CRISPR/Cas9 - patent rights to an important technology

For the reasons discussed below, it is possible that there could be a different winner in different jurisdictions. One group is lead by Professor Doudna (University of California) in collaboration with Professor Charpentier (formerly at the University of Vienna and now at Helmholtz Centre for Infection Research) – the Doudna group. The other group is lead by Professor Zhang (Broad Institute of Harvard, MIT and Harvard College) – the Zhang group. A substantial amount of money from the exploitation of the technology is at stake for all parties.

Background

CRISPR/Cas9 has been hailed as one of the most major developments in biology since PCR. In brief, CRISPR/Cas9 is a gene-editing system that utilises a target-specific guide sequence to direct the enzyme Cas9 to cut and, if required, replace DNA at a desired target. The accuracy of the CRISPR/Cas9 system has simplified the manipulation of genomes. This technique has many and varied uses including gene therapies for genetic diseases (eg, muscular dystrophy), generating improved crops and modifying embryos.

All three scientists have been awarded prizes for their work with CRISPR/Cas9. In particular, Doudna and Charpentier were awarded the 2015 Breakthrough Prize in Life Sciences. Meanwhile Zhang was awarded the 2014 Alan T Waterman Award by the National Science Foundation which recognizes an outstanding researcher under the age of 35.

Several companies have been formed which exploit the CRISPR/Cas9 technology including Editas Medicine, Intellia Therapeutics, Caribou Biosciences and CRISPR Therapeutics. Interestingly, Editas Medicine was founded by Zhang and Doudna, amongst others, but Doudna now has links with Intellia Therapeutics and is one of the founders of Caribou Biosciences. Charpentier is a founder of CRISPR Therapeutics.

The patent situation in Europe

To date, three European patents have been granted to the Zhang group (EP2771468, EP2784162 and EP2896697). These three patents all have the filing date of 12 December 2013 and claim priority from twelve priority filings – the earliest of these priority dates is 12 December 2012. During examination, anonymous third party observations were filed. Following grant, oppositions have been filed by numerous groups against two of these patents; opponents include CRISPR Therapeutics AG (a company in which Dr Charpentier has a stake) and Novozymes. At issue are novelty, inventive step, enablement, added subject-matter and entitlement to priority. The deadline for filing oppositions against the third patent does not expire until June 2016 and, at the date of writing this article, no one has filed an opposition but it is extremely likely that oppositions will be filed against this third patent nearer the deadline.

The European opposition procedure could result in the amendment or even revocation of the Zhang European patents. The opposition procedure for each case will probably take a few years. Even then, once the opposition proceedings have been held it is likely that the decisions will be appealed. So it could be several years before a final decision is reached by the EPO Board of Appeal. If one or more of the patents is maintained, possibly in an amended form, it is likely that the patent fight will continue in various national courts in Europe. Possibly further prolonging the battle, the Zhang group have two pending European applications in this family (European application numbers 15154565 and 15154566) and it is likely that more divisional applications will be filed in order to keep an application to the subject-matter pending whilst the oppositions (and potentially appeals) are ongoing.

So far, the Doudna group have just one application (European application number 13793997) which is pending. This application has a filing date of 15 March 2013 and claims priority from four priority filings - the earliest of these priority dates is 25 May 2012. This priority date is earlier than the earliest priority date of the patents granted to the Doudna group. Third party observations have been filed - some are anonymous but others are by the Broad Institute. It is likely that the Doudna group will file divisional applications in order to keep an application to the subject-matter pending.

In brief, it will be several years before the fight for these patent rights in Europe is well and truly over.

The patent situation in the US

In the US, Zhang has already obtained the grant of several patents and still has several applications pending. Doudna and Charpentier have several applications pending.

Following the enactment of the America Invents Act on 16 March 2013, the US came into line with the rest of the world and now uses a 'first to file' to determine who a patent can be granted to. However, when these cases were filed, the US still operated under the old 'first to invent' system.

The University of California asked the USPTO to determine who was the 'first to invent' the technique. The USPTO is now conducting what is known as an 'interference proceeding' to determine this. With so much at stake, it is likely that whoever loses before the patent board will file an appeal. So in the US it could also take a long time before the fight for these patent rights is concluded.

Summary

In the next few years we will be hearing a lot about the fights for these patent rights concerning the CRISPR/Cas9 technology. It will be intriguing to see how the various jurisdictions conclude what was disclosed by whom and when. Because the US operated the 'first to invent' system at the time the US cases were filed, it is possible that the outcome of the patent fight in the US may differ to that before, for example, the EPO. These conflicts are creating uncertainty for academic researchers as well as companies using the technology and potential investors. The outcome of these patent fights is likely to significantly affect who can have a licence to use the technology and the terms of that licence.