1 of 4 DOCUMENTS MERCK Kgaa, Petitioner V. INTEGRA

1 of 4 DOCUMENTS

MERCK KGaA, Petitioner v. INTEGRA LIFESCIENCES I, LTD., et al.

No. 03-1237

SUPREME COURT OF THE UNITED STATES

125 S. Ct. 2372; 162 L. Ed. 2d 160; 2005 U.S. LEXIS 4840; 73 U.S.L.W. 4468; 74 U.S.P.Q.2D (BNA) 1801; 18 Fla. L. Weekly Fed. S 394

April 20, 2005, Argued June 13, 2005, Decided

NOTICE: [***1] PRIOR HISTORY: ON WRIT OF CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR The LEXIS pagination of this document is subject to THE FEDERAL CIRCUIT. Integra Lifesciences I, Ltd. change pending release of the final published version. v. Merck KGaA, 331 F.3d 860, 2003 U.S. App. LEXIS 11335 (Fed. Cir., 2003) SUBSEQUENT HISTORY: On remand at Integra Lifesciences I, LTD. v. Merck KGaA, 2005 U.S. App. DISPOSITION: 331 F.3d 860, vacated and remanded. LEXIS 17342 (Fed. Cir., Aug. 17, 2005)

CASE SUMMARY:

PROCEDURAL POSTURE: Petitioner drug company sought certiorari review of a judgment from the United States Court of Appeals for the Federal Circuit, which affirmed the district court's denial of judgment as a matter of law to petitioner in a patent infringement action on the ground that 35 U.S.C.S. § 271(e)(1)'s safe harbor did not apply to preclinical studies involving the use of respondent companies' patents for the tripeptide sequence Arg-Gly-Asp (RGD peptide).

OVERVIEW: Respondents alleged that petitioner infringed the patents by supplying RGD peptides to a research institute, which used the RGD peptides in preclinical research designed to evaluate their suitability as potential drug candidates. A jury found that petitioner failed to show that its activities were protected by § 271(e)(1). The court of appeals held that § 271(e)(1)'s safe harbor did not apply because petitioner's sponsored research institute work was not clinical testing to supply information to the Food and Drug Administration (FDA) under the Food, Drug, and Cosmetic Act, 21 U.S.C.S. § 301 et seq., but only general biomedical research to identify new pharmaceutical compounds. The Court vacated the judgment, finding that the court of appeals applied the wrong standard in rejecting petitioner's challenge to the jury's finding. The Court held that the use of patented compounds in preclinical studies was protected under 35 U.S.C.S. § 271(e)(1) at least as long as there was a reasonable basis to believe that the compound tested could be the subject of an FDA submission and the experiments would produce the types of information relevant to drug applications under 21 U.S.C.S. § 355.

OUTCOME: The Court vacated the judgment and remanded the action for review on the basis of the proper construction of the statute and the relevant jury instruction, which the Court believed to be consistent with, if less detailed than, the Court's construction of the statute.

LexisNexis(R) Headnotes

Patent Law > Infringement Actions > Defenses > Experimental Use & Testing Page 2 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468

Patent Law > Infringement Actions > Infringing Acts > General Overview [HN1] It is generally an act of patent infringement to make, use, offer to sell, or sell any patented invention during the term of the patent therefor. 35 U.S.C.S. § 271(a). In 1984, Congress enacted an experimental use and testing exemption to this general rule. 35 U.S.C.S. § 271(e)(1).

Patent Law > Infringement Actions > Defenses > Experimental Use & Testing [HN2] See 35 U.S.C.S. § 271(e)(1).

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act [HN3] The Federal Food, Drug, and Cosmetic Act (FDCA), 21 U.S.C.S. § 301 et seq., is a Federal law which regulates the manufacture, use, or sale of drugs. 21 U.S.C.S. § 355(a). Under the FDCA, a drugmaker must submit research data to the Food and Drug Administration (FDA) at two general stages of new-drug development. First, a drugmaker must gain authorization to conduct clinical trials (tests on humans) by submitting an investigational new drug application (IND). 21 U.S.C.S. § 355(i); 21 C.F.R. § 312.1 et seq. (2005). The IND must describe preclinical tests (including tests on animals) of the drug adequate to justify the proposed clinical testing. 21 U.S.C.S. § 355(i)(1)(A); 21 C.F.R. § 312.23(a)(5), (8). 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.S. § 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. 21 C.F.R. § 314.50(d)(2), (5).

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act [HN4] 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 with the Food and Drug Administration. 21 U.S.C.S. § 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. 21 U.S.C.S. § 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. 21 U.S.C.S. § 355(j)(2)(A)(ii), (2)(A)(iv), (8)(B).

Patent Law > Infringement Actions > Defenses > Experimental Use & Testing [HN5] 35 U.S.C.S. § 271(e)(1) provides in part that it 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 § 271(e)(1) 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.

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act Patent Law > Infringement Actions > Defenses > Experimental Use & Testing [HN6] It is apparent from the statutory text that 35 U.S.C.S. § 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 Federal Food, Drug, and Cosmetic Act of 1938, 21 U.S.C.S. § 301 et seq. This necessarily includes preclinical studies of patented compounds that are appropriate for submission to the Food and Drug Administration in the regulatory process. There is simply no room in 35 U.S.C.S. § 271(e)(1) 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.

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act [HN7] The United States Supreme Court does not understand the Food and Drug Administration's (FDA) interest in information gathered in preclinical studies to be limited to that which pertains to the safety of a drug in humans. Although the FDA's regulations provide that the agency's primary objectives in reviewing an investigational new drug application (IND) are to assure the safety and rights of subjects, 21 C.F.R. 312.22(a) (2005), it does not follow that the FDA is not Page 3 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468 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. 21 C.F.R. § 312.23(a)(5). The primary way in which a drugmaker may obtain such information is through preclinical in vitro and in vivo studies.

