Litigation Alert: No Exception to Statutory Requirement that a Biosimilar Applicant Provide Notice of Intent to Market its Product

Last week in Amgen Inc. v. Apotex Inc., No. 2016-1308 (Fed. Cir. July 5, 2016), a unanimous Federal Circuit panel ruled that under the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), a biosimilar applicant must provide its biologic competitor with at least 180 days’ notice of intent to commercially market a biosimilar product. The decision makes clear that this requirement applies even if the biosimilar applicant participates in the so-called “patent dance.” The panel also restated the Federal Circuit’s holding in Amgen Inc. v. Sandoz Inc., 794 F.3d 1347 (Fed. Cir. 2015), that a biosimilar applicant cannot provide the requisite notice until the biosimilar product at issue is approved, or “licensed,” by the FDA, but attempted to limit the consequence of that holding by suggesting that the FDA can license a biosimilar product before the expiration of the reference biologic’s twelve-year period of exclusivity. Ultimately, while the Amgen v. Apotex decision favors biologic manufacturers, its long-term import depends on the outcome of Sandoz’s pending petition for certiorari before the Supreme Court.

The BPCIA Framework

The BPCIA establishes an abbreviated pathway for regulatory approval of follow-on biologic drugs, known as “biosimilars,” and in so doing attempts to balance the interests of those engaging in original biologics discovery with the public’s desire for lower cost medical treatment. Whereas a biologics license application (“BLA”) requires extensive clinical data establishing the safety and efficacy of the original biologic product, an abbreviated biologics license application (“aBLA”) requires only that the follow-on applicant establish that its product is either “biosimilar” to or “interchangeable” with the previously licensed biologic “reference product.” Compare 42 U.S.C. § 262(a) with id. § 262(k). In return, the BPCIA establishes a twelve-year period of exclusivity for an original biologic drug, regardless of patent protection, and bars the submission of a biosimilar application for four years, with both periods running from first licensure of the reference product. Id. § 262(k)(7)(A)–(B).

The BPCIA also establishes a regime to narrow and resolve patent infringement disputes between biologic and biosimilar competitors. That process, often referred to as the “patent dance,” provides for the exchange of information between the biosimilar applicant and reference product sponsor. Id. § 262(l). First, within 20 days after an aBLA is accepted by the FDA for review, a biosimilar applicant is to provide to the reference product sponsor a copy of its aBLA as well as information describing its manufacturing process. Id. § 262(l)(2)(A). Then, within 60 days of receiving the aBLA, the reference product sponsor is to provide a list of patents that it could reasonably assert against the biosimilar applicant. Id. § 262(l)(3)(A). Within 60 days of receiving that list, the biosimilar applicant is to respond with its positions on infringement and validity of those patents as well as with a list of any other patents it believes could be asserted against it. Id. § 262(l)(3)(B). Next, the reference product sponsor has 60 days to respond with its own positions on infringement and validity of its patents. Id. § 262(l)(3)(C). Following negotiation to limit the patents at issue, the BPCIA then allows the reference product sponsor to bring an action for patent infringement. Id. § 262(l)(6). Finally, a biosimilar applicant “shall provide notice to the reference product sponsor not later than 180 days before the date of first commercial marketing of the biological product licensed under subsection (k).” Id. § 262(l)(8)(A). Such notice allows the reference product sponsor to seek a preliminary injunction prohibiting such activity pursuant to any patent listed by either party as part of the patent dance but excluded from the § 262(l)(6) infringement action. Id. § 262(l)(8)(B).

In Amgen v. Sandoz, its first decision addressing the BPCIA, the Federal Circuit held that a biosimilar applicant cannot provide its notice of commercial marketing prior to receiving FDA approval for its product. The Court thus found that Sandoz’s § 262(l)(8)(A) notice was ineffective because it was provided before its biosimilar product was licensed. Sandoz’s petition for certiorari, which requests review of this finding, is currently pending. In addition, the Court also held in Amgen v. Sandoz that a biosimilar applicant is not required to engage in the “patent dance,” and that Sandoz therefore did not violate the BPCIA in refusing to provide Amgen with its aBLA and manufacturing information. In the event that Sandoz’s petition for review of the notice of commercial marketing issue is granted, Amgen has requested that the Supreme Court also review this latter holding as well.

Factual Background of Amgen v. Apotex

In October 2014, Apotex filed an aBLA with the FDA listing Amgen’s Neulasta®as the reference product. Unlike Sandoz, however, Apotex initiated and fully engaged in the BPCIA’s “patent dance.” Apotex timely provided Amgen a copy of its aBLA and manufacturing information in compliance with § 262(l)(2)(A). After Amgen provided its § 262(l)(3)(A) patent list, Apotex responded with its positions concerning the infringement and validity of those patents. At the same time that Apotex provided that § 262(l)(3)(B) response, Apotex sent a letter to Amgen providing “notice” of future commercial marketing pursuant to § 262(l)(8)(A), even though it lacked an FDA license for its allegedly “biosimilar” product. Amgen subsequently provided its § 262(l)(3)(C) response to Apotex.

