filflniteh étatesa" Qlluurt of Qppealsi
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`for the jfeiznaral Qliircuit
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`ALLERGAN, INC.,
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`Plaintiff-Appellee
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`V.
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`SANDOZ INC., LUPIN LTD., LUPIN
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`PHARMACEUTICALS, IN C., HI—TECH
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`PHARMACAL CO., INC.,
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`Defendants-Appellants
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`2014-1275
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`Appeal from the United States District Court for the
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`Eastern District of Texas in No. 6:11-cv-00441-MI-IS,
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`Judge Michael H. Schneider.
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`Decided: August 4, 2015
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`JUANITA Ross BROOKS, Fish & Richardson, P.C., San
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`Diego, CA, argued for plaintiff-appellee. Also represented
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`by CRAIG E. COUNTRYMAN; JONATHAN ELLIOT SINGER,
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`DEANNA JEAN REICI-IEL, Minneapolis, MN; DOUGLAS E.
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`MCCANN, SUSAN M. COLETTI, Wilmington, DE.
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`DEANNE MAYNARD, Morrison & Foerster LLP, Wash-
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`ington, DC, argued for defendanbappellant Sandoz Inc. _
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`Also represented by BRIAN ROBERT MATSUI; DAVID
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`Page 1 of 28
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`SENJU EXHIBIT 2134
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`LUPIN V. SENJU
`IPR2015-01100
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`Page 1 of 28
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`SENJU EXHIBIT 2134
`LUPIN v. SENJU
`IPR2015-01100
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`2
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`ALLERGAN, INC. V. SANDOZ INC.
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`CLARENCE DOYLE, ANDERS T. AANNESTAD, JAMES CEKOLA,
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`San Diego, CA.
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`WILLIAM A. RAKOCZY, Rakoczy Molino Mazzochi,
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`Siwik LLP, Chicago, IL, argued for defendants-appellants
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`Lupin Ltd., Lupin Pharmaceuticals, Inc. Also represented
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`by PAUL J. MOLINO, DEANNE M. MAZZOCHI, THEODORE
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`JOSEPH CHIACCHIO, JOHN POLIVICK.
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`STEVEN D. ROTH, Locke Lord, LLP, New York, NY, ar-
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`gued for defendant—appellant Hi-Tech Pharrnacal Co., Inc.
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`Also represented by THOMAS J. VE'1“I‘ER, Lucas & Mer-
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`canti, LLP, New York, NY.
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`Before LOURIE, LINN, and HUGHES, Circuit Judges.
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`LOURIE, Circuit Judge.
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`Sandoz Inc. (“Sandoz”), Lupin Ltd. and Lupin Phar-
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`maceuticals,
`Inc.
`(collectively, “Lupin”), and Hi-Tech
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`Pharmacal Co., Inc. (“Hi-Tech”) (collectively, “the Appel-
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`lants”)1 appeal from the decision of the United States
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`District Court for the Eastern District of Texas, following
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`a bench trial, which held that the claims of U.S. Patents
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`7,851,504 (the “’504 patent”), 8,278,353 (the ‘"353 pa-
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`tent”), 8,299,118 (the “ ’118 patent”), 8,309,605 (the “ ’605
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`patent”), and 8,338,479 (the “479 patent”), asserted by
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`Allergan, Inc. (“Allergan”), were not shown to be invalid
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`for obviousness under 35 U.S.C. §103, and that the
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`1 Watson Laboratories, Inc., Watson Pharmaceuti-
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`cals, Inc., and Watson Pharm, Inc. (collectively, “Watson”)
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`were also defendants-appellants initially. But Watson
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`has since been dismissed from this appeal on a joint
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`motion filed by Watson and Allergan. See Allergen, Inc. 0.
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`Sandoz Inc., No. 14-1275, ECF No. 121 (Fed. Cir. Apr. 17,
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`2015)
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`Page 2 of 28
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`Page 2 of 28
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`ALLERGAhLINC.v.SANDOZINC.
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`3
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`claims of the ’353 and ’118 patents were not shown to be
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`invalid for lack of an adequate written description under
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`35 U.S.C. § 112, 1] 1.3 Allergen, Inc. 0. Scmdoz Inc., No.
