CRISPR is clearly the winner in the recent round of patent battles, but the fight continues science


The genome editor CRISPR, whose invention is at the center of a fierce patent warfare, typically uses an RNA molecule (red) to target a DNA-cutting enzyme, such as CAS9 (orange).

Carlos Clarivan / Science Source

By John Cohen

The long-running patent battle over CRISPR, which could bring the Nobel Prize and millions of dollars to the genome editor who may be credited with his invention, has taken a new turn, greatly complicating the claims made by the university-led team. California.

The Patent Trial and Appeal Board (PTAB) ruled Sept. 10 that a group led by the Broad Institute had already approved the use of the original CRISPR system in eukaryotic cells, covering potentially exciting applications in lab-grown humans. Directly into cells or people. But the ruling also gives the University of California group, which the court referred to as the CVC, as it includes the University of Vienna and the scientist Emmanuel Charpatier, a step in the search for a complex component of the CRISPR tool kit.

“This is a big decision for PTAB,” says Jacob Sherko, patent attorney at the University of Illinois at Urbana-Champion. “There are some languages ​​in today’s opinion whose ability is being cast a long shadow [CVC] Going forward patents. “

Jennifer Doudna, a biochemist at the University of California, Berkeley, and now Charpitier with the Max Planck Institute, publishes the first evidence that the bacterial-derived CRISPR system could have cut target DNA in June 2012, seven months before the Feng-led broad team. Zhang may have been the genome editor who published his proof. But the CVC team did not show in its preliminary paper that CRISP worked within eukaryotic cells, as Zhang’s team did in its report, although the original CVC patent application attempted to cover any use of Technol of G. U.S. The Patent and Trademark Office Fees issued several CRIPR-related patents to Broad initially in 2014, starting a legal battle in 2016 over the CVC’s claim of patent “interference.” This led to the first PTAB trial, which probably ruled that the other uses of the eukaryotic CRISPR and genome editor were patentable by Broad and CVC, respectively. Dissatisfied, the CVC took the issue to federal court, which rejected its appeal.

The CVC then filed new claims which led the PTAB to declare a second intervention. This time the board compared which group had the best evidence for the first demonstration that CRISPR works in eukaryotic cells. PTAB’s ruling did not accept CVC’s arguments that it crossed the line before giving priority to Broad.

However, this does not resolve the dispute, but instead requires the CVC to provide further evidence at a future hearing that it was first. “interfere [hearing] Catherine Combs, a patent attorney for the UK law firm Murgitroid, says she is not involved in the case but has handled other CRISPR lawsuits in Europe. COMBS notes that there is a “big difference” between the CRISPR patent environment in the United States and Europe, where CVC is The European Union won the Upper Hand in patent office fees.

Sherco expects PTAB to face a tough, complex decision. “A group of Dudna and Subpo’s Zhangang and a group of undergraduate students need to subpoena and put a set of eight-year-old lab notebooks in the evidence,” says Sherko.

CRISPR, which contains a DNA-cutting enzyme commonly known as CAS9 and a molecule that guides it in a specific DNA sequence, is often compared to molecular scissors. The main controversy in the patent warfare focuses on the guide component. Zhang’s first description of CRISPR working in eukaryotic cells used a guide that connected two RNA molecules while the use of CVC relied on a single RNA. This single molecular guide RNA is now the standard instrument of the field.

A University of California spokesman said in a statement that he was pleased with the new ruling, noting that he had rejected several of Broad’s motions. The statement said PTAB “has ruled in our favor in most cases and will continue to intervene to determine which party was the first to discover CRISPR in eukaryotes.”[W]And it is hoped that PTAB will eventually recognize that Dudna and Charpitier’s team were the first to invent CRISPR-KS9 technology in eukaryotic cells. “

A statement issued by Broad called for something similar to the peace treaty. “Although we are ready to join the process before the PTAB and we are confident that these patents have been properly issued to Broad, we believe that all organizations should now proceed to prosecute and ensure wide and open access instead.” Have to work with. This is a transformative technology, “the statement said. “For the whole region, the best thing is for the parties to reach a resolution and focus on solving today’s real-world problems using the region’s CRISPR technology.”

Many observers of the long-running patent war have expressed hope that Broad and CVC will reach a compromise, but Sherko thinks it is now less likely. “Almost every result is in Broad’s favor,” he says. If CVC wins, he says, they will have a patent for a single nuclear guide, but Broad will not lose its eukaryotic patent and, worst of all, will have to share it. If the CVC loses, “they’re toasting, they’re empty,” Sherco says. “But I’m already wrong about compromise so everyone expects me to be wrong again.”

The PTAB judgment did not mention any date for its next hearing.