Integra Lifesciences v. Merck KGaA, No. 2002-1052 (Fed. Cir. 2007)
Last Friday, the Court of Appeals for the Federal Circuit decided Integra v. Merck, on remand from the Supreme Court. Click here for the opinion. The case has important implications for owners of "research tools" patents.
In the mid-1990s, Integra sued Merck KGaA (the German company) and Scripps for infringing five patents relating to peptides that contain the RGD sequence of amino acids. This suite of patents included both patents directed to RGD-containing peptide compounds and patents directed to laboratory methods (i.e., research tools) using the RGD-containing peptides.
Merck and Scripps defended their conduct by relying on the FDA safe harbor of 35 USC § 271(e)(1), which precludes liability for activities "reasonably related to the development and submission of information under [the Food, Drug and Cosmetic Act]." The FDA safe-harbor was passed as part of the Hatch-Waxman Act to permit "a limited amount of testing so that generic manufacturers can establish the bioequivalency of a generic substitute." In this sense, the safe harbor encompasses activities that develop information that will normally find its way into an FDA submission.
At the original trial in the district court, Integra argued for a narrow reading of the FDA safe harbor in three respects. First, Integra argued that the safe harbor includes only studies on the safety of administration to humans, and does not include experiments on mode of action (i.e., ADME and PK studies). Second, Integra argued that the safe harbor excludes studies on related compounds that were not the subject of any FDA submission. Third, Integra argued that the safe harbor can only include experiments complying with the FDA’s Good Laboratory Practices (GLP), since only data from GLP-compliant studies qualify for submission to the FDA.
A jury verdict and bench opinion accepted Integra's narrow reading of the safe harbor statute, and found Merck and Scripps liable for infringement. A divided panel of the Federal Circuit affirmed. The Supreme Court granted certiorari on the limited question of "whether uses of patented inventions in preclinical research, the results of which are not ultimately included in a submission to the [FDA], are exempted by [the FDA safe harbor]." The term "patented inventions" presumably included both patented compounds and patented research tools that use those compounds.
The Supreme Court reversed the Federal Circuit, but only in regards to patented compounds. The Court intended its decision to "provide a wide berth for the use of patented drugs in activities related to [FDA submission]." Notably, the Court did not say "patented use of drugs" or "patented use of patented drugs." Thus, it would seem that the Supreme Court had left the Federal Circuit’s exclusion of research tools from the safe harbor undisturbed:
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 [patented] compound in research that, if successful, would be appropriate to include in a submission to the FDA, that use is "reasonable related" to the [safe harbor criteria].
In fact, the Supreme Court emphasized in footnote 7 that it had abstained from answering the question of the applicability of § 271(e)(1) to research tools. Thus, the Court's ruling expanded the scope of the safe harbor in two important ways: It permitted drugmakers to experiment freely on a broader genus of patented compounds, and brought most types of pre-clinical testing into the safe harbor.
Upon remand, the Federal Circuit's task seemed apparent: look at the activities conducted by Merck and Scripps which gave rise to the district court's infringement verdict, and determine if any of those activities, as a matter of law, involve non-patented uses of patented compounds at a stage after the drugmaker had a reasonable basis for believing that the patented compound had a particular physiological effect. The Supreme Court, after all, gave the Federal Circuit no general warrant to reconsider whether the FDA safe harbor should include research tools (i.e., patented uses of the compounds).
In last Friday's decision, however, the majority of the Federal Circuit vacated the district court's verdict in its entirety and found that, as a matter of law, all of the defendants' activities are protected by the FDA safe harbor. The sweeping holding includes activities that would infringe both Integra's composition patents and its method patents (i.e., research tool patents). The majority relied largely on a sentence in the Supreme Court's opinion that states that the FDA safe harbor "exempt[s] from infringement all uses of patented compounds 'reasonably related' to [FDA submission]." The majority appears to imply that "all" includes non-patented uses as well as patented uses. Or maybe that's not what they mean at all?!?
Now comes the odd twist: following oral argument at the Federal Circuit, Integra's counsel sent the CAFC a letter in which he disclaimed that research tools were at issue in the case. The majority holds that this statement by counsel negated any effect of its holding on research tool patents. But can a mere letter from counsel transform a method claim into a composition claim? In effect, the majority has treated the letter as an implied withdrawal of Integra's two method patents from the court's consideration. In dissent, Judge Rader would prefer to disregard the letter and remand that portion of the case to the district court.
Owners of research tools would probably like to see this case head back to the Supreme Court for further clarification. Of course, the significance of Integra's surprise disclaimer is difficult to estimate. Even if the letter's legal significance is shaky, it likely indicates that Integra has thrown in the towel after its decade-long fight. After LabCorp v. Metabolite, the Court is probably reluctant to grant certiorari on patent cases having funky procedural postures.