The US Patent and Trademark Office yesterday (February 28) ruled that the Broad Institute of MIT and Harvard will retain its intellectual property over the use of CRISPR-Cas9 gene editing in eukaryotes. While the University of California, the University of Vienna, and Emmanuel Charpentier (collectively known as the CVC group in legal filings) maintain their original patent over the use of CRISPR-Cas9 to edit genes in vitro and in prokaryotes and some other intellectual property pertaining to the technology, the ruling in this latest proceeding effectively invalidates filings that specifically covered use in eukaryotes, potentially forcing companies that have licensed the technology from the CVC group to negotiate new deals with the Broad or other stakeholders. The ruling is the latest twist in the battle for ownership of a technique being explored commercially for everything from crop improvement to treating genetic diseases.
The new ruling finds that, “in the eukaryotic aspect, Broad is the only inventor [of CRISPR-Cas9], and UC Berkeley’s claims [involving the eukaryotic environment]—they now get struck out,” says Catherine Coombes, a European patent attorney with the global firm Murgitroyd. “So what you have is a situation in the US whereby the UC Berkeley still have some broad subject matter claims, but Broad alone has claimed CRISPR-Cas9 in the eukaryotic environment for the time being.”
Coombes adds that several proceedings are still ongoing, including interference claims by biotech companies ToolGen and Sigma, which filed for intellectual property for CRISPR’s use in eukaryotes back in the fourth quarter of 2012, just before the Broad did. She explains that in its new ruling, the Patent Trial and Appeal Board (PTAB) simply stated that the Broad’s claims of first use of CRISPR technology in eukaryotes—the so-called “reduction to practice” of CRISPR in prokaryotes—predated the CVC group’s, but “deftly sidestepped determining Broad’s earliest reduction to practice,” effectively avoiding weighing in on ToolGen’s and Sigma’s interference claims. She notes that companies with licenses for the now-invalidated CVC patents “might well hold back those discussions [with the Broad] for now and see how the other interferences proceed.”
The legal battle for intellectual property over CRISPR technology dates back several years, and the PTAB has previously sided with the Broad over the CVC group. While those familiar with the matter say that it is likely the new ruling will be appealed, Arizona State University science policy expert Bob Cook-Deegan says it’s unlikely to be overturned. “[S]ince the findings are based on a lot of fact-finding, and [the Court of Appeals] is mainly about matters of law unless the fact-finding is egregiously off, I don’t think UC can be too optimistic about re-securing its claims on eukaryotic CRISPR-Cas9,” he wrote in an email to ASU colleagues that he also shared with The Scientist.
He and Coombes both point out that the situation for CRISPR intellectual property is quite different in Europe, where, in contrast to the first-to-invent system in the US, patents can have overlapping subject matter. In this situation, companies interested in using CRISPR technology would have to negotiate licenses from both the CVC group, which holds a broad patent for CRISPR, and the Broad, which holds patents on its use in eukaryotes—assuming that its patents stand.
The varying patent laws in different countries “makes it an interesting landscape for the licensing perspective,” Coombes says. “Already today [March 1] I’ve got several clients emailing me saying, ‘What does this [new ruling] mean for me? Does this change who I should get a license from?’ And they’re not easy questions to be able to answer at the moment.”
She adds that even once these ongoing disputes on the foundational CRISPR patents are settled, which she estimates will take years, there will be other aspects of the technology to consider, including approaches to reduce off-target effects, improve efficiency of cleavage, and develop safe scaffolds for use in humans. “The key patent rights for CRISPR-Cas technology for human therapeutics may not [have been] granted yet.”
Charpentier, now at the Max Planck Institute for Infection Biology, and UC Berkeley’s Jennifer Doudna shared the 2020 Nobel Prize in Chemistry for adapting CRISPR to gene editing, and that innovation remains uncontested, notes Cook-Deegan. “What the Nobel committee decided was a whole different thing than the specific invention of CRISPR in eukaryotes.”