Oxcarbazepine - USA

On Sep 06, 2018 Federal Circuit upheld a New Jersey court’s decision that Supernus Pharmaceuticals Inc.’s patents related to its anti-epilepsy drug (Oxtellar XR) are valid and infringed by ANDA filer Twi Pharmaceuticals Inc.

Twi Pharmaceuticals, Inc. appealed from a decision of the United States District Court for the District of New Jersey holding, after bench trial, that Supernus Pharmaceuticals, Inc.’s U.S. Patent Nos. 7,722,898 (“the ’898 patent”), 7,910,131 (“the ’131 patent”), and 8,821,930 (“the ’930 patent) are not invalid and would be infringed. These patents provide controlled-release oxcarbazepine formulations for once-a-day administration. The asserted patents purport to achieve these objectives by (1) using matrix polymers that comprise a homogeneous matrix structure, and (2) “incorporat[ing] a combination of solubility-enhancing excipients and/or release-promoting agents into the formulations to enhance the bioavailability of oxcarbazepine and its derivatives.”

Representative claim 1 of the ’898 patent recites:

1. A pharmaceutical formulation for once-a-day administration of oxcarbazepine comprising a homogeneous matrix comprising:

(a) oxcarbazepine;

(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 pHdependent 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.

On Oct. 7, 2015, the district court held a Markman hearing in related case (“Actavis”), during which it construed claim term “at least one agent that enhances the solubility of oxcarbazepine” 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 claim term “homogeneous matrix” as a “matrix in which the ingredients or constituents are uniformly dispersed.” The district court then held a four-day bench trial in this litigation from April 3–6, 2017. In a decision dated August 15, 2017, the district court concluded that the asserted patents are not invalid and would be infringed by TWi’s proposed tablets. In particular, the district court found that TWi’s proposed tablets satisfied the “homogeneous matrix” and the solubility agent limitations under its constructions of those terms, and that the common specification and prosecution histories of the asserted patents demonstrate that the “homogeneous matrix” limitation is not indefinite and does not lack adequate written description support. In making these determinations, the district court, at times, referenced its decision in Actavis.

“On appeal, First, TWi contended that the district court erred because it gave its decision in Actavis “de facto preclusive effect” in this case. CAFC however, disagreed & said that district court did not give its decision in Actavis de facto preclusive effect in this case. The district court explicitly stated in its post-trial decision that its decision in Actavis has “some relevance to this action,” but that its “findings of fact and conclusions of law set forth are based upon the evidence and argument presented in this litigation.”

Second, TWi argued that Supernus’s admissions in the common specification preclude a finding that the accused agent satisfies the “solubility agent limitation”. As described above, the asserted patents require both a release promoting agent and a solubility agent. Twi argued that the accused agent cannot satisfy the solubility agent limitation because the common specification, at Table 1, characterizes a formulation that contains the accused agent, but not a release-promoting agent, as a “non-enhanced” formulation. CAFC said that “non-enhanced” formulations can include formulations that do not contain either a solubility agent or a release promoter. Applied to Table 1, the “non-enhanced” formulation containing the accused agent does not preclude a finding that the accused agent is a solubility agent. This is because it is entirely possible that the formulation is “non-enhanced” solely because it lacks a release-promoting agent and not because it lacks a solubility agent. Thus, the district court did not err in finding that this statement in the specification does not amount to an admission of non-infringement, nor did it err in ultimately concluding, based on expert testimony, that the accused agent infringes the solubility agent limitation.

Third, TWi also argued that the district court erred in finding that the proposed tablets infringe the “homogeneous matrix” limitation. Specifically, it contended that the district court changed its construction of “homogeneous matrix” from a “matrix in which the ingredients or constituents are uniformly dispersed,” as construed in the district court’s Markman order, to “no localization of constituents,” as stated in its post-trial decision. CAFC said that 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. Supernus raised concerns that TWi may attempt to avoid infringement by arguing that the asserted patents require complete uniformity, which Supernus contends is unattainable. In response to Supernus’s concerns, the district court stated that, in its view, the asserted patents do not require any specific degree of uniformity, just some degree of uniformity. 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.

Finally, TWi argued that the district court erred in finding that the “homogeneous matrix” limitation was not indefinite and did not lack written description support. CAFC disagreed to this also & held that the specification, prosecution history, and expert testimony support the district court’s conclusions. Thus, the district court did not err.