Box 1. Box 1 First salvo comes in Europe

The Kreutzer-Limmer patent is among the best known RNAi patents outside of the US. Kreutzer-Limmer was issued by the European Patent Office (EPO) to Ribopharma, a German biotech, in 2002. Alnylam purchased Ribopharma in 2003, and soon after was embroiled in a battle with its competitors over the patent's coverage, which extends to Germany, Australia and South Africa. As issued, Kreutzer-Limmer had broad claims covering double-stranded RNA molecules less than 21 nucleotides in length. Under pressure from Sirna, AstraZeneca, Autgen, Janssen Pharmaceutica and Sanofi-Aventis, which objected to the patents 'ambiguous' coverage, the EPO in 2006 eviscerated Kreutzer-Limmer's claims to cover blunt-ended, double-stranded RNA molecules 15 to 21 nucleotides long, joined by a chemical linker. The consequence of EPO's action is debatable. Alnylam's spokesperson, Cynthia Clayton, describes Kreutzer-Limmer—which is featured on the company's website—as a "fundamental patent." Sirna's Bharat Chowrira, meanwhile, claims the EPO's 2006 changes rendered Kreutzer-Limmer irrelevant. "This is a structure that no one uses anymore, so it's not commercially important," he says.