Making Drugs And Devices Without Breaking The Law

Making Drugs And Devices Without Breaking The Law

January 12, 2006

By: H. Roy Berkenstock

Question: When is practicing a patented use not an infringement of the patent?

Answer: When the activity is solely for uses reasonably related to the development and submission of information under a federal law which regulates the use of drugs. So says 35 U.S.C. 271(e)(1), otherwise known as the safe harbor for clinical investigation of drugs under a new drug application filed with the Food and Drug Administration. Until a recent Supreme Court case was decided, Merck KGaA. v. Integra Life Sciences I, Ltd., the activity which otherwise would be infringing had to be a part of the generation of the data to satisfy the clinical investigation (safety and efficacy) part of the review. Depending upon how enthusiastically the Court of Appeals for the Federal Circuit applies the holding, the safe harbor will be significantly expanded.

Section 271(e)(1) was enacted into the Patent Laws as the Bolar Amendment to the Hatch-Waxman Act in 1984. It was in response to the Federal Circuit's refusal in Roche Products, Inc. v. Bolar Pharmaceutical expand the experimental use exemption existing in the common law. That defense was narrowly construed to truly experimental activity -- such as that "solely for amusement, to satisfy idle curiosity, or for strictly philosophical inquiry." Bolar Pharmaceutical involved the development of generic drugs with Bolar attempting to produce its product through the comparison testing against the patented drug, and to have its generic product ready by the time the patent on the Roche FDA approved drug expired.

The Federal Circuit decision caused a great deal of concern to the public  particularly the generic drug industry) in that the practical effect was to extend the patent term on drugs well beyond the then seventeen-year term set by Congress. The literal language of the new section clearly reflects the attempt by Congress to support the generic drug industry: "It shall not be an act of infringement to make, use, sell, or offer to sell . . . a patented invention . . . solely for uses under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products."

In 1990 the Supreme Court addressed the issue of medical devices being  covered by Section 271(e)(1). In Eli Lilly & Co. v. Medtronic, Inc., the issue was whether Medtronic's testing and marketing of a medical device would constitute patent infringement if the activity was related to obtaining regulatory approval under the FDCA.  The Court held this testing would not constitute infringement. It found that this phrase from Section 271 was ambiguous: "a Federal law which regulates the manufacture, use and sale of drugs."  The Court held that 271(e)(1) was designed to remedy unintended distortions of the standard seventeen-year patent term produced by the requirement that certain products receive premarket regulatory approval. The first distortion was the effective extension of the patent. The other was the Hatch-Waxman Act patent term extension to compensate for the elapsed patent term under the FDA approval process.

Since the 1990 Medtronic decision, the district courts have not been tested on the facts found in Merck. Merck's activity (actually that of its research contractor, The Scripps Institute) was not directly related to the drug approval process within the direct scrutiny of the FDA. The complained activity grew out of a research project on angiogenesis, the process by which new blood vessels sprout from existing blood vessels, and play a critical role in many diseases, including solid tumor cancers. In the course of the work to develop integrin antagonists as giogenesis inhibitors, the Scripps scientist discovered that it was possible to inhibit angiogenesis by blocking the v3 integrins on proliferating endothelial cells. Shortening a long story, Integra owned five patents on "RGD peptides" which relate to promoting cell adhesion by attaching to v3 integrins, receptors commonly located on the outer surface of certain endothelial cells. While the Integra patents covered the use of RGD peptides, there was no suggestion of their use or positive activity in the cancer field.

After Integra became aware of Merck's use of the RGD peptides, it initiated a suit for patent infringement. The district court found that certain Merck activity was protected by the common law research exemption, and after considering whether other of the activity was covered by 271(e)(1), decided it was not.  Ultimately the district court awarded Integra $15,000,000 in damages. The Federal Circuit, in keeping with its earlier view on the research exemption, decided that it did not apply. The Federal Circuit further found that 271(e)(1) did not apply because the Merck/Scripps activity was not part of the FDA clinical investigation process.  Specifically "the Scripps work sponsored by [petitioner] was not clinical testing to supply information to the FDA, but preliminary general biomedical research to identify new pharmaceutical compounds."

Citing its Eli Lilly case, the Supreme Court concluded in Merck KGaA. v. Integra Life Sciences I, Ltd. "that Section 271(e)(1)'s exemption from infringement extends to all uses of patented inventions that are reasonably related to the development and submission of any information under the FDCA." The practical impact of the decision provides a safe harbor for any preclinical research so long as there is a reasonable basis to believe the compounds tested could be the subject of an FDA submission, and the research is expected to provide the type of information relevant to an IND or NDA.

While the Supreme Court has substantially broadened the 271(e)(1) safe harbor, it did send the case back to the Federal Circuit to review the evidence presented to construe its sufficiency under the adopted standard. Stay tuned for the rest of the news!