18 January 2018 - Authored by:Daniel Lim
Yesterday, the Opposition Division (OD) of the European Patent Office (EPO) has revoked one of the Broad Institute’s foundational CRISPR-Cas9 patents in Europe (EP2771468), upholding the preliminary opinion, which also found all claims of the patent to be invalid. The revocation of the patent will be suspended pending the completion of the appeal process, which the Broad has already flagged it will pursue.
This was the first opposition hearing for a CRISPR patent in Europe and understandably attracted a fair amount of attention as a potential indicator of further twists in the on-going patent dispute over the technology. The normally sparsely attended hearings in the Munich headquarters of the EPO saw around 40 observers packed into the room for this important case.
In the end, the hearing, which was scheduled to be heard over four days, lasted little more than one and a half, almost all of which was dedicated to technical arguments around whether the patent was entitled to claim priority from a number of early patent filings. The two earliest priority documents (12 December 2012 and 2 January 2013), amongst others, named Luciano Marraffini of Rockefeller University as an inventor-applicant, but Marraffini was not an applicant on the later patent and had not assigned priority rights to the Broad. Indeed, until mid-2017 the Broad and Rockefeller University were in an inventorship dispute over a number of early CRISPR patents.
The priority dispute
The key issue discussed was whether the EPO had the power to decide on entitlement to priority. The Broad considered that national law (in this case US law) should apply; under the relevant US law inventorship (and valid claim to priority) would be defined by the person’s contribution to the subject matter of the invention and so the omission of Marraffini could be justified on the basis that he did not contribute to the later filed invention. The opponents argued that the EPO is competent to rule on priority and bound to do so by Article 87 of the European Patent Convention (EPC), invoking the case law of the EPO and suggesting that the Broad was asking the OD to “throw 100 years of case law out the window”.
Unsurprisingly, the OD declined to do so, despite the Broad’s best efforts and some late drama as the Broad sought to introduce a press release detailing the settlement between the Broad and Rockefeller University (dated the day before the hearing) on the morning of the second day. Despite the finding in the binding arbitration between the Broad and Rockefeller University that the inventorship on the Broad’s patent applications should remain unchanged (which might have supported the Broad’s priority claim under US law), under European patent law there had to have been an assignment of Marraffini’s right to claim priority to the applicants named on the patent application before the date of its filing. The findings in the arbitration and subsequent settlement did not have retroactive effect and could not cure that key deficiency at the time of filing after the fact. The loss of priority claims to P1 and P2 meant that key prior art documents D3 (Mali) and D4 (Hwang) were admitted for the purposes of novelty and obviousness, knocking out most/all of the claims.
The post-priority wash-up
Having lost the key priority point, the rest of the hearing was a swift procession, as the Broad declined to advance arguments on novelty over D3 and D4 and proposed 64 auxiliary requests (alternative claim sets designed to overcome invalidity objections), but none of which were directed to overcoming a case on lack of novelty over D3 and D4. The OD rejected all 64 auxiliary requests in short order and immediately moved to ruling that the patent did not meet the requirements of the EPC and was revoked in its entirety.
It is telling that the Broad immediately issued an “update on patent process in Europe“ upon the OD’s priority decision but no further update after the actual revocation decision itself. In the statement the Broad indicated they would appeal the decision to the EPO’s Technical Board of Appeal (TBA) and clearly foreshadowed the line of attack to be taken into appeal, stating that the decision “affects many other European patents that rely on U.S. provisional patent applications, and is inconsistent with treaties [i.e. Paris Convention] designed to harmonize the international patent process, including that of the United States and Europe“. The statement ended with a who’s who list of assorted patent luminaries who the Broad claims supports their position, including Lord Hoffmann, retired Law Lord and the Honorable Paul R Michel, retired Chief Judge of the Court of Appeals for the Federal Circuit, both of whom provided statements relied upon by the Broad in the proceedings (D117 and D119, respectively).
An appeal to the TBA and potentially even further to the Enlarged Board of Appeal is unlikely to be heard soon – based on our recent experience it will likely be at least another 2 years before the appeal is heard and the issue is finally determined. In the meantime, oppositions will likely be heard in respect of further CRISPR-Cas9 patents, including additional European patents from the Broad, and those from the University of California, Berkeley (UCB) (EP2800811), MilliporeSigma (EP3138910) and Cellectis (EP3004337). (N.B. As of 17 January 2018 the opposition period has yet to expire for these patents. Oppositions have already been filed against the UCB and MilliporeSigma patents but not the Cellectis patent as yet.)
Consequences of the decision
Unlike the US interference decision and the various scientific scares over off-target effects and (more recently) human immunity/immune response to saCas9 and spCas9, the OD’s decision has had negligible effects on the share prices of the “big 3″ CRISPR biotechs – Editas Medicine (who in the exclusive licensee of the Broad’s CRISPR patent portfolio for human therapeutics), Intellia Therapeutics and CRISPR Therapeutics. This could indicate a view amongst investors that the foundational CRISPR-Cas9 patents are of decreasing importance as the companies move closer to designating lead products for development (CRISPR Therapeutics has already filed the first CRISPR Clinical Trial Application in Europe, for CTX001 for the treatment of beta-thalassemia) and further develop specific patent protections for their particular products. Alternatively, it could be indicative of a US-focused investor group (all three companies are listed on the NASDAQ).
In terms of the other Broad patents, the decision indicates that some of those will also be vulnerable this same priority point – i.e. seeking to claim an early priority date from earlier filings where Marraffini was listed as an inventor, without having named him as an inventor on the later application. It is likely that the claims of those patents will also be substantially or wholly revoked, in light of this decision. However, the Broad has other patents covering later, more specific inventions and different Cas proteins like Cpf1 which will not be affected.
For this reason, in the grander scheme of things, the decision may not really change much, either for the key CRISPR licensors (like the Broad, UCB and the spinout companies they license) or companies looking to secure freedom to operate using CRISPR-Cas9 technology. The key CRISPR institutions and companies will continue to research, invent and patent new CRISPR related technologies, ranging (for example) from new Cas variants and delivery mechanisms to specific guide sequences and treatment regimens. Ultimately, losing this patent or even a set of patents with the same priority issue might diminish the value of the Broad’s fundamental CRISPR patent portfolio pending appeal and reduce the royalties derived, but the Broad will remain at the leading edge of CRISPR research and licensing despite the setback.
Is there any upside for the Broad from the decision? Not really. But the patent practitioners of Europe can breathe a sigh of relief that the EPO has not “thrown 100 years of case law out the window”. At least until the appeal.