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act [HN8] The Food and Drug Administration (FDA) does not evaluate the safety of proposed clinical experiments in a vacuum; rather, it asks whether the proposed clinical trial poses an "unreasonable risk." 21 U.S.C.S. § 355(i)(3)(B)(i). This assessment involves a comparison of the risks and the benefits associated with the proposed clinical trials. Ac- cordingly, the FDA directs that an investigational new drug application must provide sufficient information for the investigator to make his/her own unbiased risk-benefit assessment of the appropriateness of the proposed trial. Such information necessarily includes preclinical studies of a drug's efficacy in achieving particular results.

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act [HN9] The Food and Drug Administration's (FDA) requirement that preclinical studies be conducted under good laboratory practices applies only to experiments on drugs to determine their safety. 21 C.F.R. § § 58.3(d), 58.1(a), 312.23(a)(8)(iii) (2005). Only a nonclinical laboratory study subject to the good laboratory practice regulations under 21 C.F.R. pt. 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. 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 investigational new drug application. Rather, such studies must include a brief statement of the reason for the noncompliance.

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act Patent Law > Infringement Actions > Defenses > Experimental Use & Testing [HN10] Basic scientific research on a particular compound, performed without 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 not "reasonably related to the development and submission of information" to the Food and Drug Administration (FDA). It does not follow from this, however, that 35 U.S.C.S. § 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, the exemption is sufficiently broad to protect the use of patented compounds in both situations.

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act Patent Law > Infringement Actions > Defenses > Experimental Use & Testing [HN11] Congress did not limit 35 U.S.C.S. § 271(e)(1)'s safe harbor to the development of information for inclusion in a submission to the Food and Drug Administration (FDA); nor did it create an exemption applicable only to the research relevant to filing an abbreviated new drug application 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. The United States Supreme Court declines 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 within the meaning of § 271(e)(1).

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act Patent Law > Infringement Actions > Defenses > Experimental Use & Testing Patent Law > Infringement Actions > Infringing Acts > General Overview Page 4 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468

[HN12] The use of a patented compound in experiments that are not themselves included in a "submission of information" to the Food and Drug Administration (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 investigational new drug application (IND) or a new drug application (NDA). It 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. This is especially true at the preclinical stage of drug approval. FDA regulations provide only that the 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 C.F.R. § 312.22(b).

Governments > Agriculture & Food > Federal Food, Drug & Cosmetic Act Patent Law > Infringement Actions > Defenses > Experimental Use & Testing [HN13] The use of patented compounds in preclinical studies is protected under 35 U.S.C.S. § 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 investigational new drug application or a new drug application under 21 U.S.C.S. § 355(i) and 21 U.S.C.S. § 355(b)(1) of the Federal Food, Drug, and Cosmetic Act of 1938, 21 U.S.C.S. § 301 et seq.

DECISION: The United States Court of Appeals for the Federal Patent-infringement exemption of 35 U.S.C.S. § Circuit, in affirming in pertinent part, concluded that § 271(e)(1) held to protect, under some conditions, use of 271(e)(1)'s safe harbor did not apply, as the research in patented compounds in preclinical drug research where question was not clinical testing to supply information to results of such research are not ultimately submitted to the Food and Drug Administration (FDA), but only gen- Food and Drug Administration. eral biomedical research to identify new pharmaceutical compounds ( 331 F.3d 860). SUMMARY: [**161] On certiorari, the United States Supreme Beginning in 1988, a drug company provided funding Court vacated and remanded. In an opinion by Scalia, J., for research conducted by a scientist in the field of an- expressing the unanimous view of the court, it was held giogenesis, a process by which new blood vessels sprout that: from existing vessels. The research included experiments (1) The use of patented compounds in preclinical with compounds known as RGD peptides to determine studies is protected under § 271(e)(1)--even where the such peptides' efficacy as angiogenesis inhibitors and results of such research are not ultimately included in a suitability as potential drugs. submission of information to the FDA--as long as there is Two entities that held patents on the peptides in a reasonable basis for believing that the experiments in question filed a patent-infringement suit in the United question will produce the types of information that are States District Court for the Southern District of Califor- relevant to (a) an investigational new drug application, nia against the drug company, the scientist, and the re- which a drug maker must submit to the FDA, pursuant to a search institute at which the scientist had worked. A jury provision of the Federal Food, Drug, and Cosmetic Act found that (1) the defendants had infringed respondents' (FDCA) (21 U.S.C.S. § 355(i)), when seeking authoriza- patents, and (2) the drug company had failed to show that tion to conduct human clinical trials; or (b) a new drug its activities were protected by a provision of federal application, which a drug maker must submit to the FDA, patent law (35 U.S.C.S. § 271(e)(1)) under which it was pursuant to another FDCA provision (21 U.S.C.S. § generally not an act of patent infringement to make, use, 355(b)(1)), when seeking authorization to market a new or sell a patented invention solely for uses reasonably drug. related to the development and submission of information (2) Such use of patented compounds is protected in under a federal law regulating the manufacture, use, or experimentation on drugs that are not ultimately the sub- sale of drugs. The District Court, in response to post-trial ject of a submission to the FDA, at least where a drug- motions, affirmed the jury's damages award against the maker (a) has a reasonable basis for believing that a pat- drug company. ented compound may work, through a particular biological process, to produce a particular physiological Page 5 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468 effect; and (b) uses the compound in research that, if seq.), and (2) necessarily includes preclinical studies of successful, would be appropriate to include in a submis- patented compounds that are appropriate for submission sion to the FDA. to the Food and Drug Administration in the regulatory process. There is no room in § 271(e)(1) for excluding (3) Remand was necessary in the case at hand, be- certain information from the exemption on the basis of the cause the sufficiency of the evidence presented at trial had phase of research in which such information is developed not yet been reviewed under the standards set forth in a or the particular submission in which such information jury instruction that was consistent with the Supreme could be included. Court's construction of § 271(e)(1).

