By Doug Macron
While Alnylam Pharmaceuticals had the opportunity to license a recently issued US patent related to modified siRNAs stemming from the work of one of its founders, the company deemed the intellectual property as unnecessary, company executives said last week.
The officials also provided details on Alnylam's biologics-manufacturing initiative, and indicated that deals for the unit's technology would be forthcoming in the near future.
In response to a financial analyst's question during the company's second-quarter financials conference call last week, Alnylam President and COO Barry Greene said that the new IP, exclusively licensed for therapeutic applications by peer Silence Therapeutics, had "zero" impact on how the RNAi drug shop designed its siRNA payloads.
The patent, US patent No. 7,750,144, is entitled "Methods and Compositions for Enhancing the Efficacy and Specificity of RNA Silencing," and it claims "methods of enhancing the efficacy and specificity of RNA silencing," as well as ”compositions for mediating RNA silencing," according to its abstract. The patent is based on the work of University of Massachusetts Medical School researcher and Alnylam co-founder Phillip Zamore.
In July, the US Patent and Trademark Office issued the patent, and Silence CEO Philip Haworth told Gene Silencing News at the time that the IP covers modifications that boost the potency of an siRNA while decreasing its potential for off-target effects, and are believed to be incorporated in a number of drug candidates under development by other companies (GSN 7/15/2010).
But to Alnylam, the so-called Zamore IP, which includes four issued US patents, is of little value.
Following up on Greene's statement about the so-called Zamore IP's affect on Alnylam's drug-design efforts, the company's CEO John Maraganore noted that Zamore is "a founder at Alnylam and we were obviously aware of that patent years ago."
Alnylam "chose not to license it … because it wasn't worth anything from our perspective," he added.
While Alnylam may have decided that the Zamore IP was simply unnecessary, the company's somewhat stormy relationship with UMMS may have also been at play in its decision to pass on a license.
Cornerstones of Alnylam's IP estate are the Tuschl-I and Tuschl-II patent families, which generally relate to the use of siRNAs 21 to 23 nucleotides in length to trigger RNAi in mammals. While Alnylam holds the exclusive rights to Tuschl-II, one of the co-owners of Tuschl-I — UMMS — opted to license its ownership of that IP to Alnylam rival Sirna Therapeutics in 2003 (GSN 9/12/2003).
Last summer, Alnylam sued UMMS and two other co-owners of Tuschl-I for allegedly misappropriating certain features of Tuschl-II into their own patent filings (GSN 7/9/2009). As reported by Gene Silencing News, Alnylam has also charged that UMMS improperly claimed ownership of the Tuschl-I IP through its hiring of Zamore (GSN 1/28/2010).
Also during last week's conference call, Greene and Stuart Pollard, Alnylam's vice president of scientific and business strategy, touted the firm's nascent effort to apply its RNAi technology to the manufacture of biological drugs.
Alnylam unveiled the biologics initiative last year as part of a bid to realize value from its RNAi expertise in areas beyond therapeutics (GSN 11/19/2009).
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According to Greene, Alnylam has discovered novel delivery lipids capable of delivering siRNAs to manufacturing cell lines "with potent gene-silencing activity resulting in improved protein quality" in cell-line cultures in a one-liter bioreactor.
"We also demonstrated the ability of scaling this delivery of siRNAs [to] at least 40 liters," Greene said during the call. "This is a very significant step up in scale as it pertains to the ultimate applications of this technology at about 100-plus-liter scale."
Maraganore added during the call that Alnylam's findings have been "very reproducible as we have gone from … small-volume shake flask-type volumes through one-liter volumes, three-liter volumes, and now 40-liter volumes.
"The reproducibility of the knockdown data and the beneficial effects on cell-growth characteristics and the consistency of the cell-growth characteristics are superimposable across those scales and that’s very important," he said.
Pollard noted that 40 liters is "the sort of scale that gets people very interested."
While biologics manufacturing can occur at scales as high as 10,000 and 20,000 liters, he said, "showing very robust RNA interference and impact on critical pathways [at 40 liters] is capturing processing-development and manufacturing folks' interest. This is very encouraging and points towards applications at the scales of commercial manufacturing."
Such applications, he added, include increased biologics yield and improved drug quality.
"One of the beauties of using RNAi is we can attack [targeted] … pathways simultaneously or individually, and it allows for tailoring to not only improve things like yield, but also to maintain or even improve quality features of the product," Pollard said.
Maraganore noted that Alnylam was not providing specific guidance on when any partnerships deals with its biologics unit may be struck, but said that "there’s quite a bit of interest in it and I'm sure you will see something … reasonably soon."