Issued Baulcombe Patents Fundamental to Mainstream RNAi Therapeutics in USA

Yesterday, UK-based Plant Biosciences Limited (PBL) announced that it was awarded a fundamental RNAi patent in the US. The patents can be considered necessary for commercializing RNAi in the US as long as both strands of the RNAi trigger are between 20-24 nucleotides in length.

Claim 1 of US patent 8,097,710:

1. A method of silencing a gene in cells by post-transcriptional gene silencing (PTGS) which method comprises introducing into said cells a composition that contains short RNA molecules (SRMs),

which SRMs are isolated short sense RNA molecules (SSRMs) and isolated short antisense RNA molecules (SARMs) at the same abundance;

wherein said SARMs are complementary to a region of a target RNA transcribed from a gene which is silenced when said short RNA molecules are present in cells containing said gene and said SSRMs correspond to said target RNA; and

wherein the SSRMs and SARMs consist of 20, 21, 22, 23 or 24 nucleotides,

whereby said gene is silenced.

The patent issuance is a testament to the seminal contributions the plant RNAi community have made to the field. In fact, there was considerable unhappiness that the Nobel Prize committee did not recognize this when it awarded the RNAi-related Prize to Fire and Mello. Baulcombe, it was felt, should have been added as a 3^rd recipient.

The issued patent is based on work by Hamilton and Baulcombe from the Sainsbury Laboratory in Norwich, UK, who found that small RNAs were generated during post-transcriptional gene silencing (PTGS), that is RNAi in plants (Hamilton and Baulcombe SCIENCE 1999). It was then instantly realized, also in light of the fact that a previously discovered microRNA (in C. elegans) was in that size range, that small silencing RNAs are likely the universal (i.e. plants and animals) mediators of RNAi.

I can say the above pretty confidently from my own experience as my exposure to RNAi began in 2000 (before the Tuschl II publication) in- you guessed it- a plant laboratory in the UK (Edinburgh University). There I was an undergrad designing plant RNAi expression vectors and it was pretty obvious then that small RNAs are involved in microRNA and RNAi silencing, two phenomena which had been linked genetically through work in a diverse set of organisms: slime mold, C. elegans, Arabidopsis, fruit flies and the likes. The only remaining uncertainty at that time was whether RNAi would also exist in humans, although I can well remember a speculation in my ‘RNA World’ elective class by David Tollervey that he more or less was certain that RNAi would be shown to exist in humans (not sure whether this was based on scientific intuition or rumors in the scientific community).

(My other claim to getting close to RNAi fame is that David Baulcombe, now Sir David Baulcombe, was my D.Phil. examiner regarding my graduate work on Dicer biology in humans)

I can well imagine that this uncertainty was an issue as PBL argued its case for an all-organism-encompassing patent, but it now seems that it prevailed.

Note on Alnylam patent infringement suit

The timing of the patent issuance, of course, is a bit ironic since the biggest violator of this patent as of January 17 is Alnylam which, as you will know, has just sued Tekmira for patent infringement. It is also of note that since Alnylam has cited an RNAi-unrelated patent by ISIS (US 7,695,902) in the suit, Alnylam has officially revealed itself as a patent troll. Benitec may want to take note since Alnylam acquired the Nucleonics patents which I suspect was done to provide similar cannon fodder for the courts in future litigations.

Also, since Alnylam only threw patents licensed from other companies into the fray, it is a lesson to any company about the perils of licensing IP to Alnylam: Alnylam is more likely than not to first expose such licensed patents before it will expose their own (note: a patent infringement suit such as this one predicts that the patents will be challenged by the alleged infringer and thus stands to be revoked or cut back in scope).

My Keystone meeting was great, and I also learned of interesting work by Alnylam. But I can tell you that coming home from a long trip and the first thing I see is that Alnylam is looking hard to come up with reasons to bury Tekmira under legal costs has quickly eroded any of that goodwill. Somebody needs to stop the insanity, and it's not going to be Alnylam's legal advisers which are making a fortune out of this.