[**LEdHN3] LAWYERS' EDITION HEADNOTES: PATENTS § 290

-- infringement -- exemption -- drug research [**LEdHN1] Headnote: [3] PATENTS § 290 -- infringement -- exemption -- use of compound in drug Preclinical studies related to a drug's efficacy, research mechanism of action, pharmacokinetics, and pharma- Headnote: [1A] [1B] [1C] cology are within the scope of the patent-infringement exemption afforded by a provision of federal patent law Under certain conditions, a provision of federal pat- (35 U.S.C.S. § 271(e)(1))--under which it is generally not ent law (35 U.S.C.S. § 271(e)(1))--under which it is an act of patent infringement to make, use, or sell a pat- generally not an act of patent infringement to make, use, ented invention solely for uses reasonably related to the or sell a patented invention solely for uses reasonably development and submission of information under a fed- related to the development and submission of information eral law regulating the manufacture, use, or sale of under a federal law regulating the manufacture, use, or drugs--for such information may reasonably be included sale of drugs--is sufficiently broad to protect the use of in an investigational new drug application, which a drug patented compounds in preclinical research where the maker must submit to the Food and Drug Administration, results of such research are not ultimately included in a pursuant to a provision of the Federal Food, Drug, and submission of information to the Food and Drug Ad- Cosmetic Act (21 U.S.C.S. § 355(i)), when seeking au- ministration (FDA). Thus, the use of patented compounds thorization to conduct human clinical trials. in preclinical studies is protected under § 271(e)(1) as

long as there is a reasonable basis for believing that the [**LEdHN4] experiments in question will produce the types of infor- PATENTS § 290 mation that are relevant to (1) an investigational new drug -- infringement -- exemption -- drug research application, which a drug maker must submit to the FDA, Headnote: [4] pursuant to a provision of the Federal Food, Drug, and Cosmetic Act (FDCA) (21 U.S.C.S. § 355(i)), when Preclinical experiments related to a drug's efficacy, seeking authorization to conduct human clinical trials; or mechanism of action, pharmacokinetics, and pharma- (2) a new drug application, which a drug maker must cology were not necessarily disqualified from the protec- submit to the FDA, pursuant to another FDCA provision tion of the patent-infringement exemption afforded by a (21 U.S.C.S. § 355(b)(1)), when seeking authorization to provision of federal patent law (35 U.S.C.S. § market a new drug. [**162] 271(e)(1))--under which it was generally not an act of patent infringement to make, use, or sell a patented in- [**LEdHN2] vention solely for uses reasonably related to the devel- PATENTS § 290 opment and submission of information under a federal -- infringement -- exemption -- drug research law regulating the manufacture, use, or sale of drugs--on Headnote: [2] the asserted ground that such experiments were not conducted in conformity with good-laboratory-practices With respect to a provision of federal patent law (35 regulations promulgated by the Food and Drug Admini- U.S.C.S. § 271(e)(1))--under which it is generally not an stration (FDA), for: act of patent infringement to make, use, or sell a patented invention solely for uses reasonably related to the devel- (1) The FDA's requirement that preclinical studies be opment and submission of information under a federal conducted under "good laboratory practices" applied only law regulating the manufacture, use, or sale of drugs--§ to experiments to determine the safety of drugs (21 CFR § 271(e)(1)'s exemption (1) extends to all uses of patented 58.3(d)), not to preclinical studies of a drug's efficacy, inventions that are reasonably related to the development mechanism of action, pharmacology, or pharmacokinet- and submission of any information under the Federal ics. Food, Drug, and Cosmetic Act (21 U.S.C.S. § § 301 et Page 6 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468

