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LEXANDRIA, Va. — If the number and tenor of questions addressed to each side during oral arguments in the CRISPR patent fight is any indication of what the patent judges are thinking, the University of California has a steep hill to climb if it wants to overturn the 2014 decision awarding key CRISPR patents to the Broad Institute of MIT and Harvard and win them for itself.

A 45-minute hearing on Tuesday morning before a three-judge panel of the Patent Trial and Appeal Board, the arm of the US Patent and Trademark Office that hears challenges to patent decisions, offered the only oral arguments in the bitter fight over whether UC or the Broad deserves key patents on the CRISPR-Cas9 genome-editing technology. The Broad was granted its first such patent in April 2014, nearly two years after Feng Zhang and his colleagues engineered CRISPR-Cas9 to edit mammalian genomes.

“My gut-level impression is that the questioning of the Broad’s attorney was really light, but they grilled UC a lot more,” Jacob Sherkow, a patent expert at New York Law School who has followed the CRISPR case closely, said right after the hearing adjourned. “The heat of the questions is not perfectly indicative of the outcome, but if you read the tea leaves, it was bad for UC.”

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The Broad, whose lead attorney Steve Trybus of law firm Jenner & Block in Chicago was asked only a couple of questions during his 20-minute argument, said it was pleased with how the morning went.

The hearing, Broad spokesman Lee McGuire said in a statement, “reinforced the fact that the Broad … [was] first to invent the subject matter in patent applications with regard to CRISPR genome editing in eukaryotic cells. The underlying facts have not changed and we are confident the patent office will continue to recognize the leadership of the Broad, MIT and Harvard in developing this transformative technology.”

When the Broad was granted its first CRISPR patent, in April 2014, the patent office was considering UC’s CRISPR patent application, filed in May 2012. Since then, UC has made several changes to the achievements it wants to patent, but in general it described using CRISPR for DNA editing in simple organisms such as bacteria, called prokaryotes.

The Broad, which filed for a patent in December 2012, described such editing in eukaryotes — organisms whose cells, like those of all animals and plants, have a genome-containing nucleus. Although the Broad filed after UC, it paid a small fee for accelerated review and came away victorious. Since then it has been awarded another dozen CRISPR-related patents.

That left UC’s patent application in limbo — or, perhaps, purgatory. Although the Broad won its patent, UC’s application is still live. UC therefore argued that the patent awarded to the Broad “interfered” with the claims in its own pending application, and last January the patent office announced it would consider that argument. In legalese, the office declared an “interference proceeding,” meaning the parties were claiming the same invention. UC could therefore make its case that its CRISPR invention predated the Broad’s.

In a statement, the University of California said it used the hearing to underscore the fact that researchers there “were the first to invent the use of CRISPR-Cas9 systems for gene editing and that their earliest patent application, filed in 2012, broadly enabled gene editing in cell types including eukaryotes.”

That issue was a focus of Tuesday’s hearing. UC attorney Todd Walters of the law firm Buchanan Ingersoll & Rooney maintained that extending the CRISPR work of UC biochemist Jennifer Doudna and her collaborator Emmanuelle Charpentier was obvious to any “person of ordinary skill in the art” of genome engineering. If so, then the Broad’s success in CRISPR’ing animal cells is un-patentable in view of UC’s success in describing CRISPR genome-editing more generally. The patent office was therefore right to declare the interference from an overlapping claim, and will next have to decide who invented what first.

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“UC is trying to define [Doudna’s] invention very broadly,” said Chris Jagoe, a partner at law firm Kirkland & Ellis whose practice focuses on litigation related to chemical, pharmaceutical, and biotech patents. “They say they described CRISPR as a system independent of the environment” — that is, Doudna’s discoveries cover both non-eukaryotic and eukaryotic cells even though her experiments did not use CRISPR to edit genomes in the latter.

If the interference board agrees with that expansive definition of Doudna’s achievement, UC can eventually make the case that she made the key invention before Zhang, and UC therefore is entitled to patents originally awarded to the Broad. (On March 16, 2013, US law was changed to award patents to inventors who were “first to file,” but the disputed CRISPR-Cas9 patent applications are subject to the earlier “first to invent” system.)

UC attorney Walters spent much of his 20 minutes arguing, as UC has done repeatedly in written motions, that getting CRISPR to work in eukaryotic cells “was obvious,” as he put it. No fewer than six different groups made progress toward that goal in the six months after Doudna’s seminal 2012 paper, he said, evidence that people “skilled in the art” of genome engineering “had a reasonable expectation of success,” and they moved CRISPR into eukaryotic cells “in the exact way” that UC made it work in non-eukaryotic cells.

“There was no special sauce here,” Walters said.

The Broad’s lawyers, in contrast, argued that extending Doudna’s work to eukaryotic cells was a major feat. Its patent claims therefore do not overlap with UC’s, argued Trybus. If so, the interference should never have been declared: The Broad should keep its patents, and UC can go for patents on CRISPR in non-eukaryotic cells. If the judges agree with the Broad, it’s a de facto decision that Doudna and Zhang came up with two separate inventions and are entitled to patents on them.

From the judges’ questions, it seemed they were skeptical of UC’s “no special sauce needed” argument. Judge Sally Lane cited a comment “from one of your own inventors,” Doudna, about the “frustration” of getting CRISPR to work in eukaryotic cells.

Chief judge Deborah Katz also challenged Walters on the obviousness of extending CRISPR genome editing to eukaryotes, asking whether UC scientists had made any public statements about how easy it would be to do that. Walters did not answer directly.

If the judges decide that the Broad’s CRISPR patent does not interfere with UC’s patent application — that the two sets of inventors describe two very different inventions — then UC could patent Doudna’s non-eukaryotic inventions, Jagoe said. Since the most lucrative CRISPR patents will be those that cover the use of this genome-editing technology in plants and animals, including people, however, “if UC only wins a patent limited to non-eukaryotic cells, it would be a big loss for them.”

That raises again the question of whether the two sides will settle rather than continue a case that threatens to become biotech’s Jarndyce and Jarndyce. Once an interference proceeding starts, said Jagoe, “it tends to keep going until something changes. If one side gets an indication [from the judges] that its arguments aren’t getting a lot of traction, it could influence a settlement decision.”

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  • The potential value of the CRISPR methodologies in advancing GMOs to the benefit of mankind is phenomenal. The CRISPR technology evolved over time in research and institutional labs throughout the world by incremental, almost intuitive, steps and these small steps were payed for by public funds. Advances made by scientists using CRISPR methadologies should not be the sole factor determining patent rights as CRISPR technologies developed through public funding. The public should not have to pay exorbitant prices for products and services developed and patented by CRISPR technology solely.

  • The question is whether or not the CRISPER Cas9 process was nearly identical to the UC process in Eukaryotes. Did they do anything remarkably different than UC to get it to work? That’s the key question.

  • I greatly appreciate the Bleak House reference at the end of this article, though I fear that it’s entirely too apt.

  • CRISPR techno should be shared by the scientific and industrial world with no attached patent rights. This tech of intuitive gene manipulation for deletions and alterations has the potential for improvements in crop yields, biofuel yields and healthier populations. It took many reaseach grants to get to CRISPR with tax payers money. The people ouw this tech not research institutions feed by tax dollars…why should we pay again through patent right ownership profiteering. Many good advances are going to come from this tech and these advances should not be litigated in court rooms…. IMHO.

    • This is why I am hoping that UC wins this case. They filed first and Zhang springboarded off of their work in my opinion. I believe UC is simply looking for small cross licensing deals. Zhang is a public company.

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