Thursday, January 19, 2012

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 3rd 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.


Anonymous said...

Benitec are smarter & more constructive than in years gone by. They are also wiser for the many years of litigation and USPTO work. They won't blue with Alny unless they can beat them.

Alny should be aware that although Benitec may be smaller in market cap, a patent stoush with Benitec also means a stoush with CSIRO legal team. These guys live for this stuff and have a big budget for fighting big companies. As Sony, AT&T, T-Mobile, Verizon, Acer, etc have all found out.

Well done to Baulcombe. However the interference against Fire and Mello from CSIRO's Waterhouse application is still being examined. It's well overdue for an outcome so maybe this Baulcomb patent award will clear the block and we'll know if CSIRO / Waterhouse has priority over Fire and Mello, from a patent point of view.

Anonymous said...

having a quick read of this Baulcombe patent - the application went to the BPAI, and examiner's rejections partially reversed.

However, the BPAI judges affirmed the examiner's obviousness rejections for claims 116 thru to 124 in light of the Fire and Graham patents.

So it seems the Baulcombe patent didn't get through without being reduced in scope due to the seminal Fire and Graham patents.

Anonymous said...

ALNY are more desperate than an african child for a slice of bread. The desperation smells very bad, i feel sorry for them. They just got greedy!!!!

Anonymous said...

It looks like Benitec is about to unviel its arsenal.You are either with us or against us. The sooner you decide the less you will pay.

Anonymous said...

Benitec is at 2 cents Mr $oz. They are constantly turning to share holders for hard earnt cash, what does that say about the people at the helm. Answer me this why did their last ceo leave , taking into consideration all the hard work she put in? That aside why didnt CSIRO take up their entitelment @ the last ssp??? CSIRO are the ones in the know how, you should be following them. Benitec is abit like the Italian ship that half sank over the weekend...

Anonymous said...

nonlogListen why are bagging Benitec, Merck is our shadow do some research !

Anonymous said...

I tell you what Benitec hasthe UK rulling in its favour! Pfizer taking hepc into phase one gods knows how much this means to Benitec! Calimune going into Phase one ! Gradalis needs license for 5 projects ! Benitec coh HIV project is teamed up with big pharama! and there is also 2 other thing i cant talk about so put that in you pipe and wait till the moment you realise who slow you where!!! HAHAH just joking dont listen to me i am a mean man.

Anonymous said...

LIsten to me carefuly No body is interested in Benitec, Even a blind man can see this. The 099 was granted more than a year ago, The big boys would have made a move ages ago but NOOO.There is no value left in Benitec its all been sucked out.YOU honestly think the big boys would leave such value untouched, you must deaf as well as blind.

Anonymous said...

(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).
Challenged, revoked and re-issued patent is not what it was.

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