eye, and damage to corneal cells, and to exacerbate other 

eye disorders. Id. at 40–54. It is not clearly erroneous to 

find that those known side effects would have discouraged 

a person of ordinary skill from using higher concentrations of BAK in a bimatoprost formulation, especially 

when 50 ppm BAK was known to be an adequate preservative in Lumigan 0.03%.

While it is true that the prior art, such as Abelson, also disclosed ophthalmic formulations containing 200 ppm 

BAK, the district court correctly found that those formulations, with the exception of Xalatan® and Xalacom, were 

“not for chronic long-term use” and “would teach nothing 

about whether it was safe to use 200 ppm BAK with a 

lifelong glaucoma drug.” Id. at 53 (emphasis added). 

With respect to Xalatan® and Xalacom, both of which 

contain 200 ppm BAK and latanoprost, a prostaglandin 

ester analog, the district court found that “the majority of 

BAK in solution complexed with latanoprost and was not 

free in solution to interact with the epithelial cells,” id. at 

40, 53–54; and, moreover, that Xalatan® “showed a decrease in cell membrane integrity and a significant increase in apoptosis” as compared to a formulation with 

less BAK, which would have discouraged the skilled 

artisan from increasing the amount of BAK in a bimatoprost formulation, id. at 52. Those factual findings are 

not clearly erroneous.

Moreover, the district court did not clearly err in finding that the prior art taught that BAK would not increase 

the permeability of bimatoprost, but might instead decrease it. Id. at 35, 38–47. The district court found that

Higaki and Camber taught that BAK reduced the permeability of uncharged prostaglandin analogs that are 

similar to bimatoprost, id. at 38–40, and that the other 

cited references, including Lee, Keller, and Abelson, did 

not teach that BAK would enhance the permeability of
18 ALLERGAN, INC. v. SANDOZ INC. 

bimatoprost because those references studied large, 

charged, or hydrophilic molecules that are dissimilar to 

bimatoprost, id. at 41–47. In view of those factual findings, there would not have been a reason to use 200 ppm 

BAK in a bimatoprost formulation. See DePuy Spine, Inc. 

v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1326

(Fed. Cir. 2009) (“An inference of nonobviousness is

especially strong where the prior art’s teachings undermine the very reason being proffered as to why a person of 

ordinary skill would have combined the known elements.”).

The record thus shows that the prior art “criticize[d], 

discredit[ed], or otherwise discourage[d]” the use of 

200 ppm BAK in a bimatoprost formulation. In re 

Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012) (quoting In 

re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004)). We 

therefore need not address the Appellants’ additional 

argument that the district court erred in finding that 

Laibovitz and Lyons taught away from 0.01% bimatoprost. The Appellants do not argue, and there is no 

evidence to suggest, that Laibovitz and Lyons favored 

using 200 ppm BAK in a bimatoprost formulation. Accordingly, we conclude that the district court did not 

clearly err in finding that the prior art taught away from 

the claimed formulation. 

We also conclude that the district court did not clearly 

err in finding that the claimed formulation exhibited 

“unexpected results,” which differed in kind, not just in 

degree, from the prior art. Opinion at 57–58, 76. As 

indicated, the prior art taught that 200 ppm BAK would 

either have no impact on the permeability of bimatoprost 

or decrease it. Allergan’s inventors surprisingly determined that the opposite was true, namely, that 200 ppm 

BAK enhanced the permeability of bimatoprost. That is

an unexpected difference in kind that supports nonobviousness. In re Applied Materials, Inc., 692 F.3d 1289, 

1298 (Fed. Cir. 2012) (“Evidence that the variables inter-
ALLERGAN, INC. v. SANDOZ INC. 19

acted in an unpredictable or unexpected way could render 

the combination nonobvious.”) (citing KSR, 550 U.S. at 

421).

