United States:
Biosimilars Can Sit Out Patent Dance, But May Have To Wait Out Second Exclusivity Period
23 July 2015
Foley & Lardner
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In Amgen v.
Sandoz, Fed. Cir., No. 15-1499 (July 21, 2015), a divided
panel of the Federal Circuit issued its first decision interpreting
the Biologics Price Competition and Innovation Act (BPCIA), and did
so in a manner that favors biosimilar applicants in one respect
while favoring reference product sponsors (e.g., owners of
original biologic products) in another. On the issue of whether
biosimilar applicants are required to share their applications with
reference product sponsors, the court ruled in favor of Sandoz,
finding that they do not have to share their applications or engage
in the patent dispute resolution procedures of the BPCIA. On the
issue of whether and when biosimilar applicants are required to
give pre-marketing notice to reference product sponsors, the court
ruled in favor of Amgen, finding that the 180 days'
pre-marketing notice is a "standalone requirement" that
cannot be given until the biosimilar product is approved. With two
dissenting opinions presenting alternative interpretations of the
BPCIA, the decision may raise at least as many questions as it
answers, including whether the full Federal Circuit may grant
rehearing en banc. Stakeholders in this area also should
keep in mind the potential availability of inter partes
review and post-grant review proceedings to address patent validity
issues wholly outside of the BPCIA.
The Biosimilar Framework
Since 1991, Amgen has marketed filgrastim, a recombinantly
produced, human granulocyte colony-stimulating factor protein
(C-CSF) under the brand name Neupogen®. Neupogen® is used
in patients at risk of infection such as those receiving
chemotherapy. In May of 2014, Sandoz sought FDA approval of a
biosimilar of Neupogen® (filgrasim-sndz or Zarxio") under
the BPCIA, by filing an abbreviated pathway application created by
the BPCIA (an "aBLA" or "subsection (k)
application").
Similar to the Hatch-Waxman Act that governs traditional generic
drugs, the BPCIA allows a biosimilar applicant to rely on the
FDA's previous approval of the reference product
(e.g., the original biologic product), such that the
biosimilar applicant does not need to provide clinical data
demonstrating the safety and efficacy of its product, as long as it
submits information demonstrating that its product is
"biosimilar" or, alternately,
"interchangeable," with the reference product. As noted
by the Federal Circuit, the BPCIA seeks to balance the
innovator's investment in developing the reference product with
the price competition a generic will bring to the market by
providing that the biosimilar application cannot be filed until the
reference product has been approved for at least four years, and
that a biosimilar application cannot be approved until the
reference product has been approved for at least 12 years. However,
since Amgen's Neupogen® product had been approved for more
than 12 years before the BPCIA was enacted, these time periods were
not relevant in this case.
The Biosimilar Patent Dance
Like the Hatch-Waxman Act, the BPCIA includes patent dispute
resolution procedures, but the similarity ends there. The BPCIA
lays out a "unique and elaborate" process that commences
when the biosimilar applicant shares its biosimilar application
with the reference product sponsor, continues with exchanges of
patent lists, and validity/infringement contentions and
negotiations of the patents to be litigated, requires the reference
product sponsor to assert the negotiated patents to avoid
limitations on remedies, and culminates with a last-chance
opportunity to assert additional patents after the biosimilar
applicant provides 180 days' pre-marketing notice.
The Neupogen®/Zarxio" Biosimilar Dispute
Sandoz notified Amgen of its biosimilar application, but did not
provide a copy to Amgen and did not follow any of the other patent
dispute resolution procedures of the statute. As to pre-marketing
notice, Sandoz first notified Amgen of its intent to commercially
market Zarxio" in July of 2014, before it was approved, and
gave notice again when it became the first approved biosimilar
product on March 6, 2015.
Amgen sued Sandoz in the United States District Court for the
Northern District of California alleging, among other things,
violation of California's unfair competition laws and
conversion based on Sandoz' alleged failure to comply with the
BPCIA. The district court sided with Sandoz, and found no violation
of the BPCIA to support Amgen's state law claims.
The Federal Circuit Decision
The Federal Circuit decision was authored by Judge Lourie. Judge
Chen joined the portion of the decision that found the application
sharing and patent dispute resolution procedures to be optional.
Judge Newman joined the portion of the decision that found that the
180 days' pre-marketing notice was required and could not be
given until after approval.
In her dissenting opinion, Judge Newman expressed her views that
the court's ruling on the application sharing provisions upset
the BPCIA's carefully crafted balance between the reference
product sponsor and biosimilar applicant:
The BPCIA reflects an explicit balance of obligations and
benefits. When a beneficiary of the statute withholds compliance
with provisions enacted to benefit others, the withholder violates
that balance. The consequences of the majority's ruling are
significant, for the structure of the BPCIA requires that the
subsection (k) applicant comply with the information exchange
provisions, as a threshold to resolution of the Sponsor's
patent rights.
In his dissenting opinion, Judge Chen expressed his views that
the court's ruling on the pre-marketing notice provisions
grants reference product sponsors a windfall of an additional
period of exclusivity beyond the 12 years expressly provided in the
statute:
The practical consequence of the majority's interpretation
is that (l)(8)(A) provides an inherent right to an automatic
180-day injunction. The majority provides no basis in the statutory
language to support this automatic injunction.
What's Next for Biosimilars?
Under this decision, biosimilar applicants can choose whether to
follow the patent dispute resolutions of the BPCIA or leave it to
the reference product sponsor to bring a declaratory judgment
action asserting patent infringement. Will biosimilar applicants be
willing to share their confidential applications in order to
resolve the patent issues early in the approval process, or will
they want to defer patent litigation costs until they know their
product has been approved? Or, will biosimilar applicants use
inter partes review and post-grant review proceedings, as
applicable, to invalidate potentially relevant patents? Will
reference product sponsors who learn of a biosimilar application
assert their patents early, or wait until they receive
pre-marketing notice? These questions will have to be answered on a
case-by-case basis, depending on the products and patents at issue,
and carefully weighing the potential risks and benefits.
The content of this article is intended to provide a general
guide to the subject matter. Specialist advice should be sought
about your specific circumstances.
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