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`6:11-cv-00441, ECF No. 303, slip op. at 77, 79 (ED. Tex.
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`Jan. 13, 2014) (“Opinion”). Additionally, Lupin challenges
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`the district court’s determination that the claims of Aller-
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`gan’s patents were not shown to be invalid for lack of
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`enablement under § 112, 1| 1.
`Id. at 80-81. Hi-Tech also
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`challenges the district court’s finding that it infringed the
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`claims of the ’504, ’605, and ’479 patents literally and
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`under the doctrine of equivalents.
`Id. at 64-66. For the
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`reasons that follow, We affirm in all respects.
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`BACKGROUND
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`I
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`Glaucoma is an eye disease associated with elevated
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`intraocular pressure (“IOP”). Treatments that effectively
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`reduce IOP can slow the progression of the disease. If left
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`untreated, however, elevated IOP can damage the optic
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`nerve and lead to permanent vision loss and blindness. In
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`2001, the US. Food and Drug Administration (the “FDA”)
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`approved Lumigan® 0.03% (“Lumigan 0.03%”), a once-
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`daily topical solution developed by Allergen, for treating
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`open angle glaucoma and ocular hypertension. Lumigan
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`0.03% contains 0.03% by weight of bimatoprost and 50
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`parts per million (“ppm”) benzalkonium chloride (“BAK”),
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`among other ingredients.
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`Bimatoprost, the active ingredient in Lurnigan 0.03%,
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`is a prostaglandin analog that effectively lowers IOP, but
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`can cause hyperemia, i.e., red eye, when administered to
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`2
`Because the applications resulting in the patents
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`asserted in this case were filed before the enactment of
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`the Leahy-Smith America Invents Act (“AIA”), Pub. L. No.
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`11229, 125 Stat. 284 (2011), we apply the pre-AIA ver-
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`sion of 35 U.S.C. § 103 and § 112.
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`Page 3 of 28
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`Page 3 of 28
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`4
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`ALLERGAN, INC. V. SANDOZ INC.
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`the ocular surface. One structural difference between
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`bimatoprost and two other prostaglandin analogs that
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`were approved for treating glaucoma at the time of its
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`approval,
`Xalatan® (latanoprost)
`and
`Travatan®
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`is
`(travoprost),
`that bimatoprost contains an amide,
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`instead of an ester as in latanoprost and travoprost.
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`Opinion. at 7-8. It was understood that both latanoprost
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`and travoprost, but not birnatoprost, act as prodrugs of
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`the corresponding acids. Id.
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`BAK is a preservative for inhibiting bacterial growth
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`in ophthalmic solutions.
`It was known, however, that
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`BAK is cytotoxic and that it can damage the cells on the
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`ocular surface and cause undesirable side effects.
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`Although Lumigan 0.03% was effective at lowering
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`IOP, it also caused frequent and severe hyperemia. Many
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`patients thus stopped using it without consulting their
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`physicians, which led to gradual vision loss. To address
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`that problem, Allergan explored a number of alternative
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`formulations of bimatoprost and surprisingly discovered
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`that increasing the concentration of BAK from 50 ppm to
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`200 ppm significantly increased the corneal permeability
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`of bimatoprost.
`Id. at 12-13. After further research,
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`Allergan developed Lumigan® 0.01% (“Lumigan 0.01%”).
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`Lumigan 0.01% is a topical solution containing 0.01%
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`bimatoprost and 200 ppm BAK; otherwise,
`it has the
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`same ingredients as Lumigan 0.03%. Thus, as compared
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`with Lumigan 0.03%, Lumigan 0.01% has a three-fold
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`lower birnatoprost concentration and a four-fold higher
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`BAK concentration. Clinical studies showed that Lumi-
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`gan 0.01% has similar efficacy to Lumigan 0.03%, via,
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`IOP-lowering within 0.5 mmHg of that of Lumigan 0.03%,
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`but it causes less frequent and severe hyperemia than
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`Lumigan 0.03%.
`Id. at 20~21.
`In 2010, the FDA ap-
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`proved AIlergan’s New Drug Application for Lumigan
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`0.01% for the same approved uses as Lumigan 0.03%.
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`Page 4 of 28
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`Page 4 of 28
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`ALLERGAN, INC. v. SANDOZ INC.
