## Facts

- Integra owned patents covering certain RGD peptide sequences used in angiogenesis-related research.
- Merck sponsored preclinical angiogenesis research at The Scripps Research Institute and supplied patented RGD peptides for use in experiments.
- The research involved screening and evaluating multiple peptide candidates and conducting additional preclinical work (including toxicology) on selected candidates with the aim of advancing toward FDA-regulated clinical development.
- Integra sued Merck for willful patent infringement and for inducing infringement by providing the patented peptides to Scripps researchers.
- Merck asserted that its conduct was exempt from infringement under 35 U.S.C. § 271(e)(1) because the uses were reasonably related to developing and submitting information to the FDA under the FDCA.
- A jury found infringement and rejected the § 271(e)(1) defense; the district court upheld the verdict.
- The Federal Circuit affirmed the rejection of the defense, characterizing the work as general biomedical research to identify new compounds rather than FDA-directed testing.
- The Supreme Court granted review to determine the scope of § 271(e)(1) as applied to preclinical research.

## Issues

1. Whether 35 U.S.C. § 271(e)(1) exempts from infringement the use of patented compounds in preclinical experiments when the work is undertaken with a reasonable relation to generating information for potential FDA IND/NDA submissions.
2. Whether the exemption can apply even if particular experiments or particular tested compounds are not ultimately included in, or do not become the subject of, an FDA submission.
3. What limits the “reasonably related” standard imposes on claims that exploratory research falls within the safe harbor.

## Decision

- The Court held that § 271(e)(1) can protect the use of patented compounds in preclinical studies when there is a reasonable basis to believe (i) the tested compound could be the subject of an FDA submission and (ii) the experiments will generate information of the type relevant to an IND or NDA.
- The Court rejected the view that the safe harbor is limited to clinical testing or to experiments whose results are actually submitted to the FDA.
- The Court agreed that the statute does not exempt all experimental activity that might, in an attenuated way, lead to an FDA process, and excluded from the safe harbor basic scientific research lacking intent or reasonable belief tied to developing a particular drug and producing FDA-relevant information.
- The Court vacated the Federal Circuit’s judgment and remanded for application of the correct legal standard to the evidence.

## Legal Principles

- 35 U.S.C. § 271(e)(1) provides a broad exemption for making and using patented inventions solely for uses reasonably related to the development and submission of any information under federal drug-regulation law.
- The safe harbor is not confined to generic drug approval activities or to the final stages of clinical development.
- Preclinical studies may fall within the exemption, including studies bearing on safety, efficacy, and mechanism of action, if directed toward generating IND/NDA-type information.
- The “reasonably related” inquiry is assessed based on whether, at the time of the work, there was a reasonable basis to expect FDA-relevant information, not on whether the data were ultimately submitted or the compound ultimately advanced.
- Purely exploratory research on a compound, performed without intent to develop a particular drug or without a reasonable belief it will produce the intended physiological effect, is outside § 271(e)(1).

## Conclusion

The Court construed § 271(e)(1) to protect a wide range of preclinical uses of patented compounds tied by a reasonable basis to producing FDA-relevant IND/NDA information, vacating the narrower Federal Circuit approach and remanding for reconsideration under the proper standard.


Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005)