Case Name: Shire Dev. LLC v. Watson Pharms., Inc., No. 2013-1409, 2014 U.S. App. LEXIS 5719 (Fed. Cir. Mar. 28, 2014) (Circuit Judges Rader, Prost, and Hughes presiding; Opinion by Hughes, J.) (appeal S.D. Fla., Middlebrooks, J.)

Drug Product and Patent(s)-in-Suit: Lialda^® (mesalamine); U.S. Patent No. 6,773,720 (“the ’720 patent”)

Nature of the Case and Issue(s) Presented: 5-aminosalicylic acid, also known as mesalazine or mesalamine, must be formulated so that it can transit the digestive system intact before reaching its target—the large intestine. In order to achieve this objective, mesalamine is formulated into a tablet having hydrophilic properties in its outer layer and a lipophilic layer mixed with the active ingredient in its inner layer. The ’720 patent teaches an inner lipophilic matrix and an outer hydrophilic matrix to address the limitations of the prior art systems.  Shire owns the ’720 patent, and sued Watson for patent infringement after Watson submitted an ANDA seeking FDA approval to manufacture and sell a generic version of Lialda.

The district court construed several disputed claim terms, including “inner lipophilic matrix” and “outer hydrophilic matrix.” After trial, the district court found that Watson’s ANDA product infringed claims 1 and 3 of the ’720 patent, that the claims were not invalid under 35 U.S.C. § 112, ¶ 1, and that Shire was entitled to injunctive relief. The district court found that the mesalamine in Watson’s ANDA product was dispersed in both the lipophilic and hydrophilic matrices because the mesalamine was present in both the granules and the spaces outside the granules. Watson appealed the issues of claim construction, infringement, and invalidity. The Federal Circuit reversed the district court’s claim constructions with regard to the terms “inner lipophilic matrix” and “outer hydrophilic matrix” and also reversed the lower court’s finding of infringement.

Why Watson Prevailed:  The Federal Circuit took issue with the district court’s claim construction. The district court construed the term “inner lipophilic matrix” to mean “a matrix including at least one lipophilic excipient, where the matrix is located within one or more substances,” and the term “outer hydrophilic matrix” to mean “a matrix of at least one hydrophilic excipient, where the matrix is located outside the inner lipophilic matrix.” In doing so, the district court rejected Watson’s argument that the inner matrix and outer matrix must be separate and distinct. The district court acknowledged that the applicants described their matrices as separate to distinguish over the prior art references, but found that nowhere in the prosecution history, claims, or specification did the term “separate and distinct” appear. The Federal Circuit determined that the district court correctly found no prosecution disclaimer because the statements in the prosecution history were not unambiguous disavowals. During prosecution, Shire carefully characterized the prior art as not having separate matrices, but never actually stated that the claimed invention does have separate matrices.

The Federal Circuit concluded that the logical reading of the claim requires separation between the matrices because the matrices are defined by mutually exclusive spatial characteristics—one inner, one outer—and mutually exclusive compositional characteristics—one hydrophilic, one lipophilic. The Federal Circuit found further support that the separation was required based upon the fact that, during prosecution, the applicants added claim limitations citing Markush groups that identified specific hydrophilic and lipophilic components.

Under the construction adopted by the district court, a single mixed matrix with both hydrophilic and lipophilic components could contain both an inner lipophilic matrix and an outer hydrophilic matrix. Indeed, the Federal Circuit concluded, any arbitrarily selected volume in a single mixed matrix could potentially satisfy the district court’s construction of “inner lipophilic matrix” because that volume would necessarily contain “at least one lipophilic excipient” and it would be “inside” the surrounding volume.  Similarly, under the district court’s construction, that same arbitrarily selected volume would constitute an “outer hydrophilic matrix” because it would contain “at least one hydrophilic excipient” and would be “outside” the inner lipophilic matrix. This construction could not be correct, because the claims at issue required two matrices with a defined spatial relationship between them.