OCTOBER TERM, 2004
Syllabus
MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.,
et al.
certiorari to the united states court of appeals for
the federal circuit
No. 03—1237. Argued April 20, 2005–Decided June 13, 2005
It is not “an act of [patent] infringement to . . . use . . . 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... use...ofdrugs.” 35 U. S. C. § 271(e)(1). The
Federal Food, Drug, and Cosmetic Act of 1938 (FDCA) is such a law.
Under the FDCA, a drugmaker must submit research data to the Food
and Drug Administration (FDA) in an investigational new drug application
(IND) when seeking authorization to conduct human clinical trials,
and in a new drug application (NDA) when seeking authorization to
market a new drug. Respondents filed a patent-infringement suit,
claiming, inter alia, that petitioner had willfully infringed their patents
by supplying respondents’ RGD peptides to other defendants for use
in preclinical research. Petitioner answered, among other things, that
§ 271(e)(1) exempted its actions from infringement. The jury found otherwise
and awarded damages. In post-trial motions, the District Court
affirmed the jury’s award and denied petitioner’s motion for judgment
as a matter of law. The Federal Circuit affirmed that denial, finding
that § 271(e)(1)’s safe harbor did not apply. It reversed the District
Court’s refusal to modify the damages award and remanded for further
proceedings.
Held: The use of patented compounds in preclinical studies is protected
under § 271(e)(1) at least as long as there is a reasonable basis to believe
that the compound tested could be the subject of an FDA submission
and the experiments will produce the types of information relevant to
an IND or NDA. The statutory text makes clear that § 271(e)(1) provides
a wide berth for the use of patented drugs in activities related to
the federal regulatory process, including uses reasonably related to the
development and submission of any information under the FDCA. Eli
Lilly & Co. v. Medtronic, Inc., 496 U. S. 661, 665—669. This necessarily
includes preclinical studies, both those pertaining to a drug’s safety in
humans and those related to, e. g., a drug’s efficacy and mechanism of
action. Additionally, § 271(e)(1) exempts from infringement the use of
patented compounds in preclinical research, even when the patented
compounds do not themselves become the subject of an FDA submission.
194 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
The “reasonable relation” requirement cannot be read effectively to
limit § 271(e)(1)’s stated protection of activities leading to FDA approval
for all drugs to those activities leading to FDA approval for generic
drugs. Similarly, the use of a patented compound in experiments not
themselves included in a “submission of information” to the FDA does
not, standing alone, render the use infringing. Because the Federal
Circuit applied the wrong standard in rejecting petitioner’s challenge to
the jury’s finding that petitioner failed to show that its activities were
covered by § 271(e)(1), the trial evidence has yet to be reviewed under
the standard set forth in the jury instruction, and developed in more
detail here. Pp. 202—208.
331 F. 3d 860, vacated and remanded.
Scalia, J., delivered the opinion for a unanimous Court.
E. Joshua Rosenkranz argued the cause for petitioner.
With him on the briefs were M. Patricia Thayer, James
N. Czaban, and Donald R. Dunner.
Daryl Joseffer argued the cause for the United States as
amicus curiae in support of petitioner. With him on the
brief were Acting Solicitor General Clement, Assistant Attorney
General Keisler, Deputy Solicitor General Hungar,
Douglas N. Letter, Mark S. Davies, Alex M. Azar II, Richard
Lambert, John M. Whealan, and Heather F. Auyang.
Mauricio A. Flores argued the cause for respondents.
With him on the brief were Raphael V. Lupo, Cathryn
Campbell, Mark G. Davis, M. Miller Baker, Richard B. Rogers,
and David M. Beckwith.*
*Briefs of amici curiae urging reversal were filed for AARP by Sarah
Lenz Lock, Bruce Vignery, and Michael Schuster; for Eli Lilly and Co.
et al. by James J. Kelley, Thomas G. Plant, and John A. Cleveland, Jr.;
for Eon Labs, Inc., by Shashank Upadhye; for Genentech, Inc., et al. by
Carter G. Phillips, Virginia A. Seitz, Jeffrey P. Kushan, and Gary H.
Loeb; for the New York Intellectual Property Law Association by David
F. Ryan; and for Pharmaceutical Research and Manufacturers of America
by Roderick R. McKelvie and Brooks Mackintosh.