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`5
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`II
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`Allergan owns the ’504, ’353, ’118, ’605, and ’479 pa-
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`tents, which are all listed in the FDA’s Approved Drug
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`Products with. Therapeutic Equivalence Evaluations
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`(commonly known as the “Orange Book”) as claiming
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`Lumigan 0.01% and its approved uses. After Allergen
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`received FDA-approval of Lumigan 0.01%, Sandoz, Lupin,
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`Hi-Tech, and Watson each submitted an Abbreviated New
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`Drug Application (“ANDA”) to the FDA, seeking approval
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`to engage in the comrnercial manufacture, use, importa-'
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`tion, sale, or offer for sale of generic versions of Lumigan
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`0.01% prior to the expiration of the ’504, ’353, ’118, ‘£305,
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`and ’479 patents.
`In response, Allergan sued each of the
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`ANDA applicants in the United States District Court for
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`the Eastern District of Texas, asserting that their ANDA
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`filings infringed those patents. The district court consoli-
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`dated those actions into one case.
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`The asserted patents all derive from an application
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`filed on March 16, 2005 and share a common specifica-
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`tion. The patents are entitled “Enhanced Bimatoprost
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`Ophthalmic Solution,” ".504 patent col. 1 ll. 1—2,3 and refer
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`to what is Lumigan 0.03% in the background section, id.
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`col. 1 ll. 34—36. The specifications of the patents describe
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`a composition comprising 0.005% to 0.02% bimatoprost
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`and 100 ppm to 250 ppm BAK, which is an aqueous liquid
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`“formulated for ophthalmic administration” and “useful in
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`1
`treating glaucoma or ocular hypertension."
`Id. col.
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`ll. 61-67. The specifications also specifically describe a
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`formulation comprising 0.01% bimatoprost and 200 ppm
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`BAK, among other formulations, as a “best mode” of the
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`invention. Id. col. 211. 59, 64-67.
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`3
`Because the asserted patents share an identical
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`specification in relevant part, we refer only to the ’504
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`patent when discussing the specifications of those pa-
`tents.
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`Page 5 of 28
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`Page 5 of 28
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`G
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`ALLERGAN, INC. V. SANDOZ INC.
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`Additionally, the specifications disclose in Uitro and in
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`uivo experimental data in rabbits, showing that increas-
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`ing the concentration of BAK from 50 ppm to 200 ppm
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`significantly increased the permeability of bimatoprost
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`across ocular membranes.
`Id. col. 4 ll. l0~58, col. 5 l. 19-
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`col. 6 l. 5, Figs. 1 8; 2. Finally, in a constructive example,
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`the specifications describe the once-daily ophthalmic
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`administration to a glaucoma patient of a formulation
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`containing 0.015% bimatoprost, 125 ppm BAK, and
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`0.015% EDTA, stating that “intraocular pressure drops
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`more and less hyperemia is observed than would be
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`observed for [a formulation containing 0.03% himatoprost
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`and 50 ppm BAK,]” and “[l]owered intraocular pressure
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`persists for as long as the treatment continues.” Id. col. 6
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`11. 7-14.
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`Allergan asserted the following claims against each of
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`the ANDA applicants: claim 2 of the ’504 patent; claim 15
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`of the ’-479 patent; claims 1, 6, 10, and 12 of the ’605
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`patent; claims 1, 7, and 8 of the ’353 patent; and claims 1,
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`7, and 8 of the ’118 patent (collectively, “the asserted
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`claims”). Those claims collectively are directed to compo-
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`sitions comprising bimatoprost and BAK and methods of
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`using them to treat glaucoma or to lower IOP.
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`Each of the asserted claims requires a composition
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`comprising 0.01% bimatoprost and 200 ppm BAK. Claim
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`2 of the ’504 patent, claim 15 of the ’-479 patent, and
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`claims 1, 6, 10, and 12 of the ’605 patent (collectively, “the
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`Group I claims”) further require the composition to have a
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`pH of "about 7.3.” Claims 1, 7, and 8 of the ’353 patent
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`and claims 1, 7, and 8 of the ’118 patent (collectively, “the
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`Group II claims”) do not contain such a pH limitation, but
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`they require a particular clinical profile of the claimed
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`composition as compared to a composition comprising
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`0.03% bimatoprost and 50 ppm BAK.
