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Broad Institute scientist prevails in epic patent fight over CRISPR

Jennifer Doudna, a CRISPR pioneer, photographed in the Li Ka Shing Center on the Campus of the University of California at Berkeley in 2016. (Nick Otto for The Washington Post)

The CRISPR patent fight appears to be over, at least for the moment. A ruling by the U.S. Patent Trial and Appeal Board found no “interference” in patents awarded to Feng Zhang at the Broad Institute of MIT and Harvard.

The loser, pending appeals, is the University of California, and the much-heralded biochemist  Jennifer Doudna, who, along with Emmanuelle Charpentier, in 2012 published a groundbreaking paper showing how to exploit a natural bacterial gene-editing system known as CRISPR. The patent office determined that Zhang's later innovations, which used CRISPR to edit mammalian cells, were not simply elaborations of what Doudna and Charpentier had already discovered.

In a teleconference with reporters Wednesday, Doudna did not sound deterred by the ruling, saying she will press forward with her own patent application based on the earlier work. “Our patent will likely be issued,” she said.

She explained that her patent would cover the use of CRISPR in all cells, while the Zhang patent would more narrowly cover applications of CRISPR in plant and animal (“eukaryotic”) cells. She drew an unusual analogy: “They will have a patent on green tennis balls. We will get a patent on all tennis balls.”

Such a situation could potentially make attractive some kind of settlement between the institutions and the inventors to distribute the money from CRISPR licenses.

Control of CRISPR, biotech's most promising breakthrough, is in dispute

The University of California at Berkeley issued a statement saying that it is considering an appeal:

“We continue to maintain that the evidence overwhelmingly supports our position that the Doudna/Charpentier team was the first group to invent this technology for use in all settings and all cell types, and was the first to publish and file patent applications directed toward that invention, and that the Broad Institute’s patents directed toward use of the CRISPR-Cas9 system in particular cell types are not patentably distinct from the Doudna/Charpentier invention. For that reason, UC will carefully consider all options for possible next steps in this legal process, including the possibility of an appeal of the PTAB’s decision,” the statement said.

The Broad Institute issued a statement saying it agreed with the decision, “which confirms that the patents and applications of Broad Institute and UC Berkeley are about different subjects and do not interfere with each other.”

The patent fight has received a great deal of interest because there are potentially enormous sums of money involved, and the dispute pitted major academic institutions against one another. At the same time, CRISPR has unnerved ethicists because it could potentially lead to permanent changes in the human species. A major report from the National Academy of Sciences and the National Academy of Medicine, published Tuesday, said gene editing on the human “germline,” making changes that would persist in sperm or eggs and could be passed along to future generations, could potentially proceed someday but only under very limited circumstances to block devastating congenital diseases.

Pondering "what it means to be human" on the frontier of gene editing

“The Broad appears to be the decisive winner,” said Jacob Sherkow, a professor at New York Law School who has been closely following the case.

There is a bit of an academic wrestling match over who should get credit for discovering CRISPR. Doudna and Charpentier were recently awarded one of the biggest prizes in science, and the research is likely to get more awards, potentially a Nobel Prize. Patent ownership won’t by itself settle the question of who gets credit, Sherkow said.

“I hope that nobody thinks that this decision from the patent office should detract from Jennifer Doudna and her team’s technical accomplishments in any way,” Sherkow said. “Patent law is strange, unto itself, and it doesn’t necessarily neatly align with scientific advance.”

He said that the outcome was not surprising to him, given the tenor of the judges' questions during oral arguments held in December. But he predicted that the University of California, Berkeley, would appeal the decision — a process that could take about a year.

What a finding of no interference means, in laymen’s terms, is “that the thing Berkeley invented was different from the thing that the Broad invented,” Sherkow said. Because of that, the patent applications do not interfere with each other — and therefore the Broad’s patents stand. If the patents had been found to interfere, the Patent Trial and Appeal Board would have had to figure out who owned what.

This animation depicts the CRISPR-Cas9 method for genome editing – a powerful new technology with many applications in biomedical research, including the potential to treat human genetic disease or provide cosmetic enhancements. (Video: Feng Zhang/McGovern Institute for Brain Research/MIT)

CRISPR is the acronym for Clustered Regularly Interspaced Short Palindromic Repeats, and is a natural system used by bacteria to patrol their genomes for invasive viral genetic material. The system snips away the invasive material and repairs the genome. But then scientists figured out how to exploit the system in the laboratory, targeting genes and potentially very short stretches of a cell's genome.

As The Post reported last year:

In 2012, Jennifer Doudna and Emmanuelle Charpentier reported that they could reprogram this mechanism; instead of snipping invading viruses, they could use CRISPR to cut DNA very precisely, opening the doorway to genome editing. In 2013, Feng Zhang at the Broad Institute and George Church at Harvard Medical School led teams that showed it was possible to use the technology to edit the genomes of human and mouse cells. Although genome editing had been tried before, previous techniques tended to be far more painstaking and limited. CRISPR was versatile and simple to use; it allowed for easy and efficient genome editing — and it worked in all kinds of cells.

Zhang was granted CRISPR patents in 2014 and 2015; Doudna and Charpentier challenged that, saying they came up with the gene editing technique first. The patent office essentially said Zhang's work is sufficiently distinct that it deserved its own set of patents. In the Berkeley statement, the university said it will continue to apply for patents based on the earlier discoveries.

Doudna also issued a statement through the university:

“As a proud member of UC Berkeley’s faculty, I am engaged in bringing the power of the CRISPR-Cas9 technology to benefit humanity and develop new industries in biomedicine, agriculture, public health, and environmental technologies,” she said.  “I am pleased that research using CRISPR-Cas9 continues to drive exciting advances in many areas of biology.”

This story has been updated.