It is not a big secret that antisense therapeutics companies ISIS and Santaris are fierce competitors. Today, ISIS filed an unusual, because rather aggressive lawsuit against Santaris Pharma that alleges the Danish company to be selling to the industry technology that is covered by at least two of ISIS’ literally thousands of patents. Because ISIS considers itself the gate-keeper of oligonucleotide therapeutics, and because some of the business development in RNAi Therapeutics has probably occurred under the mantle of the Research Exemption, a ruling in favor of ISIS Pharmaceuticals could have wide ramifications, actually well beyond oligonucleotide therapeutics.
Under the Research Exemption doctrine, the result of Merck vs Integra, it is generally assumed that patented technologies can be used for research purposes quite broadly as long as product, in this case drugs, are not marketed. Without this safe harbor, much of the preclinical pharmaceutical research and academic research would be a legal nightmare.
Nevertheless, ISIS believes this standard does not apply here, because Santaris in a way is selling ISIS technology as part of its platform partnerships. These include relationships with Pfizer, Enzon, GSK, and Shire. Moreover, it probably irks ISIS that Santaris has been rather successful in its business development efforts, and even had the guts to hire a former top ISIS executive, Art Levin, to set up a business development branch in ISIS’ backyard San Diego.
My impression is that Santaris’ LNA-based antisense compounds are more potent than ISIS’ generation 2.0 2’-MOE phosphorothioate gapmers, and this is why Santaris is likely to be the more attractive company to partner from a technical point-of-view. ISIS apparently has realized this as well as it is following Santaris' example in developing conformationally constrained (‘locked’) nucleic acid chemistries (expect Santaris to counter-sue ISIS on that). Anti-miR122 for the treatment of HCV infection is one example where Santaris’ data have been more promising than Regulus’ using ISIS chemistries. Ironically, GSK dumped Santaris’ stronger science on HCV in favor of Regulus for what had to be concerns about IP (I believe though that it was miR-122-specific IP, not antisense platform-related IP that was responsible for GSK’s move).
I don’t want to speculate whether Santaris in fact makes use of technology covered by ISIS patents or not. It is, however, a case worth watching for the entire pharmaceutical industry. Closer to home, it illustrates how aggressive, and so far successful ISIS is in using its sheer number of patents in ‘extorting’ concessions from other oligonucleotide therapeutics companies. Wherever you look, ISIS is getting a piece of the pie. I have been studying ISIS’ patents with regard to RNAi Therapeutics, and cannot really find anything of value there, except maybe if you are interested in using the 2’-fluoro modification which is useful, but dispensable. Still, ISIS was able to extract surprising concessions from Alnylam when Alnylam IPO’d a few years ago and has even called Alnylam a ‘satellite company’ without much public protest by Alnylam. Same story with the multi-million $ that Alnylam gave ISIS for the ill-fated single-strand RNAi collaboration. It goes to show that when it comes to public perceptions and business development, quantity and brand recognition often still trump quality and due diligence.
Post-scriptum (9 October, 2011): On October 7, Exiqon and Santaris on October 7, 2011, settled their legal differences that resulted from Santaris suing Exiqon for selling LNA-based reagents that were used for the development of drugs incorporating LNAs,,,and thus would not fall under the Research Exemption- an ironic twist of fate. In the settlement, Exiqon paid Santaris a minimal amount. It is difficult to conclude from this anything about the outcome of the ISIS-Santaris litigation.