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`Claim 2 of the ’504 patent is representative of the
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`Group I composition claims and reads as follows:
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`ALLERGAN, INC. V. SANDOZ INC.
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`7
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`2. A composition having a pH of about 7.3 which
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`comprises about 0.01% bimatoprost, about 200
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`ppm. benzalkoniurn chloride, citric acid monohy-
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`drate, a phosphate buffer, and NaCl wherein said
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`composition is an aqueous liquid which is formu-
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`lated for ophthalmic administration.
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`Id. col. 6 11. 21-25 (emphases added).
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`Claim 1 of the ’605 patent is representative of the
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`Group I method claims and reads as follows:
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`1. A method of lowering elevated intraocular
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`pressure in a patient with open-angle glaucoma or
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`ocular hypertension which comprises applying to
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`the eyes of the patient an aqueous solution com-
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`prised of: about 0.01% w/v bimatoprost; about 200
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`the
`ppm benzalkonium chloride;
`solution
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`having a pH of about 7.3; a phosphate buffer; and
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`water.
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`’605 patent col. 5 11. 47-55 (emphases added).
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`As indicated, the Group II claims all contain clinical
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`profile limitations. Claims 1, 7, and 8 of the ’353 patent
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`are directed to compositions and read as follows:
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`1. A first composition administered once daily for
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`lowering intraocular pressure in a person with
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`glaucoma or ocular hypertension, the first compo-
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`sition comprising about 0.01% wfv bimatoprost
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`and about 0.02% wfv benzalkonium chloride,
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`wherein the first composition lowers intraocular
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`pressure and results in less hyperemia as com-
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`pared to the once daily administration of a second
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`composition comprising 0.03% wiv bimatoprost
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`and 0.005% wfv benzalkonium chloride.
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`7. A first composition administered once daily for
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`lowering intraocular pressure in a person with
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`glaucoma or ocular hypertension, the first compo-
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`Page 7 of 28
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`Page 7 of 28
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`8
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`ALLERGAN, INC. V. SANDOZ INC.
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`sition comprising about 0.01% wlv bimatoprost
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`and about 0.02% wlv benzalkonium chloride,
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`wherein the first composition lowers intraocular
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`pressure without a substantial reduction in the in-
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`traocuiar pressure lowering benefit provided by
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`the once daily administration of a second composi-
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`tion comprising 0.03% wfv bimatoprost and
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`0.005% wfv benzalkonium chloride.
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`8. The composition of claim 7 wherein the once
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`daily administration of the first composition re-
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`sults in less hyperemia as compared to the once
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`daily administration of the second composition.
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`’353 patent col. 5 11. 48-56, col. 6 11. 3-15 (emphases
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`added)!‘ Claims 1, 7, and 8 of the ’118 patent are directed
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`to methods of treatment; they contain the same clinical
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`profile limitations as those in claims 1, 7, and 8 of the ’353
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`patent. ’118 patent col. 5 11. 48-56, col. 611. 3-16.
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`III
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`The district court held a five-day bench trial in July
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`2013 on the issues of obviousnese and infringement. The
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`defendants also argued that the claims were invaiid for
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`lack of written description and enablement in pre- and
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`post-trial briefings. In January 2014, the court rendered
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`its findings of fact and conclusions of law on all of those
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`3..
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`The district court concluded that the asserted claims
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`would not have been obvious in View of the cited prior art,
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`which included: (1) U.S. Patent 5,688,819 (“Woodward”);
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`(2) U.S. Patent 6,933,289 (“Lyons’ ; (3) Laibovitz et at,
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`Comparison of the Ocular Hypotensiue Lipid AGN 1.92024
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`The parties agree that 0.02% W/v corresponds to
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`200 ppm, and 0.005% wfv corresponds to 50 ppm.
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`Page 8 of 28
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`Page 8 of 28
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`ALLERGAN, INC. V. SANDOZ INC.
