Section 271(e)(1) of the patent code, known as the "safe
harbor" provision, immunizes from infringement suits various
acts that are undertaken in order to submit information to the Food
and Drug Administration ("FDA"). The scope of these
various acts and thus of the safe harbor remains in flux. Last
year, in Classen,1the Federal Circuit held that
the safe-harbor clause does not shelter acts undertaken to gather
"information that may be routinely reported to the FDA, long
after marketing approval has been obtained." This August,
however, the Federal Circuit held that Section 271(e)(1)
does apply to post-approval "submissions that are
required to maintain FDA approval." Momenta
Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc. Judge
Moore, who had dissented in Classen, wrote the majority
opinion in Momenta. Chief Judge Rader, who was part of the
majority in Classen, wrote a fierce dissent in
Momenta, arguing that the majority opinion conflicts with
Classen and "will render worthless manufacturing test
method patents."2
Safe Harbor for FDA Submissions
Under the FDA safe-harbor clause:3
It shall not be an act of infringement to make, use, ... or sell
... 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 or
veterinary biological products.
Congress enacted this provision as part of the 1984 Hatch-Waxman
Act. According to the Supreme Court, in enacting Section 271(e)(1),
Congress was responding to case law4 holding that the
manufacture and use of a patented invention constituted an act of
infringement, "even if it was for the sole purpose of
conducting tests and developing information necessary to apply for
regulatory approval."5 The Federal Circuit expanded
on this theme in 2008, writing that "[t]he basic idea behind
this provision was to allow competitors to begin the regulatory
approval process while the patent was still in force, followed by
market entry immediately upon patent
expiration."6
Controversy arises over whether the safe harbor protects acts that
go beyond those required for seeking regulatory approval for
generic drugs. Appellate cases have therefore focused on whether
Section 271(e)(1) shelters otherwise-infringing activity performed
while testing a medical device to obtain premarket
approval,7 performing preclinical research on a drug for
which no new drug application was ever filed,8 selling
machinery used in the development of regulatory
submissions,9 testing after submission of a Biologics
License Application,10 analyzing the effect of the
scheduling of immunization,11and most recently in
Momenta, testing the purity of commercial batches.
Knowing the outer limits of the safe harbor is important to
manufacturers, since they have continuing regulatory obligations.
These obligations include filing submissions to the FDA regarding
changes or deviations from the approved manufacturing process,
labeling changes, adverse events, and investigations of adverse
events.12 Manufacturers sometimes must also perform and
report upon post-approval studies and clinical trials, or submit a
risk evaluation and mitigation strategy.13 A
manufacturer may also want to supplement an NDA to obtain approval
for additional indications. Furthermore, as became critical in
Momenta, manufacturers must continually test their
commercial batches to ensure that their products conform to
approved specifications.14
The Momenta
Decision
Both parties in Momenta are generic manufacturers of
enoxaparin (the generic of Lovenox®, which is marketed by
Sanofi-Aventis). Enoxaparin is a drug used to prevent and treat
deep vein thrombosis. Plaintiff Momenta received FDA approval to
market enoxaparin in July 2010 and thereafter obtained revenues of
$260 million per quarter from sales of that drug. Slip. Op. at 6.
Momenta also holds a patent that claims a method of testing the
purity of a sample of enoxaparin. Id. Defendant Amphastar
received FDA approval for its generic product on September 19,
2011. Momenta filed suit two days later, alleging that Amphastar
infringed Momenta's patent, and that Amphastar has chosen to
satisfy ongoing FDA testing regulations through an infringing
method. The district court enjoined Amphastar from launching its
product through a TRO issued on October 7, 2011 and a preliminary
injunction issued on October 28. The Federal Circuit stayed the
injunction on January 25, 2012, and vacated it in its recent
opinion.
Judge Moore wrote the majority opinion, joined by Judge Dyk. The
panel held that under the "plain language" of the
safe-harbor clause, that statute "is not restricted to
pre-approval activities." Slip. Op. at 19-20. "As long as
the use of the patented invention is done to generate information
that will be submitted pursuant to a relevant federal law, that use
falls within the safe harbor." Slip Op. at 22. The majority
held that Amphastar was not required to use a non-infringing
testing method, whether or not such a method was available. Slip.
Op. at 21. Classen was distinguished on the ground that
Amphastar's submissions "are not 'routine
submissions' to the FDA, but instead are submissions that are
required to maintain FDA approval." Slip Op. at 18.