Moreover, the district court properly found that Laibovitz taught that reducing bimatoprost from 0.03% to 

0.01% resulted in significantly reduced efficacy, Opinion

at 31–33, but that such a reduction in bimatoprost did not 

result in less hyperemia, id. at 34. The claimed formulation, which comprises 0.01% bimatoprost and 200 ppm 

BAK, unexpectedly maintained the IOP-lowering efficacy 

of Lumigan 0.03%, while exhibiting reduced incidence and 

severity of hyperemia, even though the prior art taught 

that BAK could cause hyperemia at high concentrations. 

Those results exhibited by the claimed formulation thus

constitute an unexpected difference in kind, viz., the 

difference between an effective and safe drug and one 

with significant side effects that caused many patients to 

discontinue treatment. 

Finally, we reject the Appellants’ argument that the 

unexpected results do not support nonobviousness because they are merely the inherent properties of an otherwise obvious formulation. As indicated, the prior art 

did not disclose, either explicitly or implicitly, the claimed

formulation; rather, it taught away from such a formulation. A person of ordinary skill in the art thus would not 

have had a reason to select the claimed formulation from 

the prior art ranges or to modify Lumigan 0.03% to arrive 

at the claimed formulation. The unexpected properties of 

the claimed formulation, even if inherent in that formulation, differ in kind from the prior art, thereby supporting 

a conclusion of nonobviousness. See W.L. Gore & Assocs., 

Inc. v. Garlock, Inc., 721 F.2d 1540, 1555 (Fed. Cir. 1983) 

(“Inherency and obviousness are distinct concepts.”); In re 

Spormann, 363 F.2d 444, 448 (CCPA 1966) (“That which 

may be inherent is not necessarily known. Obviousness 

cannot be predicated on what is unknown.”). 
20 ALLERGAN, INC. v. SANDOZ INC. 

This is not a case where the claims merely recite the 

unknown properties of an otherwise obvious formulation. 

E.g., Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 

1354 (Fed. Cir. 2012) (“[A]n obvious formulation cannot 

become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations.”); 

In re Kao, 639 F.3d 1057, 1070 (Fed. Cir. 2011) (“Maloney’s express teachings render the claimed controlled 

release oxymorphone formulation obvious, and the 

claimed ‘food effect’ adds nothing of patentable consequence.”). Here, the previously unknown and unexpected

properties of a new and nonobvious formulation constitute

additional, objective evidence of nonobviousness. 

We have considered the remaining arguments on the 

issue of obviousness but find them unpersuasive. For the 

foregoing reasons, we affirm the district court’s holding 

that the asserted claims would not have been obvious in 

view of the cited references.

II

We next consider the Appellants’ arguments contending that the district court erred in finding that the Group 

II claims are not invalid for lack of an adequate written 

description, and Lupin’s arguments contending that the 

court erred in holding that the asserted claims are not 

invalid for lack of enablement. 

Section 112 of the patent statute provides in relevant 

part that:

The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, 

concise, and exact terms as to enable any person 

skilled in the art to which it pertains, or with 

which it is most nearly connected, to make and 

use the same . . . .
ALLERGAN, INC. v. SANDOZ INC. 21

35 U.S.C. § 112, ¶ 1 (2006). “[T]his statutory language 

mandates satisfaction of two separate and independent 

requirements: an applicant must both describe the 

claimed invention adequately and enable its production 

and use.” Alcon Research Ltd. v. Barr Labs., Inc., 745 

F.3d 1180, 1188 (Fed. Cir. 2014) (citing Ariad Pharm., 

Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1344 (Fed. Cir. 

2010) (en banc); Vas-Cath Inc. v. Mahurkar, 935 F.2d 

1555, 1562–63 (Fed. Cir. 1991)).

a.

