Antisense Firms Must Navigate A Patent Minefield

With so many companies working on multiple approaches to interrupting messenger RNA and, hence, protein production, it comes as no surprise that the intellectual property (IP) surrounding antisense is a tangled web of cross-licensing agreements.

As the owner of patents describing the mechanism of action for antisense, Isis Pharmaceuticals has a finger in almost every pie. The company has more than 1,500 patents covering most angles of antisense technology. "Part of our strategy is to own as much of the patent real estate as possible," says Frank Bennett, senior vice president of research at Isis.

While much of that IP came from internal discovery, Isis bolstered its position in 2001 through a cross-licensing agreement with Hybridon, now called Idera Pharmaceuticals. Isis paid $34.5 million for access to Hybridon's antisense patent portfolio, while allowing Hybridon the freedom to work under Isis' suite of patents. Both companies retained the right to sublicense their respective portfolios to third parties.

Though Idera has shifted its development efforts away from first- and second-generation antisense to focus on RNA interference (RNAi)-based therapeutics, the company continues to have a stake in the broader antisense arena. Idera has more than 500 patents, including IP that covers second-generation chemistry, oral delivery of oligonucleotide-based drugs, and some 25 gene targets related to cancer, viral infections, or angiogenesis, says Sudhir Agrawal, Idera's chief executive officer and chief scientific officer. "Whoever is using second-generation technology is working under a license from Idera," he notes.

This complicated web of IP ownership has extended into subsequent generations of antisense technology. Because Isis owns much of the IP surrounding mechanism of action and oligonucleotide chemistry, companies working in RNAi, microRNA, and other antisense approaches almost universally need access to Isis IP.

For example, Alnylam Pharmaceuticals agreed in 2004 to align its IP fortress with Isis to enable both companies to further develop RNAi-based therapeutics. As part of the deal, Isis took a minority stake in Alnylam and will get a share of the profits from any licenses related to short interfering RNAs that Alnylam grants to third parties.

Despite its practical monopoly in antisense IP, Bennett says, Isis is most interested in facilitating other companies' abilities to exploit antisense technology, "rather than be an impediment."