Allergan, Inc. v. Sandoz, Inc.

Appellate court reversed in part district court's finding of non-obviousness when prior art taught claimed combination drug.

July 15, 2013

Robins Kaplan GENERICally Speaking: A Hatch-Waxman Litigation Bulletin

Case Name: Allergan, Inc. v. Sandoz, Inc., Nos. 2011-1619, 2011-1620, 2011-1635, 2011-1639, 2013 U.S. App. LEXIS 8837 (Fed. Cir. May 1, 2013) (Circuit Judges Dyk, Prost, and O’Malley presiding; Opinion by Prost; Opinion concurring-in-part and dissenting-in-part by Dyk) (Appeal from E.D. Tex., Ward, J.)

Drug Product and Patent(s)-in-Suit: Combigan® (0.2% brimonidine / 0.5% timolol); U.S. Pat. Nos. 7,642,258 (“the ’258 patent”), 7,320,976 (“the ’976 patent”), 7,323,463 (“the ’463 patent”), and 7,030,149 (“the ’149 patent”).

Nature of the Case and Issue(s) Presented: Allergan is the assignee of the ‘258, ‘976, ‘463, and ‘149 patents, the claims of which cover compositions, methods of using and product packaging concerning combining brimonidine and timolol to treat glaucoma. Before trial, the district court granted summary judgment of non-infringement as to claims 1-3 of the ‘149 patent. The parties stipulated to infringement with respect to all remaining asserted claims. The sole remaining issue at trial was whether the asserted claims were obvious under 35 U.S.C. § 103. At the conclusion of the bench trial, the district court found that each of the asserted claims was non-obvious. In response to the district court’s ruling, defendants Sandoz Inc., Laboratories, Inc., Alcon Research, Ltd., Alcon, Inc., Falcon Pharmaceuticals, Ltd., Apotex Inc., Apotex Corp., and Watson Laboratories (collectively, “Sandoz”) appealed. The issue on appeal was whether prior art teaching the use of a combination of alpha2-agonists and beta-blockers rendered the asserted patents invalid as obvious.

Why Allergan Partially Prevailed: First, Sandoz argued that the ‘463 patent was obvious. The prior art disclosed that timolol and brimonidine were commercially available and used in the treatment of ophthalmic conditions at the time of invention.  Indeed, the prior art disclosed the serial administration of the combination of the two drugs to reduce intraocular pressure, and that the combination was more effective than either drug administered by itself. The district court made four findings as to Sandoz’s argument concerning the ’463 patent: (i) there would have been no motivation to combine because the FDA did not view patient compliance as a factor in gaining approval; (ii) the formulation of the two drugs was unpredictable; (iii) the prior art taught away from the claimed invention; and (iv) there were secondary considerations that supported its finding of nonobviousness.

The Federal Circuit addressed each of these findings in turn.  First, the Federal Circuit determined that the district court had erred in concluding that there was no motivation to combine because the FDA did not consider that a fixed combination product could increase patient compliance. It held that the motivation to combine could be found in many different places and forms, and was not limited to the reasons that the FDA decides to approve or deny a particular drug application. Under the proper standard, the Federal Circuit noted that there was ample evidence in the record establishing a motivation to combine brimonidine and timolol into a fixed combination product. Additionally, the Federal Circuit noted the existence of at least four other fixed combination products on the market at the time of invention that were used to treat glaucoma. The cited evidence provided more than ample support for the fact that there was a motivation to combine present in the prior art. Second, the Federal Circuit found that although Allergan chemists experienced some difficulties in formulating Combigan, the difficulties largely involved incorporating compounds other than the claimed, active ingredients. The evidence indicated that a great deal of difficulties the formulators encountered was due to attempts to incorporate a proprietary preservative, which was not an element in any of the asserted claims. Therefore, the Federal Circuit held that the district court’s conclusion that there was no reasonable expectation of success was erroneous. The Federal Circuit also quickly dispatched with Allergan’s argument that the prior art taught away from the claimed invention. The Court then addressed the district court’s findings with respect to secondary considerations of nonobviousness. While the Federal Circuit did not disturb the district court’s analysis, it did hold that the evidence of secondary considerations the district court cited was not substantial enough to rebut obviousness.

The Federal Circuit next addressed claim 4 of the ‘149 patent. Claim 4 contained a limitation that the daily number of doses of brimonidine be reduced from 3 to 2 times a day without a loss of efficacy. The evidence at trial was clear that reducing the dosage of brimonidine from 3 to 2 doses per day resulted in a loss of efficacy later in the day. The fixed combination product which incorporated timolol could be dosed at twice a day without the loss of efficacy experienced when brimonidine was dosed in isolation. Sandoz attempted to rebut this finding by citing to prior art establishing a similar low dose regimen when timolol was added to other ophthalmic drugs. But the Federal Circuit, affirming the district court’s holding, found that it was not obvious that adding timolol would have a similar effect on all other ophthalmic drugs, such as brimonidine.

Judge Dyk authored a separate opinion, concurring with the majority that the ‘463 patent was invalid as obvious and dissenting with respect to the Court’s conclusion that claim 4 of the ‘149 patent was non-obvious. Judge Dyk found it impossible to reconcile the majority’s seemingly inconsistent holding. He noted that while a new and non-obvious method of using an existing (or obvious) composition could be patentable, a newly-discovered result or property of an existing (or obvious) method of use is not. Judge Dyk concluded that this was exactly what Allergan was attempting to claim in the ‘149 patent, and that the result of the claimed dosing regimen was merely a newly-discovered result of a known process.

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