Briefs of amici curiae urging affirmance were filed for Applera Corp.
et al. by Edward R. Reines; for Benitec Australia Ltd. by Eric A. Kuwana,
Marc R. Labgold, and Kevin M. Bell; for Invitrogen Corp. et al. by
Drew S. Days III, Beth S. Brinkmann, Seth M. Galanter, David C. Doyle,
Opinion of the Court
Justice Scalia delivered the opinion of the Court.
This case presents the question whether uses of patented
inventions in preclinical research, the results of which are
not ultimately included in a submission to the Food and Drug
Administration (FDA), are exempted from infringement by
35 U. S. C. § 271(e)(1).
I
It is generally an act of patent infringement to “mak[e],
us[e], offe[r] to sell, or sel[l] any patented invention . . . during
the term of the patent therefor.” § 271(a). In 1984,
Congress enacted an exemption to this general rule, see
Drug Price Competition and Patent Term Restoration
Act of 1984, § 202, 98 Stat. 1585, as amended, 35 U. S. C.
§ 271(e)(1), which provides:
“It shall not be an act of infringement to make, use, offer
to sell, or sell within the United States or import into
the United States a patented invention (other than a
new animal drug or veterinary biological product (as
those terms are used in the Federal Food, Drug, and
Cosmetic Act and the Act of March 4, 1913) . . . ) 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 ....”
and Andrea L. Gross; for Vaccinex, Inc., by Kenneth C. Bass III and Linda
Alcorn; and for the Wisconsin Alumni Research Foundation et al. by Rolf
O. Stadheim and George C. Summerfield.
Briefs of amici curiae were filed for the American Intellectual Property
Law Association by Donald R. Ware, Denise W. DeFranco, and Melvin C.
Garner; for the Biotechnology Industry Organization by Richard J.
Oparil; for the Consumer Project on Technology et al. by Joshua D. Sarnoff;
for Intellectual Property Professors by John Fitzgerald Duffy and
Katherine J. Strandburg; for the Patent, Trademark & Copyright Section
of the Bar Association of the District of Columbia by Lynn E. Eccleston
and Susan M. Dadio; for the San Diego Intellectual Property Law Association
by Madison C. Jellins, Doug E. Olson, and John E. Peterson;
and for Sepracor Inc. by Kenneth J. Burchfiel and Michael R. Dzwonczyk.
196 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
The Federal Food, Drug, and Cosmetic Act (FDCA),
ch. 675, 52 Stat. 1040, as amended, 21 U. S. C. § 301 et seq., is
“a Federal law which regulates the manufacture, use, or sale
of drugs.” See § 355(a); Eli Lilly & Co. v. Medtronic, Inc.,
496 U. S. 661, 665—666, 674 (1990). Under the FDCA, a
drugmaker must submit research data to the FDA at two
general stages of new-drug development.1 First, a drugmaker
must gain authorization to conduct clinical trials
(tests on humans) by submitting an investigational new drug
application (IND). See 21 U. S. C. § 355(i); 21 CFR § 312.1
et seq. (2005).2 The IND must describe “preclinical tests (including
tests on animals) of [the] drug adequate to justify the
proposed clinical testing.” 21 U. S. C. § 355(i)(1)(A); see 21
CFR §§ 312.23(a)(5) and (a)(8) (specifying necessary information
from preclinical tests). Second, to obtain authorization
to market a new drug, a drugmaker must submit a new drug
application (NDA), containing “full reports of investigations
which have been made to show whether or not [the] drug is
safe for use and whether [the] drug is effective in use.” 21
U. S. C. § 355(b)(1). Pursuant to FDA regulations, the NDA
must include all clinical studies, as well as preclinical studies
related to a drug’s efficacy, toxicity, and pharmacological
properties. See 21 CFR §§ 314.50(d)(2) (preclinical studies)
and (d)(5) (clinical studies).
1 Drugmakers that desire to market a generic drug (a drug containing
the same active ingredients as a drug already approved for the market)
may file an abbreviated new drug application (ANDA) with the FDA.
See 21 U. S. C. §355(j). The sponsor of a generic drug does not have to
make an independent showing that the drug is safe and effective, either
in preclinical or clinical studies. See §355(j)(2)(A). It need only show
that the drug includes the same active ingredients as, and is bioequivalent
to, the drug that it is mimicking. See §§355(j)(2)(A)(ii) and (iv);
§ 355(j)(8)(B).
