Big Molecule Watch
May 29, 2015

Legal Issues and Early Litigation Concerning the BPCIA: Amgen v. Sandoz

As discussed in our introductory post, the BPCIA lays out a series of steps to resolve patent disputes involving biosimilars. According to these steps, once a biosimilar applicant receives notice from FDA that its application has been accepted for review, the applicant provides the reference product sponsor with a copy of its biosimilar application and manufacturing information for its proposed biosimilar. The two parties then identify patents that might be the subject of litigation, exchange contentions about patents, and eventually litigate those patent disputes either in immediate litigation or upon notice that the biosimilar applicant intends to engage in commercial marketing of its product in 180 days (at the earliest).

The question that has drawn much of the early litigation concerning the BPCIA is: are the steps laid out in these patent dispute resolution provisions mandatory, such that a party can be compelled by court order to comply with the provisions?  If yes, then patent litigation involving biosimilars would proceed along an established schedule whereby the parties would define the scope of patents subject to litigation, and any such patent litigation would begin no more than 250 days after FDA accepts the biosimilar application for review. If no, then there is no scheduled timeline for the initiation of patent litigation, and no provisions for the exchange of patent information prior to the start of such litigation.

Amgen v. Sandoz is the first case to reach a judicial determination of this important question, and to interpret other aspects of the patent dispute resolution provisions.

Factual and Procedural Background in Amgen v. Sandoz

Sandoz’s biosimilar application was the first to be accepted for FDA review under the BPCIA abbreviated pathway, on July 7, 2014. Sandoz’s application referenced Amgen’s biological product Neupogen® (filgrastim), which is used to treat side effects of certain forms of cancer therapy. After its application was accepted by FDA, Sandoz wrote a letter to Amgen stating that it did not intend to engage in the patent dance steps, and offering to instead provide its biosimilar application to Amgen under certain specified confidentiality provisions.  Sandoz also told Amgen that it expected FDA approval as early as March 8, 2015, and that it intended to launch its biosimilar product immediately upon FDA approval.

Amgen then filed a complaint in the District Court for the Northern District of California (on October 24, 2014), asking the court to order Sandoz to follow the patent dance steps.  Amgen alleged that Sandoz had violated the BPCIA by not providing its application and manufacturing information within 20 days of FDA acceptance as “required” under the first step of the patent dance, and argued that Sandoz should not be allowed to use the abbreviated pathway to FDA approval without also following the patent dance steps.

Amgen also argued that Sandoz was trying to avoid the BPCIA requirement that a biosimilar applicant “provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing” of its biosimilar product.  According to Amgen, Sandoz was under the misimpression that its July 2014 letter constituted sufficient notice of commercial marketing, and Amgen asked the court to correct this alleged misimpression with a declaratory judgment saying that Sandoz cannot provide legal notice of commercial marketing as required by the BPCIA until after FDA has approved its biosimilar product.

The district court issued an order on March 19, 2015, ruling in favor of Sandoz and holding that the patent dance steps are not mandatory, and that biosimilar applicants do not have to wait for FDA approval before they can provide sufficient notice of commercial marketing.

Amgen immediately appealed that order.  The appeal is currently pending before the Federal Circuit.  Two of our Big Molecule Watch authors attended the oral argument in that appeal and have summarized the hearing in the post below.

Amgen also sought to force compliance with the patent dance by another route: five days after filing its complaint in the district court, Amgen submitted a Citizen Petition with FDA, requesting that FDA accept applications under the abbreviated pathway only if the applicants first certify that they will comply with the patent dance provisions.  FDA denied that petition six days after the district court issued its order in the case, noting that the questions raised in the petition “are the subject of litigation that may clarify how [the patent dispute resolution provisions] should be interpreted.”

While these issues were being litigated, Sandoz obtained approval for its biosimilar product, Zarxio, on March 6, 2015, making it the first to obtain FDA approval under the BPCIA’s abbreviated pathway.  Despite this approval, Sandoz has yet to launch its product because it agreed to delay marketing for a period of time while Amgen sought an injunction to prevent the Zarxio launch.  Although the district court denied Amgen’s motion for an injunction, the Federal Circuit granted an injunction, so Sandoz’s launch will be delayed at least until the Federal Circuit Court orders otherwise, or issues a decision in the case.