(2) FDA regulations did not provide that even that a patented compound may work, through a particular safety-related experiments not conducted in compliance biological process, to produce a particular physiological with good laboratory practices regulations were not suit- effect--and where the drugmaker uses the compound in able for submission in an investigational new drug ap- research that, if successful, would be appropriate to in- plication, which a drug maker was required to submit to clude in a submission to the FDA--that use is "reasonably the FDA, pursuant to a provision of the Federal Food, related" to the development and submission of informa- Drug, and Cosmetic Act (21 [**163] U.S.C.S. § 355(i)), tion under federal law within the meaning of § 271(e)(1). when seeking authorization to conduct human clinical trials. [**LEdHN7] APPEAL § 1692.3 [**LEdHN5] -- remand -- issue not decided below PATENTS § 290 Headnote: [7] -- infringement -- exemption -- use of compound in drug On certiorari to review a Federal Court of Appeals' research judgment that drug testing involving the use of some Headnote: [5] patented compounds did not fall within a pat- For purposes of 35 U.S.C.S. § 271(e)(1)--which ent-infringement exemption provided by 35 U.S.C.S. § provides that it is generally not an act of patent in- 271(e)(1), the United States Supreme Court vacated the fringement to make, use, or sell a patented invention judgment and remanded the case for further proceedings, solely for uses reasonably related to the development and where: submission of information under a federal law which (1) The Court of Appeals had rejected a challenge to regulates the manufacture, use, or sale of drugs--basic the sufficiency of the evidence presented at trial on the scientific research on a particular compound, performed basis of a construction of § 271(e)(1) that was not con- without the intent to develop a particular drug or a rea- sistent with (a) the text of that provision, or (b) a relevant sonable belief that the compound will cause the sort of jury instruction that was consistent with the Supreme physiological effect that the researcher intends to induce, Court's construction of § 271(e)(1). is not "reasonably related to the development and submission of information" to the Food and Drug Admini- [**164] (2) The evidence thus had not yet been re- stration. viewed under the standards set forth in the jury instruction. [**LEdHN6] PATENTS § 290 SYLLABUS: -- infringement -- exemption -- use of compound in drug research It is not "an act of [patent] infringement to . . . use . . . Headnote: [6A] [6B] or import into the United States a patented invention . . . solely for uses reasonably related to the development and Under certain conditions, a provision of federal pat- submission of information under a Federal law which ent law (35 U.S.C.S. § 271(e)(1))--under which it is regulates the . . . use . . . of drugs." 35 U.S.C. § 271(e)(1). generally not an act of patent infringement to make, use, The Federal Food, Drug, and Cosmetic Act of 1938 or sell a patented invention solely for uses reasonably (FDCA) is such a law. Under the FDCA, a drug maker related to the development and submission of information must submit research data to the Food and Drug Admini- under a federal law regulating the manufacture, use, or stration (FDA) in an investigational new drug application sale of drugs--is sufficiently broad to protect the use of (IND) when seeking authorization to conduct human patented compounds in experimentation on drugs that are clinical trials, and in a new drug application [***2] (NDA) not ultimately the subject of a submission to the Food and when seeking authorization to market a new drug. Re- Drug Administration (FDA), for (1) the exemption of § spondents filed a patent-infringement suit, claiming, inter 271(e)(1) is applicable not only to the research relevant to alia, that petitioner had willfully infringed their patents by filing an abbreviated new drug application, pursuant to 21 supplying respondents' RGD peptides to other defendants U.S.C.S. § 355(j), for approval of a generic drug (that is, a for use in preclinical research. Petitioner answered, drug containing the same active ingredients as a drug among other things, that § 271(e)(1) exempted its actions already approved for the market); and (2) Congress ex- from infringement. [**165] The jury found otherwise empted from infringement all uses of patented compounds and awarded damages. In post-trial motions, the District reasonably related to the process of developing informa- Court affirmed the jury's award and denied petitioner's tion for submission under any federal law regulating the motion for judgment as a matter of law. The Federal manufacture, use, or distribution of drugs. Thus, at least Circuit affirmed that denial, finding that § 271(e)(1)'s where a drugmaker has a reasonable basis for believing safe harbor did not apply. It reversed the District Court's Page 7 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468 refusal to modify the damages award and remanded for OPINION: [*2376] Justice Scalia delivered the opinion further proceedings. of the Court. Held: [**LEdHR1A] [1A] This case presents the question whether uses of patented inventions in preclinical The use of patented compounds in preclinical studies research, the results of which are not ultimately included is protected under § 271(e)(1) at least as long as there is a in a submission to the Food and Drug Administration reasonable basis to believe that the compound tested (FDA), are exempted from infringement by 35 U.S.C. § could be the subject of an FDA submission and the ex- 271(e)(1). periments will produce the types of information relevant to an IND or NDA. The statutory text makes clear that § I 271(e)(1) provides a wide berth for the use of patented [HN1] It is generally an act of patent infringement to drugs in activities related to the federal [***3] regulatory "mak[e], us[e], offe[r] to sell, or sel[l] any patented in- process, including uses reasonably related to the devel- vention . . . during [*2377] the term of the patent there- opment and submission of any information under the for." § 271(a). In 1984, Congress enacted an exemption FDCA. Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, to this general rule, see Drug Price Competition and 665-669, 110 L. Ed. 2d 605, 110 S. Ct. 2683. This nec- Patent Term Restoration Act of 1984, § 202, 98 Stat. essarily includes preclinical studies, both those pertaining 1585, as amended, 35 U.S.C. § 271(e)(1), which pro- to a drug's safety in humans and those related to, e.g., a vides: drug's efficacy and mechanism of action. Additionally, § 271(e)(1) exempts from infringement the use of patented [HN2] "It shall not be an act of in- compounds in preclinical research, even when the pat- fringement to make, use, offer to sell, or ented compounds do not themselves become the subject sell within the United States or [**166] of an FDA submission. The "reasonable relation" re- import into the United States a patented quirement cannot be read effectively to limit § 271(e)(1)'s invention (other than a new animal drug or stated protection of activities leading to FDA approval for veterinary biological product (as those all drugs to those activities leading to FDA approval for [***5] terms are used in the Federal Food, generic drugs. Similarly, the use of a patented compound Drug, and Cosmetic Act and the Act of in experiments not themselves included in a "submission March 4, 1913) . . .) solely for uses rea- of information" to the FDA does not, standing alone, sonably related to the development and render the use infringing. Because the Federal Circuit submission of information under a Federal applied the wrong standard in rejecting petitioner's chal- law which regulates the manufacture, use, lenge to the jury's finding that petitioner failed to show or sale of drugs . . . ." that its activities were covered by § 271(e)(1), the trial evidence has yet to [***4] be reviewed under the stan- [HN3] The Federal Food, Drug, and Cosmetic Act dard set forth in the jury instruction, and developed in (FDCA), ch. 675, 52 Stat. 1040, as amended, 21 U.S.C. § more detail here. 301 et seq, is "a Federal law which regulates the manufacture, use, or sale of drugs." See 21 U.S.C. § 355(a); Eli 331 F.3d 860, vacated and remanded. Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 665-666, 674, 110 L. Ed. 2d 605, 110 S. Ct. 2683 (1990). Under the FDCA, a drugmaker must submit research data to the COUNSEL: FDA at two general stages of new-drug development. n1 First, a drugmaker must gain authorization to conduct E. Joshua Rosenkranz argued the cause for peti- clinical trials (tests on humans) by submitting an inves- tioner. tigational new drug application (IND). See 21 U.S.C. § Daryl Joseffer argued the cause for the United States, 355(i); 21 CFR § 312.1 et seq. (2005). n2 The IND must as amicus curiae, by special leave of court. describe "preclinical tests (including tests on animals) of [the] drug adequate to justify the proposed clinical test- Mauricio A. Flores argued the cause for respon- ing." 21 U.S.C. § 355(i)(1)(A); see 21 CFR § § dents. 312.23(a)(5) and (a)(8) (specifying [***6] necessary