2 We cite the current versions of federal statutes and regulations. The
provisions cited are materially unchanged since the period of petitioner’s
alleged infringement.
II
A
Respondents, Integra Lifesciences I, Ltd., and the Burnham
Institute, own five patents related to the tripeptide
sequence Arg-Gly-Asp, known in single-letter notation as
the “RGD peptide.” U. S. Patent Nos. 4,988,621, 4,792,525,
5,695,997, 4,879,237, and 4,789,734, Supp. App. SA11—SA19.
The RGD peptide promotes cell adhesion by attaching to
avfl3 integrins, receptors commonly located on the outer surface
of certain endothelial cells. 331 F. 3d 860, 862—863 (CA
Fed. 2003).
Beginning in 1988, petitioner Merck KGaA provided funding
for angiogenesis research conducted by Dr. David Cheresh
at the Scripps Research Institute (Scripps). Telios
Pharmaceuticals v. Merck KGaA, Case No. 96—CV—1307
(SD Cal., Sept. 9, 1997), App. 30a. Angiogenesis is the process
by which new blood vessels sprout from existing vessels;
it plays a critical role in many diseases, including solid tumor
cancers, diabetic retinopathy, and rheumatoid arthritis. 331
F. 3d, at 863. In the course of his research, Dr. Cheresh
discovered that it was possible to inhibit angiogenesis by
blocking the avfl3 integrins on proliferating endothelial cells.
Ibid. In 1994, Dr. Cheresh succeeded in reversing tumor
growth in chicken embryos, first using a monoclonal antibody
(LM609) he developed himself and later using a cyclic RGD
peptide (EMD 66203) provided by petitioner.3 App. 190a.
Dr. Cheresh’s discoveries were announced in leading medical
journals and received attention in the general media. See
Altman, Scientists Report Finding a Way to Shrink Tumors,
N. Y. Times, Dec. 30, 1994, p. A1; Brooks et al., Integrin
F. 3d 860, 869 (CA Fed. 2003). Petitioner does not contest that ruling
here.
3 In the proceedings below, the Court of Appeals held that respondents’
patents covered the cyclic RGD peptides developed by petitioner. 331
198 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
avfl3 Antagonists Promote Tumor Regression by Inducing
Apoptosis of Angiogenic Blood Vessels, 79 Cell 1157 (Dec. 30,
1994); Brooks, Clark, & Cheresh, Requirement of Vascular
Integrin avfl3 for Angiogenesis, 264 Science 569 (Apr. 22,
1994).
With petitioner’s agreement to fund research at Scripps
due to expire in July 1995, Dr. Cheresh submitted a detailed
proposal for expanded collaboration between Scripps and
petitioner on February 1, 1995. App. 95a—107a. The proposal
set forth a 3-year timetable in which to develop “integrin
antagonists as angiogenesis inhibitors,” id., at 105a, beginning
with in vitro and in vivo testing of RGD peptides at
Scripps in year one and culminating with the submission of
an IND to the FDA in year three, id., at 106a—107a. Petitioner
agreed to the material terms of the proposal on February
20, 1995, id., at 124a—125a, and on April 13, 1995, pledged
$6 million over three years to fund research at Scripps, id.,
at 126a. Petitioner’s April 13 letter specified that Scripps
would be responsible for testing RGD peptides produced by
petitioner as potential drug candidates but that, once a primary
candidate for clinical testing was in “the pipeline,”
petitioner would perform the toxicology tests necessary for
FDA approval to proceed to clinical trials. Id., at 127a; see
21 CFR § 312.23(a)(8)(iii) (2005) (requirement that “nonclinical
laboratory study” include a certification that it was performed
under good laboratory practices); see also § 58.3(d)
(2004) (defining “[n]onclinical laboratory study”). Scripps
and petitioner concluded an agreement of continued collaboration
in September 1995. Case No. 96—CV—1307, App. 31a.
Pursuant to the agreement, Dr. Cheresh directed in vitro
and in vivo experiments on RGD peptides provided by petitioner
from 1995 to 1998. These experiments focused on
EMD 66203 and two closely related derivatives, EMD 85189
and EMD 121974, and were designed to evaluate the suitability
of each of the peptides as potential drug candidates. 331
F. 3d, at 863. Accordingly, the tests measured the efficacy,
specificity, and toxicity of the particular peptides as angiogenesis
inhibitors, and evaluated their mechanism of action
and pharmacokinetics in animals. Ibid. Based on the test
results, Scripps decided in 1997 that EMD 121974 was the
most promising candidate for testing in humans. Ibid.
