CRISPR is a clear winner in the latest round in the patent battle, but the battle continues Science

Genome editor CRISPR, whose invention is at the heart of a fierce patent battle, is typically an RNA molecule to guide a DNA-cutting enzyme such as Cas9 (orange) to target a DNA sequence (blue) to be cut. (Red) uses.

Carlos Clarivan / Science Source

By John Cohen

The long-running patent battle over CRISPR, a Nobel Prize and a multi-million dollar prize, whichever is credited to its invention, has taken a new turn that claims to have been made by a team led by the university Complicates a lot. California.

The Patent Trial and Appeal Board (PTAB) ruled on 10 September that a group led by the Broad Institute has “priority” in patents already granted for the use of the original CRISPR system in eukaryotic cells, developed in the laboratory of human Includes potentially attractive applications. Cells or directly into people. But the ruling also provides the University of California group, which the court refers to as the CVC because it includes the University of Vienna and scientist Emmanuelle Charptier, a leg up on the invention of an important component of the CRISPR tool kit.

“This is a major decision by the PTAB,” says Jacob Sherkov, a patent attorney at the University of Illinois at Urbana-Champagne, who has closely followed the case, but is not involved. “In today’s opinion there is some language that is going to cast a long shadow on the ability of [CVC] Advancing patents

Jennifer Dudna, a biochemist at the University of California at Berkeley, and now Charnpier with the Max Planck Institute, published evidence for the first time that the bacterial-derived CRISPR system could cut target DNA in June 2012, led by the Fang-led Broad team was. Zhang published his own evidence that this may be a genome editor. But the CVC team in its initial paper did not show that CRISPR functioned inside eukaryotic cells, as Zhang’s team reported in its report, even though the original CVC patent application largely covered any use of the technology. Have tried. The US Patent and Trademark Office issued several CRISPR-related patents for Broad’s debut in 2014, sparking a legal battle in 2016 based on CVC’s claims of patent interference. This led to the first PTAB trial, which appears to give a mixed judgment, judging that the eukaryotic CRISPR and other uses of the genome editor were patented by separate inventions, Broad and CVC, respectively. Dissatisfied, the CVC took the issue to a federal court, which denied its appeal.

The CVC subsequently filed new claims which led the PTAB to announce a second intervention. This time the board made a more direct comparison of which group had the best evidence for the first demonstration that CRISPR functioned in eukaryotic cells. The PTAB decision did not accept the CVC’s argument that it preferred Broad and crossed the line earlier.

However, it does not settle the dispute, but instead requires the CVC to provide more evidence in future hearings that it was earlier. “Interference [hearing] It is currently moving forward to find out who was the first to invent, ”says Patent Attorney Catherine Coombs of Murgitroyd, a UK law firm that has not been involved in the case, but other CRISPR lawsuits in Europe. Handles. The “large gap” between the CRISPR patented environment in the United States and Europe, where the CVC is, Coombs notes Won the upper hand in the European Union’s Patent Office.

Sherkow expects PTAB to face a difficult, complex decision. “This is what Doudna and Uppo Zhang need to tame and add a group of graduate students, and put a bunch of eight-year-old lab notebooks into the evidence,” says Sherkov.

CRISPR, which typically involves a DNA-cutting enzyme known as Cas9 and a molecule that guides it to a specific DNA sequence, is often compared to molecular scissors. An important dispute in the patent fight focuses on the guide component. Zhang’s first description of CRISPR working in eukaryotic cells used a guide that combined two RNA molecules while using CVC relied on a single RNA. This single molecule guide RNA is now the standard tool in the field.

A statement from a University of California spokesman said it is “delighted” with the new regime, noting that it has denied many of Broad’s motions. The statement said that PTAB has ruled in our favor in most instances and that the intervention will continue to determine which party is the inventor of CRISPR.[W]E is confident that PTAB will eventually recognize that Dodna and the Charpereier team were the first to invent the CRISPR-Cas9 technique in eukaryotic cells. ”

Broad issued a statement urging him to do something for the peace treaty. “While we are ready to engage in the process before PTAB and believe that these patents have been issued to Broad, we believe that it is time for all institutions to move beyond litigation and instead offer broad, open access Have to work together to make sure. This transformative technology, “the statement said. “The best thing, for the entire region, is for the parties to reach a resolution and focus on using CRISPR technology to solve today’s real-world problems.”

Many observers of the patent fight have expected Broad and CVC to reach a settlement, but Sherkov feels it is now underfunded. “Almost every result has piled in Broad’s favor,” he says. If CVC wins, he says, they will have a patent for a single-molecule guide, but Broad will not lose his eukaryotic patent and, at least, will have to share it. If the CVC loses, “They are toast, they come empty,” Sherkov says. “But I was wrong about the settlement so there is every hope before I go wrong again.”

The PTAB ruling does not specify a date for its next hearing.