CRISPR/Cas9 gene editing was invented just over six years ago, and the technology’s inventors have spent more than half of that time locked in a legal dispute over who holds the rights to fundamental patents on the technology. In a highly anticipated decision released today, a U.S. federal court ruled in favor of the Broad Institute of MIT & Harvard, agreeing with a lower court that Broad’s patents for CRISPR/Cas9 gene editing didn’t interfere with a patent application from CRISPR’s other inventors at the University of California, Berkeley, and the University of Vienna.
That decision is a victory for Broad scientist Feng Zhang and Editas Medicine, a company he cofounded to develop therapies that use CRISPR to treat genetic diseases in humans. But it leaves two other major CRISPR companies without a foundational U.S. patent on the technology they are based on. One is Intellia Therapeutics, cofounded by UC Berkeley’s Jennifer Doudna; the other is CRISPR Therapeutics, cofounded by Emmanuelle Charpentier, formerly of the University of Vienna.
UC Berkeley could request a rehearing in a federal circuit court or attempt to take the case to the Supreme Court. But Jacob Sherkow, a professor at New York Law School who has tracked the case carefully, says both scenarios are unlikely, since no new legal issues have emerged. “This is almost certainly the end of this particular patent dispute,” Sherkow says.
The ruling of no interference means that the courts never heard arguments to decide who the original inventors of CRISPR/Cas9 were, which is the question that UC Berkeley wanted answered in the first place.
UC Berkeley filed a patent application describing CRISPR/Cas9 gene editing in May 2012. Broad filed multiple patents later, but they were reviewed and approved first, since Broad paid for an expedited patent-review process. In response, UC Berkeley launched a so-called patent interference to determine if UC Berkeley’s patent application and Broad’s accepted patents described the same invention.
At the U.S. Patent & Trademark Office (USPTO) in December 2016, Broad’s lawyers argued that the two sides invented different things. UC Berkeley’s patent application only showed how to use CRISPR/Cas9 to edit DNA in test tubes and in prokaryotic organisms like bacteria. Broad’s patents, in contrast, specifically described using CRISPR/Cas9 in eukaryotic cells, which include plants and animals, including humans. Broad argued that its invention was unique and separately patentable.
One of UC Berkeley’s lawyers argued that “no special sauce” was required to use CRISPR/Cas9 in eukaryotic cells, and therefore Broad’s patents conflicted with UC Berkeley’s application. USPTO disagreed, and decided that Broad’s patents described a nonobvious invention. That decision halted the interference proceeding, keeping it from a next step where USPTO judges would hear arguments to determine the original inventor of CRISPR/Cas9, as UC Berkeley wanted.
UC Berkeley appealed the USPTO decision to the U.S. Court of Appeals for the Federal Circuit, which heard the case in April. Today, the federal court affirmed USPTO’s decision.
“It is time for all institutions to move beyond litigation,” Broad said in a statement following the ruling. Although Broad makes CRISPR/Cas9 tools freely available to academic and nonprofit researchers, it is unclear how the court’s decision will affect Intellia, whose license for CRISPR/Cas9 comes from UC Berkeley, and CRISPR Therapeutics, whose license comes from Charpentier.
That’s because UC Berkeley’s patent application, which was in limbo until the patent dispute ended, is still waiting to undergo review. But Sherkow says it is unlikely that USPTO will approve the patent in its entirety, since Broad now holds patents for using CRISPR/Cas9 in eukaryotes.
To complicate matters further, it recently became clear that another CRISPR scientist, Virginijus Šikšnys of Vilnius University, filed a patent for CRISPR/Cas9 just weeks before UC Berkeley filed its patent in 2012. While UC Berkeley and Broad were entangled in their dispute, the Šikšnys patent was approved and made public, meaning that USPTO can now hold the Šikšnys patent against UC Berkeley. “That has the potential to sink whatever is left from Berkeley’s patent application,” Sherkow says.
UC Berkeley has had better success obtaining foundational CRISPR/Cas9 patents outside the U.S., including in China and Europe. UC Berkeley scientists have also discovered new versions of CRISPR that could provide alternatives to the Cas9 version that Broad now controls.
As for how CRISPR’s inventors will go down in history, “the scientific prizes say it all,” Sherkow says. Doudna, at UC Berkeley, and Charpentier, now at the Max Planck Institute for Infection Biology, have both won prestigious scientific awards, including the Breakthrough Prize and the Kavli Prize in Nanoscience. The latter was shared with Šikšnys “for the invention of CRISPR/Cas9.”
“The Kavli Prize gives you an idea of what the principal advance was that the scientific community thought was the most important,” Sherkow says. The patent dispute decision, he adds, “is only going to affirm in scientists’ minds that patent law is simply not aligned with the actual process of scientific discovery and invention.”