Who owns CRISPR — one of the most important genetic inventions of our time?

It’s hard to believe that a patent hearing would be so popular, but the line to get into Hearing Room A at the United States Patent and Trademark Office (PTO) in Alexandria, Virginia, this morning stretched into a crowd of almost 100 people. The first to arrive, at 5:45AM ET, was a patent attorney who took a day off to be here. The second in line, a biotech investor, got here at 6:15AM. Most of the people in line are wearing black or gray business suits; they’re patent lawyers, investors, biotech industry representatives, and journalists. Some of them look nerdy. A lot of them wear glasses and black moccasins.

“Some in the scientific community say the Broad stole it,” one whispers.

“What if it was a discovery, not an invention?” another muses.

At around 10AM, about 70 people are all packed in a small room with a US flag in the corner, a wooden bench with three seats, and a webcam on each wall. The three judges of the Patent Trial and Appeal Board walk in and everyone stands up. The atmosphere is electric. The case being discussed is one that will have consequences for decades to come: who will own the intellectual property — potentially worth billions of dollars — for the revolutionary gene-editing tool CRISPR-Cas9?

CRISPR is arguably told The New Yorker that they pledge to release all intellectual property to researchers for free, but licensing fees could still be imposed for private companies wanting to use the technology and that are ready to invest millions of dollars in CRISPR research.

“The commercial value of the patent is enormous,” says Jacob Sherkow, an associate professor at New York Law School, who’s been following the case closely. “Literally astronomical, billions and billions of dollars.” (Being recognized as the true CRISPR inventor also holds another type of value — fame, and particularly prizes and the money that comes with them.)

CRISPR is already in use in some scientific studies. The gene-editing tool can be used to create A clinical trial in China is using the technology to edit cancer patients’ immune cells so that they can fight lung cancer.

The patent dispute hinges on a few technical points. In today’s oral arguments at the PTO, the University of California, Berkeley and microbiologist Emmanuelle Charpentier are pitted against the Broad Institute and MIT. The Broad argues that its patents on the use of CRISPR to edit animal and human cells don’t overlap with UC Berkeley’s patent applications. UC Berkeley is arguing that the patents do overlap, because without UCB’s pioneering work on CRISPR, the Broad’s work could never have taken place. Both parties are basically “still trying to draw the landscape before they determine who was the first to set foot on it,” says Sherkow.

James Bareham / The Verge

It all began in 2012, when UC Berkeley biochemist Jennifer Doudna and others, including Charpentier, published a seminal Science paper on CRISPR. In this paper, Doudna showed that the gene-editing technology can be used to cut DNA in a test tube at targeted sites. Later, Doudna filed a patent application for CRISPR.

Then in 2013, in another were later awarded a bunch of other CRISPR patents.) So UC Berkeley asked for a so-called “interference proceeding” — an official reassessment to determine who was the first to invent the gene-editing tool CRISPR-Cas9.

Since the proceeding was granted in January of this year, hundreds of pages of court documents have been filed by both parties. What they’re arguing about is not just who invented CRISPR first, but also who first unveiled key aspects of the technology. And there’s the rub. UC Berkeley claims that after the publication of Doudna’s 2012 CRISPR paper, anyone could have applied the technique to edit eukaryotic cells — the cells of animals and people. It was an “obvious” development of the technology, so Zhang’s patents are without merit. No way, says the Broad — it was a huge inventive leap to actually apply that knowledge to edit complex organisms like human cells. And that’s what Zhang did, so he deserves the patents.

That’s what was mainly discussed at today’s hearing. UC Berkeley attorney Todd Walters argued that six other research groups were working on using CRISPR in eukaryotic cells six months after Doudna’s 2012 paper was published, and they were using the same system Doudna used. “There was no special sauce here,” Walters said. So Zhang and his team had “a reasonable expectation of success” and they used “conventional methods” — meaning that Zhang didn’t do anything particularly inventive to successfully use CRISPR in animal and human cells.

The Broad’s lead attorney Steven Trybus fiercely opposed that argument. Even though other groups were trying to use the CRISPR system in eukaryotic cells, no one before Zhang was able to make the system work. So there was hope of success, but that’s different from a reasonable expectation of success. “There was no reasonable expectation of success before 2012,” Trybus said. “There was no reasonable expectation after 2012.”

The judges seemed skeptical of UC Berkeley’s argument that extending the CRISPR technology to eukaryotic cells was “obvious.” If it was so obvious, why didn’t Doudna do it herself? Judge Deborah Katz asked. Doudna’s lab wasn’t equipped to experiment CRISPR in eukaryotes immediately after the publication of her 2012 paper, Walters explained. Katz also asked if UC scientists explicitly indicated that using CRISPR in eukaryotic cells would actually work. “Are there statements on the record?” she asked. Walters didn’t really answer the question, but argued that Doudna said the use of CRISPR in eukaryotes was “now a very real possibility.” Another judge, Sally Lane, said that Doudna herself experienced “many frustrations” trying to get CRISPR to work in human cells.

“My gut-level impression is that the questioning of the Broad’s attorney was really light,” says Sherkow, the NYU professor. “They grilled Todd Walters a lot more heavily.”

One of the main points Walters also tried to make in his 20-minute argument was that the judges were focusing on the wrong thing. The judges decided months ago that the hearing is focused on the use of CRISPR in any eukaryotic cell to edit the cell’s genome. But UC Berkeley argues that their patent claims talk about a method that works in all kinds of cells — including eukaryotic cells. So the judges shouldn’t only focus on CRISPR in eukaryotic cells.

Anna Webber / Getty Images

After almost an hour of back-and-forth arguments, judge Richard Schafer in a black suit and black-and-red striped tie looked up. “The case is submitted,” he said. “The arguments are complete.”

Everyone stood up and left the hearing room, immediately beginning to discuss the case. Many, including Robert Cook-Deegan, a professor at Arizona State University who directed the Center for Genome Ethics, Law & Policy at Duke University for 10 years, thought that the judges were much more critical of UC Berkeley’s arguments. But that doesn’t provide any real clues into what the judges are actually thinking or what they might decide, he says.

A final decision on the patent dispute might come by late January / early February, Sherkow says, and there are a few ways it might play out. The judges could decide to strip the Broad and MIT of their patents and award intellectual property rights to UC Berkeley. They could also decide to keep the status quo. Or, they could decide to award some patents to the Broad and some to UC Berkeley. “There doesn’t have to be a winner takes all,” Cook-Deegan says. “It could be two partial winners and two partial losers here.”

Whatever decision, it will almost certainly be appealed to the US Court of Appeals for the Federal Circuit, Sherkow says. That could push a final decision many months or even years from now.

One thing is clear, a settlement does not look likely, Sherkow says. “I have this feeling that the ship has sailed,” he says. Both parties have already spent millions of dollars on the case, and if UC Berkeley and the Broad had any intentions to settle, it would have happened months ago. Maybe they’ll change their mind after the PTO judges make a final decision, Sherkow says. “It’s going to be a big, meaty decision,” he says.