By Donald Zuhn --
Last month, in Supernus Pharmaceuticals, Inc. v. TWi Pharmaceuticals, Inc., the Federal Circuit affirmed a decision by the U.S. District Court for the District of New Jersey finding that U.S. Patent Nos. 7,722,898; 7,910,131; and 8,821,930 were not invalid and would be infringed by Defendants-Appellants TWi Pharmaceuticals, Inc. and TWi International LLC, DBA TWi Pharmaceuticals. The '898, '131, and '930 patents are owned by Plaintiff-Appellee Supernus Pharmaceuticals, Inc.
Seeking approval to market generic versions of Oxtellar XR®, an oxcarbazepine extended-release tablet for treatment of partial epilepsy seizures in adults and children over the age of six, TWi filed an Abbreviated New Drug Application (ANDA) with the FDA. In response to that filing, Supernus brought an action for infringement of the '898, '131, and '930 patents, and TWi counterclaimed for invalidity.
The '898, '131, and '930 patents share a common specification, which discloses that twice daily, immediate release formulations of oxcarbazepine were known in the art, but were disadvantageous because they require multiple daily administrations and can result in increased side effects. Sustained release formulations were therefore preferred, but according to the common specification, such formulations were difficult to achieve because oxcarbazepine is poorly soluble in water. The asserted patents provide controlled-release oxcarbazepine formulations for once-a-day administration by (1) using matrix polymers that comprise a homogeneous matrix structure, and (2) incorporating a combination of solubility-enhancing excipients and/or release-promoting agents into the formulations to enhance the bioavailability of oxcarbazepine and its derivatives. Claim 1 of the '898 patent recites:
1. A pharmaceutical formulation for once-a-day administration of oxcarbazepine comprising a homogeneous matrix comprising:
(b) a matrix-forming polymer selected from the group consisting of cellulosic polymers, alginates, gums, cross-linked polyacrylic acid, carageenan, polyvinyl pyrrolidone, polyethylene oxides, and polyvinyl alcohol;
(c) at least one agent that enhances the solubility of oxcarbazepine selected from the group consisting of surface active agents, complexing agents, cyclodextrins, pH modifying agents, and hydration promoting agents; and
(d) at least one release promoting agent comprising a polymer having pH-dependent solubility selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxycellulose phthalate, polyvinylacetate phthalate, polyvinylbutyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, and Eudragit L100-55 (Methacrylic Acid-Ethyl Acrylate Copolymer (1:1)), and methyl acrylate-methacrylic acid copolymers.
The claim limitations at issue on appeal are shown in bold-italics.
At trial, the District Court held a Markman hearing and construed (1) the claim term "at least one agent that enhances the solubility of oxcarbazepine" (referred to by the Federal Circuit as the "solubility agent limitation") as "an agent, other than oxcarbazepine, that enhances the solubility of oxcarbazepine, which agent cannot also serve as the sole matrix-forming polymer in 1(b) or the sole release promoting agent in 1(d) in claim 1," and (2) the claim term "homogeneous matrix" as a "matrix in which the ingredients or constituents are uniformly dispersed." In between the Markman hearing and a bench trial, the District Court decided a related case, Supernus Pharms., Inc. v. Actavis Inc. (D.N.J. Feb. 5, 2016), which involved the same plaintiff and asserted patents, but different defendants and accused products. In that case, the District Court determined that the asserted patents were not invalid and would be infringed. Following the bench trial in the instant case, the District Court determined that the asserted patents were not invalid and would be infringed by TWi's proposed oxcarbazepine extended-release tablets, and that the homogeneous matrix limitation was not indefinite and did not lack adequate written description support in the common specification.
On appeal, TWi argued that the District Court erred (1) by giving its decision in Supernus Pharms., Inc. v. Actavis Inc. de facto preclusive effect in the instant case, (2) in concluding that the proposed tablets would infringe the solubility agent and homogeneous matrix limitations, and (3) in finding the asserted patents not invalid as indefinite or for lack of written description. With respect to TWi's first argument, the Federal Circuit determined that the District Court did not give its decision in Actavis de facto preclusive effect, agreeing with Supernus that "the district court made express findings based on the record presented in this litigation and relied on Actavis only to the extent that the records were similar or the parties had agreed to be bound by a subsidiary conclusion from Actavis." The Federal Circuit also disagreed with TWi's argument that the District Court improperly relied on results from tests that were admitted as evidence in Actavis, but not in the instant case, finding that "[t]o the contrary, the district court made only a passing reference to the Oxtellar XR® tests, and based its infringement determination solely on tests and evidence admitted in this litigation" (citation omitted).
With respect to TWi's second argument, the opinion notes that TWi contended that its tablets could not satisfy the solubility agent limitation because the common specification, at Table 1, characterizes a formulation that contains the accused agent in TWi's tablets, but not a release-promoting agent, as a "non-enhanced" formulation. In particular, TWi pointed to disclosure in the common specification stating that "improvements were made to the formulations by incorporating solubility enhancers and/or release-promoting excipients (such formulation[s] are referred to as enhanced formulations)" (emphasis in opinion), and arguing that the term "and/or" in this statement means "and" or "or". Supernus, however, argued that in the context of the common specification, "and/or" means solely "and," and the District Court sided with Supernus on the issue. The Federal Circuit agreed with Supernus and the District Court, reading "enhanced" formulations, in the context of the common specification, to require both a "combination of solubility and release promoters." In particular, the Federal Circuit noted that "the common specification describes the presence of both a solubility agent and a release-promoting agent as essential to formulating an 'enhanced' formulation" (emphasis in opinion).
TWi also argued that the District Court failed to apply its own construction of the solubility agent limitation, which the District Court agreed implicitly required that the solubility agent enhance solubility by more than a de minimis amount. The Federal Circuit, however, noted that "the district court did not use the magic words 'de minimis,'" and instead "found, consistent with expert testimony, that the patents do not require any specific amount of enhancement and that the accused agent enhanced solubility by a statistically significant amount." "That TWi disagrees with the district court's assessment that a statistically significant increase satisfies the claim limitation as construed," the opinion explains, "is not grounds for error."
Regarding the homogeneous matrix limitation, TWi argued that the District Court changed its construction of that term from a "matrix in which the ingredients or constituents are uniformly dispersed," as construed in the Court's Markman order, to "no localization of constituents," as stated in the Court's post-trial decision. The Federal Circuit, however, concluded that the "district court did not change the construction of the term in its post-trial decision, but rather clarified what was already inherent in its construction, as permitted." More specifically, the Federal Circuit explained that:
[T]he district court stated, the term "was added to the claims to distinguish Supernus's invention, which has all four matrix components in the tablet core, from the prior art references, which contained certain matrix constituents solely in the coating, which the Patent Examiner viewed to be part of the matrix." Thus, the district court clarified that inherent in its construction of "homogeneous matrix" is this understanding that, where the degree of uniformity is irrelevant, "uniformly dispersed" necessarily implicates an absence of localization [citations omitted].
As for TWi's third argument, the Federal Circuit determined that the District Court did not err in finding that the "homogeneous matrix" limitation was not indefinite and did not lack written description support.
The Federal Circuit therefore affirmed the District Court's decision that that the asserted patents were not invalid and would be infringed by TWi's proposed tablets.
Supernus Pharmaceuticals, Inc. v. TWi Pharmaceuticals, Inc. (Fed. Cir. 2018)
Panel: Circuit Judges O'Malley, Clevenger, and Stoll
Opinion by Circuit Judge O'Malley