Over the same period, Scripps performed similar tests on
LM609, a monoclonal antibody developed by Dr. Cheresh.4
App. 277a, 285a—298a. Scripps also conducted more basic
research on organic mimetics designed to block avfl3 integrins
in a manner similar to the RGD peptides, id., at 223a—
224a; it appears that Scripps used the RGD peptides in these
tests as “positive controls” against which to measure the
efficacy of the mimetics, id., at 188a.
In November 1996, petitioner initiated a formal project to
guide one of its RGD peptides through the regulatory approval
process in the United States and Europe. Id., at
129a. Petitioner originally directed its efforts at EMD
85189, but switched focus in April 1997 to EMD 121974.
Case No. 96—CV—1307, App. 31a. Petitioner subsequently
discussed EMD 121974 with officials at the FDA. Id., at
397a. In October 1998, petitioner shared its research on
RGD peptides with the National Cancer Institute (NCI),
which agreed to sponsor clinical trials. Id., at 214a—217a.
Although the fact was excluded from evidence at trial, the
lower court’s opinion reflects that NCI filed an IND for EMD
121974 in 1998. 331 F. 3d, at 874 (Newman, J., dissenting).
4 Scripps licensed the patent for the monoclonal antibody to Ixsys, a
California biotechnology company. App. 271a. Based on research conducted
at Scripps and at Ixsys in consultation with Dr. Cheresh, an IND
application for a humanized version of the antibody called Vitaxin was
filed with the FDA on December 30, 1996. Id., at 271a—274a, 404a. In
addition to toxicology tests, the application included information from
Dr. Cheresh’s in vitro and in vivo experiments related to the antibody’s
mechanism of action and efficacy as an inhibitor of angiogenesis. Id., at
399a—404a. Ixsys began clinical testing of the antibody as an angiogenesis
inhibitor in February 1997. Id., at 304a.
200 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
B
On July 18, 1996, respondents filed a patent-infringement
suit against petitioner, Scripps, and Dr. Cheresh in the District
Court for the Southern District of California. Respondents’
complaint alleged that petitioner willfully infringed
and induced others to infringe respondents’ patents
by supplying the RGD peptide to Scripps, and that
Dr. Cheresh and Scripps infringed the same patents by using
the RGD peptide in experiments related to angiogenesis.
Respondents sought damages from petitioner and a declaratory
judgment against Dr. Cheresh and Scripps. Id., at 863.
Petitioner answered that its actions involving the RGD peptides
did not infringe respondents’ patents, and that in any
event they were protected by the common-law research exemption
and 35 U. S. C. § 271(e)(1). 331 F. 3d, at 863.
At the conclusion of trial, the District Court held that,
with one exception, petitioner’s pre-1995 actions related to
the RGD peptides were protected by the common-law research
exemption, but that a question of fact remained as to
whether petitioner’s use of the RGD peptides after 1995 fell
within the § 271(e)(1) safe harbor. With the consent of the
parties, the District Court gave the following instruction
regarding the § 271(e)(1) exemption:
“To prevail on this defense, [petitioner] must prove by
a preponderance of the evidence that it would be objectively
reasonable for a party in [petitioner’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 whether to approve the
product in question.
“Each of the accused activities must be evaluated separately
to determine whether the exemption applies.
“[Petitioner] does not need to show that the information
gathered from a particular activity was actually
submitted to the FDA.” App. 57a (one paragraph
break omitted).
The jury found that petitioner, Dr. Cheresh, and Scripps infringed
respondents’ patents and that petitioner had failed
to show that its activities were protected by § 271(e)(1). It
awarded damages of $15 million.
In response to post-trial motions, the District Court dismissed
respondents’ suit against Dr. Cheresh and Scripps,
but affirmed the jury’s damages award as supported by substantial
evidence, Civ. Action No. 961307 JMF (SD Cal., Mar.
26, 2001), App. to Pet. for Cert. 52a, and denied petitioner’s
motion for judgment as a matter of law, Civ. Action
No. 96CV—1307 JMF (SD Cal., Mar. 6, 2001), App. to Pet.
for Cert. 50a. With respect to the last, the District Court
explained that the evidence was sufficient to show that “any
connection between the infringing Scripps experiments and
FDA review was insufficiently direct to qualify for the
[§ 271(e)(1) exemption].” Id., at 49a.
