Both the Broad ‘camp’ and CVC ‘camp’ (the University of California, the University of Vienna and Emmanuelle Charpentier) have recently suffered disappointment at opposition oral proceedings before the EPO Opposition Division (OD) in relation to claims broadly encompassing use of Cas9 nucleases in eukaryotic cells. In contrast, Toolgen’s EP3346003B concerning delivery of Cas9 ribonucleoproteins (RNPs) to cleave plant cell DNA was upheld in November 2025 with reliance on a main claim merely requiring PEG-mediated delivery of a Cas9 RNP into protoplasts. Furthermore, of significance for application of Cas9 gene modification in the therapeutic field, it must now be expected that Toolgen’s EP4357457B in litigation against Vertex and its associated CMOs (main claim directed to compositions comprising SpCas9 and sgRNA in defined molar ratio, also now opposed) will very soon be supplemented by additional granted claims at the EPO off divisionals of the same family re Cas9 RNP use.
Despite a number of third party observations, notice of intention to grant has issued in December 2025 for EP4342987A with a main claim broadly covering delivery of a preformed Cas9 RNP complex into eukaryotic cells, in vitro or ex vivo, for targeted mutagenesis of endogenous DNA. Despite third party observations, notice of intention to grant has also recently issued for EP4397760B with a main claim directed to in vitro or ex vivo cleaving of a target DNA, inducing targeted mutagenesis or genome editing in a mammalian cell by SpCas9 RNP delivery employing a sgRNA. Such claims will almost certainly additionally be opposed but the message from Toolgen is clear- do not ignore us if using Cas9 RNPs.
The Broad camp and CVC camp may have suffered recent disappointments in opposition proceedings, but this does not mean the end of the road for either in securing claims from the EPO of broad applicability to Cas9 use. The foremost problem for CVC remains battling alleged lack of priority to their earliest US provisional filing in May 2012 in view of lack of explicit reference to need for the protospacer adjacent motif (PAM) for target DNA cleavage. It remains unclear why for example Figure 1A of that filing merely shows a faint unlabelled line to the PAM position as shown below. The written decision of the OD as issued 12 December 2025 for EP3597749B confirms that the Opposition Board were not convinced that this absence could be rectified by reference to common general knowledge (CGK).
The Board saw lack of consistent disclosures ahead of the earliest priority date to support as CGK that a PAM is essential for any Cas9 target DNA cleavage, even in vitro. In so finding they considered they were rightly aligned with the preliminary opinion of the Board of Appeal in relation to the first issued EP of the family, EP2800811B – self- revoked ahead of the appeal oral proceedings in 2024. The consequence was finding of lack of inventive step over the famous Jinek et al. 2012 Science paper. However, it cannot be ignored that CVC’s representatives have basis for more expansive argumentation against the PAM issue finding via more than one route, including defence of opposition proceedings to the guide RNA claims of EP4289948B.
A little earlier in October, the Broad camp saw revocation of EP3252160B with an amended main request claim 1 directed to a composition comprising a CRISPR- Cas9 system and specifying a guide sequence linked to a tracr sequence which is at least 50 nucleotides long “wherein the guide sequence directs sequence-specific binding of a CRISPR complex to a target sequence in a eukaryotic cell,” The written decision of the OD as issued 22 December 2025 followed their negative preliminary opinion. Notably both provide unfavourable comments on novelty and inventive step with reference to stopped appeal T1088/22 re Sigma-Aldrich’s EP3138911B. However, the Broad camp has many routes still open to carry on fighting for coverage of Cas9 use in eukaryotic cells.
Hence, the CRISPR IP saga rolls on into 2026 with no apparent lessening just yet of licensing considerations and Toolgen showing preparedness to litigate if provoked to do so.