With the pre-suit portion of the patent dance complete, on August 6, 2015, Amgen sued Apotex for infringement of two of the patents that it had previously identified. In light of the Federal Circuit’s decision in Amgen v. Sandoz, Amgen challenged the effectiveness of Apotex’s alleged prior notice of future commercial marketing, seeking a preliminary injunction that would require Apotex to provide § 262(l)(8)(A) notice to Amgen only if and when it receives a license from the FDA and barring any commercial marketing for 180 days from that notice. In connection with that motion, the parties stipulated that Amgen would be irreparably harmed if Apotex enters the market without giving notice, that the balance of hardships favors Amgen, and that the public interest favors the issuance of an injunction. The merits of the preliminary injunction therefore turned exclusively on Amgen’s likelihood of success on the legal question presented: whether the § 262(l)(8)(A) notice requirement is a mandatory one enforceable by injunction, even if the biosimilar applicant otherwise engaged in the “patent dance.” The district court found that the BPCIA notice requirement is mandatory and issued Amgen’s requested injunction. Apotex appealed.

The Federal Circuit’s Decision

The Federal Circuit affirmed the district court’s grant of preliminary injunctive relief to Amgen, holding that the § 262(l)(8)(A) post-licensure notice requirement is mandatory and enforceable regardless of whether the biosimilar applicant engages in the patent dance. After observing that the statutory provision’s use of “shall” supports a categorical notice requirement, and that it had already so ruled in Amgen v. Sandoz, the Federal Circuit rejected Apotex’s argument that § 262(l)(8)(A) does not apply to biosimilar applicants, such as itself, who comply with the § 262(l)(2) provision seeking to channel any potential patent disputes with the reference product sponsor. The Court explained that the language of § 262(l)(8)(A) contains no words that make the applicability of its notice rule turn on whether the applicant took the earlier step of initiating the information exchange process by providing its aBLA and manufacturing information to the reference product sponsor in compliance with § 262(l)(2). The Court also elaborated on its understanding of the purpose of the § 262(l)(8)(A) notice requirement as “ensur[ing] that, starting from when the [biosimilar] applicant’s product, uses, and processes are fixed by the license, the necessary decision-making regarding further patent litigation is not conducted under time pressure that will impair its fairness and accuracy.” That purpose applies equally to biosimilar applicants who engage in the patent dance, explained the Court, because not all relevant patents are litigated as part of the initial § 262(l)(6) infringement action.

The Federal Circuit also defended its previous holding that § 262(l)(8)(A) notice of intent to commercially market a biosimilar product cannot be provided until the FDA licenses that product. In particular, the Court addressed the criticism that this ruling effectively extends the twelve-year biologic exclusivity period by 180 days, observing that it “ha[s] been pointed to no reason that the FDA may not issue a license before the 11.5-year mark and deem the license to take effect on the 12-year date.”

Finally, the Federal Circuit also held that a preliminary injunction that requires the biosimilar applicant to provide notice under § 262(l)(8)(A) is an appropriate remedy when the applicant fails to do so otherwise, and rejected Apotex’s argument that the only available remedy is a patent-merits declaratory judgment action under § 262(l)(9).

Industry Implications

The longevity of the Federal Circuit’s decision in Amgen v. Apotex is unclear in light of the pending certiorari petitions challenging the Amgen v. Sandoz decision. In particular, as mentioned above, Sandoz has specifically challenged the Federal Circuit’s finding that a biosimilar applicant cannot provide the required 180-day notice of commercial marketing prior to FDA approval of the biosimilar product, contending that this holding effectively extends the statutory exclusivity period of the reference product beyond what Congress intended. The decision as to whether to grant certiorari will not occur before the October Term, as the Supreme Court recently called for the views of the Solicitor General. But ultimately, should certiorari be granted and Sandoz prevail, the pre-licensure notice provided by Apotex would be rendered effective. Thus, if Apotex also files a petition for certiorari in the meantime, it seems likely that the Court would then vacate the Amgen v. Apotex decision and remand it for reconsideration in light of its opinion in the Amgen v. Sandoz case.

Perhaps with an eye toward the Supreme Court’s imminent certiorari ruling, the Federal Circuit responded to criticism of the Amgen v. Sandoz decision by suggesting that post-licensure notice will not extend the twelve-year exclusivity period because the FDA can license a biosimilar product any time after the aBLA is submitted. In so opining, the Federal Circuit appears to be relying on the BPCIA provision that “[a]pproval of an application” for a biosimilar product “may not be made effective… until the date that is 12 years after the date on which the reference product was first licensed.” 42 U.S.C. § 262(k)(7)(A). It is far from clear, however, whether that provision provides the FDA with the statutory authority to issue such tentative licenses, or whether the FDA must do so even if it does. Also unclear is whether the courts would interpret § 262(l)(8)(A) to allow a biosimilar applicant to give notice of commercial marketing once it receives a tentative license, or will instead require the license to be effective—and thus the exclusivity period to have ended—before notice can be given.