Digging Deeper: The Legal Arguments in Amgen v. Sandoz

There are two main questions at issue in Amgen v. Sandoz:

  1. Are the BPCIA patent dispute resolution provisions mandatory?
  2. Can a biosimilar applicant provide the required 180-day notice of commercial marketing of its biosimilar product prior to FDA approval of the product, or must it wait until after it has obtained FDA approval to provide notice?

On the first question, Amgen argues that part of the balance struck by the BPCIA was that in order to take advantage of the abbreviated regulatory pathway, biosimilar applicants must comply with the provisions of the patent dance.  Amgen argues that the mandatory nature of the patent dance provisions is evident from the mandatory-sounding language used in those provisions, which state that the biosimilar applicant “shall” provide information in accordance with the patent dance schedule, and which describe an applicant’s non-participation as a “fail[ure]” to provide “required” information.  Moreover, Amgen argues, the purpose of the statute was to provide certainty as to the scope of patent disputes and to promote early resolution of such disputes; this purpose would be defeated if courts interpret the patent dance provisions to be permissive rather than mandatory.

In response, Sandoz has countered that the BPCIA gives biosimilar applicants an option: either exchange information in accordance with the patent dance provisions, or face an immediate action for a declaration of patent infringement.  According to Sandoz, the only question at issue is what consequences a biosimilar applicant faces if it chooses not to engage in the patent dance, and to that question the BPCIA (42 U.S.C. § 262(l)(9)(C)) provides the clear answer: if a biosimilar applicant fails to follow the patent dance, then the reference product sponsor—but not the applicant—can bring an immediate infringement action against the applicant.  Sandoz argues that Amgen’s reliance on the language of the statute is misplaced, since such language, when accompanied by an alternative or a specified consequence, does not mean “mandatory,” and does not entitle Amgen to compel compliance with the patent dance.

The district court agreed with Sandoz, holding that the patent dance provisions provide only a “carrot of a safe harbor for applicants,” (by restricting when a reference product sponsor can initiate patent litigation) but “contain[] no stick to force compliance” if the applicant chooses to forgo that safe harbor and invite immediate litigation.

On the second question, Amgen argues that, as a matter of law, biosimilar applicants must wait until after they obtain FDA approval in order to provide notice of commercial marketing under the BPCIA.  According to Amgen, only this interpretation would properly serve the purpose of the provision, which is to provide reference product sponsors enough time to seek a court order to prevent the biosimilar’s launch until after patent disputes have been resolved.

Arguing again from the language of the statute, Amgen also reasons that the BPCIA notice provision requires the applicant to provide the reference product sponsor with notice of the first commercial marketing “of the biological product licensed under subsection (k) (i.e. under the abbreviated pathway).”  Since the statute elsewhere refers to the applicant’s biosimilar product as  “the biological product that is the subject of the subsection (k) application,” Amgen argues that the different phrasing in the notice provision indicates that notice can only be given for an already-approved product.  Amgen has also pointed to prior litigation in support of its text-based argument on the notice provision: in Sandoz v. Amgen, the court stated that “Sandoz cannot, as a matter of law, have provided a ‘notice of commercial marketing’ because…its [proposed biosimilar] product is not ‘licensed under subsection (k).’”

Sandoz argues in response that FDA approval is not required before notice is given, and that Amgen’s contrary interpretation would effectively give reference product sponsors an unwarranted 180 days of additional exclusivity—i.e. time during which biosimilar products cannot be marketed—beyond the 12 years of exclusivity already afforded to reference product sponsors under the BPCIA. (Under the BPCIA, biosimilar applicants cannot file applications referencing a new biologic product until 4 years after the reference product was approved, and FDA cannot approve a biosimilar application referencing the new biologic product until 12 years after the reference product was approved.)

Sandoz also offers a textual argument of its own, noting that the BPCIA authorizes a “subsection (k) applicant” to provide the required notice, which means the notifying party need only have requested FDA approval: once a party has actually received approval, it is no longer properly called an “applicant.”  This textual choice, Sandoz argues, indicates that FDA approval is not required before an “applicant” can provide notice of intended commercial marketing.  The statements from the prior Sandoz v. Amgen litigation, Sandoz notes, were in dicta only and did not constitute a judicial interpretation of the BPCIA.

The district court again sided with Sandoz, largely because it found Amgen’s interpretation “problematic” as it “would tack an unconditional extra six months of market exclusivity onto the twelve years reference product sponsors already enjoy under [the BPCIA].”