Silence Therapeutics reported that a number of valuable RNAi trigger patents related to the Zamore Design Rules that were issued last year in the US were upheld following a re-examination request by an anonymous 3rd party. Even stronger claims related to the same Zamore patent series have been issued in
The Zamore Design Rule patents are owned by the
Especially the patent covering guide strand selectivity methods (‘thermodynamic end-stability rule’; US 7,750,144) is widely recognized in the art for greatly increasing the likelihood of finding efficacious RNAi triggers and is incorporated in essentially all bioinformatic sequence pre-selection algorithms. It has to be said though that the claims do not cover the entire spectrum of approaches of achieving differential end-stability. They do, however, cover chemical and structural approaches that have been reported by a few companies such as Marina Biotech and Sirna/Merck before. Moreover, because the coverage involves modified nucleotides, there will be the concern that even if such modifications were applied for other purposes (e.g. stability or immune abrogation), they may fall under the patents. Consequently, a company with a promising late-stage candidate may want to take a license instead of taking a chance in an infringement lawsuit.
This makes it the second time within a week (see PKN3 opposition by Alnylam) that important patents by Silence Therapeutics were upheld essentially unchanged following challenges. Alnylam’s management once laughed off the value of the Zamore patents in a conference call following their issuance last year. They obviously considered them serious enough to oppose them in Europe and Alnylam is certainly the most likely identity behind Mr. Anonymous (have your say by participating in the survey on the right). Less likely, but not entirely out of the question would be a Big Pharma company like Novartis which is considering taking a license to the Zamore patents, but first wanted to kick the tires before it did so (patents that have been unsuccessfully challenged are considered stronger).
With all these patent successes, and at least one more likely to come, Silence Therapeutics need to monetize their assets in the form of non-dilutive funding.
Hemophilia Gene Therapy Success Bodes well for ddRNAi Therapeutics
Following years of public scorn and derision, including by Alnylam which in 2006 waved off ddRNAi Therapeutics and gene therapy as ‘dangerous’, gene therapy is back with a vengeance. This week, a consortium of researchers reported in the New England Journal of Medicine that an self-complementary AAV8-delivered Factor IX transgene was able to significantly correct hemophilia B in a small clinical trial.
4 out of the 6 patients treated were able to largely discontinue the standard frequent (often 2-3 times a week) and expensive use of prophylactic recombinant FactorIX protein therapy which accounts for estimated healthcare costs north of $20M a lifetime. This means that even in the limited duration of the trial (6-16 months of follow-up), the low cost of the gene therapy ($30k cost of goods for a treatment that is expected to last many years if not a lifetime) meant that this therapy is already saving money (and improving quality of life). If the results can be confirmed in a larger trial and the side-effects, including transient liver enzyme elevations can be controlled with similar efficiency as in this small one, approval may not be that far away.
The hemophilia results also bode well for ddRNAi Therapeutics. First of all, the study has validated the safety and efficacy of delivering the highly promising AAV vector family by peripheral vein infusion to the liver. This represents progress over a previous hemophilia gene therapy study which employed considerably more invasive direct hepatic infusion. In particular, it is likely that, should the ddRNAi collaboration by Tacere/Pfizer for HepC continue, it would involve not only the same vector family (AAV) and target organ (liver), but also the same serotype (AAV8) and self-complementary genome strategy as employed in this hemophilia trial.