“Whether a claim satisfies the written description requirement is a question of fact that, on appeal from a 

bench trial, we review for clear error.” Alcon, 745 F.3d at 

1190. The written description requirement is met when

the disclosure “allow[s] one skilled in the art to visualize 

or recognize the identity of the subject matter purportedly 

described.” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 

F.3d 956, 968 (Fed. Cir. 2002). There is no rigid requirement that the disclosure contain “either examples or an 

actual reduction to practice”; the proper inquiry is whether the patentee has provided an adequate description that 

“in a definite way identifies the claimed invention” in 

sufficient detail such that a person of ordinary skill would 

understand that the inventor had made the invention at 

the time of filing. Ariad, 598 F.3d at 1352. That assessment “requires an objective inquiry into the four corners 

of the specification,” as “the hallmark of written description is disclosure.” Id. at 1351.

The Appellants argue that the claims of the ’353 and 

’118 patents (the Group II claims), which recite clinical 

profile limitations, are not adequately supported by the 

written description because the written description does 

not disclose any efficacy or hyperemia data of a formulation comprising 0.01% bimatoprost and 200 ppm BAK. 

The Appellants assert that the district court erred by 

relying on the permeability data of test formulations 
22 ALLERGAN, INC. v. SANDOZ INC. 

(which are not efficacy or hyperemia data), the constructive example (which relates to a formulation comprising

0.015% bimatoprost and 125 ppm BAK), and the clinical 

protocol (which is not part of the specifications). Hi-Tech 

additionally argues that there are no “blaze marks” in the 

specifications to allow the skilled artisan to immediately 

discern the clinical profile claim limitations.

Allergan responds that the district court did not clearly err in finding that the Appellants failed to prove lack of 

an adequate written description by clear and convincing 

evidence. Allergan argues that the written description 

here adequately describes the claimed invention because 

it identifies the exact formulation of Lumigan 0.01% as a 

best mode of the invention and Lumigan 0.01% exhibited

the claimed clinical results. Allergan also responds that 

the district court referenced the clinical protocol simply to 

corroborate what the specifications show. Allergan also 

maintains that the disclosed permeability data and the 

constructive example are relevant to the written description inquiry as they would allow the skilled artisan to 

predict the clinical performance of Lumigan 0.01%.

We agree with Allergan that the specifications of the 

asserted patents provide an adequate written description 

of the invention claimed by the Group II claims. The 

specifications specifically describe a formulation comprising 0.01% bimatoprost and 200 ppm BAK as one of the

best modes of the invention. ’504 patent col. 2 ll. 59, 64–

67. The Group II claims all require the same amounts of 

bimatoprost and BAK. The specifications thus disclose

the claimed formulation as characterized by those ingredients, and the skilled artisan would immediately discern 

the claimed formulation in that disclosure. 

It is true that the Group II claims also recite clinical 

profile limitations and the specifications do not explicitly

describe the clinical efficacy and hyperemia profile of the 

claimed formulation. But the Appellants have empha-
ALLERGAN, INC. v. SANDOZ INC. 23

sized, in connection with their obviousness challenge, that 

the inherent properties of a formulation comprising 0.01% 

bimatoprost and 200 ppm BAK produce the claimed 

clinical profile. Sandoz’s Opening Br. 51 (stating that 

“the claimed clinical effects necessarily result from using 

0.01% bimatoprost and 200 ppm BAK” (emphasis in 

original) (citing J.A. 5537–41, 5764–66)); Lupin’s Opening 

Br. 23 (incorporating Sandoz’s opening brief by reference); 

Hi-Tech’s Opening Br. 24 (same). A claim that recites a 

property that is necessarily inherent in a formulation that 

is adequately described is not invalid as lacking written 

description merely because the property itself is not 

explicitly described. On this particular record, we agree 

with the district court that the Appellants have failed to 

prove invalidity for lack of an adequate written description by clear and convincing evidence. See Enzo Biochem, 

323 F.3d at 963 (“Compliance with the written description 

requirement is essentially a fact-based inquiry that will 

necessarily vary depending on the nature of the invention 

claimed.” (internal quotation marks omitted)).

We do find, however, that the district court erred by 

relying on the undisclosed clinical protocol to support its 

written description determination. As we have explained, 

“[i]t is the disclosures of the applications that count.” 

Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1571 (Fed. 

