Biosimilars and Biologics BPCIA The Patent Dance Commercial Marketing Amgen v. Sandoz

1. June 21, 20181
Biosimilars: A U.S. Perspective
Jay Erstling
January 12, 2017
Biosimilars and Biologics
BPCIA
The Patent Dance
Commercial Marketing
Amgen v. Sandoz

2. SM
© 2017 Patterson Thuente Pedersen, P.A., some rights reserved - www.ptslaw.com
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Biosimilars: A U.S. Perspective
Jay Erstling
Global IP Convention 2017
12 January 2017
New Delhi, India
TM

3. Definitions: Biosimilars and Biologics
Biosimilar: A biological product approved by the US Food and Drug
Administration (FDA) that it is highly similar to an original FDA-approved
biological product.
The biological product is referred to as the “reference product” and the
producer as the “reference product sponsor”
To get FDA approval as a biosimilar, there can be no clinically meaningful
differences in safety or effectiveness from the reference product.
• Only minor differences in clinically active components are permitted
Biologic: A product manufactured in a living system such as a
microorganism, or plant or animal cells.
Most biologics are very large, complex molecules or mixtures of
molecules.
• Many are produced using recombinant DNA technology.
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4. Differences between Biologics and Drugs
A small-molecule drug is typically manufactured through chemical synthesis,
by combining specific ingredients in an ordered way
Has a well-defined structure, and its components can generally be
determined through chemical analysis
A biologic is manufactured in living cells, then extracted and purified
Generally more structurally complex, bigger, heavier and less stable
• Often cannot be fully characterized in the laboratory
• No way to guarantee that each dose of the drug will be identical
• Require more testing before approval
A generic drug is the chemical equivalent of its parent
A biosimilar will likely have slight variations in its structure from its parent
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5. Therefore the need for special legislation
Biologics Price Competition and Innovation Act (BPCI Act)
BPCI Act was adopted as Title VII of the Patient Protection and Affordable
Care Act (Affordable Care Act) signed into law by President Obama on 23
March 2010
• One of the more significant but least noticed parts of “Obamacare”
• Codified at 42 U.S.C. § 262.
– Under the Public Health Service Act
Creates an abbreviated approval “pathway” for biological products that are
demonstrated to be “highly similar” or “interchangeable” with an FDA-
approved reference biological product
Goal is to allow reliance on what is already known about the reference
product, avoid unnecessary duplication of testing, and decrease the cost
of biological products
• Analogous to the U.S. Hatch-Waxman Act and the pathway it
creates for generic drugs
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6. Brief Overview of BPCIA
Requires that a biosimilar be “highly similar” to an already-approved
innovative biologic product
There should be “no clinically meaningful differences” between the
biologic and the reference product “in terms of safety, purity, and potency
of the product”
Also gives the FDA authority to deem a biosimilar to be “interchangeable”
Interchangeability requires a significantly higher standard to confirm that
an interchangeable biosimilar will achieve the same clinical result as the
reference product in any given patient
Provides regulatory exclusivity for the reference product
An application for approval of a biosimilar application cannot be made
effective until 12 years after the date on which the reference product was
first licensed
And an application may not be submitted until 4 years after the date of
licensure of the reference product
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7. The Patent Dance
Act establishes rules for resolving patent disputes between producers of the
biosimilar and the reference product (§ 262(l))
Within 20 days of FDA’s acceptance of the biosimilar application, the
applicant must provide a copy of the application (and optionally other
information about the manufacturing process) to the reference product
sponsor.
• So that the sponsor can determine whether the biosimilar would
infringe any patents owned or exclusively licensed by the sponsor
Within 60 days, the reference product sponsor must identify patents that it
owns or exclusively licenses that it believes would be infringed if the
biosimilar were made, used, sold in the US without a license from the
reference product sponsor
• Reference product sponsor must also identify patents that it is
willing to license
• No remedy for patents that are not identified
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8. The Patent Dance (2)
Within the next 60 days, the biosimilar applicant must provide a statement
either that it is not going to market the product before the patents have
expired or that it considers the patents invalid, unenforceable, or not
infringed by the biosimilar.
• May optionally also provide the reference product sponsor with a list
of patents that it believes the reference product sponsor could
assert
– Stating why they are invalid, unenforceable or not infringed, or
that it will not market its biosimilar until the product has expired
60 days later, the reference product sponsor must provide a detailed
statement why it believes the patents are valid and infringed
The parties then have to negotiate to identify the patents to be litigated
• If the negotiations are successful, the reference product sponsor
must initiate litigation within 30 days
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9. Patent Dace (3)
If not successful within 15 days, the biosimilar applicant must identify the
number of reference product sponsor’s patents it wants to litigate
• The reference product sponsor must identify the patents it believes
should be litigated
• Parties exchange lists
– The number of patents identified by the reference product
sponsor may not exceed the number of patents provided by the
biosimilar applicant
» But if the applicant indicates none, the reference product
sponsor may identify one
The reference product sponsor must then bring patent infringement
litigation within 30 days
• Helps to ensure that alleged infringement of the most relevant
patents is litigated early in the application process
