Merck Kgaa v. Integra Lifesciences I, Ltd., No. 03-1237.

• Court: United States Supreme Court
• Writing for the Court: Justice Scalia
• Citation: 545 U.S. 193,162 L. Ed. 2d 160,125 S. Ct. 2372
• Parties: MERCK KGAA v. INTEGRA LIFESCIENCES I, LTD., ET AL.
• Docket Number: No. 03-1237.
• Decision Date: 13 June 2005

545 U.S. 193 125 S. Ct. 2372 162 L. Ed. 2d 160 MERCK KGAA
v.
INTEGRA LIFESCIENCES I, LTD., ET AL. No. 03-1237. Supreme Court of United States. 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 drugmaker must submit research data to the Food and Drug Administration (FDA) in an investigational new drug application (IND) when seeking authorization to conduct human clinical trials, and in a new drug application (NDA) when seeking authorization to market a new drug. Respondents filed a patent-infringement suit, claiming, inter alia, that petitioner had willfully infringed their patents by supplying respondents' RGD peptides to other defendants for use in preclinical research. Petitioner answered, among other things, that §271(e)(1) exempted its actions from infringement. The jury found otherwise and awarded damages. In post-trial motions, the District Court affirmed the jury's award and denied petitioner's motion for judgment as a matter of law. The Federal Circuit affirmed that denial, finding that §271(e)(1)'s safe harbor did not apply. It reversed the District Court's refusal to modify the damages award and remanded for further proceedings.

Held: The use of patented compounds in preclinical studies is protected under §271(e)(1) at least as long as there is a reasonable basis to believe that the compound tested could be the subject of an FDA submission and the experiments will produce the types of information relevant to an IND or NDA. The statutory text makes clear that §271(e)(1) provides a wide berth for the use of patented drugs in activities related to the federal regulatory process, including uses reasonably related to the development and submission of any information under the FDCA. Eli Lilly & Co. v. Medtronic, Inc., 496 U. S. 661, 665-669. This necessarily includes preclinical studies, both those pertaining to a drug's safety in humans and those related to, e. g., a drug's efficacy and mechanism of action. Additionally, § 271(e)(1) exempts from infringement the use of patented compounds in preclinical research, even when the patented compounds do not themselves become the subject of an FDA submission.

[545 U.S. 194]

The "reasonable relation" requirement cannot be read effectively to limit § 271(e)(1)'s stated protection of activities leading to FDA approval for all drugs to those activities leading to FDA approval for generic drugs. Similarly, the use of a patented compound in experiments not themselves included in a "submission of information" to the FDA does not, standing alone, render the use infringing. Because the Federal Circuit applied the wrong standard in rejecting petitioner's challenge to the jury's finding that petitioner failed to show that its activities were covered by § 271(e)(1), the trial evidence has yet to be reviewed under the standard set forth in the jury instruction, and developed in more detail here. Pp. 202-208.

331 F. 3d 860, vacated and remanded.

SCALIA, J., delivered the opinion for a unanimous Court.

CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR THE FEDERAL CIRCUIT

E. Joshua Rosenkranz argued the cause for petitioner. With him on the briefs were M. Patricia Thayer, James N. Czaban, and Donald R. Dunner.

Daryl Joseffer argued the cause for the United States as amicus curiae in support of petitioner. With him on the brief were Acting Solicitor General Clement, Assistant Attorney General Keisler, Deputy Solicitor General Hungar, Douglas N. Letter, Mark S. Davies, Alex M. Azar II, Richard Lambert, John M. Whealan, and Heather F. Auyang.

Mauricio A. Flores argued the cause for respondents. With him on the brief were Raphael V. Lupo, Cathryn Campbell, Mark G. Davis, M. Miller Baker, Richard B. Rogers, and David M. Beckwith.^*

[545 U.S. 195]

JUSTICE SCALIA delivered the opinion of the Court.

This case presents the question whether uses of patented inventions in preclinical research, the results of which are not ultimately included in a submission to the Food and Drug Administration (FDA), are exempted from infringement by 35 U. S. C. § 271(e)(1).

I

It is generally an act of patent infringement to "mak[e], us[e], offe[r] to sell, or sel[l] any patented invention . . . during the term of the patent therefor." §271(a). In 1984, Congress enacted an exemption to this general rule, see Drug Price Competition and Patent Term Restoration Act of 1984, § 202, 98 Stat. 1585, as amended, 35 U. S. C. §271(e)(1), which provides:

"It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention (other than a new animal drug or veterinary biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Act of March 4, 1913) . . .) solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs . . . ."

