What’s at stake and why

Patent Rights Related to CRISPR-Cas9 Technology

The Patent Trial and Appeal Board (PTAB) at the United States Patent and Trademark Office (USPTO) is considering whether the Doudna/Charpentier research team or a research group at the Broad Institute of MIT and Harvard is entitled to U.S. patent rights on the CRISPR-Cas9 gene-editing technology through a procedure called an “interference.” The institutions behind the Doudna/Charpentier research team maintain that, because they were the first to invent the use of the CRISPR-Cas9 complex for gene editing, the first to publish on that invention and the first to file a patent application describing that invention, they are entitled to the patent rights covering the invention. Attorneys for UC and its co-owners have presented important evidence that demonstrates that the groundbreaking work of the Doudna/Charpentier team described and enabled CRISPR-Cas9 gene editing for both human and non-human cell types, and it was this work that other researchers in the field followed when utilizing CRISPR-Cas9 in various cell types.

The Broad Institute has argued that its scientists were the first to utilize the CRISPR-Cas9 technology for gene editing in eukaryotic cells, such as human cells, and that this is a separate invention over and above the inventions of the Doudna/Charpentier research team. The Broad Institute has further argued that it accomplished this prior to the publication of the Doudna/Charpentier research team’s seminal Science paper. However, the Broad Institute has failed to present any evidence that it had made the invention before the Doudna/Charpentier team’s seminal paper was published and, more critically, before the Doudna/Charpentier team made the invention. In fact, the evidence presented in the interference is contrary to the Broad Institute’s arguments.

The Doudna/Charpentier research team’s seminal 2012 Science publication not only disclosed the engineering of the CRISPR-Cas9 system for gene editing outside of the natural bacterial environment, but it also discussed how this groundbreaking gene editing system can be used to replace other technologies that had been used for gene editing in eukaryotic cells. Immediately following the 2012 publication, one of the lead investigators, Jennifer Doudna, publicly expressed her expectation that the system would be successfully used in eukaryotic cells, stating it was “now a very real possibility.” Indeed, within a few short months thereafter, numerous research groups, including Doudna’s own group, did just that – successfully utilized the engineered CRISPR-Cas9 system disclosed in the Doudna/Charpentier research team’s 2012 Science paper to edit DNA within eukaryotic cells – and they did so using only conventional techniques that were routine in the field. In short, following the Doudna/Charpentier research team’s disclosure of the necessary and sufficient components of the CRISPR-Cas9 DNA cleavage complex in the 2012 Science article, it was obvious to researchers in the field to use the engineered CRISPR-Cas9 DNA cleavage system described by the Doudna/Charpentier team in all types of cells, including eukaryotic cells. Doing so did not require any new inventive contribution, but instead required only obvious applications of routine laboratory techniques. For this reason, the Broad Institute scientists’ later application of the gene editing technology in eukaryotic cells is not a separate invention over and above the contributions of the Doudna/Charpentier research team.

The evidence that has been presented to the USPTO fails to demonstrate that its researchers successfully used the CRISPR-Cas9 system for gene editing in any eukaryotic cell type prior to the Doudna/Charpentier research team’s seminal 2012 article. The Broad Institute’s own technical expert in the current legal dispute admitted that the Doudna/Charpentier research team’s 2012 article was the first public disclosure of the necessary and sufficient components of the CRISPR-Cas9 cleavage complex. Further, a member of the Broad Institute’s research team, Fei Ran, acknowledged that the Broad Institute research team built off the “exciting discoveries” described in that 2012 article by making a few obvious modifications. A PowerPoint presentation by one of the Broad Institute’s inventors, Dr. Lin, in June of 2012 showed that the Broad Institute’s research team was unable to get any CRISPR-Cas9 system to work in eukaryotic cells prior to the Doudna/Charpentier team’s 2012 publication. Thus, the evidence that the Broad Institute has presented so far in the interference clearly demonstrates the Broad Institute’s failure to successfully make a working CRISPR-Cas9 system for gene editing prior to the Doudna/Charpentier research team’s 2012 Science publication that taught the necessary and sufficient components of the complex, and also taught how those components can be engineered for gene editing.

What was the subject of the early foundational CRISPR-Cas9 patent filing made by Doudna, Charpentier and their colleagues?

The team led by Doudna and Charpentier developed CRISPR-Cas9 systems for gene editing. The earliest patent application, which was filed by that research team in May 2012, demonstrates the engineering of the CRISPR-Cas9 cleavage system for cleaving a target DNA outside of the natural bacterial environment, and describes how to use the system in a variety of cell types including prokaryotes (simple organisms such as bacteria) and eukaryotes (higher organisms such as humans, animals and plants). This foundational intellectual property is co-owned by UC, the University of Vienna and Charpentier.

What is the status of the Doudna/Charpentier team’s foundational CRISPR-Cas9 patent application in the United States?

On Dec. 23, 2015, the United States Patent and Trademark Office (USPTO) indicated that the Doudna/Charpentier research team’s patent application was ready to be allowed (which generally means that an application will grant as a patent), but for the possibility of an interference. On Jan.11, 2016, the Patent Trial and Appeal Board (PTAB) of the USPTO declared what is technically referred to as an “interference” between UC’s patent application and 12 patents issued to the Broad Institute, Harvard University and MIT, as well as a pending Broad Institute patent application (the “Zhang patents and application”).

What is an “interference”?  

At the time the Doudna/Charpentier research team filed its patent application, the United States granted patents on a “first to invent” basis. Under “first to invent” law, if two parties have filed for patent rights claiming the same or very similar subject matter — as is the case between the Doudna/Charpentier research team’s patent application and the Zhang patents and application — the USPTO conducts an “interference” proceeding to determine who was “first to invent” the claimed invention.