Transcript Slide 1

Merck KGaA v. Integra LifeSciences
Mauricio A. Flores
Cathryn Campbell
www.mwe.com
Boston Brussels Chicago Düsseldorf London Los Angeles Miami Milan Munich New York Orange County Rome San Diego Silicon Valley Washington, D.C.
© 2005 McDermott Will & Emery. The following legal entities are collectively referred to as "McDermott Will & Emery," "McDermott" or "the Firm": McDermott Will & Emery LLP;
McDermott Will & Emery/Carnelutti Studio Legale Associato; McDermott Will & Emery Rechtsanwälte LLP; MWE Steuerberatungsgesellschaft mbH; McDermott Will & Emery UK
LLP and McDermott Will & Emery/Stanbrook LLP. These entities coordinate their activities through service agreements.
The Plaintiffs
The
Burnham Institute: patent owner
Integra
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LifeSciences: exclusive licensee.
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The Plaintiffs’ Technology
Identification
of the amino acid sequence
RGD as the site where cells attach to the
extracellular matrix
Isolated
the cellular surface receptors that
bind to the RGD site
Identified
other RGD-binding cell surface
receptors, called “integrins”
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U.S. Patent No. 4,792,525
Entitled: TETRAPEPTIDE
8. A substantially pure peptide including as
the cell-attachment-promoting constituent
the amino acid sequence Arg-Gly-Asp-R
wherein R is Ser, Cys, Thr or other amino
acid, said peptide having cell-attachmentpromoting activity, and said peptide not
being a naturally occurring peptide.
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The Defendants
Merck
KGaA:
--Sponsored infringing research at Scripps and
infringed by importing RGD peptides
The
Scripps Research Institute:
--Performed infringing research
Scripps
Principal Investigator Dr. David Cheresh:
--Performed infringing research
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The Trial
28
trial days
Infringement
and validity vigorously
contested
Fact
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issues re FDA Exemption
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35 U.S.C. Section 271(e)(1)
NOT “an act of infringement to make use or
sell or import into the United States a
patented invention . . . solely for uses
reasonably related to the development and
submission of information under a Federal
law which regulates the manufacture, use
or sale of drugs.”
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Instruction to the jury
”To prevail on this defense, [Merck KGaA] must
prove by a preponderance of the evidence that it
would be objectively reasonable for a party in
[Merck’s] and Scripps’ situation to believe that
there was a decent prospect that the accused
activities would contribute, relatively directly, to
the generation of the kinds of information that are
likely to be relevant in the processes by which the
FDA would decide to approve the product in
question.”
Proposed by Integra
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Merck’s Evidence
Scientist
after scientist testified infringing
experiments were:
–relevant to safety and efficacy
–of various closely related RGD compounds
–intended for inclusion in an Investigational New
Drug application to the FDA
–an essential part of Merck’s drug development
program.
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Merck had every advantage
Scripps’
No
reputation in community
product sales
Sued
for trying to cure cancer
Broad
standard for FDA Exemption as
articulated in jury instruction
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Result in the Trial Court
Scripps,
Cheresh and Merck found to willfully
infringe
Claims
against Scripps and Dr. Cheresh
dismissed because no damages sought against
them
Claims
based on infringing acts prior to 1995
dismissed by based on common law exception
$15
million verdict against Merck (later reduced
to $6.375 million)
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Questions Worth Asking
How
could Merck have lost before the jury?
Why
didn’t the trial court enter judgment as
a matter of law in Merck’s favor based on
the testimony of Merck and Scripps
scientists?
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Answers worth pondering
Credibility:
contradictions in sworn testimony
Credibility:
admissions re infringing tests
Credibility:
admissions that Merck was doing
the real FDA work in Germany
of Verdict: “Has Defendant Merck KGaA
met its burden of proving by a preponderance of
the evidence that all of the accused activities are
covered by the FDA Exemption?”
Form
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Merck Appeals to the Federal Circuit
FDA Exemption
Claim construction
Damages
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Merck Argues “Rational Predicate”
Everything
in the causal chain of research
toward FDA approval is exempt
Integra
responds:
–not consistent with agreed-upon jury
instruction
–In effect a general research exemption
–Would eviscerate value of research tools
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Integra Argues Rule 50, FRCP
Deference
to jury assessment of
–Weight of evidence
–Credibility
Merck
responds:
–Issue of law not fact
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The Federal Circuit Opinion
Ruled
that FDA exemption “does not
globally embrace all experimental activity
that at some point, however, attenuated,
may lead to an FDA approval process”
Went
on to rely on a narrow interpretation
that is inconsistent with the instruction
proposed by Integra and given to the jury
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The Federal Circuit’s Narrow
Interpretation of the FDA Exemption
Should
not be interpreted to “encompass drug
development activities far beyond those
necessary to acquire information” necessary for
FDA review of an application to market a generic
drug
The FDA has no interest in the hunt for new
drugs and does not require information about
compounds other than the one featured in an IND
application
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Judge Newman dissented:
Research
should be exempt under either
the Common Law Exception or the FDA
Exemption.
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Merck Petitions Supreme Court for Cert
“Cancer. Rheumatoid arthritis. AIDS. Heart disease.
Alzheimer’s. Multiple sclerosis. The list could go on
for volumes. Deadly diseases, painful disorders,
heart wrenching conditions that afflict millions of
people. All of them find themselves hoping against
hope that someone, somewhere will discover a drug
that could cure them or relieve their suffering—and
get it to them soon. This case is about how quickly
many of those prayers will be answered. The stakes
are measurable in millions of lives.”
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Merck Before the Supreme Court
Abandoned
its rational predicate theory
Focused
its attack on the Federal Circuit’s
apparent narrowing of the exemption
Asked
the Court to review the evidence
and enter judgment in Merck’s favor
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The Solicitor General Before the
Supreme Court
Agreed
with the Federal Circuit’s rejection of
“rational predicate”
Disagreed
with the Federal Circuit’s narrow
interpretation of the FDA Exemption
Argued
that Merck was entitled to judgment as a
matter of law because the exemption applies
once drug research “progresses beyond basic
research and begins efforts to develop a
“particular drug”
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Integra Before the Supreme Court
The
Federal Circuit did not narrow the
scope of the FDA Exemption, but held that
the standard articulated in the jury was
correct
The
evidence, when reviewed under the
rules requiring deference to the jury, was
sufficient to sustain the judgment for
Integra
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Amicus: Wyeth and US Merck
Drug
development is like a funnel
Blocking
at any point stops the flow of new
drugs
Virtually
every experiment in drug
development after a focus on a specific
compound is reasonably related to the
FDA process
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Amicus: PhRMA
The
Federal Circuit’s interpretation of FDA
Exemption represents a “direct and
substantial” threat to drug development
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Amicus: BIO
FDA exemption not limited to generic
drugs or required regulatory testing