• If the reference product sponsor fails to bring timely suit, the only
relief available is reasonable royalties
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10. Notice of Commercial Marketing
The Act (§ 262(l)(8)(A)) requires the biosimilar applicant to provide the
reference product sponsor with notice at least 180 days before the first
commercial marketing of the biosimilar
Triggers a second phase of litigation
• Reference product sponsor can sue on any patent claims not yet
asserted
The reference product sponsor is permitted to seek a preliminary injunction
(§ 262(l)(8)(B)) to block the biosimilar applicant from commercial
manufacture until the court has decided the patent litigation with respect to
any patents that either party had identified
“And therein lies the rub”
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11. Amgen v. Sandoz, 794 F.3d 1357 (Fed. Cir. 2015)
On Petition for Writ of Certiorari to the U.S. Supreme Court as Sandoz, Inc.
v. Amgen, Inc. and Amgen, Inc. v. Sandoz, Inc.
Will be a case of first impression if the Supreme Court agrees to hear it
The dispute
In May 2014, Sandoz filed an application for approval of its biosimilar
version of Amgen’s biologic, Neupogen®
The FDA notified Sandoz on 7 July 2014 that it had accepted the
application for review
On 8 July 2014, Sandoz notified Amgen that it intended to market its
biosimilar, Zarxio®, as soon as the FDA approved its application
• Sandoz did not provide Amgen a copy of its application, and Amgen
sued
– Amgen argued that the patent dance was mandatory and that
notice could not be given until the product was approved
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12. Amgen v. Sandoz (2)
On 6 March 2015, the FDA announced approval of Sandoz’s biosimilar
application (the first FDA licensed biosimilar under the BPCIA)
Sandoz notified Amgen that it was going to market Zarxio® immediately
• Amgen alleged that the notice of commercial marketing only
became effective after approval of the application on 6th March and
the 180-day waiting period could only start then.
Decision of the Court of Appeals for the Federal Circuit
A divided panel ruled that the information exchange and patent dance
procedures of the Act were optional and that a biosimilar applicant could
choose not to follow them
• In such case, the Act authorizes the reference product sponsor to
bring an action for infringement if the biosimilar applicant fails to
provide its application and manufacturing information
– Therefore, Sandoz’s decision to opt out was not a violation of the
Act
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13. Amgen v. Sandoz (3)
The court also ruled that a biosimilar applicant may only give effective notice
of commercial marketing after the FDA has licensed its product
As a result, Sandoz’s 8th July notice of commercial marketing was not
effective, and the 180 day period could not begin until 6th March
Notice provision is a mandatory stand-alone requirement, regardless of
whether the applicant has disclosed the application to the sponsor
• 180 day period is enforceable by injunction if the applicant does not
comply
Both parties requested a hearing en banc, but the Federal Circuit declined
the request
Both parties sought review by the U.S. Supreme Court
Would be the first Supreme Court case interpreting the BPCIA
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14. Petition for Writ of Certiorari
Sandoz filed a petition and Amgen a cross-petition asking the U.S. Supreme
Court to review the Federal Circuit’s decision
Sandoz filed its petition in February 2016, asking the Supreme Court to
review:
• “Whether notice of commercial marketing given before FDA
approval can be effective and whether, in any event, treating
[notice] as a stand-alone requirement and creating an injunctive
remedy that delays all biosimilars by 180 days after approval is
improper”
Amgen filed its cross-petition in March 2016, asking the Court to review:
• “Is an Applicant required… to provide the Sponsor with a copy of its
biologics license application and related manufacturing
information…, and where an Applicant fails to provide that required
information, is the Sponsor’s sole recourse to commence a
declaratory-judgment action… and/or a patent infringement action”
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15. U.S. Solicitor General’s Brief
The Supreme Court invited the Acting Solicitor General to submit an amicus
brief expressing the views of the U.S.
Solicitor General recommended that the Court grant certiorari and review
the questions presented in both the petition and cross-petition
• Urged review because proper interpretation will have “a significant
impact on the operation of the BPCIA and ability of… applicants
promptly to bring their biosimilars to the public”
Solicitor General’s brief sides fully with Sandoz, and argues that:
• Giving notice of commercial marketing before FDA approval is
consistent with the Act and should be permitted
• Injunctive relief should not be available for failure to furnish notice of
commercial marketing because nothing in the Act creates a cause
of action to enforce the notice provision
• Providing information under the Act is optional and if the applicant
fails to do so, the sponsor’s remedy is to bring an action for patent
infringement
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16. Likely Outcome
Why grant Certiorari?
According to Solicitor General’s brief:
• “Biologic medicines are among the most important pharmaceuticals
available today and are also among the most expensive, with costs
often exceeding tens of thousands of dollars per year. In 2013
biologics accounted for approximately $80 billion in spending in the
United States, constituting approximately 25% of all pharmaceutical
expenditures…. The BPCIA represents a carefully calibrated
legislative effort to promote innovation and competition in this
important field, and the questions presented address core questions
governing how the BPCIA operates.”
There is strong indication that the Court will grant certiorari
• Court typically follows the Solicitor General’s recommendation to
grant or deny
• If granted (decision expected on or after 6 June), the case will likely
be argued in April 2017 and decided by the end of June
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17. Thank You
Jay Erstling | +612-349-5771 | erstling@ptslaw.com
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