A divided panel of the Court of Appeals for the Federal
Circuit affirmed in part and reversed in part. The panel
majority affirmed the denial of judgment as a matter of law
to petitioner, on the ground that § 271(e)(1)’s safe harbor did
not apply because “the Scripps work sponsored by [petitioner]
was not clinical testing to supply information to the
FDA, but only general biomedical research to identify new
pharmaceutical compounds.” 331 F. 3d, at 866. It reversed
the District Court’s refusal to modify the damages award
and remanded for further proceedings.5 Id., at 872. Judge
Newman dissented on both points. See id., at 874, 877.
The panel unanimously affirmed the District Court’s ruling
5 On remand, the District Court reduced the damages award to $6.375
million. Civ. Action No. CV.96 CV 1307—B(AJB), 2004 WL 2284001, *1
(SD Cal., Sept. 7, 2004).
202 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
that respondents’ patents covered the cyclic RGD peptides
developed by petitioner. Id., at 868—869; id., at873, n. 7
(Newman, J., dissenting). We granted certiorari to review
the Court of Appeals’ construction of § 271(e)(1). 543 U. S.
1041 (2004).
III
As described earlier, 35 U. S. C. § 271(e)(1) provides that
“[i]t shall not be an act of infringement to ...use ...or
import into the United States a patented invention . . . solely
of information under a Federal law which regulates the
... use... of drugs.” Though the contours of this provision
are not exact in every respect, the statutory text makes clear
that it provides a wide berth for the use of patented drugs
in activities related to the federal regulatory process.
As an initial matter, we think it apparent from the statutory
text that § 271(e)(1)’s exemption from infringement extends
to all uses of patented inventions that are reasonably
related to the development and submission of any information
under the FDCA. Cf. Eli Lilly, 496 U. S., at 665—669
(declining to limit § 271(e)(1)’s exemption from infringement
to submissions under particular statutory provisions that
regulate drugs). This necessarily includes preclinical studies
of patented compounds that are appropriate for submission
to the FDA in the regulatory process. There is simply
no room in the statute for excluding certain information from
the exemption on the basis of the phase of research in which
it is developed or the particular submission in which it could
be included.6
6Although the Court of Appeals’ opinion suggests in places that
§ 271(e)(1)’s exemption from infringement is limited to research conducted
in clinical trials, see 331 F. 3d, at 866, we do not understand it
to have adopted that position. The Court of Appeals recognized that information
included in an IND would come within § 271(e)(1)’s safe harbor.
Ibid. Because an IND must be filed before clinical trials may begin,
such information would necessarily be developed in preclinical studies.
Respondents concede the breadth of § 271(e)(1) in this regard,
but argue that the only preclinical data of interest to
the FDA is that which pertains to the safety of the drug in
humans. In respondents’ view, preclinical studies related to
a drug’s efficacy, mechanism of action, pharmacokinetics, and
pharmacology are not reasonably included in an IND or an
NDA, and are therefore outside the scope of the exemption.
We do not understand the FDA’s interest in information
gathered in preclinical studies to be so constrained. To be
sure, its regulations provide that the agency’s “primary objectives
in reviewing an IND are ...to assure the safety
and rights of subjects,” 21 CFR § 312.22(a) (2005), but it does
not follow that the FDA is not interested in reviewing information
related to other characteristics of a drug. To the
contrary, the FDA requires that applicants include in an IND
summaries of the pharmacological, toxicological, pharmacokinetic,
and biological qualities of the drug in animals. See
§ 312.23(a)(5); U. S. Dept. of Health and Human Services,
Guidance for Industry, Good Clinical Practice: Consolidated
Guidance 45 (Apr. 1996) (“The results of all relevant nonclinical
pharmacology, toxicology, pharmacokinetic, and investigational
product metabolism studies should be provided in
summary form. This summary should address the methodology
used, the results, and a discussion of the relevance of
the findings to the investigated therapeutic and the possible
unfavorable and unintended effects in humans”). The primary
(and, in some cases, only) way in which a drugmaker
may obtain such information is through preclinical in vitro
and in vivo studies.
Moreover, the FDA does not evaluate the safety of proposed
clinical experiments in a vacuum; rather, as the
statute and regulations reflect, it asks whether the proposed
clinical trial poses an “unreasonable risk.” 21 U. S. C.
