Another showdown in the seemingly endless patent battle over who invented CRISPR, the genome editor that has revolutionized biology, took place today at the U.S. Patent and Trademark Office (USPTO). This latest hearing saw charges that one party improperly obtained early CRISPR information, as well as a detailed scientific discussion of a crucial question: Who invented the “guide RNA” molecule that allows the genome editor to work in eukaryotic cells?
On that question, “we have never received a satisfactory answer from the patent office,” says Jacob Sherkow, a patent attorney with the University of Illinois College of Law and a longtime observer of the fight. Potentially huge financial rewards go to the victor, as multiple companies have invested many millions into turning CRISPR into medical therapies.
One side claiming the CRISPR invention is known as the CVC group and includes the two researchers who won the 2020 Nobel Prize in Chemistry for their pioneering CRISPR work, Jennifer Doudna of the University of California (UC), Berkeley, and Emmanuelle Charpentier of the Max Planck Institute for Infection Biology. Doudna, Charpentier, and colleagues first described how CRISPR could edit circular or short linear stretches of DNA in a Science paper published online on 28 June 2012, but they did not show there whether it worked in eukaryotic cells, a key to human medicines.
On the other side is Feng Zhang of the Broad Institute of MIT and Harvard, and other colleagues at those universities. They reported in a 3 January 2013 online Science paper of their own that they had successfully edited human and mouse cells. Zhang has shared in some prizes for CRISPR, but notably was left off the Nobel Prize.
CRISPR relies on the guide RNA to carry an enzyme that cuts DNA to a targeted gene sequence. CVC attorney Eldora Ellison today contended to USPTO’s Patent Trial and Appeal Board (PTAB) that the guide RNA that Doudna, Charpentier, and their colleagues described in June 2012 was needed to edit eukaryotic cells, even if the group took longer than the Broad team to “reduce it to practice,” demonstrating that it worked in lab experiments. Broad attorney Raymond Nimrod repeatedly emphasized that Zhang had the system cutting genes in eukaryotic cells months before the CVC team could make it work. “While CVC was floundering, Broad had already submitted a manuscript to Science on October 5,” he said. CVC “didn’t have a definite and permanent idea. They just had a hope and a wish.”
“The Broad simply fabricates the story here,” Ellison told the three judges listening during the virtual hearing. She further asserted that Zhang’s earlier success in eukaryotic cells relied on “secret information” about Doudna’s and Charpentier’s guide RNA work that he learned on 26 June 2012 from a collaborator of his, who reviewed their Science paper. CVC in March 2021 filed evidence with USPTO supporting that claim, which Broad attorneys challenged 2 months later, claiming the collaborator had shared public information discussed at a UC Berkeley conference on CRISPR a week before the Science paper appeared.
During the oral hearing, Nimrod stressed that Zhang had CRISPR working in eukaryotic cells in July 2012, while the CVC scientists had many failures and didn’t have success until October. CVC countered that it had success in zebrafish as early as August 2012, but that the timing ultimately doesn’t matter from a patent legality standpoint. “All of this is lightning fast in the field of biology,” Ellison argued. “But more importantly, the conception the inventors had before June 26 is the same embodiment they reduced to practice later.”
Broad’s argument boils down to “we did it first,” whereas CVC is claiming that is “not the legal standard for inventorship,” says Kevin Noonan, a patent attorney who is not involved in the case. “Any advantage Broad might have had, CVC argued, is only because they had learned about how to do this from us,” Noonan adds. “If you’ve got the invention from somebody else, you’re not the inventor.”
Both sides contended that PTAB should take into account how others have viewed the CRISPR discovery. Nimrod repeatedly noted than an earlier PTAB proceeding on a different aspect of the case had sided with Broad, as had a federal court. Ellison pointed to science, not legal issues. “This panel should recognize what the scientific community and the Nobel Prize committee already has recognized,” she contended.
PTAB did not make any decision at the end of the proceeding, nor did the judges indicate when they would issue an opinion.
Biotechs working on CRISPR medicines have taken out licenses with either Broad or CVC, and this decision could be a “monster loss” for companies that bet on the wrong horse, Sherkow says. He also notes that whoever prevails will likely face patent challenges from two different companies that contend their scientists invented CRISPR. “To a certain extent it’s about which set of lawyers gets to continue this fight in a few years,” he says. “Win, lose, the patent lawyers always win.”
Noonan notes that the parties include universities working in the public interest and says it would have been better if they “had settled this a long time ago.”