Alnylam Pharmaceuticals Inc. is reaping the rewards of its work in RNA interference.
Since its founding in 2002 as the first company to focus specifically on RNAi therapeutics, Cambridge, Mass.-based Alnylam has amassed a patent portfolio that has provided the foundation for the development of the company's own therapeutic pipeline, while serving as an increasingly popular platform for licensing and collaboration deals. In the past two months alone, Alnylam has entered four nonexclusive licensing deals and one exclusive deal.
"We feel that the [intellectual property] portfolio we have has really provided us, and those parties who want to work with us, the freedom to operate," said Nagesh Mahanthappa, senior director of business development and strategy. "It's absolutely part and parcel of the value that Alnylam is generating."
The company, which specifically uses synthetic small-interfering RNAs (siRNAs) in its research and development efforts, works primarily on the therapeutic side. But its intellectual property boasted broader capabilities that were not being used.
"We are not in the reagents business, so that reflected as asset of our IP portfolio that was not necessarily realizing value for the company," Mahanthappa said, "so we started looking for the types of deals that would enable reagent or research service providers" to use it.
Alnylam has entered a total of eight agreements providing nonexclusive rights to its RNAi patents, including four deals this year. Ebersberg, Germany-based MWG Biotech AG; St. Louis-based Sigma-Aldrich Corp.; Seraing, Belgium-based Eurogentec; and Austin, Texas-based Ambion Inc. all licensed use of the RNAi property for research purposes.
But even in the area of therapeutics, the applicability of RNAi work is too broad for one company.
"Depending on how you count, you could have 15,000 to 30,000 different gene targets," he said. "We're fully aware that we cannot, on our own, possibly execute therapeutic products for all those genes."
Alnylam has entered some of the traditional deals with large pharma, but it also established its InterfeRx program aimed at small biotech companies working in areas outside of Alnylam's strategic focus.
One recent InterfeRx deal involved an exclusive license to Nastech Pharmaceutical Corp., of Bothell, Wash., in exchange for up-front, annual and milestone payments, as well as royalties on any marketed product. Nastech plans to develop RNAi therapeutics against TNF-alpha. (See BioWorld Today, July 21, 2005.)
Nastech was the third deal under the InterfeRx program. In April, Alnylam formed an agreement with Benitec Ltd., of St. Lucia, Australia, to provide Benitec an option to nonexclusively license its IP, in exchange for license fees and potential milestone and royalty payments. The company granted an exclusive option to Kamakura, Japan-based GeneCare Research Institute Co. Ltd. in January to discover, develop and commercialize RNAi therapeutics directed against two DNA helicase genes associated with cancer. Terms of that deal also included up-front, milestone and royalty payments, as well as an option for Alnylam to co-develop and co-promote products in the U.S.
The company began operations with a solid RNAi IP platform brought from its founders and their corresponding academic institutions, such as the Scripps Institute and the Massachusetts Institute of Technology. RNAi, a naturally occurring mechanism within cells that can selectively silence and regulate specific genes, has demonstrated promise in in vivo and animal studies in a variety of disease areas.
Soon after, Alnylam started looking to consolidate additional platforms through acquisitions and licensing deals to "become a one-stop shop," Mahanthappa said.
It acquired the Kreutzer-Limmer patent, covering siRNAs and their use in mediating RNAi in mammalian cells, through its 2003 purchase of Kulmbach, Germany-based Ribopharma AG, now Alnylam's European headquarters.
Earlier this year, the company reinforced its exclusivity to the Tuschl II patent application, owned by the Max Planck Society. That application covers a specific structural feature of siRNA and its use in therapeutic development. The Crooke patent, licensed from Isis Pharmaceuticals Inc., of Carlsbad, Calif., covers degradation of target mRNA mediated by chemically modified RNAi-like oligonucleotides.
"At the outset, our goal was to consolidate as much of the fundamental intellectual property as we could around the use of siRNA," Mahanthappa told BioWorld Today. He said Alnylam's patent portfolio could be described as three concentric circles.
"The biggest circle relates to the fundamental structure and function of siRNA molecules, and I think there we have established a dominating IP position," he said. "The next circle I would characterize as the chemical modification that is useful in conferring to siRNA molecules the appropriate pharmaceutical attributes.
"And the smallest circle is our IP position that relates to particular targets with particular sequencing, and is relevant on a gene-by-gene basis."
Alnylam is moving along with its own development pipeline. The company has a partnership with Whitehouse Station, N.J.-based Merck & Co. Inc. to develop ocular disease drugs. Other RNAi programs include developing treatments for respiratory synctial virus, spinal cord injury, Parkinson's disease and cystic fibrosis.