Patents still matter. An impressive demonstration late last year by Santaris and collaborators from a primate center in Texas was not enough for GSK to exercise its option for SPC3649, Santaris’ lead microRNA therapeutics candidate directed at miR-122 for the inhibition of hepatitis C virus (HCV) infection (discussed on this blog here, and in a review by Mark Kay and myself here). Instead, Alnylam/ISIS-backed Regulus announced today that GSK has decided to side with them in the development of such an miR-122 antagonist for HCV. This is an amendment to an earlier inflammatory disease collaboration between Regulus and GSK with undisclosed upfront and ~$150M in potential milestones plus the usual tiered royalties on drug sales.
GSK’s decision not to exercise the Santaris option led to speculations, also on this blog, whether it is maybe the concern that miR-122 inhibition might be tumorigenic or could have other adverse effects on the liver. While one certainly ought to pay attention to such potential, the pre-clinical safety data and the expectation that any such therapeutic would not be administered chronically would have made this an unusually conservative decision.
It now appears, however, that GSK just could not ignore the fact any more that it is Regulus that got the exclusive license to the critically important miR-122/HCV Sarnow patents. The move can also be interpreted such that while LNAs are certainly an attractive approach to inhibiting microRNAs, there are alternative chemistries of similar potency. A new type of locked nucleic acid chemistry developed by ISIS that was inspired by and looks a bit like Santaris' LNAs but for a few adornments, that supposedly also make it less toxic, is one such chemistry that I could imagine Regulus-GSK to select for their IND-enabling studies. It is worth remarking that it is probably less the miR122-related Esau patent that was the swaying factor here, since as issued in the US, the Esau patent called for a fully 2’-MOE antisense molecule against miR-122…probably not a gate-keeping chemistry for microRNA antagonists.
It will be exciting to further monitor the race between Santaris (already in the clinic) and Regulus in developing a microRNA-based HCV therapeutic, including how the IP will be sorted out. In this context, I can only appeal to the players not to engage in big patent fights at this time and let the better arguments win, but outside the patent appeals courts and civil cases. To paraphrase related comments by the new CEO of Silence Therapeutics, Phil Haworth, yesterday, this is an utter waste of money and management attention. Time to wake up!
PS: Another milestone in the deepening relationship between GSK and Alnylam, and GSK’s move into innovative, high-value medicines.