U.S. Supreme Court Clarifies and Expands the Scope of “Safe Harbor” Use of Patented Pharmaceuticals Under Sec. 271(c)(1)

Published June 27, 2005

On June 13, 2005, the U.S. Supreme Court, in a unanimous decision in the case of Merck KGaA v. Integra Lifesciences I Ltd, expanded the “safe harbor,” provided by 35 U.S.C. §271(e)(1), for use of patented drugs.

In general, one infringes a U.S. patent by making, using, selling, offering to sell, or importing the subject of one or more claims of the patent. 35 U.S.C. §271(a). Section 271(e)(1) of this statute provides an infringement exception if the activity is solely for uses that are reasonably related to the development and submission of information under a federal law regulating the manufacture, use, or sale of drugs. These federal laws include laws under which drug makers must submit research data to the FDA, during new-drug development, for approvals such as an investigational new drug (IND) application to conduct clinical trials.

This case involved a dispute between Integra, who owns patents on an “RGD” peptide that promotes cell adhesion. Merck funded research at Scripps leading to a discovery that angiogenesis could be blocked using a cyclic RGD peptide. Scripps’ research identified a promising RGD peptide that became the subject of an IND submitted to the FDA by Merck. Integra sued Merck in federal district court for direct and contributory patent infringement. The district-court jury found in favor of Integra and awarded substantial damages, ruling there was “insufficient connection” between Scripps’ infringing experiments and the FDA’s review of Merck’s IND application.

The Court of Appeals for the Federal Circuit (CAFC) affirmed, ruling that Scripps’ work did not involve clinical testing to satisfy the FDA but rather general research aimed at identifying new compounds.

The U.S. Supreme Court reversed the CFAC, ruling that §271(e)(1) provides a “wide berth” for use of patented drugs in research activity “related” to the federal regulatory process. The exemption from infringement extends to all uses of patented compounds that are reasonably related to the development of any information to the FDA or the like. Thus, patented compounds can be used in preclinical trials conducted to show efficacy, mechanism of action, pharmacokinetics, and pharmacology of a candidate drug. This information is critical to the FDA’s review because the agency must evaluate all data serving as a basis for a conclusion that clinical testing would be reasonably safe.

The Court agreed with the CAFC that the §271(e)(1) exception does not globally embrace all experimental activity. For example, basic research performed on a compound without the intent to develop a particular drug or without a reasonable belief in the expected pharmacological action of the compound would not be reasonably related to information submitted to the FDA. But, this does not mean that §271(e)(1) excludes experimentation on drug compounds that are not ultimately the subject of an FDA submission or use of a patented compound in an experiment that is not reported in the FDA submission. Experimentation is a trial-and-error process having an outcome that usually cannot be predicted a priori. For example, a candidate compound showing early promise may not survive later experiments.

Thus, the §271(e)(1) “safe harbor” (of non-infringing activity) is not limited to development of information actually included in a submission to the FDA. The safe harbor encompasses use of a patented compound in experiments not reported to the FDA, and it exempts from infringement all uses of patented compounds that are “reasonably related” to the process of developing information for making the submission. It also leaves “adequate space” for experimentation and failure on the road to regulatory approval. If a researcher has a reasonable basis for believing that a patented compound may work to produce a particular physiological effect, and if use of the patented compound in such regard is reasonably related to developing information for making a federal regulatory submission, he or she is within the safe harbor.