NEW YORK, May 30 - Some two-dozen companies have taken licenses already to the patents held by Carnegie Institution and University of Massachusetts for the RNAi inventions of Andy Fire and Craig Mello - the first RNAi inventions to be awarded USPTO protection. So when BD Biosciences Clontech issued a press release this week to announce that it had jumped on the bandwagon, the statement seemed innocuous. But one loaded line in the release hints at the battle brewing over RNAi intellectual property. Of US Patent 6,506,559, BD stated, "This patent is the first patent to issue on the use of this critical new technology in mammalian systems."
What seasoned RNAi IP observers know is that the long, double-stranded RNAi's described by Fire and Mello in 1998 proved effective at silencing genes in lower organisms, but not in mammals. In the US, it was Tom Tuschl who, several years later, first showed how short interfering RNA duplexes, 21-nucleotides in length, could induce RNA-mediated gene silencing in mammalian cell cultures.
Tuschl's work, the licenses for which are held by MIT, has not yet been awarded a patent. Some debate whether it ever will, and many question the necessity of acquiring a license from MIT to use the technology. Some are arguing that holding a license to the Fire-Mello patent gets a company all the rights it needs to practice RNA interference in any type of organism.
The Fire-Mello patents are being licensed nonexclusively by Carnegie. For an up-front fee of $35,000, annual payments of the same amount, an additional $50,000 upon each of three milestones - one being the issuance of the first patent, which occurred in January this year - and a "reasonable" royalty for "sales of products embodying the invention or produced using the same," anyone can use, make, or sell products incorporating the discoveries.
Since scientists first began conducting RNA interference studies in earnest five years ago, more than 750 papers on the topic have been published. This week saw four more added to the heap. PNAS's May 27 edition includes two separate research papers, one by Stephen Fesik of Abbott Laboratories looking into the specificity of short interfering RNAs, and another by Stanford's Pat Brown looking at RNAi in genomewide expression profiling, as well as a commentary by Andrew Dillin of the Salk Institute. In addition, PNAS Online today will publish "Allele-Specific Silencing of Dominant Disease Genes," by University of Iowa researchers Henry Paulson and Victor Miller.
"Specificity of short interfering RNA determined through gene expression signatures," describes how Fesik and his team in Abbott's global pharmaceutical Research and Development group designed siRNAs against different regions of the same target gene for three different targets and compared their effects on cells using DNA microarrays. The scientists reported that siRNA is highly specific for targeted gene knockdown and said their results establish "siRNA-mediated gene silencing as a reliable approach for large-scale screening of gene function and drug target validation."
In their paper, "Genomewide view of gene silencing by small interfering RNAs," Pat Brown and colleagues show that siRNA-induced silencing of genes with transient or stably expressed mRNA is highly gene-specific and does not produce secondary effects detectable by genomewide expression profiling.