WASHINGTON — The University of California, which has been losing the fight over U.S. patents on the revolutionary genome-editing technology CRISPR-Cas9, did not pull any rabbits out of a hat during oral arguments Monday in its appeal of the case.

The university clearly failed to win over at least one of the three judges and, at best, did not lose too much ground with a second (while the third asked almost no questions and so did not tip his hand).

“UC came into this argument from a tough spot, and I doubt that oral arguments from either side moved the needle much,” said patent attorney Michael Stramiello of Paul Hastings, who attended the arguments at the U.S. Court of Appeals for the Federal Circuit, where attorneys for the University of California fought to get a patent win by the Broad Institute of MIT and Harvard reversed.

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“It was closer than I expected,” said patent expert Jacob Sherkow of New York Law School, who also attended the argument. “But it’s still going to be tough for UC.”

That’s because in order to reverse the Broad’s win, the appeals court will have to find that the patent office committed serious legal errors, as UC’s new attorney (and former solicitor general) Donald Verrilli argued. He marshaled both legal and scientific evidence to make his case for what experts call his only path to success: persuading the judges that the patent office did not have “substantial evidence” for its decision in favor of the Broad.

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The problem for UC is that the legal definition of “substantial” differs from the plain English meaning.

“It means just enough for a reasonable person to find it persuasive,” Sherkow said. In other words, when the patent office decided that the Broad gets to keep its key CRISPR patents, did it base that on a reasonable assessment of the relevant evidence about, in particular, whether the Broad’s breakthroughs were “obvious” extensions of research by UC scientists. “You can ignore some evidence that still meet the requirement of ‘substantial evidence,'” said law professor Dmitry Karshtedt, who attended the hearing.

Judge Kimberly Moore, in particular, seemed unconvinced by Verrilli’s arguments. “That’s how science works, Mr. Verrilli,” she said toward the end of the 35-minute hearing. Verrilli spent much of his allotted 15 minutes, and much of the written briefs, arguing that because half a dozen labs, besides that of the Broad’s Feng Zhang, quickly got CRISPR to work in mammalian cells after UC scientists showed that it worked on DNA in a test tube, and used conventional techniques to do so, the Broad’s work was an obvious extension of UC’s and thus not deserving of patents.

But getting CRISPR to work in mammalian cells, and the fact that all the labs used conventional techniques of molecular biology to do it, “doesn’t mean they thought it would work,” Moore said. In pushback that could be fatal for UC, she continued, “It’s hard for me to say there wasn’t substantial evidence” to back up the patent office’s ruling against UC. When Verrilli tried to jump in, he got a sharp, “Please don’t interrupt me.”

The Broad issued a statement at the conclusion of the hearing: “Based on the oral arguments today, we are even more confident the Federal Circuit will affirm the PTAB’s judgment,” the Broad said. “We call on UCB and the companies that control its IP to join our ongoing efforts to simplify, share, and open the IP landscape.”

Not surprisingly, the University of California had a different take: “We presented compelling arguments today that the PTAB committed several legal errors, including disregarding Supreme Court and Federal Circuit precedent,” Charles F. Robinson, UC general counsel said in a statement. “Based on the questioning today, we are optimistic that the court has serious doubts about several aspects of the PTAB’s decision.”

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To recap the plot thus far: In June 2012, UC Berkeley biochemist Jennifer Doudna and her colleagues reported that CRISPR-Cas9 could be turned into a “programmable” genome-editing tool, as they demonstrated on DNA in a test tube. They’d filed their first patent application on the technique the month before. Seven months later, the Broad Institute filed for a CRISPR patent on Zhang’s discovery of how to use the system to edit the genomes of eukaryotic cells, as he reported in January 2013.

Although UC filed first for a CRISPR patent, under the law at the time, patents went to the first to invent, and Zhang submitted lab notebooks showing he managed his feat before Doudna’s paper was published. In April 2014, the Broad won a far-reaching patent on the use of CRISPR-Cas9 for editing genomes in eukaryotic cells. A year later, UC asked the patent office to declare an “interference in fact”: to decide that the Broad’s CRISPR patents (which by then numbered 10) covered inventions so similar to what UC applied for (and was still waiting for) a patent on that they should be deemed invalid.

In February 2017, the Patent Trial and Appeal Board ruled that the Broad’s 2014 CRISPR patent did not “interfere” with UC’s pending ones: The Broad’s, which covers the use of CRISPR-Cas9 to edit genomes in eukaryotic cells, was different enough from UC’s and not an obvious extension of Doudna’s work to be valid.

UC appealed, and the oral arguments were heard on Monday.

The only arguments an appeals court entertains, whether about a conviction for murder or a ruling on patent interference, are those about whether the previous tribunals conducted the proceedings properly, interpreting and applying the law correctly. In this case, that means UC must persuade the three judges that PTAB did not have “substantial evidence” to support its finding of no-interference-in-fact; that PTAB made a material legal error, such as in what evidence or testimony it allowed; or that it failed to consider certain evidence.

Verrilli got out barely two sentences before chief judge Sharon Prost jumped in. The main ground for overturning PTAB’s decision, she pointed out, would be a finding that the board did not have substantial evidence for it. But PTAB’s long, detailed written decision suggests that it did not exactly base its decision on a whim. “How do we get around that?” Prost asked Verrilli.

When he tried to answer, Moore interrupted, pointing out “problems with the cases” Verrilli had cited to support his position and the low bar for evidence to be “substantial.” “Do you see the problem I’m having?” she asked him. (Shortly after, Moore had a coughing fit and excused herself from the bench, an almost unheard-of occurrence, but told the attorneys to carry on; she returned a few minutes later.)

Arguing for the Broad, Raymond Nimrod of Quinn Emanuel had a somewhat easier time but did not get off scot-free. Prost zeroed in on the success that those half a dozen labs had using CRISPR in mammalian cells in the months after Doudna’s success with CRISPR on test-tube DNA. UC has argued throughout the patent saga that the success by so many labs indicates that it was an obvious extension of Doudna’s work, “obviousness” that would include what Zhang achieved.

“What about the [patent] board’s not placing much weight on how several people came up with it in a short period of time” after Doudna’s work, Prost asked Nimrod. He replied that PTAB did not dismiss that evidence, but simply found it not to support UC’s claim.

The fact that PTAB considered that argument might be enough to meet the fairly low requirement that its decisions be based on “substantial evidence,” Sherkow said.

A ruling is expected by late summer.