Transcript Safe Harbor or Not: Application of 271(e)(1) to Pioneering Drug

Safe Harbor or Not: Application
of 271(e)(1) to Pioneering Drug
Discovery Activities
Susan Steele
October 21, 2003
Typical Timeline in Life of Drug
Pre-1984
Drug discovery
at Pioneering Drug
Company
File
patent
Selection of
Clinical
Candidate
Patent
Granted
File
IND
File
NDA
NDA
approved
Generic Co.
starts clinical
trials
Patent
Expires
2nd
NDA
Roche v. Bolar
• Before patent expired, Bolar ordered 5 KG of drug. Began
formulation and metabolism studies required for NDA.
• Fed. Cir. held that Bolar infringed patent under the 271(a)
“use” prohibition.
– Fed. Cir. declined to create a new judicial exception to the “use”
prohibition for generic drug companies.
– “We will not rewrite the patent laws here.”
Drug Price Competition and Patent
Term Restoration Act of 1984
• 35 U.S.C. 156
– Allows for patent term extension of certain products
subject to lengthy FDA approval.
• 35 U.S.C. 271(e)(1) Safe Harbor
– Allows generic drug manufacturers to conduct
research and development activities to generate data
for ANDA before patent expires.
Typical Timeline in Life of Drug
Post 1984
Drug discovery
at Pioneering Drug
Company
File
patent
Selection of
Clinical
Candidate
Patent
Granted
File
IND
File
NDA
NDA
approved
Generic Co.
starts clinical
trials
Patent
Expires
File
ANDA
35 U.S.C. 271(e)(1)
It shall not be an act of infringement to make,
use, offer to sell or sell within the US
a patented invention
solely for purposes reasonably related
to the development and submission
of information under a Federal law
which regulates the manufacture,
use, or sale of drugs…
A Patented Invention
1. Patented invention is limited to drugs.
2. Patented invention is limited to products
eligible for a term extension.
3. Patented invention is limited to products
regulated by the FDA.
4. Patented invention refers to all patented
inventions.
Eli Lilly v. Medtronic (1990)
• Patented invention was defibrillator eligible for
term extension under 156.
• Supreme Court considered 156 and 271(e)(1)
together to interpret scope of safe harbor.
• Opinion acknowledged there may be rare
situations in which safe harbor would apply but
not term extension.
Bristol-Myers Squibb v.
Rhone-Poulenc Rorer
• RPR holds patent on key chemical
intermediates in synthesis of taxol from
natural product.
• BMS used patented chemical intermediates
in research efforts to discover second
generation taxol drug (eventual subject of
IND).
BMS v. RPR
Analysis of Patented Invention
• Fed. Cir. previously held that medical
devices reviewed by FDA (but not subject
to term extension) were patented inventions.
• District Court quickly concluded that
“patented invention” means all patented
inventions or discoveries.
35 U.S.C. 271(e)(1)
It shall not be an act of infringement to make,
use, offer to sell or sell within the US
a patented invention
solely for purposes reasonably related
to the development and submission
of information under a Federal law
which regulates the manufacture,
use, or sale of drugs…
Reasonably Related
1.
2.
3.
4.
Only activities that directly generate data submitted on
an ANDA are immunized.
Activities that are reasonably expected to generate data
submitted on an ANDA are immunized.
Activities that are reasonably expected to generate data
submitted on an IND, NDA, ANDA.
Activities that identify drugs which are the subject of an
FDA regulatory submission are immunized.
Intermedics v. Ventritex
• Would it have been reasonable, objectively,
for a party…to believe that there was decent
prospect that the “use” in question would
contribute (relatively directly) to the
generation of kinds information that was
likely to be relevant in the process by which
the FDA would decide whether to approve
the product?
BMS v. RPR
• RPR argued that 271(e)(1) should not apply
until drug candidate has been identified in
FDA filing.
• Bristol countered that 271(e)(1) should
apply “from first synthesis of an analog,” or
otherwise “frustrate Congress’ intent” of
promoting approval of drugs.
• District Court agreed with Bristol.
Integra v. Merck
• Integra owned patents on RGD peptides.
– Research tool patents and composition of matter
• Merck developed and filed IND on cyclic RGD.
• Licensing negotiations filed; Integra sued.
• Integra did not allege infringement for period after
clinical candidate was identified.
Integra v. Merck: Majority
• Consistent with Congress’ intent, “safe harbor
covers those pre-expiration activities ‘reasonably
related’ to acquiring FDA approval of a drug
already on the market.”
• Majority believes Merck’s interpretation would
wipe out the economic value of research tool
patents. Characterizes RGD patents as research
tool patents.
Integra v. Merck: Majority
• FDA does not require data in IND on
analogs tested and rejected in discovery
process.
• “Downstream clinical testing for FDA falls
within safe harbor.”
Integra v. Merck: Dissent
• Characterizes RGD patents new
compositions.
• Second comers can study patents under
research exemption (in order to discover
improvements).
• 271(e)(1) exception takes over where
research exemption ends.