(Slip Opinion) OCTOBER TERM, 2004 1
Syllabus
NOTE: Where it is feasible, a syllabus (headnote) will be released, as is
being done in connection with this case, at the time the opinion is issued.
The syllabus constitutes no part of the opinion of the Court but has been
prepared by the Reporter of Decisions for the convenience of the reader.
See United States v. Detroit Timber & Lumber Co., 200 U. S. 321, 337.
SUPREME COURT OF THE UNITED STATES
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 . . . of drugs.” 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 drug maker must submit
research data to the Food and Drug Administration (FDA) in an in-
vestigational 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. Respon-
dents filed a patent-infringement suit, claiming, inter alia, that peti-
tioner had willfully infringed their patents by supplying respondents’
RGD peptides to other defendants for use in preclinical research. Pe-
titioner 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 pro-
ceedings.
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 be-
lieve that the compound tested could be the subject of an FDA sub-
mission 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 ac-
2 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Syllabus
tivities related to the federal regulatory process, including uses rea-
sonably related to the development and submission of any informa-
tion 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. The “reason-
able 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. 8–15.
331 F. 3d 860, vacated and remanded.
SCALIA, J., delivered the opinion for a unanimous Court.
Cite as: 545 U. S. ____ (2005) 1
Opinion of the Court
NOTICE: This opinion is subject to formal revision before publication in the
preliminary print of the United States Reports. Readers are requested to
notify the Reporter of Decisions, Supreme Court of the United States, Wash-
ington, D. C. 20543, of any typographical or other formal errors, in order
that corrections may be made before the preliminary print goes to press.
SUPREME COURT OF THE UNITED STATES
_________________
No. 03–1237
_________________
MERCK KGAA, PETITIONER v. INTEGRA
LIFESCIENCES I, LTD., ET AL.
ON WRIT OF CERTIORARI TO THE UNITED STATES COURT OF
APPEALS FOR THE FEDERAL CIRCUIT
[June 13, 2005]
JUSTICE SCALIA delivered the opinion of the Court.
This case presents the question whether uses of pat-
ented 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, of-
fer 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 prod-
uct (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 develop-
2 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Opinion of the Court
ment and submission of information under a Federal
law which regulates the manufacture, use, or sale of
drugs . . . .”
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 21 U. S. C. §355(a); Eli Lilly & Co. v.
Medtronic, Inc., 496 U. S. 661, 665–666, 674 (1990). Un-
der 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 investi-
gational 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 test-
ing.” 21 U. S. C. §355(i)(1)(A); see 21 CFR §§312.23(a)(5)
and (a)(8) (specifying necessary information from preclini-
cal tests). Second, to obtain authorization to market a
new drug, a drugmaker must submit a new drug applica-
tion (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
——————
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 bioequiva-
lent 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.
Cite as: 545 U. S. ____ (2005) 3
Opinion of the Court
NDA must include all clinical studies, as well as preclini-
cal studies related to a drug’s efficacy, toxicity, and phar-
macological properties. See 21 CFR §§314.50(d)(2) (pre-
clinical studies) and (d)(5) (clinical studies).
II
A
Respondents Integra Lifesciences I, Ltd., and the Burn-
ham 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 αvβ3 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, et al. v. Merck KGaA, et al., Case
No. 96–CV–1307 (SD Cal., Sept. 9, 1997), App. 30a. An-
giogenesis 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
αvβ3 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.
——————
3 In the proceedings below, the Court of Appeals held that respon-
dents’ patents covered the cyclic RGD peptides developed by petitioner.
331 F. 3d 860, 869 (CA Fed. 2003). Petitioner does not contest that
4 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Opinion of the Court
190a. Dr. Cheresh’s discoveries were announced in lead-
ing 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 αvβ3 Antagonists Promote Tumor Regres-
sion by Inducing Apoptosis of Angiogenic Blood Vessels, 79
Cell 1157 (Dec. 30, 1994); Brooks, Clark, and Cheresh,
Requirement of Vascular Integrin αvβ3 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 de-
tailed 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 per-
formed under good laboratory practices); see also §58.3(d)
(2004) (defining “[n]onclinical laboratory study”). Scripps
and petitioner concluded an agreement of continued col-
——————
ruling here.
Cite as: 545 U. S. ____ (2005) 5
Opinion of the Court
laboration 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 fo-
cused 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 par-
ticular peptides as angiogenesis inhibitors, and evaluated
their mechanism of action and pharmacokinetics in ani-
mals. 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 αvβ3 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 effi-
cacy 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
——————
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 angio-
genesis. Id., at 399a–404a. Ixsys began clinical testing of the antibody
as an angiogenesis inhibitor in February 1997. Id., at 304a.