545 U.S. 196

The Federal Food, Drug, and Cosmetic Act (FDCA), ch. 675, 52 Stat. 1040, as amended, 21 U. S. C. § 301 et seq., is "a Federal law which regulates the manufacture, use, or sale of drugs." See § 355(a); Eli Lilly & Co. v. Medtronic, Inc., 496 U. S. 661, 665-666, 674 (1990). Under the FDCA, a drugmaker must submit research data to the FDA at two general stages of new-drug development.¹ First, a drugmaker must gain authorization to conduct clinical trials (tests on humans) by submitting an investigational new drug application (IND). See 21 U. S. C. § 355(i); 21 CFR § 312.1 et seq. (2005).² The IND must describe "preclinical tests (including tests on animals) of [the] drug adequate to justify the proposed clinical testing." 21 U. S. C. § 355(i)(1)(A); see 21 CFR §§312.23(a)(5) and (a)(8) (specifying necessary information from preclinical tests). Second, to obtain authorization to market a new drug, a drugmaker must submit a new drug application (NDA), containing "full reports of investigations which have been made to show whether or not [the] drug is safe for use and whether [the] drug is effective in use." 21 U. S. C. § 355(b)(1). Pursuant to FDA regulations, the NDA must include all clinical studies, as well as preclinical studies related to a drug's efficacy, toxicity, and pharmacological properties. See 21 CFR §§314.50(d)(2) (preclinical studies) and (d)(5) (clinical studies).

545 U.S. 197

II A

Respondents, Integra Lifesciences I, Ltd., and the Burnham Institute, own five patents related to the tripeptide sequence Arg-Gly-Asp, known in single-letter notation as the "RGD peptide." U. S. Patent Nos. 4,988,621, 4,792,525, 5,695,997, 4,879,237, and 4,789,734, Supp. App. SA11-SA19. The RGD peptide promotes cell adhesion by attaching to α^vβ³ integrins, receptors commonly located on the outer surface of certain endothelial cells. 331 F. 3d 860, 862-863 (CA Fed. 2003).

Beginning in 1988, petitioner Merck KGAA provided funding for angiogenesis research conducted by Dr. David Cheresh at the Scripps Research Institute (Scripps). Telios Pharmaceuticals v. Merck KGaA, Case No. 96-CV-1307 (SD Cal., Sept. 9, 1997), App. 30a. Angiogenesis is the process by which new blood vessels sprout from existing vessels; it plays a critical role in many diseases, including solid tumor cancers, diabetic retinopathy, and rheumatoid arthritis. 331 F. 3d, at 863. In the course of his research, Dr. Cheresh discovered that it was possible to inhibit angiogenesis by blocking the α^vβ³ integrins on proliferating endothelial cells. Ibid. In 1994, Dr. Cheresh succeeded in reversing tumor growth in chicken embryos, first using a monoclonal antibody (LM609) he developed himself and later using a cyclic RGD peptide (EMD 66203) provided by petitioner.³ App. 190a. Dr. Cheresh's discoveries were announced in leading medical journals and received attention in the general media. See Altman, Scientists Report Finding a Way to Shrink Tumors, N. Y. Times, Dec. 30, 1994, p. A1; Brooks et al., Integrin

545 U.S. 198

α^vβ³ Antagonists Promote Tumor Regression by Inducing Apoptosis of Angiogenic Blood Vessels, 79 Cell 1157 (Dec. 30, 1994); Brooks, Clark, & Cheresh, Requirement of Vascular Integrin α^vβ³ for Angiogenesis, 264 Science 569 (Apr. 22, 1994).

With petitioner's agreement to fund research at Scripps due to expire in July 1995, Dr. Cheresh submitted a detailed proposal for expanded collaboration between Scripps and petitioner on February 1, 1995. App. 95a-107a. The proposal set forth a 3-year timetable in which to develop "integrin antagonists as angiogenesis inhibitors," id., at 105a, beginning with in vitro and in vivo testing of RGD peptides at Scripps in year one and culminating with the submission of an IND to the FDA in year three, id., at 106a-107a. Petitioner agreed to the material terms of the proposal on February 20, 1995, id., at 124a-125a, and on April 13, 1995, pledged $6 million over three years to fund research at Scripps, id., at 126a. Petitioner's April 13 letter specified that Scripps would be responsible for testing RGD peptides produced by petitioner as potential drug candidates but that, once a primary candidate for clinical testing was in "the pipeline," petitioner would perform the toxicology tests necessary for FDA approval to proceed to clinical trials. Id., at 127a; see 21 CFR § 312.23(a)(8)(iii) (2005) (requirement that "nonclinical laboratory study" include a certification that it was performed under good laboratory practices); see also § 58.3(d) (2004) (defining "[n]onclinical laboratory study"). Scripps and petitioner concluded an agreement of continued collaboration in September...