By: Smitha Gundavajhala
On February 28, 2022, the US Patent and Trademark Office (USPTO) handed down a ruling in one of the most bitterly fought patent turf wars in biotechnology: the battle over the use of CRISPR-Cas9 in humans. The two major groups that were vying for recognition were the Broad Institute, consisting of researchers from Harvard, and MIT and CVC, consisting of researchers from UC Berkeley, the University of Vienna, and Emmanuelle Charpentier.
CRISPR-Cas9 is a revolutionary gene editing tool that has implications for healthcare, agriculture, and more. CRISPRs are DNA sequences with proteins that act like scissors. Originally derived from bacterial genomes, CRISPR technology has since been extended to apply to eukaryotes, which are multicellular organisms. Examples of eukaryotes include plants, animals, and humans. As one might imagine, the latest evolution in CRISPR technology is immensely lucrative. The technology could be used to prevent viral infections and chronic conditions in humans, as well as to genetically modify produce to carry more nutrients. Both Broad Institute and CVC stood to lose a great deal in their hard-fought dispute about the CRISPR-Cas 9 patent.
The dispute between these parties was complicated by timelines, the change in US patent law, and the contradictory decisions of different jurisdictions across the world. Jennifer Doudna of UC Berkeley was the first to file a patent application in 2012, a few months before Feng Zhang and the Broad Institute filed their patent application. However, prior to 2013, the USPTO’s rules were different: the agency awarded patents to the entity that was the “first to invent,” rather than the entity that was “first to file.”
Thus, when Doudna asked USPTO to declare an “interference” between the two patents in 2015, the office had to consider which group was the first to invent by “reducing the concept to practice.” CVC argued that Broad Institute’s patent for gene editing in eukaryotes was a mere extension of CVC’s seminal work on CRISPR-Cas9. In 2017, the Patent Trial and Appeal Board (PTAB) ruled that Broad Institute’s patents were not derived from CVC’s patents. In 2019, PTAB again declined to declare an interference regarding claims to CRISPR-Cas9 technology used in eukaryotes, and confirmed that the Broad Institute’s patents were properly issued.
Ultimately, Doudna’s patent application did not explicitly address CRISPR-Cas9 applications for eukaryotes, and Zhang’s patent application did. Thus, Zhang and the Broad Institute were determined to be the “first to invent” CRISPR-Cas9 gene editing for humans. This year’s USPTO decision represents potential losses of billions in licensing revenue for UC Berkeley and priority of invention for Broad Institute.
However, this turf war is far from over and recognition of the Broad Institute’s and CVC’s patents varies across jurisdictions. Currently, CVC maintains fundamental CRISPR-Cas9 patents in over 80 jurisdictions, including China, Japan, and the European Union. CVC and the Broad Institute also face challenges in other countries: South Korea’s ToolGen and Germany’s Sigma Aldrich still have open interference motions with the Broad Institute. From the looks of it, the international fight for CRISPR-Cas9 patent recognition won’t be over any time soon, even while the dust has seemingly settled in the United States.