6 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Opinion of the Court
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).
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 respon-
dents’ 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 peti-
tioner and a declaratory judgment against Dr. Cheresh
and Scripps. Id., at 863. Petitioner answered that its
actions involving the RGD peptides did not infringe re-
spondents’ patents, and that in any event they were pro-
tected 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 follow-
ing instruction regarding the §271(e)(1) exemption:
Cite as: 545 U. S. ____ (2005) 7
Opinion of the Court
“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 in-
formation that are likely to be relevant in the proc-
esses by which the FDA would decide whether to ap-
prove 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 infor-
mation gathered from a particular activity was actu-
ally submitted to the FDA.” App. 57a.
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 damage award as sup-
ported 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 suffi-
cient 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
8 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Opinion of the Court
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 informa-
tion 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 that respondents’ patents covered
the cyclic RGD peptides developed by petitioner. Id., at
868–869; id., at 873, n. 7 (Newman, J., dissenting). We
granted certiorari to review the Court of Appeals’ con-
struction of §271(e)(1). 543 U. S. ___ (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 for uses reasonably related to the development and
submission 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 regu-
latory process.
As an initial matter, we think it apparent from the
statutory text that §271(e)(1)’s exemption from infringe-
ment 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
——————
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).
Cite as: 545 U. S. ____ (2005) 9
Opinion of the Court
provisions that regulate drugs). This necessarily includes
preclinical studies of patented compounds that are appro-
priate for submission to the FDA in the regulatory process.
There is simply no room in the statute for excluding cer-
tain 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
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, pharma-
cokinetics, 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 inter-
est 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 char-
acteristics 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); Department of Health and Human Services,
Guidance for Industry, Good Clinical Practice: Consoli-
dated Guidance 45 (Apr. 1996) (“The results of all relevant
——————
6 Although the Court of Appeals’ opinion suggests in places that
§271(e)(1)’s exemption from infringement is limited to research con-
ducted 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.
10 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Opinion of the Court
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 pro-
posed clinical experiments in a vacuum; rather, as the
statute and regulations reflect, it asks whether the pro-
posed 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 testing would be “reasonably
safe”); §56.111(a)(2) (2004) (providing that the Institu-
tional Review Boards that oversee clinical trials must
consider whether the “[r]isks to subjects are reasonable in
relation to anticipated benefits”). This assessment in-
volves a comparison of the risks and the benefits associ-
ated with the proposed clinical trials. As the Govern-
ment’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 In-
dustry, supra, at 43. Such information necessarily in-
cludes preclinical studies of a drug’s efficacy in achieving
Cite as: 545 U. S. ____ (2005) 11
Opinion of the Court
particular results.
Respondents contend that, even accepting that the FDA
is interested in preclinical research concerning drug char-
acteristics 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). See 21 CFR §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 regula-
tions 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 pep-
tides 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 in-
stead 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
12 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Opinion of the Court
approval. For instance, the FDA does not require in-
formation about drugs other than the compound fea-
tured in an [IND] application. Thus, the Scripps work
sponsored by [petitioner] was not ‘solely for uses rea-
sonably 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 the intent to develop a particular drug or a rea-
sonable 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 in-
fringement categorically excludes either (1) experimenta-
tion 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 suffi-
ciently 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,
——————
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 develop-
ment of information for the regulatory process.
Cite as: 545 U. S. ____ (2005) 13
Opinion of the Court
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 experi-
ments. 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 ingredi-
ent 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. Con-
gress did not limit §271(e)(1)’s safe harbor to the develop-
ment 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 distri-
bution of drugs. See Eli Lilly, 496 U. S., at 674. We de-
cline 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 par-
ticular physiological effect, and uses the compound in
research that, if successful, would be appropriate to in-
clude in a submission to the FDA, that use is “reasonably
related” to the “development and submission of informa-
14 MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD.
Opinion of the Court
tion under . . . Federal law.” §271(e)(1).
For similar reasons, the use of a patented compound in
experiments that are not themselves included in a “sub-
mission 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 pro-
vide 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 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 pro-
tected 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 of United States as Amicus Curiae 23.
* * *
Before the Court of Appeals, petitioner challenged the
sufficiency of the evidence supporting the jury’s finding
Cite as: 545 U. S. ____ (2005) 15
Opinion of the Court
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 consis-
tent 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. Accord-
ingly, 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 com-
pound 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.