Drug Development an IP Wasteland?
Merck KGaA v Integra Life Sciences Ltd., 545 US___ (2005)
Slip op. 03-1237

Briefed by: Anna Longwell, Esq., 2005

Abstract

The Supreme Court has interpreted the patent law at 35 USC 271(e)(1), which allows freedom from liability for infringement if patented articles are made, used, or sold “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…”. The Court found that protected use of such articles is not restricted to use of articles which are included in submissions, nor to experimental work on “successful” drug candidates. Use of patented articles in pharmacokinetic, pharmacological and other functional in vivo and in vitro studies is also protected, if the experiments are conducted to further characterize a drug candidate which will require submission to FDA for study in humans or for ultimate marketing. The fact that experiments fail and no submission is made does not read on the purpose for which the experiments were conducted. It appears the user must have a coherent plan of specific drug development to make use of the exemption (simple mass screening of compounds does not appear to fit), and the exemption extends to products tested for comparison to the drug of interest, if such comparative testing is reasonably related to filing a submission.

History

Integra holds patents related to Arg-Gly-Asp proteins called RGD peptides. RGD peptides bind αvβ3 integrins, surface proteins on endothelial cells, a component of blood vessels. Scripps Institute studied the blocking of integrins, and subsequent inhibition of angiogenesis, the growth and proliferation of blood vessels. Angiogenesis is accelerated in a number of diseases, from cancer to macular degeneration. Inhibiting angiogenesis can have therapeutic applications. In 1995, Merck signed a contract with Scripps to develop integrin antagonists as angiogenesis inhibitors. The contract described the parties’ intent to develop information for an FDA submission, beginning with in vitro and in vivo characterization, continuing to animal safety studies and manufacturing studies, and culminating with an IND in year 3. Scripps would do the preliminary screening of a number of potential candidates. Merck would take over, with GLP toxicology studies and other tests necessary to file an IND on the best candidate. Scripps studied the RGD peptides and some other blocking agents in drug screening tests. In 1996, Merck initiated a formal project directed at drug development of one of the RGD peptides, and in 1997, switched the lead compound to another of the peptides. Merck conducted meetings with the FDA and began discussing a clinical trial with the NCI. NCI filed an IND for one of the compounds in 1998. The Integra compounds were studied both as potential drug candidates and as “positive controls” in other drug selection experiments. Integra sued Merck in 1996. District Court (DC) found that pre-1995 activity was protected under the common law research exemption, but that the jury would have to decide whether the subsequent activity was protected under the FDA submission exception at USC 271(e). D has burden of proof, and the jury found for Integra, that Merck had failed to show that the activity was reasonably related, and it was infringing. Merck moved for dismissal post trial, but DC affirmed the jury’s damage award and denied the motion for judgment as a matter of law. The Court of Appeals for the Federal Circuit (C of A) upheld the denial because they considered the Scripps work sponsored by Merck “general biomedical research to identify new pharmaceutical compounds”, but instructed DC to modify the damages. Merck appealed, the S. Ct granted cert.

Findings

S. Ct. found the C of A’s rejection of the Merck challenge was based on an incorrect interpretation of the law. They declined to review the evidence in the case, but vacated the judgment of the C of A, and remanded the case for consideration of the evidence under the interpretation described in the summary.

Conclusions

The 271(e) exemption is broad, and includes products studied as drug candidates, and products used in the study of drug candidates, as long as the activity is (or is reasonably thought to be) related to the information required by a sponsor to determine suitability for an intended FDA submission. This case is not going to settle much, but casts a pall of uncertainty over IP for many products used in the drug discovery process.