Under conditions of low stress NF-κB (Nuclear Factor-κB) remains safely bound by IκB (Inhibitor κB) proteins in the cellular cytoplasm. However, when stress does strike, NF-κB is thought to be released by its IκB minders. Once free, NF-κB homes in on a cell's nucleus, where it binds a particular consensus sequence (5'GGGACTTTCC-3') of certain genes and promotes their transcription. thereby plays an important role in regulating vital cellular processes, such as programmed cell death (apoptosis), tumor production (tumorigenesis), inflammation, autoimmune reactions, and replication of viruses. In short, NF-κB is a master regulator of many diseases.
The regulatory importance of NF-κB was discovered by research groups led by David Baltimore (MIT), Phillip Sharp (The Whitehead Institute), and Tom Maniatis (Harvard University). Their host institutions successfully obtained U.S. Patent No. 6,410,516 ("the '516 patent"), whose claims cover various applications of their discovery, and licensed it to ARIAD Pharmaceuticals, Inc.. Previously, ARIAD successfully sued Eli Lilly & Company for infringing claims of the '516 patent with its osteoporosis drug, Evista® (raloxifene HCl), and its septic shock drug, Xigris® (drotrecogin alfa).
Now ARIAD and its licensors have decided to sue Amgen, Inc., and Wyeth, whose cytokine-derived drugs, Enbrel® (etanercept - a tumor necrosis factor (TNF) blocker) and Kineret® (anakinra - an interleukin-1 (IL-1) receptor antagonist), for infringing other claims of the '516 patent.
The pioneering biological research that elucidated the regulatory activities of NF-κB was elegant and masterful. The resulting '516 patent, some of whose claims have already survived judicial validity challenges, has given ARIAD and its licensors commanding roles as keepers of the biological gate through which many drugs must, or will have to, pass to be therapeutically effective: NF-κB regulates hundreds of genes, which in turn play roles in hundreds of human diseases. Providing that the validity of claims of the '516 patent continue to be upheld, the patent masters of NF-κB will continue to wield their power for years to come: the '516 patent will not expire until at least 2019.