Since its invention in 2012, the CRISPR-Cas9 gene editing system, which functions like a set of programmable molecular scissors to precisely cut, insert, delete and modify DNA, has become one of the most significant technologies in the history of biology. The invention is now routinely used across academia and commercial biotech in the investigation of fundamental biological processes and the discovery of new therapeutic targets.
The significance of the CRISPR-Cas9 system was recognised in 2020 by the award of the Nobel Prize for chemistry to Prof. Jennifer Doudna (University of California, Berkeley) and Prof. Emmanuelle Charpentier (Umeå University).
Doudna and Charpentier were the first academics to publish evidence of the utility of the invention to edit DNA and the first to file applications to patent the method. Importantly, their patent's method claims were limited to in vitro cleavage of DNA.
Seven months after the original Doudna / Charpentier publication, a team led by Prof. Feng Zhang at the Broad Institute in Boston published evidence that CRISPR-Cas9 could be used in vivo to edit genomic DNA and the Broad Institute, together with MIT and Harvard, filed a joint application to patent the invention.
At the time the competing CRISPR-Cas9 patents were filed, the USA operated a "first to invent" patent system, rather than the "first to file" system adopted in the rest of the industrialised world.
This meant that competing patent applications covering essentially the same invention could be filed at different times. In the event of competing patent claims covering the same invention, the parties could litigate the issue via "interference proceedings", and the patent would be awarded to the applicant who could prove they were the first to conceive of the invention and diligently reduce it to practice.
Not long after the CRISPR-Cas9 patent applications were filed, the USA switched to a first-to-file-patent system, meaning that the CRISPR-Cas9 patent applications were among the last US patents to be subject to the first-to-invent system.
Not surprisingly, interference proceedings ensued before the Patent Trial and Appeal Board ("PTAB"). The Broad Institute argued that the Zhang team were the first to apply the CRISPR-Cas9 system to human cells, whereas the Doudna / Charpentier groups had merely proposed it. The University of California argued that the Zhang team had learned of the invention from the Doudna / Charpentier team.
The interference proceedings ended in a split decision. The PTAB determined that the University of California had not proved conception of the invention prior to Broad Institute's actual reduction to practice in October 2012, because the Zhang team did not know that their CRISPR-Cas9 system would work in eukaryotic cells (i.e. cells with a defined nucleus, such as human cells).
The patent covering use of the CRISPR-Cas9 system to edit genomic DNA in eukaryotic cells was therefore awarded to the Broad Institute. The patent covering other uses, including editing DNA in prokaryotic cells (i.e. cells without a defined nucleus, such as bacterial cells) was awarded to the University of California.
The University of California unsuccessfully appealed the PTAB's decision to the federal court. The entitlement issue appeared resolved and, in the years that followed, the competing parties commercialised their respective CRISPR-Cas9 patents through the sale of licences in the USA and abroad.
However, the University of California has appealed the decision of the federal court not to overturn the PTAB's decision. In a decision dated 12 May 2025, the United States Court of Appeals for the Federal Circuit ("CAFC") remitted the case back to the PTAB on the grounds that it had "legally erred by conflating the legal standards for conception and reduction to practice", ruling that conception does not require certainty of success.
Given that lack of certainty was one of the reasons cited by the PTAB in its original decision, it is possible that the PTAB could reach a different conclusion on its rehearing of the matter, potentially transforming the legal and commercial landscape for the CRISPR-Cas9 system.
What happens next?
There is no deadline for the PTAB's rehearing of the matter and, even when such a decision is finally made, there remains the possibility of another further appeal. A conclusion of the matter is likely years away, but there is nothing to stop the parties from continuing their commercialisation activities for the time being. Day-for-day term restoration is available for patents for time spent in interference proceedings, meaning that the successful party will likely be able to generate licence revenues for many years to come.