information from preclinical tests). Second, to obtain JUDGES: Scalia, J., delivered the opinion for a unani- authorization to market a new drug, a drugmaker must mous Court. submit a new drug application (NDA), containing "full

reports of investigations which have been made to show OPINIONBY: SCALIA 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 Page 8 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468 studies, as well as preclinical studies related to a drug's in chicken embryos, first using a monoclonal antibody efficacy, toxicity, and pharmacological properties. See 21 (LM609) he developed himself and later using a cyclic CFR § § 314.50(d)(2) (preclinical studies) and (d)(5) RGD peptide (EMD 66203) provided by petitioner. n3 (clinical studies). 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 n1 [HN4] Drugmakers that desire to market a Way to Shrink Tumors, N. Y. Times, Dec. 30, 1994, p A1; generic drug (a drug containing the same active Brooks, et al., Integrin [alpha] [nu] [beta] <3> Antago- ingredients as a drug already approved for the nists Promote Tumor Regression by Inducing Apoptosis market) may file an abbreviated new drug appli- of Angiogenic Blood Vessels, 79 Cell 1157 (Dec. 30, cation (ANDA) with the FDA. See 21 U.S.C. § 1994); Brooks, Clark, and Cheresh, Requirement of 355(j). The sponsor of a generic drug does not Vascular Integrin [alpha] [nu] [beta] <3> for Angiogene- have to make an independent showing that the sis, 264 Science 569 (Apr. 22, 1994). 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 in- n3 In the proceedings below, the Court of gredients as, and is bioequivalent to, the drug that Appeals held that respondents' patents covered the it is mimicking. See § § 355(j)(2)(A)(ii) and (iv); cyclic RGD peptides developed by petitioner. § 355(j)(8)(B). 331 F.3d 860, 869 (CA Fed. 2003). Petitioner [***7] does not contest that ruling here.

[***9] n2 We cite the current versions of federal With petitioner's agreement to fund research at statutes and regulations. The provisions cited are Scripps due to expire in July 1995, Dr. Cheresh submitted materially unchanged since the period of peti- a detailed proposal for expanded collaboration between tioner's alleged infringement. 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 II inhibitors," id., at 105a, beginning with in vitro and in vivo A testing of RGD peptides at Scripps in year one and cul- minating with the submission of an IND to the FDA in Respondents Integra Lifesciences I, Ltd., and the year three, id., at 106a-107a. Petitioner agreed to the Burnham Institute, own five patents related to the tripep- material terms of the proposal on February 20, 1995, id., tide sequence Arg-Gly-Asp, known in single-letter nota- at 124a-125a, and on April 13, 1995, pledged $6 million tion as the "RGD peptide." U.S. Patent Nos. 4,988,621, over three years to fund research at Scripps, id., at 126a. 4,792,525, 5,695,997, 4,879,237, and 4,789,734, Supp. Petitioner's April 13 letter specified that Scripps would be App. SA11-SA19. The RGD peptide promotes cell ad- responsible for testing RGD peptides produced by peti- hesion by attaching to [alpha] [nu] [beta] <3> integrins, tioner as potential drug candidates but that, once a pri- receptors commonly located on the outer surface of cer- mary candidate for clinical testing was in "the pipeline," tain endothelial cells. 331 F.3d 860, 862-863 (CA Fed. petitioner would perform the toxicology tests necessary 2003). for FDA approval to proceed to clinical trials. Id., at 127a; Beginning in 1988, petitioner Merck KGaA provided see 21 CFR § 312.23(a)(8)(iii) (2005) (requirement that funding for angiogenesis research conducted by Dr. David "nonclinical laboratory study" include a certification Cheresh at the Scripps Research Institute (Scripps). [***10] that it was performed under good laboratory [*2378] Telios Pharms., Inc. v. Merck KGaA, 1997 U.S. practices); see also § 58.3(d) (2004) (defining Dist. LEXIS 24187, Case No. 96-CV-1307 (SD Cal., Sept. "[n]onclinical laboratory study"). Scripps and petitioner 9, 1997), App. 30a. Angiogenesis is the process by which concluded an agreement of continued collaboration in [**167] new blood vessels sprout from existing vessels; it September 1995. Case No. 96-CV-1307, App. 31a. plays a critical role in many diseases, including solid Pursuant to the agreement, Dr. Cheresh directed in [***8] tumor cancers, diabetic retinopathy, and rheu- vitro and in vivo experiments on RGD peptides provided matoid arthritis. 331 F.3d, at 863. In the course of his by petitioner from 1995 to 1998. These experiments research, Dr. Cheresh discovered that it was possible to focused on EMD 66203 and two closely related deriva- inhibit angiogenesis by blocking the [alpha] [nu] [beta] tives, EMD 85189 and EMD 121974, and were designed <3> integrins on proliferating endothelial cells. Ibid. In to evaluate the suitability of each of the peptides as po- 1994, Dr. Cheresh succeeded in reversing tumor growth Page 9 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468 tential drug candidates. 331 F.3d, at 863. Accordingly, spondents' patents by supplying the RGD peptide to the tests measured the efficacy, specificity, and toxicity of Scripps, and that Dr. Cheresh and Scripps infringed the the particular peptides as angiogenesis inhibitors, and same patents by using the RGD peptide in experiments evaluated their mechanism of action and pharmacokinet- related to angiogenesis. Respondents sought damages ics in animals. Ibid. Based on the test results, Scripps from petitioner and [***13] a declaratory judgment decided in 1997 that EMD 121974 was the most promis- against Dr. Cheresh and Scripps. Id., at 863. Petitioner ing [**168] candidate for testing in humans. Ibid. Over answered that its actions involving the RGD peptides did the same period, Scripps performed similar tests on not infringe respondents' patents, and that in any event LM609, a monoclonal antibody developed by Dr. Cheresh. they were protected by the common-law research ex- n4 App. [*2379] 277a, 285a-298a. Scripps also con- emption and 35 U.S.C. § 271(e)(1). 331 F.3d, at 863. ducted more basic research on organic mimetics designed At the conclusion of trial, the District Court held that, to block [alpha] [nu] [beta] <3> [***11] integrins in a with one exception, petitioner's pre-1995 actions related manner similar to the RGD peptides, id., at 223a-224a; it to the RGD peptides were protected by the common-law appears that Scripps used the RGD peptides in these tests research exemption, but that a question of fact remained as "positive controls" against which to measure the effi- as to whether petitioner's use of the RGD peptides after cacy of the mimetics, id., at 188a. 1995 fell within the § 271(e)(1) safe harbor. With the consent of the parties, the District Court gave the fol- lowing instruction regarding the § 271(e)(1) exemption: n4 Scripps licensed the patent for the monoclonal antibody to Ixsys, a California biotech- "To prevail on this defense, [petitioner] nology company. App. 271a. Based on research must prove by a preponderance of the conducted at Scripps and at Ixsys in consultation evidence that it would be objectively rea- with Dr. Cheresh, an IND application for a hu- sonable for a party in [petitioner's] and manized version of the antibody called Vitaxin Scripps' situation to believe that there was was filed with the FDA on December 30, 1996. a decent prospect that the accused [**169] Id., at 271a-274a, 404a. In addition to toxicology activities would contribute, relatively di- tests, the application included information from rectly, to the generation of the kinds of Dr. Cheresh's in vitro and in vivo experiments re- information that are likely to be relevant in lated to the antibody's mechanism of action and the processes by [***14] which the FDA efficacy as an inhibitor of angiogenesis. Id., at would decide whether to approve the 399a-404a. Ixsys began clinical testing of the an- product in question. tibody as an angiogenesis inhibitor in February "Each of the accused activities must 1997. Id., at 304a. be evaluated separately to determine

