Broad Institute down (but not out) in the European fight over CRISPR IP
Following the upholding in January 2020 of the revocation of the Broad Institute’s lead European patent (EP 2771468) by a European Patent Office (EPO) Appeal Board, there has been speculation that the University of California and its co-applicants (UC) have the upper hand in the European fight over the IP of clustered regularly interspaced short palindromic repeats (more commonly known as ‘CRISPR’), the latest incarnation of genome editing and deliberate alteration.
This is particularly apparent since UC’s own lead European patent in the fight (EP 2800811) was upheld earlier this year by an opposition board with amended claims, but no notable change in claim scope. The claims still cover use of sgRNA (single guide RNA) in any environment.
However, there are more rounds to come in this fight.
As is widely known, Broad’s lead European patent has been revoked as a result of a formal priority issue arising from the fact that the parent international application did not name one of the inventor/applicants on the first two priority documents (P1 and P2) as an inventor, and their successor in title as a co-applicant.
Luciano Marraffini was not named as an inventor, nor Rockefeller University as an applicant. As a result, priority to P1 and P2 under article 87(1) of the European Patent Convention (EPC) was lost and publications of the inventors were deemed prior art for the claims under consideration.
However, there is a sign that Broad may be considering making a petition for review of the appeal decision to the EPO Enlarged Board of Appeal (EBA) under article 112a EPC. This stems from Broad having requested (in February 2020) a number of amendments to the minutes of the opposition appeal hearing.
There is a need, it suggests, for a correction to faithfully reflect the course of the requests and decision-making of the appeal board, a move very quickly contested by opponents.
Petition for review
The suggestion is that Broad is seeking to set up the best foundation for petition for review under the ground of article 112a(2)(c), essentially that there was a fundamental violation of its right to be heard in accordance with article 113 EPC.
This might be argued in respect of the manner in which the appeal board reached its decision not to refer the priority issue to the EBA. Such a petition may be made up to two months from notification of the written appeal decision, and at the time of writing the decision had yet to be issued. However, petitions of this type have historically had an extremely low success rate.
Broad already has a lifeline in place to attempt to keep desired granted claim coverage in Europe: a European family deriving from one of its nine other parallel Patent Cooperation Treaty (PCT) applications which does name Marraffini and Rockefeller, published international application WO 2014/093595.
Two members of this family relate to CRISPR-Cas use in the selection of prokaryotic cells, but granted EP 2825654 of that family has very different claims. Claim 1 of that patent, in summary, is directed to a vector system comprising a sequence capable of expressing a CRISPR enzyme fused to a nuclear localisation signal and capable of providing a guide sequence for directing the CRISPR-Cas complex to a target sequence in a eukaryotic cell (organisms whose cells have a nucleus enclosed within membranes).
This claim is not restricted explicitly to use of Cas9. Nor does it require targeting a eukaryotic gene sequence, just a sequence in a eukaryotic cell.
Oral proceedings in relation to EP 2825654 are scheduled for September 23 and 24 this year. At that hearing, it’s expected that the argument will focus on the obviousness of the claims over Jinek et al’s 2012 paper, the first report of a successful use of a CRISPR-Cas 9 system in vitro with a sgRNA.
Will this produce success for Broad, as in the first interference proceedings in the US? In those proceedings, before both a Patent Trial and Appeal Board (PTAB) and the Court of Appeals for the Federal Circuit, Broad claims re CRISPR-Cas9 complex use in eukaryotic cells were held non-obvious over claims of UC covering the application of CRISPR-Cas9 complexes in any environment.
Although in that interference Broad kept its claims, a second interference is now ongoing between US claims of Broad and UC focusing on sgRNA and eukaryotic cells.
The same European family as the one that includes granted EP 2825654 provides flexibility for Broad to acquire still more claims free of formal priority issue. EP 3252160A of that family remains in examination with claim 1 directed to compositions comprising CRISPR-Cas9 complexes.
Broad’s other lifelines
In the meantime, Broad has salvaged in opposition proceedings to EP 2896697 (a European patent deriving from a further parallel PCT filing) narrow claims directed to vector systems providing CRISPR-Cas9 complexes with particular guide sequences.
These are the claims of Auxiliary Request 6g as upheld by the opposition board. Appeal proceedings are now pending. However, even if only such narrow claims are retained, how will they be construed by national European courts which are bound to consider beyond the literal interpretation?
Add to this that Broad has claims covering other important Cas enzymes such as Cas 12a (previously known as Cpf1) and Cas 12b (previously known as C2c1). These include the granted claims of EP 3009511 covering Cas 12a upheld in opposition proceedings late last year, and the granted claims of EP 3283625 of Wageningen University in the Netherlands, which is the subject of an agreement with Broad.
Cas 12b is a smaller Cas enzyme which may be favoured for many CRISPR-Cas applications. Already, for example, use is licensed to US-based Beam Therapeutics for application in its base-editing approach to gene mutation.
Moreover, the opposition decision re UC’s EP 2800811 will certainly be appealed by the opponents. Will an appeal board uphold use of common general knowledge to correct the missing PAM (protospacer adjacent motif, a DNA sequence essential for DNA sequence targeting by the Cas9 nuclease) from UC’s earliest priority document and uphold breadth of claim?
Broad may be down but is certainly not out in Europe in the CRISPR IP fight. It looks as though it’ll be a long time before we have any real clarity.
Claire Irvine is a partner at HGF. She can be contacted on cirvine@hgf.com
