U.S. PATENT LAW: Case Probes What's Fair Game in the Search for New Drugs
*Eli Kintisch*
How much freedom does a drug company have to use someone else's patented research tools in the course of developing new therapies? This month, the U.S. Supreme Court will hear oral arguments in a patent case between a German pharmaceutical giant and a small U.S. biomedical company involving a 20-year-old federal law originally passed to speed generic drugs to market. Legal experts say that the court's answer to that question could alter the ground rules for intellectual property claims not just in the pharmaceutical industry but also across many areas of basic research.
On 20 April, the high court will hear arguments pitting Merck KGaA (not affiliated with the U.S.-based Merck & Co.) against the Plainsboro, New Jersey-based Integra. The 9-year-old dispute rests upon an interpretation of a 1984 federal law--known as the "FDA safe harbor"--that gives drug researchers an exemption from patent liability for work "reasonably related" to the Food and Drug Administration (FDA) approval process. The outcome of the case will hinge on the court's definition of "reasonably related" research. Merck's position is supported in briefs filed by the U.S. government, big pharma, and the seniors' lobbying group AARP. Arrayed on the other side are small and large biotech companies that primarily sell patented tools to scientists.
Congress created the safe-harbor exemption in 1984 so that companies making generic drugs could work with patented materials in preparing FDA applications without having to wait until the patent expired. Federal courts have since steadily expanded the kinds of research covered by the exemption to include research on novel drugs and medical devices.
The trigger for the legal battle was a 1994 discovery by David Cheresh, a cell biologist at the Scripps Research Institute in La Jolla, California, that molecules that bind to a surface protein called v3 inhibit blood vessel growth, or angiogenesis (/Science/, 22 April 1994, p. 569). Merck soon cut a deal with Cheresh and Scripps to begin to identify drug candidates in animal models and, as the agreement stated, "satisfy (FDA) regulatory requirements."
Figure 1 <http://www.sciencemag.org/cgi/content/full/308/5719/174/F1> Figure 2 *Trigger.* David Cheresh's discovery that blocking v3 (/left/) inhibits angiogenesis led to a search for new drugs--and a patent dispute.
CREDITS (LEFT TO RIGHT): J. P. XIONG /ET AL./, /SCIENCE/ *293*, 1745 <http://www.sciencemag.org/cgi/content/full/293/5536/1743b> (2001); THE SCRIPPS RESEARCH INSTITUTE
A small firm called Telios, though, held patent rights on the use of peptides containing a particular sequence, known as RGD, that binds to v3. Cheresh's work involved RGD peptides. Telios sued in U.S. District Court, soon after which Integra bought the intellectual property from Telios. In 2000, the jury found that at least one and as many as 180 Merck experiments between 1994 and 1998--most involving testing how effectively several compounds starved tumors on chicken embryos--had infringed Integra's patents and awarded Integra $15 million. An appellate court upheld the ruling in 2003, calling Cheresh's work "preclinical" and not tied to FDA approval of any drug. By narrowing the exemption's scope, says patent attorney Denise DeFranco of Foley Hoag LLP in Boston, the ruling "kind of shook up some established expectations."
Not according to Integra's attorneys, who say that the appellate court was simply affirming the rights granted to any patent holder. "The biotech industry is all about new tools," says Mauricio Flores, an attorney for Integra at McDermott Will & Emery LLP in Washington, D.C. In a supporting brief, biotech companies Affymetrix and Invitrogen say that a broad interpretation of the safe harbor provision would undermine their ability to earn licensing revenue for innovations that lay the groundwork for new medicines.
The appeals court ruled that the Scripps-Merck experiments amounted to "new drug development activities." Integra lawyers point out that chicken embryos--unlike mice, for example--are not considered predictive enough of human health for FDA requirements. Merck is trying to use the safe harbor "as a cover for [patent] infringing work," Integra argues in its brief. But Merck says the embryo work addressed FDA requirements regarding efficacy and other metrics. Merck maintains that the studies came after Cheresh had "a viable drug candidate" in hand and that the safe harbor "embraces any information that a drug innovator could reasonably expect to submit to the FDA in connection with /any/ application."
Several biotech attorneys believe that the appeals court erred in ruling that Cheresh's "preclinical" work was not part of the FDA approval process. "Limitation of the safe harbor to 'clinical' experiments would ignore the extensive preclinical data required by the FDA," argues the American Intellectual Property Law Association in its brief.
Some patent attorneys are worried that the high court, regardless of its ruling on the safe harbor, might narrow a related practice that provides academics and others pursuing basic research with an exemption for "experimental use." Courts have narrowed its applicability over the last 2 decades, most recently in a case that pitted Duke University against a former professor, laser scientist John Madey (/Science/, 3 January 2003, p. 26 <http://www.sciencemag.org/cgi/content/full/299/5603/26a>).
An appellate judge mentioned the research exemption in her dissent, raising the possibility that the high court could inadvertently confirm a restrictive new standard. "That's the worst fear," says Josh Sarnoff, a law professor at American University in Washington, D.C., and an attorney for the Consumer Project on Technology, which has filed a brief in support of Merck's position.
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Sterpone Fabio University of Texas Departement of Chemistry and Biochemistry 1 University Station, CM A 5300 Austin, TX, 78712 Phone: (512)4711092 Fax: (512)4711624
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