whether the exemption applies. In November 1996, petitioner initiated a formal pro- "[Petitioner] does not need to show ject to guide one of [***12] its RGD peptides through the that the information gathered from a par- regulatory approval process in the United States and ticular activity was actually submitted to Europe. Id., at 129a. Petitioner originally directed its the FDA." App. 57a. efforts at EMD 85189, but switched focus in April 1997 to EMD 121974. Case No. 96-CV-1307, App. 31a. Peti- [*2380] The jury found that petitioner, Dr. Cheresh, tioner subsequently discussed EMD 121974 with officials and Scripps infringed respondents' patents and that peti- at the FDA. Id., at 397a. In October 1998, petitioner tioner had failed to show that its activities were protected shared its research on RGD peptides with the National by § 271(e)(1). It awarded damages of $15 million. Cancer Institute (NCI), which agreed to sponsor clinical trials. Id., at 214a-217a. Although the fact was excluded In response to post-trial motions, the District Court from evidence at trial, the lower court's opinion reflects dismissed respondents' suit against Dr. Cheresh and that NCI filed an IND for EMD 121974 in 1998. 331 Scripps, but affirmed the jury's damage award as sup- F.3d, at 874 (Newman, J., dissenting). ported by substantial evidence, Civ. Action No. 961307 JMF (SD Cal. Mar. 26, 2001), App. to Pet. for Cert. 52a, B and denied petitioner's motion for judgment as a matter of law, Civ. Action No. 96CV-1307 JMF (SD Cal., Mar. 6, On July 18, 1996, respondents filed a pat- 2001), App. to Pet. for Cert. 50a. With respect to the last, ent-infringement suit against petitioner, Scripps, and Dr. the District Court explained that the evidence was suffi- Cheresh in the District Court for the Southern District of cient to show that "any connection between the infringing California. Respondents' complaint alleged that petitioner Scripps experiments and FDA review was insufficiently willfully infringed and induced others to infringe re- Page 10 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468 direct to qualify for the [§ 271(e)(1) exemption]. [***15] the exemption on the basis of the phase of research in " Id., at 49a. which it is developed or the particular submission in which it could be included. n6 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 n6 Although the Court of Appeals' opinion of law to petitioner, on the ground that § 271(e)(1)'s safe suggests in places that § 271(e)(1)'s exemption harbor did not apply because "the Scripps work sponsored from infringement is limited to research conducted by [petitioner] was not clinical testing to supply informa- in clinical trials, see 331 F.3d at 866, we do not tion to the FDA, but only general biomedical research to understand it to have adopted that position. The identify new pharmaceutical compounds." 331 F.3d, at Court of Appeals recognized that information in- 866. It reversed the District Court's refusal to modify the cluded in an IND would come within § 271(e)(1)'s damages award, and remanded for further proceedings. n5 safe harbor. Ibid. Because an IND must be filed Id., at 872. Judge Newman dissented on both points. See before clinical trials may begin, such information id., at 874, 877. The panel unanimously affirmed the would necessarily be developed in preclinical District Court's ruling that respondents' patents covered studies. 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- [**LEdHR3] [3] [*2381] Respondents concede struction of § 271(e)(1). 543 U.S. ___, 160 L. Ed. 2d 609, the breadth of § 271(e)(1) in this regard, but argue that the 125 S. Ct. 823 (2004). only preclinical data of interest to the FDA is that which pertains to the safety of the drug in humans. In respon-

