Dicerna and Arrowhead Gain Broad Dicer-Substrate Patent Rights

A day after Alnylam claimed ownership over Dicerna’s Dicer-substrate technology, Dicerna shot back with the announcement of a newly allowed US patent that gives it and most likely its co-licensee Arrowhead Research (via mdRNA/Marina Biotech and then Roche) broad control over the Dicer-substrate RNAi trigger space.  Specifically, claims from the Rossi-Kim invention were awarded that broadly cover ~25-30bp dsRNAs with essentially no other structural limitations.

Below 25bp, Dicer does not effectively recognize dsRNAs for processing into small siRNAs; above 30bp, the risk of inducing immune responses is thought to increase considerably as do manufacturing costs.

If you are wondering how Dicerna and Alnylam could be claiming possession over the same trigger structures, it is worth noting that while Dicerna’s patent cover 25-30bp in general, Alnylam is limited to 25bp dsRNAs that further contain a 3’ overhang.  Moreover, it is expected that since the invention by Tuschl explicitly aimed at using dsRNAs downstream of Dicer for RNAi gene silencing purposes, Alnylam’s 25bp claim is unlikely to prevail if the company should file an infringement suit against Dicerna (or Arrowhead Research should it adopt Dicer substrates).  

A simple way to get around all the uncertainty is to simply use RNAi triggers of 26bp and more.  Of course, for Dicerna’s lead candidate DCR-MYC, a 25/27 design, this train has already left the station and I am not sure whether Dicerna was forward-thinking enough to consider 26bp and longer for the orphan PH1 indication, its next clinical candidate.

Assuming that Arrowhead Research has access to the same patent, the adoption of 26bp and longer Dicer-substrate RNAi triggers could be a relatively simple strategy to remove the IP uncertainty lingering around usiRNAs: is a UNA a 'nucleotide analogue' or not?  Moreover, there is a scientific argument for Arrowhead considering Dicer substrates given that they should synergize with a conjugate approach like DPC.

Should we care about all this IP stuff?

Yesterday, I read a comment on InvestorVillage that investors would do best to ignore all the IP noise, including on my blog :(.  I agree that as long as the capital markets are a valid source of capital for small biotech companies, the issues around fundamental RNAi trigger IP, which will largely expire in 2019-2021, will be mute by the time products have come to the market and/or a court decision has been rendered. 

However, the outcome from the lawsuit by ISIS against Roche/Santaris where ISIS accused Santaris (now part of Roche) of monetizing ISIS IP by entering into partnerships with Big Pharma, could remove a lot of business development from Safe Harbor protection.  From there, challenging capital raises on similar grounds is only one step away. Personally, I don't think it will come to this since essentially all business development deals and capital raises in this industry ultimately aim at helping get drugs onto the FDA-regulated market.

And at the end of the day, as is also illustrated by mega-blockbuster Sovaldi, as long as the scientific data is compelling, none of this will prevent a drug from reaching the market and biotech companies making deals.