In Integra Lifesciences I, Ltd. v. Merck KGaA, No. 02 Civ. 1052, 1065 (Fed. Cir. 2007) (Rader, J., dissenting), the Court of Appeals for the Federal Circuit addressed the Food & Drug Administration (FDA) pharmaceutical research exemption (i.e., "safe harbor") provision under 35 U.S.C. 271(e)(1), which states that,
"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 . . . 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 or veterinary biological products."
The research exception was intended to encourage the development of new drugs by allowing researchers to collect information for FDA submissions, such as Investigational New Drug applications, New Drug Applications, and Abbreviated New Drug Applications, without fear of liability to patent holders.
The research at issue in this case involved studies of the efficacy, mechanism of action, pharmacology, pharmacokinetics, and safety of three structurally related RGD peptides, included the following testing:
-
αvβ3 receptor binding assay (efficacy);
-
angiogenesis chick chorioallantoic membrane (CAM) assay (efficacy, mechanism of action, and pharmacokinetics);
-
angio-matrigel tests (efficacy and mechanism of action);
-
cell adhesion assay (efficacy);
-
chemotaxis assay (efficacy and mechanism of action);
-
chick embryo pharmacokinetics assay (pharmacokinetics);
-
fluorescence-activated cell sorting (FACS) analysis (mechanism of action and efficacy); and
-
rabbit pharmacokinetics assay (pharmacokinetics)
At the trial, a jury found that the research infringed Integra's patents. The district court sustained the verdict, describing the experiments as "insufficiently direct to qualify" for the FDA exemption. On appeal, a split panel of the Federal Circuit affirmed, holding that the work "was not clinical testing to supply information to the FDA, but only general biomedical research to identify new pharmaceutical compounds." At the Supreme Court, the issue on appeal was,
"[W]hether uses of patented inventions in preclinical research, the results of which are not ultimately included in a submission to the [FDA], are exempted from infringement by 35 U.S.C. 271(e)(1)."
The Supreme Court provided examples of different types of research that qualifies for the research exemption:
"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 in a submission to the FDA, that use is "reasonably related" to the "development and submission of information under . . . Federal law." * * *
"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 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 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."
The Supreme Court explained that the criterion of whether the experimental investigation of a patented compound is reasonably related to the development of information for submission to the FDA is established at the time of the experiment, and does not depend on the success or failure of the experimentation or actual submission of the experimental results.
Upon returning to the Federal Circuit for further consideration, the Federal Circuit concluded that all of the research work at issue was done after the initial recognition of the "particular biological process" whereby the RGD peptide blocks the cell surface receptors, and the recognition of the "particular physiological effect" of angiogenesis inhibition.
"All of the experiments charged with infringement were conducted for the purposes of determining the optimum candidate angiogenesis inhibitor and proceeding with commercial development of the selected candidate in compliance with regulatory procedures, initially using three structurally related RGD peptides."
The Federal Circuit concluded that the RGD compound experiments that were not taken to clinical trials did not become infringing when the specific drug was selected as the drug candidate for clinical trials, because studies of compounds that are not ultimately proposed for clinical trials are within the FDA exemption when there is a reasonable basis for identifying the compounds as working through a particular biological process to produce a particular physiological effect.
Comments:
-
The dissent stated that the FDA exemption covers activities that develop information that will ultimately be submitted to the FDA, not patented processes and tools beyond the scope of the "patented compounds" that the Supreme Court placed within the statutory exemption (two of the patents-at-suit were related to "research tools")
-
-
This case raises evidentiary questions related to documenting the circumstances surrounding a researcher's initial recognition of a drug's "particular biological process" and a "particular physiological effect"
