Case Name: Ferring B.V. v. Watson Labs., Inc.—Florida II, No. 2014-1416 (Fed. Cir. Aug. 22, 2014) (Circuit Judges Lourie, Dyk, and Reyna presiding; Opinion by Reyna, J.) (Appeal from D. Nev., Jones, J.)
Drug Product and Patent(s)-in-Suit: Lysteda® (tranexamic acid); U.S. Patents Nos. 7,947,739 (“the ’739 patent”), 8,022,106 (“the ’106 patent”), and 8,273,795 (“the ’795 patent”)
Nature of the Case and Issue(s) Presented: The patents-in-suit claim oral dosage forms and method of treating menorrhagia and require three elements: (i) about 650 mg of tranexamic acid; (ii) a so-called modified release material that comprises either about 10% to about 35% or about 5% to about 50% by weight of the formulation; and (iii) a specified dissolution release rate of the tranexamic acid in water as measured by a particular USP method.
Watson’s generic tablets are made of a “core” mixture comprising 650 mg of tranexamic acid and various excipients. Watson’s initially-filed ANDA specified that the hardness of the cores was 13-20 kp. In an amendment approved by the FDA, Watson modified its specification to require a core hardness of 13-17 kp. The cores are surrounded by a pH-dependent film coating, which is 2.91% by weight of the total weight of the composed tablet; it is designed to resist degradation in water, but to dissolve immediately in acidic conditions. Finally, Watson’s ANDA contains no specification that addresses its dissolution rate in water. But biobatch data submitted by Watson demonstrates the dissolution rate of tranexamic acid as measured by the USP 27 Apparatus Type II method as follows: 5% at 15 minutes; 16% at 45 minutes; 29% at 90 minutes, and 37% at 120 minutes.
Watson submitted paragraph IV notices that its generic product would not infringe the patents-in-suit, which it also claimed were invalid. Ferring sued. After receiving FDA approval, Watson launched its generic tranexamic acid product at risk, which Ferring did not move to enjoin. At trial, Ferring relied on Watson test data to prove infringement. Those data showed dissolution profiles of experimental, uncoated 650 mg tranexamic acid cores of various specified hardness. The district court found that the asserted claims would not have been obvious, and that both the uncoated cores and the finished, coated commercial tablets with a core hardness of 17 kp and greater infringed the asserted claims. Watson filed an amendment to its ANDA further narrowing its specification to require a hardness of 13-16.5 kp, but the district court nevertheless issued a final judgment permanently enjoining Watson from manufacturing and selling its generic product. Watson appealed, and the Federal Circuit affirmed the district court’s judgment on validity and reversed the judgment on infringement.
Why Watson Prevailed: Concerning validity, the Federal Circuit found 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. First, the references disclosed 500 mg tranexamic acid formulations, but no higher tablet strength. Second, the references did not disclose the claimed amounts of modified release polymers. Third, Watson did not identify any prior-art references disclosing the critical dissolution limitations of the patented claims, but merely asserted in a conclusory manner that those limitations would have been obvious or could have been predicted while failing to address why one of skill in the art would choose the specific release profiles claimed. Coupled with the finding of a long-felt but unmet need as evidenced by the FDA’s decision to “fast track” NDA approval, the Federal Circuit found that the patents-in-suit were not invalid as obvious.
With regard to infringement, the district court considered Watson’s submission of the ANDA itself to be an act of infringement and ostensibly refused to consider all FDA-approved amendments to the ANDA specification in its infringement analysis. The Federal Circuit found that in doing so, the district court erred. Filing an ANDA only constitutes a technical act of infringement for jurisdictional purposes. Once jurisdiction is established, the ultimate infringement inquiry is focused on a comparison of the asserted claims against the product that is likely to be sold following ANDA approval. Thus, the Federal Circuit found that the focus that both Ferring and the district court gave to infringement of the uncoated cores of Watson’s generic product was misplaced because of relevance is the final, coated commercial tablets for which Watson sought FDA approval. The dissolution data collected by both parties during discovery concerning showed that of the hundreds of coated commercial products tested (as opposed to the experimental non-coated cores), only about four individual tablets were found to meet the claimed dissolution rate limitations. Further, the district court found that Watson’s accused products would not infringe at a core hardness level of less than 17 kp. Given Watson’s latest FDA-approved amendment narrowing the ANDA specification to a hardness of 13-16.5 kp, the Federal Circuit found that Watson’s ANDA product will not infringe the asserted claims.
Accordingly, the Federal Circuit vacated the district court’s permanent injunction.
