On 24 March 2017, the examining division of the European Patent Office (EPO) issued a communication under rule 71(3) EPC of its intention to grant EP 2 800 811 (the Patent), which is co-owned by the University of California Berkeley (UCB), the University of Vienna and Emmanuelle Charpentier. The Patent is entitled “Methods and compositions for RNA-Directed Target DNA Modification and for RNA-Directed Modulation of Transcription” and claims a broad method of modifying a target DNA by (essentially) use of the CRISPR/Cas9 complex. A link to the entry for the Patent on the European Patent Register is here.
This communication of intention to grant the Patent comes two and a half years after examination of the Patent by the EPO was first requested by the applicants (on 8 August 2014), and in which time nine separate sets of third party observations were filed, and numerous rounds of communications, claim amendments and replies took place between the applicants and examining division.
The issue of the rule 71(3) communication from the examining division marks the end of substantive phase of the prosecution and paves the way for the patent to be granted. It now remains for the applicants to pay the necessary fees and file translations of its claims, after which the EPO will issue its formal decision to grant, published in the European Patent Bulletin (Bulletin). The grant of the Patent will take effect from the moment of publication in the Bulletin. If the applicants move quickly (as one expects they will) this could come as soon as around 6 weeks after the rule 71(3) communication.
Overcoming such extensive observations and in intensive examination procedure to achieve grant represents a considerable achievement and a huge boost to the fortunes of UCB, Charpentier and their associated companies (Caribou Biosciences, Intellia Therapeutics, CRISPR Therapeutics and ERS Genomics) and sublicensees.
Crucially, the claims of the Patent have emerged from the prosecution procedure without being limited to use of CRISPR/Cas9 in prokaryotes. For example, claim 1 of the Patent in the form intended to be granted is to:
A method of modifying a target DNA, the method comprising contacting the target DNA with a complex comprising :
(a) a Cas9 polypeptide and
(b) a single-molecule DNA-targeting RNA comprising:
(i) a DNA-targeting segment comprising a nucleotide sequence that is complementary to a sequence in the target DNA, and
(ii) a protein-binding segment that interacts with said Cas9 polypeptide, wherein the protein-binding segment comprises two complementary stretches of nucleotides that hybridize to form a double stranded RNA (dsRNA) duplex,
wherein said two complementary stretches of nucleotides are covalently linked by intervening nucleotides,
wherein said contacting is in vitro or in a cell ex vivo; and
wherein said modifying is cleavage of the target DNA
Claim 4 makes that lack of limitation to prokaryotes explicit, claiming use of the method on target DNA present in different cell types, including plant cells and cells for vertebrate or invertebrate animals (all eukaryotic cells).
Accordingly the Patent is wider in scope than those which have already been granted to the Broad Institute of Harvard and MIT (the Broad) in the US and Europe, which are limited to the use of CRISPR/Cas9 in eukaryotes. As we have previously noted (see our article here on the implications of the USPTO’s decision in the CRISPR interference action), there is a real possibility that both UCB and the Broad will retain valid CRISPR/Cas9 patents of wide scope which users of CRISPR/Cas9 technology (including UCB and the Broad themselves) will need to licence from each party.
The impending grant of this Patent, with wide claims not limited to use in prokaryotes, will represent the biggest shift in power between UCB/Charpentier and the Broad, being the first granted patent for UCB/Charpentier in a major territory. Of course, just as in the case of the Broad’s eight granted European Patents, it is extremely likely that numerous oppositions to the Patent will be filed in the nine month opposition period following grant.
Including appeals from a first instance decision by the opposition division of the EPO, it could be several years before a final position on the validity and form of claims of the Patent is reached. However, this fact will not deter UCB, Charpentier and their associated companies, who will take comfort from the examining division’s view on the patentability and valid scope of the Patent and likely seek to use the grant of the patent as leverage to encourage further investment, licensing and collaboration opportunities.