The majority also took an expansive view of when a document
qualifies as a "submission" within the meaning of the
safe-harbor clause. Testing results are not, in most instances,
sent to the FDA. Rather, FDA regulations require manufacturers to
maintain batch records that are subject to FDA
inspection.15 The majority held that using an invention
to develop such records "satisfies the requirement that the
uses be reasonably related to the development and submission of
information to the FDA." Slip. Op. at 16. Furthermore,
"the safe harbor is not limited to acts which only produce
information for the FDA but protects all acts, even
interim research steps and acts that might produce other useful
data, as long as there is a reasonable basis for believing that the
act will produce the types of information that are relevant to a
submission to the FDA." Slip. Op. at 22 n.2.
The Momenta
Dissent
Chief Judge Rader responded with a lengthy and sharply worded
dissent. He relied heavily on the policy underlying Section
271(e)(1), as shown by its legislative history. (Chief Judge Rader
is no doubt very familiar with that legislative history, having
served as counsel to Senator Hatch while the Hatch-Waxman
Amendments were being debated.) In Chief Judge Rader's view,
"§ 271(e)(1) won approval because it was limited in time,
quantity, and type." Dissent Op. at 8. The safe-harbor clause
"only applies to pre-marketing
approval," "only applies to experimentation," and
does "not apply to commercial sales." Dissent Op. at 8,
9, 10. The dissent argued that the distinction between pre-approval
and post-approval uses was the core of the Classen
decision; the majority's decision, applying the safe-harbor
clause to post-approval conduct, "cannot be genuinely
reconciled with Classen ... [and] should instead request
the entire court to resolve the issue en banc."
Dissent Op. at 16.
The dissent notes that "Amphastar uses Momenta's patented
method in the manufacture of each commercial batch it sells."
Dissent Op. at 14. The dissent views such uses as being neither
preapproval, nor limited, nor experimental. Id. In Chief
Judge Rader's view, affording safe harbor to such uses
"repeals the incentives and protections of the patent act in
this area" and "does violence to patent law and future
research incentives in this field." Dissent Op. at 17.
Conclusion
The debates in the Classen and Momenta opinions
underscore a division regarding what policy underlies the
safe-harbor clause. Is the clause's protection limited to
efforts to gain marketing approval, or does the language of the
statute indicate a broader purpose? Momenta is unlikely to
be the last word on this issue. A petition for certiorari in the
Classen case is pending before the Supreme Court. The
Court has already expressed interest in the case, having invited
the Solicitor General to submit a brief. Although the safe-harbor
clause is applicable only to a specialized area of the law, the
Momenta decision can only increase the likelihood that the
Supreme Court will address the safe-harbor clause for a third
time.16
Drug manufacturers, and others who hold patents relevant to the
manufacture of drugs, should monitor developments closely.
Footnotes
1 Classen Immunotherapies, Inc. v. Biogen Idec, 659 F.3d 1057 (Fed. Cir. 2011).
2 Dissent Op. at 2, 16.
3 35 U.S.C. § 271(e)(1).
4 Roche Products Inc. v. Bolar Pharmaceutical Co., 733 F.2d 858 (Fed. Cir. 1984).
5 Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 670 (1990).
6 Proveris Scientific Corp. v. Innova Systems, Inc., 536 F.3d 1256, 1261 (Fed. Cir. 2008).
7 Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661 (1990) (applying safe harbor).
8 Merck KGAA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005) (applying safe harbor).
9 Proveris Scientific Corp. v. Innovasystems, Inc., 536 F.3d 1256 (Fed. Cir. 2008) (rejecting safe-harbor defense).
10 Amgen, Inc. v. International Trade Comm'n, 565 F.3d 846 (Fed. Cir. 2009) (remanded for further fact-finding; uses would be exempt if "supplemental to the BLA and intended for submission to the FDA").
11 Classen Immunotherapies, Inc. v. Biogen Idec, 659 F.3d 1057 (Fed. Cir. 2011) (rejecting safe-harbor defense).
12 FD&C Act § 506A; 21 C.F.R. §§ 314.70, 314.80.
13 FD&C Act §§ 505(o)(3)(A), 505-1(a), 506B.
14 21 C.F.R. § 211.165(a).
15 21 C.F.R. §§ 211.180, 211.188.
16 The previous two Supreme Court cases were Merck KGAA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005) (addressing how early in the drug discovery process the safe harbor reaches) and Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661 (1990) (addressing whether the safe harbor applies when seeking pre-marketing approval for a medical device).
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