13 July 2018

CRISPR – testing the fundamentals of patent law

CRISPR (“Clustered Regularly Interspaced Short Palindromic Repeats”) technology potentially provides a cheap, efficient and easy way to precisely modify genetic information and has the potential to revolutionise medicine. Perhaps unsurprisingly in view of this, the patent landscape surrounding this technology is extremely complicated and contentious.

The value of CRISPR technology is expected to rise to more than $6Billion by 2022, and around 1344 patent families relating to CRISPR technology have now been filed. Components of the CRISPR systems are the subject of 3,035 patents and patent applications, and methods of delivering (1,861) and applying (2,451) CRISPR also constitute a significant number of patents and patent applications. Of the total patent filings, 29% have been made in North America compared to 12% in Europe (where the UK is the largest filer), and 22% have been made via the PCT.

In terms of ownership, The Broad Institute is associated with 297 patents and patent  applications, and the University of California is associated with 131. Other major players include DowDuPont (514), Harvard University (343), MIT (316), and Sangamo Biosciences (150). The Broad Institute’s Feng Zhang alone is associated with 355 patents and patent applications, and another famous name in the field, Jennifer Doudna of the University of California- Berkeley, is associated with 71.

It is not just the sheer volume of CRISPR-related patent filings that is likely to pose challenges for the commercialisation of this potentially lucrative technology, as perhaps more significant is the uncertainty surrounding the validity of the patent rights.

The original CRISPR dispute is ongoing in the US, where the Broad Institute is in conflict with the University of California, Berkeley, which originally developed The CRISPR Cas-9 methods, but only for use in bacterial cells. The US Patent Trial and Appeal Board ruled in favour of the Broad Institute, on the grounds that extending the use of CRISPR to eukaryotic cells (and thus humans) was not obvious, and Chief Judge Paul Michel has indicated that the pending appeal from that decision “raises questions about the application of basic obviousness precedents and their attendant doctrinal standards and analytic methodologies”, which are crucial to almost all contentious and non-contentious patent matters.

Likewise, the European Patent Office’s recent revocation of a key CRISPR patent has also tested the foundations of patent law, albeit in relation to different legal matters, concerning priority claims and the filing of international patent applications.

European patent EP2771468 was granted on 11 February 2015 to three co-proprietors, The Broad Institute, MIT, and Harvard College. The patent derived from a PCT application filed on 12 December 2013, which claimed priority from twelve US provisional applications, the earliest of which was filed on 12 December 2012.

Grant of the patent by the European Patent Office (EPO) was opposed by nine separate parties. Amongst other reasons, revocation was requested on the ground that the patent was not entitled to claim priority from at least two of the priority documents.

In Europe, when a priority-claiming patent application is filed, the applicant of the priority-claiming patent application must be the person who filed the earlier application, or that person’s successor in title (Art. 87(1) EPC). Thus, the priority claim is not valid if the assignment from the applicant to their successor was made after the filing date of the subsequent application.

If the earlier application has joint applicants, the right to claim priority from the application belongs jointly to all of the applicants, and priority can only be claimed from the earlier application if the priority-claiming application designates all of the applicants of the earlier application, or their successors in title (see, for example, T788/05).

Some of the applications from which EP2771468 claimed priority had been filed under the old US “first-to- invent” rules and therefore named the inventors as patent applicants. However, the US has less stringent priority requirements than the EPO. In the US, the priority-claiming application requires just one joint inventor in common with the earlier application. In addition, there is no requirement in the US for the assignment to occur before the filing of the priority-claiming application.

The opponents of EP2771468 argued that the priority claims based on two US provisional applications (P1 and P2) were invalid, on the grounds that one or more of the applicants  of P1 and P2, or their successors in title, were not listed as applicants  for the PCT application from which EP2771468 derived. This argument is factually correct; Luciano Marraffini of the Rockefeller University is listed as an Applicant on the priority applications in question, but not on the PCT application. No evidence was submitted to the EPO that Marraffini had assigned his rights to one of the applicants of the PCT application before that application was filed.

The proprietors argued in response that the right to claim priority should be interpreted according to national (i.e. US) law. P1 and P2 both relate to more than one invention and it was argued that under US law, it is a requirement that all the inventors that have contributed to all of the disclosed inventions are named as applicants of a provisional application.

Thus, as an inventor, it was a requirement for Marraffini to be listed as an inventor-applicant of P1 and P2.

The proprietors further argued that only an inventor or an inventor’s successor in title may be named as an inventor-applicant on a patent application. Thus, it was argued that only the inventors of the subject matter to which the priority-claiming PCT was directed could be listed as applicants of the PCT application, and this did not include Marraffini, who had not contributed to the invention to which the PCT application was directed.

Although too late to be taken into consideration by the EPO, arbitration in the US two days before the EPO proceedings actually determined that Marraffini should not be named as an inventor on the patent.

In its decision, the EPO held that the right to claim priority had not been properly assigned from the inventors to the named applicants. As a result of this finding, the claimed subject matter was found to lack novelty over a number of documents which became relevant as prior art due to the lack of priority entitlement.

It is testament to the value of the CRISPR technology that The Broad has already filed a notice of appeal against the decision. The Broad Institute appears to accept that the decision was in line with the EPO’s “formal requirements”, but argues that the EPO’s approach to priority is inconsistent with the Paris Convention and other international treaties aimed at harmonising patent law worldwide.

The appeal has suspensive effect and the EPO’s decision will not become final unless the EPO’s Technical Board of Appeal confirms it. It is clear that this story will not reach its conclusion for some time yet.

If the EPO Board of Appeal overturns the original decision and sides with The Broad Institute on the question of priority, this will mark a radical departure from decades of jurisprudence on a fundamental concept in European patent law. Nevertheless, it is a sign of the importance of this technology that The Broad considers this a battle worth fighting.