The Fight for CRISPR Patents

For over a decade, there has been a battle for the coveted patents relating to the CRISPR/Cas9 gene editing technique. Two main groups, the University of California and the Broad Institute, are litigating the rights to the patents specifically covering the editing of eukaryotic cells

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Test Tube by Martin Lopez on Pexels

The innovations of the 21st century have brought incredible solutions to modern problems and jarring consequences. One of the latest innovations, CRISPR/Cas9 gene editing, has been wreaking havoc on the academic minds of various fields. This technology invites new questions about the ethics of modifying the genome, the extent to which it may be used, and even who deserves the patent rights to such a complex system. The first patents for the CRISPR/Cas9 system were filed over a decade ago in 2012, and the legal battle has ensued since. 

The “CRISPR” acronym stands for “Clustered Regularly Interspaced Short Palindromic Repeats,” and Cas9 represents “CRISPR associated protein 9.” It is an advanced gene editing technology that has been shown to effectively treat genetic diseases, such as blindness. It has the potential to edit human embryos, altering people’s genes before they are born. The application to human embryos is virtually limitless and would perhaps one day allow us to eliminate genetic diseases, increase resistance to diseases, or even alter appearance. Such advanced technology has been developed by many scientists in many labs over the years and thus has created multiple claims to the profitable patent claims of CRISPR/Cas9.  

There are two main camps vying for CRISPR patents. One group includes the University of California, Berkeley, the University of Vienna, and Emmanuelle Charpentier, collectively referred to as “CVC.” The other group includes the Broad Institute, MIT, and Harvard, collectively referred to as “Broad.” In terms of the patent battle in the United States, Broad has been more successful than CVC.

While there are numerous CRISPR/Cas9 related patents owned between CVC and Broad, the patents that cover the technology most applicable in medicine relate to using CRISPR/Cas9 in eukaryotic cells— meaning cells in humans, plants, and animals. CRISPR/Cas9 was originally developed with prokaryotic cells— meaning bacterial cells. While useful in research settings, the applications of CRISPR/Cas9 in prokaryotes do not go as far as those in eukaryotes and will not be as profitable. The coveted eukaryotic patent was awarded to Broad in April of 2014. 

The first round of litigation followed this patent in 2015. The crux of the issue stems from the fact that CVC filed for CRISPR/Cas9 patents first for all environments based on their development of the technology in prokaryotes and test tube practices. However, they did not show success in eukaryotic cells until approximately six months later. Broad published their success in eukaryotic cells using CRISPR/Cas9 just months before CVC, immediately filing for the patent and requesting accelerated examination. Because Broad had the first success in eukaryotic cells, their patent application was considered first and ultimately awarded. Following this decision, CVC requested that the USPTO declare interference based on CVC allegedly inventing the use of CRISPR in eukaryotes first. As a result of this interference claim and subsequent litigation, the USPTO did not consider or award CVC a patent until 2018.

Ultimately, the PTAB ruled that there was no interference between CVC and Broad’s CRISPR patents in 2017. This ruling was based on the idea that Broad’s work was not a direct continuation of CVC’s work and was not apparent to anyone of ordinary art and skill, therefore being patently distinguishable. Further, CVC’s patents were for their work in test tubes and bacteria, apparently unrelated to Broad’s work in eukaryotes. CVC appealed to the United States Court of Appeals for the Federal Circuit, which ultimately affirmed the PTAB’s ruling in 2018. Of note, the 2017 PTAB ruling did not decide which group was the “first to invent” the use of CRISPR/Cas9 in eukaryotes. 

The second round of litigation, Regents of the University of California v. Broad Institute, Inc., is pending a decision (as of November 9, 2024) from the Federal Circuit since oral argument took place on May 7, 2024. CVC again asked for the USPTO to declare interference against the same Broad eukaryotic patents and CVC patents. Interestingly, this case follows the 2020 Nobel Prize in Chemistry, awarded to two scientists on the CVC side, Emmanuelle Charpentier and Jennifer Doudna, for using CRISPR/Cas9 in eukaryotic cells. The CVC claim heavily debates what constitutes conception concerning patents, challenging the PTAB’s apparent requirement for CVC to know that CRISPR/Cas9 would work beyond prokaryotic cells in eukaryotic cells. CVC requested that its priority date be the date of filing for its first patent for all environments on May 25, 2012. However, the PTAB ruled that CVC’s priority date was January 28, 2013. The PTAB ruled that Broad’s priority date was December 12, 2012, the date of Broad’s patent filing, making Broad the Senior Party and CVC the Junior Party. 

A decision from the Federal Circuit is anticipated by the end of 2024. CVC’s primary argument was that they deserved the patent because Broad only used ordinary techniques and skills to make CRISPR effective in eukaryotic cells, and the PTAB did not find that Broad did anything beyond that. Broad argues that they made twelve adaptations to practice on eukaryotic cells, but conceded that while these techniques had not been used in this context before, they were modified versions of routine prior art techniques. 

CVC previously relied on its successful European eukaryote patents to bolster their argument for the equivalent patent in the United States. However, as of August, a European appeals board ruled that CVC’s earliest filings were not descriptive enough to merit those patents. Consequently, CVC seeks to cancel those patents to prevent further rulings that may damage its claims in the United States.  

The Federal Circuit’s decision will impact the licensing of CRISPR/Cas9, a $2.56 billion industry as of 2022. With the new FDA approval of CRISPR-based gene therapy, Broad is eligible for $40 million per year in licensing fees for ten years, which they may be required to share if CVC successfully appeals. Consequently, seemingly minute procedural questions in the PTAB could drastically affect tens of millions of dollars.