Regents of the University of California & Ors v Broad Institute, Inc. & Ors (10 September 2018)
The interference action between the University of California (UC) and Broad Institute (Broad) has seemingly come to an end, with the United States Court of Appeals for the Federal Circuit Court (CAFC) affirming that the patent claims that had been granted to Broad in relation to its CRISPR/Cas9 gene editing patents are separately patentable from the claims of a patent application made by UC. Unless UC can find a basis to request a re-hearing or petition to the Supreme Court, the CAFC’s decision draws to a close this heated battle between the two US educational institutions over the question of who was the first to invent the use of the CRISPR/Cas9 platform in eukaryotic cells.
Prokaryotic v Eukaryotic – the question of ‘reasonable expectation of success’
In its decision, the CAFC considered whether the work of Broad’s scientists in applying the CRISPR/Cas9 system to mammalian cells was obvious in light of what UC’s scientists were able to accomplish previously in vitro in a non-cellular experimental environment. The work of UC’s researchers (led by Dr Jennifer Doudna) was published in 2012 but did not report the results of experiments using CRISPR/Cas9 in a eukaryotic cell. It was noted that the claims in UC’s patent application were similarly silent as to the application of CRISPR/Cas9 in any particular cell type or environment.
The interference claim that initially came before the US Patent Trial and Appeal Board (PTAB) for determination therefore turned on the question of whether a person of ordinary skill in the art, in light of the work reported by UC, would have had a reasonable expectation of success in applying the CRISPR-Cas9 system in eukaryotes cells. PTAB published its decision in February 2017, finding that given the differences between prokaryotic and eukaryotic systems, the person of ordinary skill in the art would not have had such an expectation. Accordingly, it was determined that there was no interference-in-fact, because both the UC and the Broad patents were unique in their own right and therefore, both valid.
As noted in the CAFC decision, ‘reasonable expectation of success’ is a question of fact. The Court therefore took into account evidence such as:
- Broad’s expert testimony that there are fundamental differences between prokaryotic and eukaryotic cellular conditions that would make the effectiveness of CRISPR/Cas9 in eukaryotes unpredictable.
- In a September 2012 article, UC’s expert witness (Dr Doudna) stated that whether the CRISPR/Cas9 system would work in eukaryotes “remains to be seen” and “only attempts to apply the system in eukaryotes will address these concerns”.
- Dr Doudna, one of the named inventors of the UC patent, acknowledged the “huge bottleneck” in making genetic modifications in animals and humans. Further, following the publication of the initial UC research, Dr Doudna stated “[o]ur 2012 paper was a big success, but there was a problem. We weren’t sure if CRISPR/Cas9 would work in eukaryotes”. She further explained that she had “many frustrations” in getting CRISPR/Cas9 to work in human cells, and that she thought success in doing so would be “a profound discovery”.
- Broad presented evidence of three other systems derived from prokaryotes that had been adapted for use in eukaryotes, and the PTAB found that in each instance, there was either limited efficacy or the technology required a specific strategy to adapt it for use in eukaryotic cells.
Whether prior art needs to provide ‘specific instructions’
UC also argued before the CAFC that the PTAB erred in adopting a test requiring that there be specific instructions in the prior art to establish a reasonable likelihood of success.
The CAFC determined that the PTAB did not adopt that strict test nor was there an error in the PTAB’s analysis. While the PTAB noted in its decision that specific instructions in prior art have directed findings of a reasonable expectation of success, it also made clear that other considerations must also be accounted for in determining whether there was a reasonable expectation of success, such as whether there were examples in the prior art of the success or failure of similar systems. It was noted by the CAFC that the PTAB did not suggest that its conclusions were based solely on the fact that there were no specific instructions in the art describing how to apply CRISPR/Cas9 in eukaryotes.
Lastly, UC argued that the PTAB erred in dismissing evidence of simultaneous inventions as irrelevant. As submitted by UC, simultaneous invention could be compelling evidence of obviousness, because it would show that the claimed invention was the result of ordinary skill, rather than a genuine invention. UC noted that there were six research groups that independently applied CRISPR/Cas9 in eukaryotic cells within months of its disclosures.
This argument was also rejected by the CAFC, which noted that the PTAB expressly recognised UC’s evidence of simultaneous invention and concluded that while such evidence was evidence of the motivation to combine the prior art references, it did not necessarily indicate an expectation of success. Given the specific context of the prior art at the time, the PTAB determined that in this instance, the evidence of simultaneous invention did not establish a reasonable expectation of success.
As a result of this decision, the relevant UC and Broad patents each remain valid in the United States. It remains to be seen whether UC will find a viable avenue by which it can seek to appeal the CAFC’s decision.
Thanks to Esme Wong for her assistance in preparing this article.