The U.S. Patent & Trademark Office (USPTO) released a long-awaited decision in the contentious patent battle over CRISPR/Cas9 gene-editing technology yesterday. The Broad Institute of Harvard University & MIT called the outcome a victory, while the University of California, Berkeley, put on a smile and sent a different message: We’re just getting started.
CRISPR’s usefulness as a research tool is unquestioned, and its potential as a gene-editing therapy puts tens of billions of dollars at stake for several CRISPR-centered companies. “It is definitely a big win for Broad but I wouldn’t pin it as a total loss for Berkeley,” says Jacob Sherkow of the New York Law School, who has been tracking the case closely.
Berkeley filed its CRISPR patent in 2012, ahead of Broad. But Broad expedited its own patent’s review process for a fee and got it approved first, spurring Berkeley to initiate a legal proceeding called a patent interference to determine if Broad’s patent covered the same invention as Berkeley’s.
On Feb. 15, judges at USPTO declared “that there is no interference-in-fact” between the two parties, meaning that Broad’s patent stands, and the institute gets to keep a dozen CRISPR-related patents filed since the first one. The ruling makes no stipulations about whether Berkeley’s patent will be approved; it will now undergo its own review, which had been held up by the interference.
“This is a long game, and we’re still in early innings,” says Robert Cook-Deegan, an expert in biomedical patent law from Arizona State University. Cook-Deegan adds that Broad and the Broad-tied company Editas Medicine “have a lot more men on base, and frankly, they appear to be better coached.”
In their 51-page decision, the USPTO judges note that Broad’s patent claims are limited to using CRISPR/Cas9 in eukaryotes—organisms such as plants and animals. Berkeley’s patent makes broader claims over using CRISPR in any organism. But in 2012, when the patent was filed, the researchers had only demonstrated CRISPR’s ability to edit genes in prokaryotes—such as bacteria. They applied the technique to eukaryotes shortly thereafter.
Berkeley quickly responded to yesterday’s news in a largely positive tone. In a teleconference with the media, CRISPR co-inventor Jennifer Doudna of Berkeley made an unusual analogy, saying the situation is similar to Broad holding a patent on green tennis balls—using CRISPR only in eukaryotes—while Berkeley could soon be awarded a patent on all tennis balls—using CRISPR in any organism.
Arti K. Rai from Duke University School of Law says the judges’ opinion suggests it’s possible for Berkeley to receive a wide-ranging patent for using CRISPR in all organisms, while Broad retains the narrower patent for eukaryotes.
“Anyone who wants to practice CRISPR probably needs a license from both of the universities,” says Jorge L. Contreras of the University of Utah College of Law, who has mapped the complex web of CRISPR licensing (Science 2017, DOI: 10.1126/science.aal4222).
Gregory Graff, who studies the interplay of economics and scientific research at Colorado State University, says that if both sides emerge as “joint gatekeepers of the core technology,” he expects “there will continue to be sufficient uncertainty.”
Doudna and her CRISPR co-inventor, Emmanuelle Charpentier, now at the Max Planck Institute for Infection Biology, have ties to CRISPR Therapeutics, Intellia Therapeutics, Caribou Biosciences, and ERS Genomics. A joint press release from those four companies suggests that a new interference could be levied against Broad if Berkeley’s pending patent gets accepted.
Samarth Kulkarni, chief business officer of CRISPR Therapeutics, acknowledges that a new interference is an option, as well as bumping the patent dispute up to the U.S. Court of Appeals for the Federal Circuit. Either way, Kulkarni says, “this means business as usual; it doesn’t change any of the programs we are working on.”
Berkeley will find a way to appeal, Contreras says. “There is so much money at stake here, I would be surprised if they didn’t.”
The USPTO announcement sent Broad-tied Editas Medicine’s stock soaring more than 30% yesterday. Meanwhile, Berkeley-associated Intellia Therapeutics’ stock initially fell 16% and CRISPR Therapeutics, which is linked to Emmanuelle Charpentier, initially had a drop of 27% before rebounding later on Feb. 15.
“I don’t think stock prices reflect who is going to be better at developing drugs,” says Noubar Afeyan, founder and CEO of venture capital firm Flagship Pioneering, which was involved in the founding of Editas Medicine. Noubar says the decision “simply confirms that the patents Broad obtained were on a distinct invention.”
Academic scientists are still free to use CRISPR without a license, however. “Right now, this has zero impact on the academic environment,” says Rodger Novak, CEO of CRISPR Therapeutics. In the future, if an academic scientist using CRISPR wishes to commercialize research, that scientist would need to seek a license to do so.