By Kevin E. Noonan --
In the second of a pair of decisions issued last Friday, styled Ferring B.V. v. Watson Laboratories, Inc., the Federal Circuit affirmed a finding by the District Court that the generic ANDA challenger had not shown the asserted claims of the patents-in-suit were obvious, but reversed the District Court's finding of infringemnent.
The case involved a generic form of Lysteda® (trans-4-(aminomethyl)cyclohexanecarboxylic acid, also called tranexemic acid), used to treat heavy menstrual bleeding. The drug was known in the prior art, but was also known to be associated with dosage-dependent gastrointestinal side effects. The Orange Book-listed patents-in-suit, U.S. Patent 7,947,739, 8,022,106, and 8,273,795, were directed to "modified release" formulations; claim 1 of the '739 patent is representative (according to the Court):
1. A tranexamic acid tablet formulation, comprising:
tranexamic acid or a pharmaceutically acceptable salt thereof; and
a modified release material, wherein the modified release material comprises a polymer selected from the group consisting of hydroxyalkylcelluloses, alkylcelluloses, cellulose ethers, partial esters thereof, and mixtures thereof;
wherein the modified release material is present in the formulation in an amount from about 10% to about 35% by weight of the formulation;
wherein the formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by the USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37±0.5ºC., of less than about 70% by weight tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes, and about 100% by weight tranexamic acid or pharmaceutically acceptable salt thereof released by about 120 minutes; and
wherein each tablet of the formulation provides a dose of about 650 mg of tranexamic acid.
As discussed in the opinion, it was "undisputed" that the branded drug is encompassed within the claims of the patents-in-suit. Also relevant to the Court's opinion, defendant Watson's ANDA was approved and Watson launched "at risk" of a finding of willful infringement (despite this opportunity, Ferring did not move to enjoin the putatively infringing sales).
The District Court construed two claim terms: a single term in the claims, concerning the meaning of the word "about" as used in the claim limitation "less than about [%] by weight," which the District Court held to mean "approximately"; and the phrase "modified release material," which was construed to mean "a material that modifies the release of the active pharmaceutical ingredient [in water]."
The District Court held, and the Federal Circuit affirmed, that the claims were not obvious because the cited prior art taught dosages of the drug no greater than 500mg, and the evidence of dose-dependent gastrointestinal side effects would have suggested to the skilled worker that lower rather than higher dosages were indicated. Regarding infringement, the District Court considered evidence of dissolution rates from uncoated cores of drug and modified release material, as well as commercial tablets, and assessed infringement under § 271(a) as well as § 271(e)(2), in view of Watson's "at risk" sales. As in its companion case, the District Court suggested that changes in Watson's formulation (here, the hardness of the coatings used) would avoid infringement, and as in the companion case Watson complied by amending its ANDA to incorporate the "softer" coating. However, in this case the District Court entered judgment against Watson and imposed an injunction against further "making, using, selling or offering to sell" Watson's commercial product.
The Federal Circuit's opinion was penned by Judge Lourie, joined by Judges Dyk and Reyna. In the opinion, the Court states that that it will not "disturb" the District Court's claim construction (which neither party challenged on appeal). Regarding obviousness, the panel held that the cited prior art "neither set forth the limitations required by the asserted claims, nor provided any reason or motivation to combine those teachings to derive the claimed formulations with specific dissolution profiles." Specifically, like the District Court the panel found that the prior art taught formulations of 500mg tranexemic acid, and disclosed dose-dependent gastrointestinal side effects. The art did not disclose or suggest the specific modified release polymers used in Ferring's patented formulations or the amounts to use, and amounted to merely a series of generic teachings that tranexemic acid can be formulated with any of a number of excipients including modified release materials. Also, the Federal Circuit discerned no teaching in the art of the "critical dissolution limitations" recited in many of the claims. Finally, the opinion referenced a showing of secondary considerations (long-felt and unmet need, as well as the evidence that Ferring's drug received "Fast Track" consideration by the FDA) that supported the District Court's non-obvious determination.
The opinion reviewed District Court's infringement determinations under both § 271(e)(2) and § 271(a). With regard to § 271(e)(2) as the basis for the District Court's finding of infringement, the Federal Circuit opined that filing an ANDA was merely a device to establish jurisdiction, and that Ferring had the burden to show that the generic product described in the ANDA would be infringing. In some instances the ANDA is enough, the Court stated, but when it is not sufficient then evidence (such as "biobatch" data on the generic product) can be used to establish infringement. In this case, the ANDA did not resolve the question, and the Federal Circuit disagreed that Ferring had proven that the generic product would infringe. Lack of evidence in the ANDA (with regard to dissolution characteristics of the generic formulation) is not enough ("silence does not answer the question of infringement") and the Federal Circuit held that the District Court erred by accepting evidence from the uncoated cores; according to the opinion, Watson was given FDA approval to market the "final, coated commercial tranexamic acid tablets" and that was the accused infringing article whose dissolution properties had to fall within the scope of Ferring's claims. The Federal Circuit held that the evidence failed to establish that any of the claims of the patents-in-suit were infringed by the commercial embodiment Watson was authorized by the FDA to market and thus reversed.
The Court also addressed the application of the claim element "modified release material," which the District Court had construed to mean "a material that modifies the release of the active pharmaceutical ingredient." Saying that it would not disturb this construction, the opinion asserted that "just because a certain material can modify release of the active pharmaceutical ingredient tranexamic acid, does not necessarily mean that it actually does" (emphasis in opinion). Thus, the Federal Circuit required evidence to establish that Watson's accused infringing formulation satisfied this claim element, and found that Ferring had failed to adduce any such evidence at trial. This failure further supported the panel decision reversing the District Court's finding of infringement.
Again as in its companion decision, the panel awarded costs to Watson, without explanation.
Ferring B.V. v. Watson Laboratories, Inc. (II) (Fed. Cir. 2014)
Panel: Circuit Judges Lourie, Dyk, and Reyna
Opinion by Circuit Judge Lourie