Intellectual property: running interference

Nuala Moran

And the huge commercial potential of this gene silencing technology is highlighted by the outbreak of patent wars, with the threat of more legal clashes to come, according to a study of worldwide patenting in the field, carried out by Marks and Clerks, a firm of patent attorneys based in London.

The first RNAi paper appeared in the literature as recently as 1998, with the first platform patent applications filed shortly before that. There was a threefold increase in applications between 2001 and 2003, when the number of published patent applications reached 700. This trend is expected to continue for the years 2004 and 2005, and into 2006.

The most active applicants in the field are seeking to protect platform technologies, and many are academic institutions. Other applicants are seeking protection for specific therapies based on RNAi.

“Given RNAi’s enormous breadth of scope, it is not surprising that we are now seeing a gold rush for platform patent applications to cover the foundation technology,” said Gareth Williams, a partner at Marks and Clerk and co author of the report. “This is common practice, as players attempt to protect their research and licensing potential in a field that promises to be extremely lucrative.”

But while RNAi is a fertile area for R&D, Williams says there is a danger of an increasing number of legal disputes emerging, as shown by the seven oppositions that have been filed against one of the key European patents of Alnylam Pharmaceuticals Inc.

In any case there is likely to be considerable movement and consolidation within RNAi as the complex overlapping patchwork of IP rights is clarified. There are clear signs already that the main players are willing to license their rights to others, so avoiding “patent thickets” that can prevent companies from operating in some fields.

Gene silencing

The power of the technique derives from the proposition that it will be possible to design RNAi molecules that can selectively silence any gene. In principle it should be possible to come up with a construct to tackle any disease that is caused by the over expression of a protein.

In contrast to other gene silencing techniques, results of preclinical trials with RNAi have been very encouraging. The first therapeutics based on the technology are in early clinical development with initial data expected before the end of 2006.

“The technology promises much, and we fully expect to count the numbers of patent applications in their thousands in the coming years,” says the report. Many of the platform applications have been filed and it is anticipated the biggest growth will be of RNAi-based therapeutics against specific diseases.

And the report suggests that RNAi will provide a route around the weak applications that have been filed in recent years based on the recognition that a particular protein is implicated in a disease state. “It may appear that RNAi represents a way of overcoming sufficiency objections [from patent offices] After all, if an inventor has the sequence of the protein they should then be able to design and fully describe a RNAi interference molecule for inhibiting expression of that protein.”

And it will be relatively easy to test the effects of such a molecule on protein expression in a cell line, and thereby also fulfil the requirement of providing supporting data in a patent application. “RNAi may well represent a mechanism of rapidly providing a disclosure that is both sufficient and supported, and thereby accelerating the rate at which a company can file to protect its latest research,” says Marks and Clerk.

Testers undeterred

Meanwhile, in another field investigated by the report, investors in genetic diagnostic testing appear undeterred by concerns over gene ownership and its effect on freedom to further investigate genes under patent. Marks & Clerk says that 20 per cent of human genes are currently the subject of US patent claims.

Despite this, all the big operators are entering the fray and well over 2,000 patents were granted in the genetic diagnostic testing field between 1998 and 2003. In spite of the potential for these patents to come up against gene ownership patents, “Understanding the way an individual’s DNA make-up influences their response to a drug is now considered a necessary aspect of any company seeking to be, or remain, a commercial player in 21st century healthcare,” says Williams.

While it now seems likely that territory-staking applications to patent genes may not survive the scrutiny of patent offices, commercialisation in this area remains complex. But the emergence of healthcare providers in Europe and the US that are developing diagnostics and generating IP is likely to resolve this complexity, as they will be forced to respect the IP rights of others if they want to be able to market their own tests.

As the table shows, the top ten IP holders in the field are universities and specialist genomics companies. However, Bayer sneaks in at number 10, showing that pharmaceutical companies are getting involved.

“The big commercial players are generating their own patents, but also are trying to acquire as many IP portfolios as they can lay their hands on,” said Williams. “Moving forward we predict an even greater move towards licensing of patents by commercial players so that this technology can be applied to drug treatments.”