“Reasonably
related” inquiry must be fact-
specific
And
flexible
–E.g. exemption should be applied even where
infringer does “more” than what FDA requires.
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Amicus: Genentech and Biogen Idec
Biologics
require even more preclinical
testing than new drugs
Important
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to exempt such tests
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Amicus: Applera
Supported
Integra
“Solely
for uses” means that the sole
purpose should be to develop information
for the FDA
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Amicus: Invitrogen
Supported
Integra
Requested
ruling that the FDA Exemption
does not extend to patented research tools
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The Question Presented in Integra
“[W]hether uses of patented inventions in
preclinical research, the results of which
are not ultimately included in as submission
to the Food and Drug Administration (FDA),
are exempted from infringement by 35
U.S.C. Section 271(e)(1).”
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What The Supreme Court Did NOT
Decide
Whether
activities that infringe biomedical
research tool patents may be exempted
Whether
the evidence in the record in this
case is sufficient to sustain the verdict in
Integra’s favor in light of the rules that
require deference the jury’s assessment of
the weight of the evidence and the
credibility of the witnesses
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The Supreme Court’s Decision
 The
FDA exemption extends to any activity that is
reasonably related to the processes by which the FDA
makes its decision, including:
–Preclinical experiments.
–Experiments not ultimately submitted to the FDA.
–Experiments on compounds not submitted to the FDA.
–Experiments that do not comply with Good Laboratory
Practices.
 The FDA is concerned with efficacy as well as safety at
the preclinical stage.
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The Supreme Court’s Decision
The
instruction proposed by Integra and
given to the jury is not inconsistent with its
decision.
Remanded to the Federal Circuit for review
the sufficiency of the evidence
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Reasonably Related is a flexible
concept
“Properly Construed, Section 272(e)(1) leaves adequate
space for experimentation and failure on the road to
regulatory approval: At least where a drug maker has a
reasonable basis for believing that a patented compound
may work, through a particular process, to produce a
particular physiological effect, and uses the compound in
research that, if successful, would be appropriate to
include in a submission to the FDA, that use is
‘reasonably related’ to the development and submission
of information under . . . Federal law.”
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The Bottom Line
means Reasonable – no categorical
exclusions or bright line rules
Reasonable
The
standard is broad enough so that any
company whose witnesses provide a
straightforward, credible account of how their
activities relate to the FDA process is likely to get
the benefit of the exemption
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The Bottom Line
But the exemption is not a talisman; the
party claiming the benefit of the exemption
will be required to produce a careful
explanation from credible witnesses.
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A Carve-Out for Research Tools?
The Solicitor General stated:
–“The context of Section 271(e)(1) suggests that
Congress may not have intended to include research
tools within the scope of affected inventions.”
–“Including research tools that are used only in
experimentation within the scope of Section 271(e)(1)
could adversely impact the only exclusive right that
exists with respect to such tools – the right to use them
in research.”
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Defining the Carve-Out
An exception to the definition of a “patented
invention” ?
Based on the use of a patented invention?
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Consider Protective Provisions




Reps and warranties
Obligation for sponsor to monitor
patents and seek licenses
Indemnification
Sponsor to lead the defense, but
institution to receive separate
representation
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Thank you
Mauricio A. Flores
[email protected]
Cathryn Campbell
[email protected]
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