dents' view, preclinical studies related to a drug's efficacy, n5 On remand, the District Court reduced the mechanism of action, pharmacokinetics, and pharma- damages award to $6.375 million. Civ. Action No. cology are [***18] not reasonably included in an IND or CV.96 CV 1307-B(AJB), 2004 U.S. Dist. LEXIS an NDA, and are therefore outside the scope of the ex- 20725, 2004 WL 2284001, *1 (SD Cal., Sept. 7, emption. [HN7] We do not understand the FDA's interest 2004). in information gathered in preclinical studies to be so constrained. To be sure, its regulations provide that the [***16] agency's "primary objectives in reviewing an IND are . . . to assure the safety and rights of subjects," 21 CFR III 312.22(a) (2005), but it does not follow that the FDA is As described earlier, [HN5] 35 U.S.C. § 271(e)(1) not interested in reviewing information related to other provides that "[i]t shall not be an act of infringement to . . . characteristics of a drug. To the contrary, the FDA re- use . . . or import into the United States a patented inven- quires that applicants include in an IND summaries of the tion . . . solely for uses reasonably related to the devel- pharmacological, toxicological, pharmacokinetic, and opment and submission of information under a Federal biological qualities of the drug in animals. See § law which regulates the . . . use . . . of drugs." Though the 312.23(a)(5); Department of Health and Human Services, contours of this provision are not exact in every respect, Guidance for Industry, Good Clinical Practice: Consoli- the statutory text makes clear that it provides a wide berth dated Guidance 45 (Apr. 1996) ("The results of all rele- for the use of patented drugs in activities related to the vant nonclinical pharmacology, toxicology, pharma- federal regulatory process. cokinetic, and investigational product metabolism studies should be provided in summary form. This summary [**LEdHR2] [2] As an initial matter, we think should address the methodology used, the results, and a [HN6] it apparent from the statutory text [**170] that § discussion of the relevance of the findings to the investi- 271(e)(1)'s exemption from infringement extends to all gated therapeutic and the possible unfavorable and unin- uses of patented inventions that are reasonably related to tended effects [***19] in humans"). The primary (and, in the development and submission of any information under some cases, only) way in which a drugmaker may obtain the FDCA. Cf. Eli Lilly, 496 U.S., at 665-669, 110 L. Ed. such information is through preclinical in vitro and in vivo 2d 605, 110 S. Ct. 2683 (declining to limit § 271(e)(1)'s studies. exemption from infringement to submissions under particular statutory provisions that regulate drugs). This Moreover, [HN8] the FDA does not evaluate the necessarily includes preclinical studies of patented com- safety of proposed clinical experiments in a vacuum; pounds that are appropriate for submission to the FDA in rather, as the statute and regulations reflect, it asks the regulatory process. There is simply no room in the whether the proposed clinical trial poses an "unreasonable [***17] statute for excluding certain information from risk." 21 U.S.C. § 355(i)(3)(B)(i); see also 21 CFR § Page 11 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468

312.23(a)(8) (2005) (requiring applicants to include F.3d at 865; see also id., at 866 (similar). The court pharmacological and toxicological studies that serve as explained: the basis of their conclusion that clinical testing would be "The FDA has no interest in the hunt "reasonably safe"); § 56.111(a)(2) (2004) [**171] for drugs that may or may not later un- (providing that the Institutional Review Boards that dergo clinical testing for FDA approval. oversee clinical trials must consider whether the "[r]isks For [***22] instance, the FDA does not to subjects are reasonable in relation to anticipated bene- require information about drugs other than fits"). This assessment involves a comparison of the risks the compound featured in an [IND] ap- and the benefits associated with the proposed clinical plication. Thus, the Scripps work spon- trials. As the Government's brief, filed on behalf of the sored by [petitioner] was not 'solely for FDA, explains, the "FDA might allow clinical testing of a uses reasonably related to' clinical testing drug that posed significant safety concerns if the drug had for FDA." Ibid. a sufficiently positive potential to address a serious dis- ease, although the [***20] agency would not accept Second, the court concluded that the exemption "does similar risks for a drug that was less likely to succeed or not globally embrace all experimental activity that at that would treat a less serious medical condition." Brief some point, however attenuated, [**172] may lead to an for United States as Amicus Curiae 10. Accordingly, the FDA approval process." Id., at 867. n7 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 n7 The Court of Appeals also suggested that a proposed trial." Guidance for Industry, supra, at 43. Such limited construction of § 271(e)(1) is necessary to information necessarily includes preclinical studies of a avoid depriving so-called "research tools" of the drug's efficacy in achieving particular results. complete value of their patents. Respondents have [**LEdHR4] [4] Respondents contend that, even never argued the RGD peptides were used at accepting that the FDA is interested in preclinical re- Scripps as research tools, and it is apparent from search concerning drug characteristics other than safety, the record that they were not. See 331 F.3d at 878 the experiments in question here are necessarily [*2382] (Newman, J., dissenting) ("Use of an existing tool disqualified because they were not conducted in confor- in one's research is quite different from study of mity with the FDA's good laboratory practices regulations. the tool itself"). We therefore need not--and do This argument fails for at least two reasons. First, [HN9] not--express a view about whether, or to what the FDA's requirement that preclinical studies be con- extent, § 271(e)(1) exempts from infringement the ducted under "good laboratory practices" applies only to use of "research tools" in the development of in- experiments on drugs "to determine their safety," 21 CFR formation for the regulatory process. § 58.3(d). See 21 CFR § 58.1(a); § 312.23(a)(8)(iii) (2005) (only "nonclinical laboratory study subject to the [***23] good laboratory practice [***21] regulations under part [**LEdHR1B] [1B] [**LEdHR5] [5] 58" must certify compliance with good laboratory practice [**LEdHR6A] [6A] We do not quibble with the latter regulations). The good laboratory practice regulations do statement. [HN10] Basic scientific research on a par- not apply to preclinical studies of a drug's efficacy, ticular compound, performed without the intent to de- mechanism of action, pharmacology, or pharmacokinetics. velop a particular drug or a reasonable belief that the Second, FDA regulations do not provide that even compound will cause the sort of physiological effect the safety-related experiments not conducted in compliance researcher intends to induce, is surely not "reasonably with good laboratory practices regulations are not suitable related to the development and submission of informa- for submission in an IND. Rather, such studies must tion" to the FDA. It does not follow from this, however, include "a brief statement of the reason for the noncom- that § 271(e)(1)'s exemption from infringement cate- pliance." Ibid. gorically excludes either (1) experimentation on drugs The Court of Appeals' conclusion that § 271(e)(1) that are not ultimately the subject of an FDA submission did not protect petitioner's provision of the patented RGD or (2) use of patented compounds in experiments that are peptides for research at Scripps appeared to rest on two not ultimately submitted to the FDA. Under certain con- somewhat related propositions. First, the court credited ditions, we think the exemption is sufficiently broad to the fact that the "Scripps-Merck experiments did not protect the use of patented compounds in both situations. supply information for submission to the [FDA], but As to the first proposition, it disregards the reality instead identified the best drug candidate to subject to that, even at late stages in the development of a new drug, future clinical testing under the FDA processes." 331 scientific testing is a process of trial and error. In the Page 12 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468

