A new patent on disease treatments that operate through a key biological trigger, the NF-kB messenger protein, has lawyers, university researchers, and technology transfer officers bracing for an intellectual property crackdown that they fear could reach into academia. Issued June 25, 2002, to a dozen researchers including David Baltimore, who identified the NF-kB signaling pathway, the patent was granted to the Massachusetts Institute of Technology, the Whitehead Institute for Biomedical Research, and Harvard University. The patent, which expires in June 2019, covers disease treatment methods that affect the NF-kB pathway, a trigger described in more than 5,000 scholarly papers. The research institutions had already licensed the method to a biotechnology company, which has sued a pharmaceutical giant, claiming patent infringement.
Photo: Courtesy of Johns Hopkins University
The lawsuit highlights fears that the aggressive prosecution involving a patent that protects drugs already on the market is a potential threat to future scientific investigation. This fear extends even to university settings, which have historically been safe from patent fights. "It does present an area of concern because we don't want to blatantly flaunt the law," says William P. Tew, assistant dean and executive director of licensing and business development for the Johns Hopkins University School of Medicine. "But the fact is, I have thousands of researchers and it would be an administrative nightmare to try to sort out what might be infringing."
EXCLUSIVITY AND COLLABORATION Ariad Pharmaceuticals, a Cambridge, Mass.-based biotechnology firm founded in 1991 owns the exclusive license to the NF-kB patent. Within hours of the patent issuance, Ariad sued Eli Lilly and Co. in Boston, demanding damages for continued sales of two drugs: raloxifene (Evista) for osteoporosis, and drotrecogin alfa (Xigris) for septic shock. The Indianapolis-based Eli Lilly denies that its drugs infringe the NF-kB patent.
Tew and other academics fear Ariad could also charge universities with patent infringement. The company's chief executive, Harvey Berger, counters that Ariad has no intention to defend its patents against university-based research projects unconnected to commercial sponsors. But, Ariad may require licenses for corporate-sponsored academic research projects, in spite of the experimental use exception that generally protects academic labs. "Once the commercial hand touches pure academic research, that's when the exception dies," says Don J. Pelto, a Washington, DC, patent lawyer.
But when it comes to patent exemptions and legal complications, NF-kB research projects are no different from other commercially sponsored work, points out genetics researcher Inder Verma of the Salk Institute for Biological Studies in La Jolla, Calif. "If you have a commercial sponsor, it is their responsibility to make sure your work is not infringing" on the patent, he says.
BROAD CONCERNS What makes the NF-kB patent so troublesome, however, is its scope, which appears to cover dozens of important projects now underway. The schools that own the patent, of course, are in the clear. "We have full rights to practice the science [including under the patents] for our research and educational purposes," MIT technology licensing director Lita L. Nelsen writes in an E-mail. "And anyone can practice what is not covered by the patents."
The June 25 patent is the third in a series issued to MIT, Harvard, and the Whitehead Institute and licensed to Ariad. The problem, say some, is that the patents could be read to cover every therapeutic application related to NF-kB. "Claim 1 would cover a huge number of potential mechanisms, such as antibodies or ligands that bind to this transcription factor. Just about anything that blocks the activity of NF-kB would appear to come under this claim," says Michael B. Farber, a Harvard-trained scientist and now a patent lawyer in Los Angeles. "All you have to do is block the activity of this factor at the transcriptional level, the translational level, the protein level, or any combination of mechanisms, and this patent is implicated." For example, the Eli Lilly drugs at issue in the Ariad lawsuit each employ different methods of activating the NF-kB pathway: Evista is a selective estrogen receptor modulator, and Xigis is a recombinant human activated protein.
"I feel that [the patent] is overly broad," says Sankar Ghosh, a professor at Yale University School of Medicine. His recent work with NF-kB focuses on the signaling pathway's crucial role in cellular immune response. Ghosh has little fear of direct legal action against his laboratory, since it is not involved in commercializing drugs. But he worries that academic researchers will experience a spillover from Ariad's legal action. "A lot of the science we do is for the purpose of finding new drugs," the Yale researcher says. "And if this prevents research in this area, it seems to be not in the best interest of the science,"
Ariad chief executive Berger insists the NF-kB patent is not broad. "The claims in the patent are really very specific to NF-kB and to specific ways, methods of regulating NF-kB cell signaling," Berger says.
Lawyers who glanced through the hefty, 203-claim patent, however, say it is not only broad, but "extremely," "incredibly," and "surprisingly" broad. Washington patent lawyer Paul J. Berman says the breadth and assertiveness of the Ariad claims could signal a paradigm shift among academic research institutions historically devoted to collaboration. "Does the activity of this licensee [Ariad] suggest ... that institutions are going to start collecting patents and using patents in the same way that they go after and compete with each other for faculty and research dollars and grants?"
Peg Brickley (firstname.lastname@example.org) is a freelance writer in Philadelphia.