Back in September 2024, there was much publicity of disapproval of the grant texts of two European patents concerning CRISPR-Cas9 – patents claiming priority from the first relevant priority filing of the inventors’ group including the Nobel Prize winners Jennifer Doudna and Emmanuelle Charpentier. The patents, EP2800811B and EP3401400B in the joint ownership of the University of California, the University of Vienna and Emmanuelle Charpentier (commonly referred to more simply as ‘CVC’), were consequently automatically revoked ahead of opposition appeal oral proceedings. This action could be seen as a strategic ploy to remove the risk of unfavourable decisions in the face of preliminary opinions of the Appeal Board questioning sufficiency of the earliest priority filing (PD1). However, at the time, it was not possible to foresee that new claims directed to guide RNAs would quickly be allowed off a 4th generational divisional of the same family thereby in effect quickly restoring broad claim scope for CRISPR- Cas9 technology to CVC.
Intention to grant for CVC’s divisional EP4289948A was issued on 16 January 2025 with two independent claims (claims 1 and 3) directed to single guide RNAs (sgRNAs) and a further independent claim (claim 15) directed to modified DNA-targeting RNAs, i.e. covering both modified sgRNAs and modified guide RNAs formed of two separate RNAs (a cRNA and a separate tracrRNA). Final claims are also included directed to combinations of claimed guide RNAs with a naturally occurring Cas9.
The Examining Division has accepted the arguments of CVC for novelty in the face of two issues which were previously raised in the oppositions to the above-noted patents:
- novelty over the S. pyogenes 17 1nt tracr-RNA (tracr-L) reported in the 2011 Nature paper of Deltcheva et al. and later clarified by studies of Workman et al. as reported in Cell in 2021 to be a regulatory RNA which targets Cas9 to its promoter to repress transcription; and
- novelty over the Jinek et al. 2012 Science paper on the basis that PD1 provides sufficiency of disclosure of the claimed subject matter when read as it would be read by an appropriate skilled team despite lack of explicit reference to need for a PAM (protospacer adjacent sequence) in the target DNA.
Allowed claim 1 defines a sgRNA with reference to both structural features and function. More particularly, it specifies (a) a DNA targeting segment comprising a nucleotide sequence that is complementary to a sequence in the target DNA and (b) a protein-binding segment that interacts with a naturally occurring Cas9 comprising two complementary stretches of nucleotides that hybridize to form a dsRNA. It also requires that such interaction provides for site specific cleavage of the target DNA to generate a double-stranded break. This does not exclude a sgRNA that will also interact with a non-naturally occurring Cas9, e.g. a modified naturally occurring Cas9 such as a Cas9 nickase or dead Cas9.
Independent claim 3 replaces the functional requirement for site specific cleavage with further definition of the sequence complementary to a sequence of the target DNA as being greater than 15 nucleotides.
Given that independent claim 15 covers broadly modified DNA-targeting RNAs which can interact with a naturally occurring Cas9, there can be few using CRISPR-Cas9 technology in Europe outside of academic research who can ignore the prospective allowance of the relevant claims’ set. It is therefore certainly well-timed by ERS Genomics to launch also in January 2025 its ‘Express License’ platform to facilitate licensing of CVC IP for internal CRISPR-Cas9 research use by small enterprises (defined as fewer than 15 employees and under $10 million funding). For further information on the ERS Genomics’ website, see here.
The allowed claims of the ‘948 application supplement claims of a patent deriving from another divisional of the same family, EP3597749B, which remains pending but under opposition. Those claims include composition and ‘for use’ claims, but it cannot go unnoticed add still further to the guide RNA coverage sought by CVC. Independent claim 3 of the new Main Request claims filed in January 2025 is directed to a DNA-targeting RNA, or polynucleotide encoding such an RNA, in the EPO purpose-limited ‘for use’ format for coverage of medical use.
The CRISPR-Cas9 IP saga thus looks set to continue in Europe for a good while yet with no easing of FTO considerations.
If you would like further information please contact Claire Irvine, one of our life sciences team or Ben Muir, head of the life sciences team.