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`9
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`with Timoiot, 119 Archives of Ophthalmology 994 (2001)
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`(“Laibovitz”); (4) Abelson et al., How to Handle BAK Talk,
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`Rev. of Ophthalmology, Dec. 2002, at 52-54 (“Abelson”);
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`(5) Lee et al., Review: Topical Ociitar Drug Delivery:
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`Recent Developments and Fntm'e Challenges, 2 J. Ocular
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`Pharmacology 6'? (1986) (“Lee”); (6) Camber et at, Factors
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`Influencing the Corneal Permeability of Prostagiandin Fee:
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`and Its Isopropyl Ester In Vitro, 37 Int’1 J. Pharmaceutics
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`27 (1987) (“Camber”); (7) Higaki et al., Estimation and
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`Enhancement of In Vitro Corneal Transport of S-I033, a
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`Novel Antigtancoma Medication, 132 Int’1 J. Pharmaceu-
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`tics 165 (1996) (“Higaki”); and (8) Keller et al., Increased
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`Corneal Permeability Induced by the Dual Effects of
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`Transient Tear Film. Acidification and Exposure to Ben-
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`zatkoninm Chloride, 30 Experimental Eye Res. 203 (1980)
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`(“Keller”).
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`Specifically, with respect to the scope and content of
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`the prior art, the district court found that: (1) ophthalmic
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`formulation was unpredictable, and it was not a field with
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`a finite number of identified and predictable solutions,
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`Opinion at 29-31;
`(2) Laibovitz and Lyons both taught
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`that reducing bimatoprost from 0.03% to 0.01% would
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`result
`in less
`IOP-lowering efficacy,
`id. at 31-34;
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`(3) Laibovitz also taught that reducing bimatoprost from
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`0.03% to 0.01% would not result in less hyperemia, and
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`Lyons did not suggest the contrary, id. at 34-35; (4) the
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`cited prior art, including I-ligaki, Camber, Lee, Keller, and
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`Abelson, as well as Xalatan® (latanoprost), which contains
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`200 ppm BAK, did not teach that high concentrations of
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`BAK would enhance the corneal permeability of bimato-
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`prost, a neutral prostaglandin amide analog; instead, the
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`prior art suggested that BAK would decrease the permea-
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`bility of a neutral prostaglandin analog, id. at 35, 38-47;
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`and (5) the prior art taught that BAK Should be mini-
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`mized in ophthalmic formulations due to its toxicity, and,
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`in particular, taught away from using 200 ppm BAK in a
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`bimatoprost: formulation because BAK was known to
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`Page 9 of 28
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`Page 9 of 28
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`10
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`ALLERGAN, INC. V. SANDOZ INC.
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`including increased IOP, hyperemia,
`cause side effects,
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`and dry eye, making it unsuitable for chronic use at high
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`concentrations, id. at 47—54.
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`The district court then found that there would not
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`have been a reason to pursue the claimed invention or a
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`reasonable expectation of success if it were pursued.
`Id.
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`at 55-56. The court also found evidence of long-felt need,
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`unexpected results, and commercial success supporting a
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`conclusion of nonobviousness.
`Id. at 56-59. The court
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`specifically found that it was unexpected that Lumigan
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`0.01% would reduce the incidence and severity of hypere-
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`mia, as compared to Lumigan 0.03%, while maintaining
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`IOP~lowering efficacy, and that it was also unexpected
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`that 200 ppm BAK would enhance the permeability of
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`bimatoprost to such an extent so as to allow the reduction
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`of the bimatoprost concentration from 0.03% to 0.01%
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`without loss of efficacy. Id. at 57-58.
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`In View of those factual findings, the district court
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`concluded that the asserted claims would not have been
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`obvious. Id. at 74. In reaching that conclusion, the court
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`emphasized that
`the prior art taught away from the
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`claimed invention because it taught “(1) that bimatoprost
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`lost efficacy as its concentration decreased; (2) that BAK
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`had no impact on bimatoprost’s permeability; and (3) that
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`BAK was cytotoxic and could cause corneal disorders,
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`therefore encouraging the elimination or reduction in the
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`concentration of BAK.” Id. at 74—75.
