Patent owner Amgen has appealed to the Federal Circuit seeking to overturn a non-infringement ruling with respect to Apotex’s manufacturing processes for its biosimilar versions of Amgen’s NEULASTA® (pegfilgrastim) and NEUPOGEN ® (filgrastim) products. The appeal raises several claim construction and infringement issues with respect to U.S. Patent No. 8,952,138 (“the ‘138 patent”), which covers a method for creating a refold mixture that prevents a recombinant protein from misfolding and aggregating. One issue raised in the appeal—with potentially broad implications for other litigants—is whether pre-litigation representations made by Apotex are binding for the infringement analysis in a litigation under the Biologics Price and Competition Act (“BPCIA”).

In this case, Amgen argues that the district court committed clear legal error when it found non-infringement despite the fact that Apotex’s abbreviated Biologics License Application (“aBLA”) described an infringing process and despite the fact that Apotex, during the patent dance, described its product in a way that would infringe under the court’s claim construction. In other words, Amgen asks the Federal Circuit to decide two questions that could potentially impact other BPCIA litigation: (1) is the infringement analysis in a BPCIA litigation governed by the disclosures in the aBLA, and (2) are statements made by biosimilar applicants under 42 U.S.C. § 262(l)(3)(B) of the BPCIA “optional pre-litigation letters” or binding party admissions?

The aBLA

The first issue with potentially broad implications is whether an aBLA that permits (but does not require) parameters that could lead to infringement necessitates or weighs heavily in a finding of infringement. Each side claims support from Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc., 731 F.3d 1271 (Fed. Cir. 2013), where the Federal Circuit held that if a drug in a defendant’s abbreviated new drug application (“ANDA”) is specified so as to permit a product or process falling within the scope of an asserted claim, then the claim is infringed. Amgen maintains that Apotex’s aBLA discloses specifications that “would allow” Apotex to practice an infringing refolding process, and therefore under Sunovian, “a judgment of infringement must necessarily ensue.” (Dkt. 36 at 27 citing 731 F.3d at 1278). If the infringement analysis is not limited to a biosimilar applicant’s aBLA specification, Amgen argues that a clever applicant could avoid infringement by choosing operating parameters for its manufacturing that fall outside the claim scope, and then switch to different infringing parameters within the scope of its aBLA specification after FDA approval.

According to Apotex, its aBLA defines processes that do not infringe the ’138 patent, and its batch records show only non-infringing concentrations. The court relied on this evidence plus expert testimony to conclude that “the products Apotex will likely market are manufactured by a non-infringing process.” (Ord. 9/6/16 at 15).

(3)(B) Statements

Amgen next argues that the BPCIA(3)(B) statements are important exchanges on which a reference product sponsor relies in deciding which patents to include in an infringement action; and, if biosimilar applicants are free to retract (3)(B) statements without consequence, the patent dance will become “meaningless.” (Dkt. 36 at 20). Under section 262(l)(3)(B) of the BPCIA, biosimilar applicants like Apotex “shall provide” detailed statements explaining on a claim-by-claim basis why the listed patents are invalid, unenforceable, or will not be infringed by the proposed biosimilar. Apotex’s (3)(B) statement said its refold mixture contained a certain concentration of the protein of interest, filgrastim, which would fall within the claim scope under the Court’s claim construction. (At the time, Apotex had proposed a different claim construction, under which there would have been no infringement for this range.) Amgen contends that Apotex then took “evolving positions,” first abandoning its (3)(B) statement during discovery and then switching again in its rebuttal at trial to escape the Court’s construction. Amgen states that the district court ignored Apotex’s initial (3)(B) statement that this claim limitation was met, which “flouts the very purpose” of an orderly disclosure of information under the BPCIA. (CAFC 17-1010, Dkt. 36 at 20). 

In response, Apotex asserts that its (3)(B) statements were pre-litigation letters to Amgen, sent without the benefit of any disclosure from Amgen concerning its bases for infringement, its proposed claim constructions, or discovery. (Dkt. 32 at 36). Moreover, Apotex takes the position that its (3)(B) statements were simply “factually incorrect.” (Dkt. 32 at 20). And, according to Apotex, Amgen’s arguments “ring hollow” because if optional pre-litigation letters become binding, this will deter a biosimilar applicant from engaging in the BPCIA steps altogether. (Dkt. 32 at 36).

To support its case, Apotex compares the BPCIA (3)(B) statements with an ANDA filer’s paragraph IV statements under the HatchWaxman Act at 21 § U.S.C. 355(j)(2)(B). The Federal Circuit has held that while ANDA filers are statutorily required to provide this notice to patent owners, they may modify or add claims or defenses during litigation. Takeda Chem. Indus., Ltd. v. Mylan Labs, Inc., 549 F.3d 1381 (Fed. Cir. 2008). To this point, Amgen replies that changing legal theories is different from altering facts, and there is no clear explanation why Apotex’s (3)(B) statement reported a different protein concentration than that shown in its batch records.

As of the end of January, this appeal is fully briefed, and we will watch for developments as the court schedules oral arguments. One noteworthy development occurred just last week, when the Patent Trial and Appeal Board instituted trial for inter partes review (“IPR”) of the ‘138 patent” on grounds alleging obviousness over art cited by petitioner Apotex. The IPR represents another hurdle for Amgen in its quest to block or delay Apotex’s market entry.