The Federal Circuit in Regents of the University of California v. The Broad Institute weighed in on the disputed inventorship of the breakthrough CRISPR-Cas9 technology, holding that the University of California (“UC”)’s invention of the mechanism in vitro did not render obvious Broad’s claims to the mechanism in eukaryotic cells. Gibbons previously reported on the technical background of CRISPR-Cas9. This post will focus on the inventorship issue and the implications of the Federal Circuit decision.
In August 2012, UC researchers published an article showing that the CRISPR-Cas9 system, derived from prokaryotic cells like bacteria, could be used in vitro in a non-cellular experimental environment. Several research groups independently applied CRISPR-Cas9 in eukaryotic cells within months of UC’s disclosure. In February 2013, Broad researchers published an article describing the use of CRISPR-Cas9 in a human cell line. Both UC and Broad sought patent protection. UC, the senior party, claims the CRISPR-Cas system without referring to a particular cell type or environment. Broad, the junior party, claims the CRISPR-Cas system limited to use in eukaryotic cells, i.e., plant and animal cells. The Patent Trial and Appeal Board (PTAB) determined there was no interference-in-fact because, given the differences between eukaryotic and prokaryotic systems, a person of ordinary skill in the art would not have had a reasonable expectation of success in applying the CRISPR-Cas9 system in eukaryotes. The Federal Circuit held that substantial evidence supported the PTAB’s decision and affirmed.
The PTAB concluded that if UC’s CRISPR claims were prior art, they would not have rendered Broad’s claims obvious. Broad’s expert testified extensively as to the differences between prokaryotic and eukaryotic systems that rendered the application of CRISPR-Cas9 to eukaryotic cells unpredictable. Moreover, Broad presented evidence of statements by the UC inventors acknowledging doubts and frustrations about engineering CRISPR-Cas9 systems to function in eukaryotic cells and noting the significance of Broad’s success. And the PTAB found that the developments of other gene editing systems were not particularly informative in assessing the reasonable expectation of success of CRISPR-Cas9 in plant and animal cells. “In light of the record evidence, which includes expert testimony, contemporaneous statements made by skilled artisans, statements by the UC inventors themselves, and prior art failures,” the Federal Circuit concluded “that the Board’s factfinding as to a lack of reasonable expectation of success is supported by substantial evidence.”
The Federal Circuit rejected UC’s arguments to the contrary. Simultaneous invention may serve as evidence of obviousness given the totality of the circumstances. “The fact that six research groups succeeded in applying [CRISPR-Cas] in eukaryotic cells within a short period of time after [UC’s disclosure] is certainly strong evidence that there was a motivation to combine the prior art in this manner.” But it did not necessarily indicate an expectation of success prior to the completion of the experiments. The Federal Circuit thus affirmed the Board’s finding, noting that the decision is limited to “the scope of two sets of applied-for claims,” and “is not a ruling on the validity of either set of claims.”
The decision has important implications for the CRISPR-Cas9 patent landscape. Although the decision did not rule on the validity of either set of claims, it does legitimize both Broad’s and UC’s patent claims. Parties commercially active in the field may thus have to seek a license from both groups. Given the financial and scientific stakes involved, the ownership dispute over the foundational CRISPR-Cas9 mechanism in eukaryotes is likely far from over.
Gibbons will continue to monitor patenting trends and disputes involving CRISPR-Cas systems and provide periodic updates. Please contact the authors for additional information.