Cir. 1997). The clinical protocol is not part of the specifications of the asserted patents. It should not form the 

basis of the written description inquiry, even if it shows 

that the inventors had invented the claimed invention 

before the time of filing. The written description requirement requires possession as shown in the specification, not as shown by prior experimental work. 

Nevertheless, as indicated, because the specifications 

contain an adequate disclosure of the claimed formulation, the district court’s erroneous reliance on the clinical 

protocol does not affect the outcome of this case. 
24 ALLERGAN, INC. v. SANDOZ INC. 

We have considered the remaining arguments on the 

issue of written description but find them unpersuasive. 

We therefore conclude that the district court did not err in 

finding that the Appellants failed to prove by clear and 

convincing evidence that the Group II claims are invalid 

for lack of an adequate written description.

b.

Whether a claim satisfies the enablement requirement is a question of law that we review without deference. Alcon, 745 F.3d at 1188. We review the factual 

issues underlying enablement for clear error. Id. To 

prove that a claim is invalid for lack of enablement, a 

challenger must show by clear and convincing evidence 

that a person of ordinary skill in the art would not be able 

to practice the claimed invention without “undue experimentation.” Id. (quoting In re Wands, 858 F.2d 731, 736–

37 (Fed. Cir. 1988)). 

Lupin argues that the asserted claims are invalid for 

lack of enablement because the specifications contain no 

actual efficacy and hyperemia data; rather, they merely 

provide a research proposal. According to Lupin, the 

skilled artisan would not accept without doubt the asserted utility of the claimed formulation, i.e., comparable

efficacy as Lumigan 0.03% and less hyperemia. Lupin 

argues that if the claims are held to be nonobvious, then 

they must fail the enablement requirement because the 

district court found that ophthalmic formulation is unpredictable and that the prior art taught away from the 

claimed invention. 

Allergan responds that there is no inconsistency in 

the district court’s decision that the asserted claims would 

not have been obvious and that they are also enabled. 

Allergan argues that the specifications disclose the exact 

formulation of Lumigan 0.01% and the permeability data 

of test formulations, which would enable the skilled 

artisan to make and use the claimed invention. Allergan 
ALLERGAN, INC. v. SANDOZ INC. 25

also responds that, in view of the patents’ disclosure, the 

skilled artisan would not have questioned the utility of 

the claimed formulation. 

We agree with Allergan that the asserted claims are 

not invalid for lack of enablement. “[A] patent does not 

need to guarantee that the invention works for a claim to 

be enabled.” Alcon, 745 F.3d at 1189. And efficacy data 

are generally not required in a patent application. Only a 

sufficient description enabling a person of ordinary skill 

in the art to carry out an invention is needed. “Similarly, 

a patentee is not required to provide actual working 

examples; we have rejected enablement challenges based 

on the theory that there can be no guarantee that prophetic examples actually work.” Id. at 1189–90.

Here, the asserted claims require a formulation comprising specific amounts of bimatoprost and BAK. The 

patents refer to what is Lumigan 0.03%, which was a 

known drug for treating glaucoma. ’504 patent col. 1 

ll. 34–36. The specifications disclose actual in vitro and in 

vivo data, showing that increasing the amount of BAK 

unexpectedly increased the permeability of bimatoprost

across ocular membranes. Id. col. 4 ll. 10–58, col. 5 l. 19–

col. 6 l. 5, Figs. 1 & 2. In a constructive example, the 

specifications teach that a formulation containing 0.015%

bimatoprost and 125 ppm BAK would effectively reduce 

IOP and also exhibit less hyperemia than Lumigan 0.03%. 

Id. col. 6 ll. 7–14. In view of those disclosures, we agree 

with the district court that the skilled artisan would not 

have questioned the utility of the claimed formulation and 

would be able to make and use the claimed invention 

without undue experimentation.

