On November 13th, in an opinion drafted by Judge Taranto, the Federal Circuit affirmed the Southern District Court of Florida’s judgment that Apotex’s biosimilar versions of Neulasta® and Neupogen® do not infringe Amgen’s U.S. Patent No. 8,952,138 (covering methods of refolding recombinant proteins expressed in non-mammalian cells). The opinion touched on two key issues that may affect other biosimilar litigants: how statements in “patent dance” letters and parameters in abbreviated Biologics License Applications (“aBLAs”) impact infringement analyses.
Filed in October 2015, Amgen v. Apotex was the first Biologics Price Competition and Innovation Act (“BPCIA”) litigation to reach a decision on the merits. While previous BPCIA cases had terminated by settlement or based on jurisdictional rulings, the Amgen v. Apotex district court found that Amgen had failed to prove that Apotex’s protein refolding process used in the manufacture of its biosimilar drugs met two claim limitations: (1) a high protein concentration construed to require “at or above about 1 g/L” protein and (2) a redox component having a redox buffer strength “2 mM or greater,” which the district court construed as 2 to 100 mM.
Amgen appealed the district court’s refusal to give weight in the infringement analysis to certain pre-litigation representations made by Apotex during the “patent dance” and to certain technical parameters in Apotex’s aBLAs. Amgen argued that the representations in the “patent dance” should be probative (although not necessarily binding) in an infringement analysis. Amgen also urged that a finding of infringement should be mandated if the aBLA encompasses an infringing process, consistent with a similar outcome in the Hatch-Waxman context.
The Federal Circuit agreed that Amgen failed to prove that Apotex’s process meets the “at or above about 1 g/L” limitation. Having affirmed a finding of non-infringement based on the “at or above about 1 g/L” claim limitation, the Court declined to address any issues related to the “2 mM or greater” limitation.
The Court first addressed the probative value of Apotex’s patent dance letters, in which Apotex represented that its process had a protein concentration of 0.9-1.4 g/L (i.e., an infringing range under the district court’s subsequent claim construction). Noting that Amgen had specifically disclaimed any argument that the patent dance letters were binding, the Court agreed with Amgen that “statements in the pre-litigation letters are party admissions and have some probative weight.” (Op. at 8.) At the same time, the Court found that the district court did not improperly disregard the pre-litigation letters. Rather, the district court had simply found that letters were “not sufficientlyprobative to outweigh other evidence presented at trial indicating that the information in the letters was inaccurate.” (Id.)
The Federal Circuit also addressed Amgen’s argument that “the district court’s noninfringement finding rests on too restrictive a view of Apotex’s FDA applications.” (Id. at 12.) Amgen argued that the district court was required to assess infringement based on the full range of processes that would be consistent with Apotex’s aBLAs, consistent with Federal Circuit precedent in the Hatch-Waxman context, Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc., 731 F.3d 1271 (Fed. Cir. 2013). That is, if Apotex’s aBLAs expressly allowed for an infringing concentration of protein, then that limitation would be met as a matter of law. Apotex did not challenge the importation of the Sunovion analysis into the BPCIA context, but did dispute the applicability of Sunovion to the facts of this case.
The Federal Circuit implicitly agreed with the propriety of using the Sunovion framework in the BPCIA context, but found that the district court had sufficient basis to find that Apotex’s aBLAs did not authorize a range of parameters that included an infringing process. Even if the Federal Circuit “did not read the applications as affirmatively constraining the process” to a non-infringing range, the Court would have concluded that the aBLAs were “silent on the point” related to infringement and would have applied Glaxo, Inc. v. Novopharm, Ltd., 110 F.3d 1562 (Fed. Cir. 1997). (Id. at 14.) In Glaxo, the court looked to extrinsic evidence, such as the samples and data submitted to the FDA, to resolve a question of infringement left open by the abbreviated new drug application. Id. at 1569. Here, Apotex had submitted batch records of its actual manufacturing process to resolve any question of infringement left open by Apotex’s aBLAs. Thus, Apotex’s aBLAs did not mandate a finding of infringement.
The Federal Circuit’s opinion gives biosimilar applicants and reference product sponsors additional guidance on how to prepare for future litigation. For example, biosimilar applicants should remember, when making statements during the “patent dance,” that those statements are party admissions that have at least some probative weight in subsequent litigation. Alternatively, biosimilar applicants may opt to forgo the “patent dance” altogether. Given the likely applicability of the Sunovion/Glaxo framework, biosimilar applicants should be more attuned to potential infringement implications in laying out broad parameters in their aBLAs, perhaps even including litigators in the review before the aBLAs are submitted to FDA. And both biosimilar applicants and reference product sponsors should keep the Sunovion/Glaxo framework in mind when developing infringement and non-infringement positions, both pre-suit and during litigation.