Patent rulings and scientific honors don’t always mesh, as the team that won the Nobel Prize for creating the genome editor CRISPR learned yesterday. After a 7-year patent battle, a U.S. court rejected its intellectual property claim to a key use of CRISPR, potentially costing it many millions in licensing fees.
According to a ruling by an appeal board of the U.S. Patent and Trademark Office (USPTO), a different group, led by the Broad Institute of MIT and Harvard, made the “actual reduction to practice” of CRISPR’s ability to edit eukaryotic cells, including humans. This means companies developing CRISPR-based medicines must now negotiate with Broad and its partners, Harvard University and the Massachusetts Institute of Technology, for the use of the editor. “There is a disconnect in between what patent law considers first to get there and what I think an average scientist considers first to get there,” says Jacob Sherkow, a patent attorney with the University of Illinois College of Law who has followed the tortuous saga.
The losing team—the so-called CVC group—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. “This borders on a total loss for the CVC,” Sherkow says.
The victory should be sweet for Broad, whose lead CRISPR researcher, Feng Zhang, was not given a share of the CRISPR Nobel Prize. And the loss is particularly bitter for Intellia Therapeutics, a company co-founded by Doudna that yesterday announced what many see as a milestone success for CRISPR medicine. The therapy uses an injection of CRISPR to cripple a mutated gene responsible for a nerve disorder.
Doudna, Charpentier, and colleagues first described CRISPR, which is derived from a bacterial immune mechanism, in an online paper published by Science on 28 June 2012. They showed how they could guide an enzyme to cut a specific location on circular or short linear stretches of DNA. That demonstration did not take place inside cells, however. Zhang’s group was the first to report that CRISPR could edit human and mouse cells, in an online paper published on 3 January 2013, also by Science.
USPTO’s Patent and Trial and Appeal Board (PTAB) ruling, an 84-page document that goes through the timing and struggles of each group’s experiments with fish and mammalian cells, determined the Broad group had succeeded with edits inside cells by 5 October 2012, earlier than the CVC. PTAB also dismissed the CVC’s arguments that Broad relied on the advances reported by Doudna and Charpentier to succeed. USPTO issued Broad a patent for CRISPR in April 2014, and the CVC the next year challenged that award in what’s known as an interference. PTAB ruled in favor of Broad, and the CVC took the issue to federal court and lost again.
But that dispute was over the use of CRISPR for anything, and the CVC wanted to focus another interference claim on eukaryotic use alone, which led to new submissions of evidence and another hearing—and the latest defeat.
The “University of California is disappointed by the PTAB’s decision and believes the PTAB made a number of errors,” a statement from UC Berkeley said. “CVC is considering various options to challenge this decision.” The statement notes that the CVC has more than 40 issued U.S. patents for other aspects of CRISPR and has “foundational” CRISPR intellectual property in 30 countries
In a statement, Broad noted its powerful patent position. “As the PTAB and U.S. federal courts have repeatedly established, the claims of Broad’s patents to methods for use in eukaryotic cells, such as for genome editing, are patentably distinct and not reasonably expected from results of biochemical ‘test tube’ experiments,” the statement says. And Broad
stressed that it long has sought a joint-licensing agreement with the CVC to end the costly patent battle.
Sherkow says the CVC may now see the wisdom of settling, which he suspects may happen because each side has something the other one wants. “CVC and its surrogates have really awesome clinical trial data, but they don’t have a patent license,” Sherkow says. “And the Broad Institute, meanwhile, has really good patents, but not great clinical data. So usually, when each side has something the other side wants, it presents an opportunity for settlement.”
But he adds a cautionary note. “If this interference [case] has taught anything, it’s that there’s some chum in the water,” Sherkow says. “And it’s difficult to get the sharks to cooperate.”