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`The district court also rejected the defendants’ argu-
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`ment raised in post-trial briefings that our decision in
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`Galderma Laboratories, L.P. U. Tolmor, Inc, 737 F.3d 731
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`(Fed. Cir, 2013), compels a conclusion of obviousness in
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`this case. The defendants argued that Woodward dis-
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`closed a formulation comprising 0.001%—1% bimatoprost
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`and 0-1000 ppm BAK for treating glaucoma, and that the
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`amounts of birnatoprost and BAK in the claimed formula-
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`tion fall within those prior art ranges, thus rendering the
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`Page 10 of 28
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`Page 10 of 28
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`ALLERGAN, INC. V. SANDOZ INC.
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`11
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`claims obvious. The district court reasoned that “Allergan
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`has met its burden of producing rebuttal evidence,
`i.e.,
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`‘that (I) the prior art taught away from the claimed
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`invention;
`(2)
`there were new and unexpected resuits
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`relative to the prior art; or (3) there are other pertinent
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`secondary considerations.” Opinion at 75 (quoting Gal-
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`dermn, 737 F.3d at 738). The court again emphasized
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`that the prior art taught away from 200 ppm BAK, noting
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`that the defendants’ own expert, Dr. Samples, had serious
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`concerns about BAK and strongly warned against its use.
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`Id. at 75-76. The court also emphasized that the unex—
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`pected results were “of a different kind, not just of differ-
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`ent degree.” Id. at 76 (emphases in original).
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`The district court thus concluded that the defendants
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`failed to prove by clear and convincing evidence that the
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`asserted claims would have been obvious. Id. at 77.
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`b.
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`The district court also rejected the defendants’ inva-
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`lidity challenges based on the written description and
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`enablement requirements, which they raised only in pre-
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`and post-trial briefings.
`Id- at 77-81. The court noted
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`that the defendants “did not present any evidence or
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`argument” on those issues at trial. Id. at 77, 79.
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`Specifically, the defendants alleged that the Group II
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`claims, which recite clinical profile limitations, were
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`invalid for lack of an adequate written description. The
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`district court found, however, that the patents explicitly
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`describe the formulation of Lumigan 0.01%, and that
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`Lumigan 0.01% has the clinical profile recited in the
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`Group II claims. Id. at 78. The court also found addition-
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`al support in the titles of the patents, the disclosed in
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`uiiro and in viva permeability data of bimatoprost, as well
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`as the constructive example comparing the IOP-lowering
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`efficacy and hyperemia profile of a test formulation to
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`that of Lumigan 0.03%. The court therefore found that
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`the Group II claims have adequate written description
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`Page 11 of 28
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`Page 11 of 28
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`12
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`ALLERGAN, INC. V. SANDOZ INC.
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`support, “especially given the express disclosure that
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`Lumigan 0.01% is an example of the best mode of the
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`invention.” Id. The court additionally reasoned that the
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`inventors had possession of the claimed invention because
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`a clinical protocol prepared in November 2004, before the
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`March 2005 application filing date, describes the formula-
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`tion of Lumigan 0.01% and the later-claimed clinical
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`profile. Id. at 79.
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`Lupin also alleged that the asserted claims were inva-
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`lid for lack of enablement. The district court rejected that
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`argument, reasoning that A1lergan’s patents disclose the
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`formulation of Lurnigan 0.01% and that
`the patents’
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`disclosure would enable one of ordinary skill in the‘ art to
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`make and use the claimed invention without undue
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`experimentation. Id. at 80—~81.
`C.
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`The district court also found that each of the ANDA
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`products infringed each of the asserted claims. Relevant
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`to this appeal,
`the court found that Hi-Tech’s ANDA
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`product infringed the Group I claims, which require the
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`claimed composition to have a pH of “about 7.3.” Before
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`trial, the parties agreed to construe a “pH of about 7.3” as
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`a “pH of approximately 7.3,” and the court adopted that
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`construction. Allergen, Inc. v. Sandoz Inc., No. 6:11-cv-
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`00441, 2013 WL 139350, at *9 (E.D. Tex. Jan. 10, 2013).
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`Hi-Tech’s ANDA specified that its proposed product has a
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`pH of 6.8-7.2 during the product's shelf life. Opinion at
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`27. After considering the evidence presented at trial, the
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`court found that I-Ii-Tech’s ANDA product literally in~
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`fringed the Group I claims.
