UC Berkeley scientist Jennifer Doudna earned a Nobel Prize for her work on CRISPR-Cas9, a revolutionary method to edit DNA.

But her lab now has lost enormously lucrative patent rights to the tool.

Ending — for now — a long, vitriolic and expensive fight over commercial application of a pioneering tool that is transforming biological research, a board of the U.S. Patent and Trademark Office ruled on Monday that the patent for use of the genome-editing technology in humans belongs to the Broad Institute of Harvard and MIT, not UC Berkeley.

UC’s claims “are unpatentable,” according to the decision.

 

It’s a major blow for UC, representing a potential loss of $100 million to $10 billion in U.S. licensing revenues, according to Jacob Sherkow, a professor at the University of Illinois College of Law who studies the intersection of scientific innovation and patent law, regulation and bioethics. While UC can keep what it’s earned so far, he said, its take will be limited in the future.

“This means that a number of UC Berkeley’s patents that are directed to the canonical CRISPR system — when used in the cells of higher organisms, like humans — are not valid,” said Sherkow.

But UC will continue to reap the benefits of CRISPR’s use in Europe, noted Hank Greely, director of Stanford’s Center for Law and the Biosciences. In a sharp departure from the position of the U.S. Patent and Trademark, the European Patent Office has upheld UC’s patent.

“The Broad Institute has been winning in the U.S., notably yesterday, but the UC parties have largely won overseas,” Greely said.

Whoever owns them, the patents will lose value due to continued innovation, as scientists start pursuing other gene-editing technologies, he added. The patents should expire in less than 11 years.

“New methods of using CRISPR, new CRISPR-associated proteins and new kinds of genome editing will be available as ‘invent arounds’ to evade the patents,” he said.

Vowing to challenge Monday’s decision, Doudna said in a statement Monday that “today’s USPTO ruling is surprising and contrary to what more than 30 countries and the Nobel Prize Committee have decided regarding the invention of CRISPR-Cas9 genome engineering technology for use in all cell types, including human cells.”

“The University of California is disappointed by the PTAB’s decision and believes the PTAB made a number of errors,” the university said in a statement. UC retains rights to more than 40 other CRISPR-related patents that were not involved in this case, it added.

In response, the Broad Institute said that “this decision once again confirmed Broad’s patents were properly issued.”

In 2020, Doudna and French scientist Emmanuelle Charpentier won the Nobel Prize in chemistry for their invention of the technique in bacteria. But Feng Zhang of the Broad Institute won the race to apply the method to human cells.

“Zhang is not the first to conceive of using CRISPR Cas-9,” said Sherkow. “He was the first to get it to work in eukaryotic cells. And, at least with respect to this patent decision… that’s what mattered.”

The gene-editing tool gives scientists near godlike power, allowing them to rewrite the code of life by moving genes from one living creature to another. Doctors are now testing it as a cure for genetic disorders such as sickle cell disease, cancer and hereditary blindness.

It’s not the first time there’s a disconnect between a Nobel Prize and a patented invention. The patents for at least three historic discoveries — recombinant DNA, Magnetic Resonance Imaging and human embryonic stem cells — all went to someone other than the original creator, said Sherkow, because the standards are different.

“Patent law has this particularly wonky standard about ‘definite and permanent conception in the mind’s eye of the inventor’ and ‘reduced the invention to practice’ — that kind of stuff,” he said. “The Nobel Prize is ‘who got most of the way there first’ and ‘who first contributed to the theoretical understanding.”

Monday’s ruling throws a monkey wrench into the business model of several up-and-coming biotech companies, such as Caribou Biosciences of Berkeley and Boston’s Intellia Therapeutics and CRISPR Therapeutics, which aim to create treatments using CRISPR.

They hold licenses from UC, so they must now negotiate a new deal with Broad. And because their approach seems to be working — for instance, the Intellia treatment substantially reduces levels of a disease-causing liver protein — these licenses will likely cost more than they would have originally.

Intellia’s stock price slid 9.2% on the news, while CRISPR Therapeutics fell 1.4%. Shares of Editas Medicine Inc., which holds a licensing agreement with the Broad Institute, jumped 17% in late trading Monday.

UC has fought for years in its quest to gain control over the rights to the powerful gene-editing technology.

The UC research team, which includes Doudna and Charpentier, claimed the CRISPR invention belonged to them because, in a paper published online in June 2012, they first described how it could edit DNA in bacteria.

But they did not prove that it worked in cells with a nucleus, called eukaryotic cells — a crucial step to using the tool in treatments for human disease. In its opinion, the Patent Trial and Appeal Board detailed the difficulties that Doudna’s lab had in getting their invention to work — meaning that UC’s concept was not a “definite and permanent idea” worthy of a patent.

Feng Zhang and colleagues at the Broad Institute didn’t conceive of the idea. But in January 2013, they reported that they had used Doudna’s approach in animal cells with a nucleus, called eukaryotic cells — and that they had successfully edited mouse and human cells.

UC contends that Doudna’s innovation was essential to Zhang’s success.

“The law is clear,” said Eldora L. Ellison, lead patent strategist on CRISPR-Cas9 matters for UC, at the Board’s hearing. “You cannot take someone else’s idea, try to throw a patent on it, then spend 10 years claiming you’re the inventor.”

The litigation has been extremely expensive for both UC and Broad. Some experts have long urged the two universities to agree to a truce and share through what’s known as a cross-license agreement, the CRISPR spoils.

“Given the time to commercialization for medical therapies,” said Greely, “the eventual patent-owners seem, to me, unlikely to make profits nearly worth what they’ve spent in litigation.”