Just over a week ago, the US Federal Circuit provided BPCIA “dance lessons” for reference product sponsors and biosimilar applicants, as it handed down its decision in Amgen v Hospira, the third of the Amgen “trilogy” of BPCIA cases.

The Fed. Cir. dismissed Amgen’s appeal from an interlocutory decision regarding discovery by Judge Andrews of the District Court (Delaware) for lack of jurisdiction, and denied Amgen’s petition for mandamus. In doing so, it addressed the remedies available under the BPCIA when the Sponsor believes a biosimilar applicant has not provided sufficient information under 42 U.S.C § 262 (l)(2)(A) for the Sponsor to (as Amgen claimed) “assess the reasonableness of asserting claims of infringement”.

As discussed below, the strategic implications of the Fed. Cir. decision are:

  • For sponsors: list it or lose it.

  • For biosimilar applicants: get your FTO right, and brace yourself for a long patent list.

Background

  • Hospira filed abbreviated BLA (a-BLA) 125545 for a biosimilar epoetin (Epogen®) in December 2014 under subsection (k) [42 U.S.C § 262 (k)], and provided (without more) a copy of its application to Amgen under paragraph (l)(2)(A).

  • In March 2015 Amgen alleged that Hospira did not fully comply with (l)(2)(A) because Hospira did not provide the specific composition of the cell culture media used.

  • The parties started the patent dance in any event. Amgen listed certain patents under (l)(3)(A), and the parties danced their way to the current BPCIA patent proceedings commenced in Delaware on 18 September 2015.

  • Importantly, Amgen did not include its cell culture medium patents in the (l)(3)(A) list and did not sue Hospira for infringement of any cell culture patents.

  • Interestingly, Hospira did not engage in negotiations under subsection (l)(4), but rather “accepted” the (l)(3)(A) list provided by Amgen.

  • Amgen sought further information about the cell culture media from Hospira, through requests for discovery and then through a motion to compel discovery in the context of the BPCIA proceedings (on different patents), which was denied by the District Court.

  • Amgen appealed this interlocutory decision to the Fed. Cir..

What to do when the information under (l)(2)(A) is insufficient to determine infringement

In denying Amgen’s appeal, the Court considered the potential remedies available to the Sponsor when the Sponsor believes the biosimilar applicant has not provided sufficient information under (l)(2)(A) for the Sponsor to (as Amgen claimed) “assess the reasonableness of asserting claims of infringement”. In short:

  1. Injunction compelling disclosure under (l)(2)(A): Not available

  2. Injunction compelling disclosure under state law: Availability TBC, issue reserved in both Sandoz & Hospira

  3. Patent infringement proceedings for failing to comply with (l)(2)(A): Not available, non-compliance is not a statutory act of infringement

  4. Patent infringement proceedings under 35 USC §271(e)(2)(C)(i) on patents included in originator list under (l)(3)(A)(i): Available

  5. (Where no disclosure is given by applicant under (l)(2)(A)) patent infringement proceedings under 35 USC §271(e)(2)(C)(ii) on any patent that could be identified in the first originator list): Available

Amgen did not include its cell culture patents in the first originator list, and did not commence patent infringement proceedings on those cell culture patents, and therefore declined to pursue the remedies available to it under options 4 and 5 above. Amgen may now have no remedy on those cell culture patents against Hospira under the BPCIA, or at all, depending on what “in this section” means in 35 U.S.C § 271(e)(6)(C).

In relation to commencing proceedings on a listed patent with incomplete information, the Fed. Cir. also confirmed there is no BPCIA sanction for “holding or asserting a mistaken belief [of infringement] in good faith”, and there is no Rule 11 issue where the Sponsor forms this view based on “an inquiry limited by an applicant’s withholding of information”.

Sponsors: list it or lose it

The Fed. Cir. decision confirms the clear motivation for reference product sponsors to include in their patent list each and every patent which is or might be relevant to the biosimilar product/process/use, or risk foregoing any patent remedy. The message to sponsors is this:

  • Include in your (l)(3)(A) list each and every patent you may possibly assert under the BPCIA, even if you need more information to determine infringement - you can get that later.

  • Beware: if you do not list a patent, you may lose your opportunity to sue under the BPCIA, or at all, depending on what “in this section” means in 35 U.S.C § 271(e)(6)(C). The Fed. Cir. said [my emphasis]:

“We note that the statute penalizes sponsors that decline to participate in the BPCIA’s information exchanges because under 35 U.S.C § 271(e)(6)(C) a sponsor that fails to list a patent that “should have been included in the list…. may not bring an action under this section for infringement of the patent with respect to the biological product.”

Biosimilar applicants: brace yourself for long patent lists

The decision provides the following reminders to biosimilar applicants:

  • Ensure you have conducted FTO for each and every part of your manufacturing process – don’t forget your cell culture media, bioreactors, and protein A chromatography conditions!

  • Brace yourself for long (l)(3)(A) patent lists.

  • Get yourself ready ahead of time.

    • You will only have 60 days to provide a detailed response to the (l)(3)(A) listed patents (if that is what you choose to do), so anticipate the patents to be listed and have your response ready ahead of time.

    • Or, do as Hospira did, and “accept” the (l)(3)(A) list provided by the Sponsor [rather than engaging in good faith negotiations under 42 U.S.C §262 (l)(4)], thereby “fast tracking” the patent dance. But proceed with caution, as the Courts have not yet weighed in on whether this is acceptable.

Broader Industry Context

The decision is also interesting because of the broader industry context in which it sits. Firstly, although Hospira is winning “rounds” in the Courts, it is struggling on the regulatory front. Despite being recommended for approval by the FDA Oncologic Drugs Advisory Committee on 25 May 2017, Hospira received a rejection from FDA on its proposed epoetin alfa biosimilar on 22 June 2017. Secondly, EPO is a very old product, and was one of the first biosimilar products to be launched around the world, excluding the US. The earliest priority date for the Amgen EPO patent suite was 1983. Thirty four years later, whilst the rest of the world has biosimilar EPO, Amgen is still asserting EPO related patents in the US.

It will likely be a little while yet before the US sees a biosimilar EPO.