`Id. at 64. The court also
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`found, in the alternative, that Hi-Tech's ANDA product
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`infringed the Group I claims under the doctrine of equiva-
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`lents. Id. at 64-66.
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`Accordingly, the district court entered final judgment
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`of infringement and no invalidity. The Appellants timely
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`Page 12 of 28
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`Page 12 of 28
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`ALLERGAN, INC. V. SANDOZ INC.
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`13
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`appealed to this court; we have jurisdiction under 28
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`U.S.C. § 1295(a)(1).
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`DISCUSSION
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`Following a bench trial, we review a district court’s
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`conclusions of law de novo and its findings of fact for clear
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`error. Golden Blount, Inc. 1). Robert H. Peterson C0., 385
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`F.3d 1054, 1058 (Fed. Cir. 2004). A factual finding is
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`clearly erroneous if, despite some supporting evidence, we
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`are left with a definite and firm conviction that a mistake
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`has been made. United States u.
`(7.3. Gypsum Co., 333
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`U.S. 364, 395 (1948); A320 Corp. 1). Mylan Labs, Inc., 464
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`F.3d 1286, 1289 (Fed. Cir. 2006).
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`Furthermore, patents are presumed to be valid and
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`overcoming that presumption requires clear and convinc-
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`ing evidence. 35 U.S.C. § 282; Micr'osoft Corp. 1). Mi Ltd.
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`P’ship, 564 US. _, 131 S. Ct. 2238, 2242 (2011).
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`I
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`We first consider the Appellants’ arguments contend-
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`ing that the district court erred in concluding that the
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`asserted claims would not have been obvious.
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`A patent claim is invalid as obvious if an alleged in-
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`fringer proves that the diflerences between the claimed
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`subject matter and the prior art are such that the subject
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`matter as a whole would have been obvious at the time of
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`invention to a person having ordinary skill in the art. 35
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`§ 103(a)
`(2006). Obviousness is ultimately a
`U.S.C.
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`question of law premised on underlying issues of fact,
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`including:
`(1)
`the scope and content of the prior art;
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`(2) the level of ordinary skill in the pertinent art; (3) the
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`differences between the claimed invention and the prior
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`art; and (4) objective evidence, Such as commercial suc-
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`cess, long-felt need, and the failure of others. KSR Int’!
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`Co. 0. Teleflex Inc, 550 US. 398, 427 (2007); Graham U.
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`John Deere Co., 383 U3. 1, 17-18 (1966); Monarch Knit-
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`Page 13 of 28
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`Page 13 of 28
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`14
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`ALLERGAN, INC. V. SANDOZ INC.
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`ting Maclt. Corp. U. Sulzer Mor'at GmbH, 139 F.3d 877,
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`881 (Fed. Cir. 1998).
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`The Appellants argue that the district court erred as a
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`matter of law by requiring them to establish a motivation
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`to pursue the claimed formulation by modifying Lumigan
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`0.03% and a reasonable expectation of success in doing so.
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`According to the Appellants, because the claimed amounts
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`of bimatoprost and BAK fall within prior art ranges, the
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`proper obviousness inquiry should focus only on teaching
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`away, unexpected results, and other objective indicia.
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`The Appellants also assert that the district court applied
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`an incorrect standard for teaching away because it merely
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`found that the prior art taught that the claimed formula-
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`tion would be inferior, rather than that it would not work.
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`And they argue that the prior art does not teach away
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`from 0.01% bimatoprost or 200 ppm BAK. They assert,
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`moreover, that there are no unexpected results because
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`the observed results of similar efficacy and less hyperemia
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`are only a difference in degree, not a difference in kind.
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`They also argue that those results are the inherent prop-
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`erties of an otherwise obvious formulation. Finally, they
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`argue that the district court erred in finding other objec-
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`tive indicia as supporting nonobviousness.
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`Allergen responds that this appeal turns on disputed
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`facts and that the district court did not clearly err in
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`finding those facts in Allergan’s favor, including finding
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`the prior art
`taught
`that
`(1) 0.01% bimatoprost
`that
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`would be less efficacious than 0.03% bimatoprost; (2) BAK
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`would decrease the permeability of bimatoprost; and
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`(3) 200 ppm BAK would be unsafe for chronic use with
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`bimatoprost. Allergen contends that
`the