It was a tough day in US patent court for the University of California, Berkeley.

On 6 December, lawyers for the university laid out its claim to the gene-editing tool called CRISPR–Cas9 during a hearing at the US Patent and Trademark Office (USPTO) — and drew intense, sometimes skeptical, questioning from the three judges who will decide the fate of patents that could be worth billions of dollars.

Berkeley and its rival, the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, are each vying for the intellectual property underlying CRISPR–Cas9, which is adapted from a system that bacteria use to fend off viruses. During the hearing in Alexandria, Virginia, the USPTO judges challenged Berkeley’s central claim: that once its researchers demonstrated that CRISPR–Cas9 could be used to edit DNA in bacteria, any reasonably skilled person could have adapted the technique for use in more complex cells.

If the court decides that is true, it would invalidate the patent now held by the Broad Institute. But the Berkeley argument is a difficult one to make, given that it hinges on “a really subjective standard” — especially when applied to extraordinarily accomplished scientists such as those at Broad, says Jacob Sherkow, a legal scholar at New York Law School in New York City.

Byzantine battle

The patent fight began in May 2012, when Jennifer Doudna, a molecular biologist at Berkeley, filed for a patent after her research team used CRISPR–Cas9 to alter specific stretches of bacterial DNA. In December 2012, synthetic biologist Feng Zhang of the Broad Institute filed his own patent claim, demonstrating use of the gene-editing technique in more-complex eukaryotic cells, such as those from mice and humans. Zhang asked for — and was granted — an expedited review for his patent application.

The USPTO awarded him the rights to CRISPR–Cas9 in 2014. Berkeley then asked the patent office to investigate who first invented the gene-editing technique — a process known as a 'patent interference'. That review began in January. Over the past 11 months, the rival research institutions have filed hundreds of pages of documents with the court.

The 6 December hearing was the first and only time that the two sides will speak to the judges before the court rules on the patent rights. An hour before the hearing began, the line of people waiting to watch the arguments wrapped around the Christmas tree in the lobby of the USPTO and filled two overflow rooms. Each side’s lawyer had only 20 minutes to present his case to the three judges.

During the hearing, Broad’s lawyers quoted liberally from news articles and interviews in which Doudna said that her lab had struggled to adapt CRISPR–Cas9 to eukaryotic cells. “This is the antithesis of something that would have been obvious,” said Broad’s lawyer Steven Trybus.

Berkeley’s lawyer Todd Walters downplayed these difficulties, saying that Doudna did not immediately publish CRISPR–Cas9 to edit eukaryotic cells because she knew it would work. Once the technology’s ability to edit DNA had been proven, he told the judges, “the only thing left was to do it”.

A question of intent

But the judges seemed to disagree, and grilled Walters far harder than they did Trybus, who represented the Broad. “I’m not buying that everyone who does an experiment believes it would work,” said Judge Richard Schafer. Rather, he added, a scientist such as Doudna may simply hope that her research will succeed.

This exchange suggests that Berkeley will have a hard time convincing the court that Doudna expected CRISPR–Cas9 to work in eukaryotes, Sherkow says. The university’s lawyers “were trying to clarify what a biologist in 2012 would have contemplated”, he notes.

But biochemist Dana Carroll of the University of Utah in Salt Lake City, who wrote a declaration to the court on Berkeley’s behalf, disagrees. “To embark on a project takes a certain amount of time, effort and money,” he says. “I don’t think you'd do that unless you had some expectation of success.” He points out that several other groups began working on CRISPR–Cas9 in eukaryotes at the same time as Zhang did.

Several experts who watched the proceedings say that the Broad’s prospects look brighter now, given the judges’ heavy questioning of Berkeley’s lawyer. “My impression is both will end up with something,” says legal scholar Robert Cook-Deegan of Arizona State University's campus in Washington DC.

The Broad has hedged its bets by filing 13 patents related to CRISPR. Several of these deal with an alternative CRISPR system in which the DNA-cutting enzyme is taken from a different species of bacteria. Because it was developed independently, Sherkow doubts that Berkeley could claim any rights to it.

He expects that the USPTO will decide the case in the next two months, although there is no deadline by which it must do so.

This article is reproduced with permission and was first published on December 6, 2016.