Broad Institute takes a hit in European CRISPR patent struggle

A decision from the European Patent Office (EPO) has put the Broad Institute in Cambridge, Massachusetts, on shaky ground with its intellectual property claims to the gene-editing tool CRISPR. EPO yesterday revoked a patent granted to the Broad for fundamental aspects of the technology, one of several of its patents facing opposition in Europe.

In the United States, the Broad has had better fortune. It has so far prevailed in a high-profile patent dispute with the University of California (UC), Berkeley. Last February, the U.S. Patent Trial and Appeal Board ruled that although a team led by UC Berkeley structural biologist Jennifer Doudna had first laid claim to the use of CRISPR to cut DNA in a test tube, the use of the method on human cells by molecular biologist Feng Zhang’s team at the Broad was still an advance.

But in Europe, a dispute that has gotten much less attention could derail several key Broad patents. The patent just revoked was filed in December 2013, but to show that its claims predate competing publications and patent filings from UC and other groups, the Broad cites U.S. patent applications dating back to December 2012.

Unfortunately, those earliest U.S. filings include an inventor, microbiologist Luciano Marraffini of The Rockefeller University in New York City, who was not listed on the European filing. Disagreement between Rockefeller and the Broad over Marraffini’s role in key CRISPR inventions led to a bizarre dispute, creating conflicting, identical patents with different authors, The Scientist reported in 2016.

The two institutions settled the disagreement earlier this week. But because of strict rules in Europe about the listing of inventors on patents, Marraffini’s exclusion from the European filing meant the Broad couldn’t claim the “priority date” of the earliest U.S. patents, and therefore couldn’t lay first claim in Europe to the technologies described.

The invalidated patent is one of several facing formal “oppositions” filed with EPO. One opponent of the now-revoked patent was CRISPR Therapeutics, co-founded by microbiologist Emmanuelle Charpentier, now at the Max Planck Institute for Infection Biology in Berlin, who collaborated with Doudna on early CRISPR technology and is listed on key patents. And the same issue could threaten more of the Broad’s intellectual property in Europe, says Jacob Sherkow, a patent specialist at New York Law School in New York City. “If the Broad can’t get the priority date that they want in their patents, things are just going to be really bad for them,” he says. “It looks like UC Berkeley and Emmanuelle Charpentier are going to have the dominant patent position in Europe going forward.”

The Broad said in a statement that it plans to appeal the decision. But the likelihood that EPO will reverse course is “slim,” says Catherine Coombes, a patent attorney with HGF Limited in York, U.K., who has handled some CRISPR-related litigation but is not involved with what she refers to as “the foundational” intellectual property at the center of these disputes.

She notes that the decision doesn’t threaten the many follow-on patents the Broad has filed for gene-editing technologies, including alternatives to the Cas9 enzyme used in the early CRISPR work. And the new blow to the Broad doesn’t change the fact that companies commercializing CRISPR-based products will likely have to license technology from multiple patent holders. “The CRISPR landscape is a lot murkier in Europe because it’s perfectly feasible to have lots of overlapping rights,” she says. “I can’t say that it’s suddenly a winner-takes-all scenario.”