Lupin argues that “if the asserted claims are nonobvious, they cannot possibly be enabled.” Lupin’s Opening Br. 28. We disagree. The obviousness inquiry turns 

on what the prior art would have taught a person of 

ordinary skill in the art and whether the claimed inven-
26 ALLERGAN, INC. v. SANDOZ INC. 

tion would have been obvious in view of the prior art. As 

indicated, the claims here would not have been obvious 

because, among other reasons, the prior art taught that 

BAK would not increase the permeability of bimatoprost. 

In contrast, the enablement inquiry turns on whether the 

skilled artisan, after reading the specification, would be 

able to make and use the claimed invention without 

undue experimentation, based on the ordinary skill in the 

art. Because the specifications here provide sufficient 

guidance to the skilled artisan, there is no tension in the 

district court’s decision that the asserted claims would not 

have been obvious and also are not invalid for lack of 

enablement. 

We have considered the remaining arguments on the 

issue of enablement but find them unpersuasive. We 

therefore affirm the district court’s holding that Lupin 

failed to prove by clear and convincing evidence that the 

asserted claims are invalid for lack of enablement. 

III

Finally, we address Hi-Tech’s arguments contending 

that the district court erred in finding that its ANDA 

product infringed, both literally and under the doctrine of 

equivalents, the Group I claims, which require the 

claimed composition to have a “pH of about 7.3.” A determination of infringement, whether literal or under the 

doctrine of equivalents, is a question of fact and is reviewed for clear error following a bench trial. Biovail 

Corp. Int’l v. Andrx Pharm., Inc., 239 F.3d 1297, 1300 

(Fed. Cir. 2001). “Prosecution history estoppel operates 

as a legal limitation on a patentee’s ability to invoke the 

doctrine of equivalents, and we review its application de 

novo.” Trading Techs. Int’l, Inc. v. Open E Cry, LLC, 728 

F.3d 1309, 1318 (Fed. Cir. 2013).

Hi-Tech argues that the district court erred in construing a “pH of about 7.3.” Hi-Tech also argues that the 

district court erred in finding that Hi-Tech literally in-
ALLERGAN, INC. v. SANDOZ INC. 27

fringed the Group I claims and that prosecution history 

estoppel did not bar Allergan from relying on the doctrine 

of equivalents to prove infringement. Allergan responds 

that Hi-Tech stipulated to the claim construction in the 

district court and cannot now allege error for the first 

time on appeal. Allergan also responds that the district 

court did not clearly err in finding both literal infringement and infringement under the doctrine of equivalents. 

We agree with Allergan that the district court did not 

clearly err in finding that Hi-Tech literally infringed the 

Group I claims. In the district court, the parties agreed to 

construe a “pH of about 7.3” as a “pH of approximately 

7.3,” and the district court adopted that construction. HiTech did not argue for further construction in the district 

court. That construction thus controls in this case.

It is undisputed that Hi-Tech’s ANDA specifies that 

its proposed product has a pH of 6.8–7.2 during the product’s shelf life. The district court thus correctly evaluated 

infringement based on the proposed product. Sunovion 

Pharm., Inc. v. Teva Pharm. USA, Inc., 731 F.3d 1271, 

1278–80 (Fed. Cir. 2013). After considering the expert 

testimony proffered by both sides, the district court found 

that Hi-Tech’s product would infringe the Group I claims

literally. We find no clear err in that determination. 

Moreover, if “about 7.3” is to mean anything other than 

7.3, it is not clearly erroneous for it to include a value that 

differs from it by only one decimal place. Because we 

affirm the district court’s finding of literal infringement, 

we do not need to address whether the district court erred 

in finding infringement under the doctrine of equivalents. 

We have considered Hi-Tech’s remaining arguments 

but find them unpersuasive. For the foregoing reasons, 

we affirm the district court’s finding that Hi-Tech infringed the Group I claims.
28 ALLERGAN, INC. v. SANDOZ INC. 

CONCLUSION

Accordingly, we affirm the district court’s determination that the asserted claims are not invalid for obviousness or for lack of an adequate written description and 

enablement, and that Hi-Tech infringed the claims of the 

’504, ’605, and ’479 patents.

AFFIRMED