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Patent bodies in the US and Europe have issued important decisions in patent battles over the gene-editing technology CRISPR, as Catherine Coombes of HGF reports.
Patent battles over the underlying rights for the CRISPR/Cas9 gene-editing technology have being playing out across the globe.
On February 15, 2017, the US Patent Trial and Appeal Board (PTAB) issued its decision in the patent interference proceedings between the Broad Institute of Harvard and MIT’s patents and those of UC, Berkeley and the University of Vienna. It held that there was no interference in fact, because getting CRISPR technology to work in a eukaryotic environment (instead of outside a cell or a prokaryotic environment) was a separate invention.
More recently, the European Patent Office (EPO), on March 23, announced its intention to grant EP 2800811 to UC, Berkeley with wide-ranging claims. These encompass method claims for cleaving DNA in “a single-cell eukaryotic organism, a plant cell, a cell from an invertebrate animal or a cell from a vertebrate animal”, in addition to claims for the single guide RNA (sgRNA) and compositions comprising the sgRNA. In doing so, the EPO considered that the earliest filed priority document (US 61/613,373) supports cleavage in all of these environments.
Following the decision, the university has acted swiftly to file translations of the claims and approve the text for grant, presumably in an attempt to avoid further third-party observations derailing grant.
A key issue in the examination proceedings was clarity. For claims referring to cleavage of double stranded DNA (dsDNA), it is known that a protospacer adjacent motif (PAM) is required. Cas9 has a PAM interacting (PI) domain which is involved in the conformational changes required for the cutting domains (RuvC and HNH) of Cas9 to each be able to access and cleave a strand of DNA.
Third-party observations filed during the process argued that the PAM was an essential feature for cleavage and, under established case law for clarity, an essential feature must be recited in the claims. Such a requirement would affect the patentability of the claims, as the earliest priority application was silent with regard to the requirement for a PAM, and loss of priority would bring in highly relevant publications by the applicant as prior art.
Intriguingly, while the earliest priority document omits the mention of a PAM, Figure 1 in this priority document contains the labelling line which indicates the PAM sequence in the equivalent figure (Figure 5A) of the later publication (Jinek 2012).
The applicant’s representative convinced the EPO that the recitation of the PAM was not necessary, by arguing that PAMs were part of the common general knowledge of the skilled person and, as a result, PAM was not an essential feature of the problem to be solved vis-à-vis the prior art.
As clarity cannot be raised as a grounds of opposition, such arguments that PAM should be recited in the claims cannot be raised post-grant. Instead opponents will try to argue the earliest priority application was not an enabling disclosure for cleavage in eukaryotes due to omission of both a reference to a PAM and data showing cleavage in eukaryotes.
We suspect that there will be multiple oppositions to this patent because it explicitly covers gene-editing in vertebrates and the use of CRISPR/Cas compositions in a method of treatment of a patient.
It will be interesting to see how the grant of this patent application will affect Broad/MIT’s nine granted patents in Europe, seven of which are in opposition. Specifically, if the EPO now considers UC, Berkeley’s earliest priority document to be an enabling disclosure for gene-editing in vertebrates, will the EPO now consider UC, Berkeley’s Jinek 2012 paper, containing the same data, to impact the patentability of these patents?
Catherine Coombes is a senior patent attorney at HGF. She is a European and UK chartered patent attorney focusing on the life sciences field. She has particular experience in securing and upholding patent protection relating to CRISPR technology. She can be contacted at: firstname.lastname@example.org
patent, CRISPR, gene-editing, EPO, European Patent Office, HGF. Catherine Coombes, PAM sequence, DNA, CRISPR/Cas, EPO, Patent Trial and Appeal Board,