§ 355(i)(3)(B)(i); see also 21 CFR § 312.23(a)(8) (2005) (requiring
applicants to include pharmacological and toxicological
studies that serve as the basis of their conclusion that clinical
204 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
testing would be “reasonably safe”); §56.111(a)(2) (2004)
(providing that the Institutional Review Boards that oversee
clinical trials must consider whether the “[r]isks to subjects
are reasonable in relation to anticipated benefits”). This assessment
involves a comparison of the risks and the benefits
associated with the proposed clinical trials. As the Government’s
brief, filed on behalf of the FDA, explains, the “FDA
might allow clinical testing of a drug that posed significant
safety concerns if the drug had a sufficiently positive potential
to address a serious disease, although the agency would
not accept similar risks for a drug that was less likely to
succeed or that would treat a less serious medical condition.”
Brief for United States as Amicus Curiae 10. Accordingly,
the FDA directs that an IND must provide sufficient information
for the investigator to “make his/her own unbiased
risk-benefit assessment of the appropriateness of the proposed
trial.” Guidance for Industry, supra, at 43. Such information
necessarily includes preclinical studies of a drug’s
efficacy in achieving particular results.
Respondents contend that, even accepting that the FDA is
interested in preclinical research concerning drug characteristics
other than safety, the experiments in question here are
necessarily disqualified because they were not conducted in
conformity with the FDA’s good laboratory practices regulations.
This argument fails for at least two reasons. First,
the FDA’s requirement that preclinical studies be conducted
under “good laboratory practices” applies only to experiments
on drugs “to determine their safety,” 21 CFR §58.3(d)
(2004). See § 58.1(a); § 312.23(a)(8)(iii) (2005) (only “nonclinical
laboratory study subject to the good laboratory practice
regulations under part 58” must certify compliance with
good laboratory practice regulations). The good laboratory
practice regulations do not apply to preclinical studies of a
drug’s efficacy, mechanism of action, pharmacology, or pharmacokinetics.
Second, FDA regulations do not provide that
even safety-related experiments not conducted in compliance
with good laboratory practices regulations are not suitable
for submission in an IND. Rather, such studies must include
“a brief statement of the reason for the noncompliance.”
Ibid.
The Court of Appeals’ conclusion that § 271(e)(1) did not
protect petitioner’s provision of the patented RGD peptides
for research at Scripps appeared to rest on two somewhat
related propositions. First, the court credited the fact that
the “Scripps-Merck experiments did not supply information
for submission to the [FDA], but instead identified the best
drug candidate to subject to future clinical testing under the
FDA processes.” 331 F. 3d, at 865; see also id., at 866 (similar).
The court explained:
“The FDA has no interest in the hunt for drugs that
may or may not later undergo clinical testing for FDA
approval. For instance, the FDA does not require information
about drugs other than the compound featured
in an [IND] application. Thus, the Scripps work
sponsored by [petitioner] was not ‘solely for uses reasonably
related’ to clinical testing for FDA.” Ibid.
Second, the court concluded that the exemption “does not
globally embrace all experimental activity that at some
point, however attenuated, may lead to an FDA approval
process.” Id., at 867.7
We do not quibble with the latter statement. Basic scientific
research on a particular compound, performed without
7 The Court of Appeals also suggested that a limited construction of
§ 271(e)(1) is necessary to avoid depriving so-called “research tools” of the
complete value of their patents. Respondents have never argued the
RGD peptides were used at Scripps as research tools, and it is apparent
from the record that they were not. See 331 F. 3d, at 878 (Newman, J.,
dissenting) (“Use of an existing tool in one’s research is quite different
from study of the tool itself”). We therefore need not–and do not–express
a view about whether, or to what extent, § 271(e)(1) exempts from
infringement the use of “research tools” in the development of information
for the regulatory process.
206 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
the intent to develop a particular drug or a reasonable belief
that the compound will cause the sort of physiological effect
the researcher intends to induce, is surely not “reasonably
related to the development and submission of information”
to the FDA. It does not follow from this, however, that
§ 271(e)(1)’s exemption from infringement categorically excludes
either (1) experimentation on drugs that are not ultimately
the subject of an FDA submission or (2) use of patented
compounds in experiments that are not ultimately
submitted to the FDA. Under certain conditions, we think
the exemption is sufficiently broad to protect the use of patented
compounds in both situations.