[*2383] vast majority of cases, neither the drugmaker nor information, and in what quantities, it will take to win that its scientists have any way of knowing whether an initially agency's approval." Intermedics, Inc. v. Ventritex, Inc., promising candidate will prove successful over a battery 775 F. Supp. 1269, 1280 (ND Cal. 1991), aff'd, 991 F.2d of experiments. That is the reason they conduct the ex- 808 (CA Fed. 1993). This is especially true at the pre- periments. [***24] Thus, to construe § 271(e)(1), as the clinical stage of drug approval. FDA regulations provide Court of Appeals did, not to protect research conducted on only that "[t]he amount of information on a particular patented compounds for which an IND is not ultimately drug that must be submitted in an IND . . . depends upon filed is effectively to limit assurance of exemption to the such factors as the novelty of the drug, the extent to which activities necessary to seek approval of a generic drug: it has been studied previously, the known or suspected One can know at the outset that a particular compound risks, and the developmental phase of the drug." 21 CFR § will be the subject of an eventual application to the FDA 312.22(b). We thus agree with the Government that only if the active ingredient in the drug being tested is [HN13] the use of patented compounds in preclinical identical to that in a drug that has already been approved. studies is protected under § 271(e)(1) as long as there is a reasonable basis for believing that the experiments will [**LEdHR6B] [6B] The statutory text does not produce "the types of information that are relevant to require such a result. [HN11] Congress did not limit § [*2384] an IND or NDA." Brief of United States as 271(e)(1)'s safe harbor to the development of information Amicus Curiae 23. 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 com- [**LEdHR7] [7] Before [***27] the Court of pounds "reasonably related" to the process of developing Appeals, petitioner challenged the sufficiency of the information for submission under any federal law regu- evidence supporting the jury's finding that it failed to lating the manufacture, use, or distribution of drugs. See show that "all of the accused activities are covered by [§ Eli Lilly, 496 U.S., at 674, 110 L. Ed. 2d 605, 110 S. Ct. 271(e)(1)]." App. 62a. That court rejected the challenge 2683. We decline to read the "reasonable relation" re- on the basis of a construction of § 271(e)(1) that was not quirement so narrowly as to render § 271(e)(1)'s stated consistent with the text of that provision or the relevant protection of [***25] activities leading to FDA approval jury instruction. n8 Thus, the evidence presented at trial for all drugs illusory. Properly construed, § 271(e)(1) has yet to be reviewed under the standards set forth in the leaves adequate space for experimentation and failure on jury instruction, which we believe to be consistent with, if the road to regulatory approval: At least where a drug- less detailed than, the construction of § 271(e)(1) that we maker has a reasonable basis for believing that a patented adopt today. We decline to undertake a review of the compound may work, through a particular biological sufficiency of the evidence under a proper construction of process, to produce a particular physiological effect, and § 271(e)(1) for the first time here. Accordingly, we va- uses the compound in research that, if successful, [**173] cate the judgment of the Court of Appeals and remand the would be appropriate to include in a submission to the case for proceedings consistent with this opinion. FDA, that use is "reasonably related" to the "development

and submission of information under . . . Federal law." § 271(e)(1). n8 The relevant jury instruction provided only that there must be a "decent prospect that the ac- [**LEdHR1C] [1C] For similar reasons, [HN12] cused activities would contribute, relatively di- the use of a patented compound in experiments that are rectly, to the generation of the kinds of informa- not themselves included in a "submission of information" tion that are likely to be relevant in the processes to the FDA does not, standing alone, render the use in- by which the FDA would decide whether to ap- fringing. The relationship of the use of a patented com- prove the product in question." App. 57a. It did pound in a particular experiment to the "development and not say that, to fall within § 271(e)(1)'s exemption submission of information" to the FDA does not become from infringement, the patented compound used in more attenuated (or less reasonable) simply because the experimentation must be the subject of an eventual data from that experiment are left out of the submission application to the FDA. And it expressly rejected that is ultimately passed along to the FDA. Moreover, the notion that the exemption only included ex- many of the uncertainties that exist with respect to the periments that produced information included in selection of a specific [***26] drug exist as well with an IND or NDA. Ibid. 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 [***28] approval for their new product exactly which kinds of It is so ordered. Page 13 125 S. Ct. 2372, *; 162 L. Ed. 2d 160, **; 2005 U.S. LEXIS 4840, ***; 73 U.S.L.W. 4468

L Ed Index, Drugs and Narcotics; Patents REFERENCES: Go To Full Text Opinion Annotation References

Go To Supreme Court Brief(s) Construction and application of Hatch-Waxman Act, Pub. L. No. 98-417, 98 Stat. 1585 (1984) (codified as Go To Supreme Court Transcripts amended at 21 U.S.C.A. § 355 and 35 U.S.C.A. § 271(e) (1994)). 180 A.L.R. Fed. 487. 25 Am Jur 2d, Drugs and Controlled Substances § § What is "new drug" within meaning of § 201(p) of 103, 108, 118; 60 Am Jur 2d, Patents § 793 Federal Food, Drug, and Cosmetic Act (21 U.S.C.A. § 321(p)). 133 A.L.R. Fed. 229. 35 U.S.C.S. § 271(e)(1) L Ed Digest, Patents § 290