As to the first proposition, it disregards the reality that,
even at late stages in the development of a new drug, scientific
testing is a process of trial and error. In the vast majority
of cases, neither the drugmaker nor its scientists have
any way of knowing whether an initially promising candidate
will prove successful over a battery of experiments. That is
the reason they conduct the experiments. Thus, to construe
§ 271(e)(1), as the Court of Appeals did, not to protect research
conducted on patented compounds for which an IND
is not ultimately filed is effectively to limit assurance of exemption
to the activities necessary to seek approval of a generic
drug: One can know at the outset that a particular compound
will be the subject of an eventual application to the
FDA only if the active ingredient in the drug being tested is
identical to that in a drug that has already been approved.
The statutory text does not require such a result. Congress
did not limit § 271(e)(1)’s safe harbor to the development
of information for inclusion in a submission to the FDA;
nor did it create an exemption applicable only to the research
relevant to filing an ANDA for approval of a generic drug.
Rather, it exempted from infringement all uses of patented
compounds “reasonably related” to the process of developing
information for submission under any federal law regulating
the manufacture, use, or distribution of drugs. See Eli
Lilly, 496 U. S., at 674. We decline to read the “reasonable
relation” requirement so narrowly as to render § 271(e)(1)’s
stated protection of activities leading to FDA approval for
all drugs illusory. Properly construed, § 271(e)(1) leaves adequate
space for experimentation and failure on the road to
regulatory approval: At least where a drugmaker has a reasonable
basis for believing that a patented compound may
work, through a particular biological 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.” § 271(e)(1).
For similar reasons, the use of a patented compound in
experiments that are not themselves included in a “submission
of information” to the FDA does not, standing alone,
render the use infringing. The relationship of the use of a
patented compound in a particular experiment to the “development
and submission of information” to the FDA does not
become more attenuated (or less reasonable) simply because
the data from that experiment are left out of the submission
that is ultimately passed along to the FDA. Moreover,
many of the uncertainties that exist with respect to the selection
of a specific drug exist as well with respect to the
decision of what research to include in an IND or NDA. As
a District Court has observed, “[I]t will not always be clear
to parties setting out to seek FDA approval for their new
product exactly which kinds of information, and in what
quantities, it will take to win that agency’s approval.” Intermedics,
Inc. v. Ventritex, Inc., 775 F. Supp. 1269, 1280 (ND
Cal. 1991), aff’d, 991 F. 2d 808 (CA Fed. 1993). This is especially
true at the preclinical stage of drug approval. FDA
regulations provide only that “[t]he amount of information
on a particular drug that must be submitted in an IND . . .
depends upon such factors as the novelty of the drug, the
extent to which it has been studied previously, the known or
208 MERCK KGaA v. INTEGRA LIFESCIENCES I, LTD.
suspected risks, and the developmental phase of the drug.”
21 CFR § 312.22(b). We thus agree with the Government
that the use of patented compounds in preclinical studies is
protected under § 271(e)(1) as long as there is a reasonable
basis for believing that the experiments will produce “the
types of information that are relevant to an IND or NDA.”
Brief for United States as Amicus Curiae 23 (emphasis
deleted).
***
Before the Court of Appeals, petitioner challenged the sufficiency
of the evidence supporting the jury’s finding that it
failed to show that “all of the accused activities are covered
by [§271(e)(1)].” App. 62a. That court rejected the challenge
on the basis of a construction of § 271(e)(1) that was
not consistent with the text of that provision or the relevant
jury instruction.8 Thus, the evidence presented at trial has
yet to be reviewed under the standards set forth in the jury
instruction, which we believe to be consistent with, if less
detailed than, the construction of § 271(e)(1) that we adopt
today. We decline to undertake a review of the sufficiency
of the evidence under a proper construction of § 271(e)(1) for
the first time here. Accordingly, we vacate the judgment of
the Court of Appeals and remand the case for proceedings
consistent with this opinion.
It is so ordered.
8 The relevant jury instruction provided only that there must be 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 whether to
approve the product in question.” App. 57a. It did not say that, to fall
within § 271(e)(1)’s exemption from infringement, the patented compound
used in experimentation must be the subject of an eventual application to
the FDA. And it expressly rejected the notion that the exemption only
included experiments that produced information included in an IND or
NDA. Ibid.