Biotech Trial of the Century Could Determine Who Owns CRISPR

The mood outside the U.S. Patent Office in Alexandria, Virginia, yesterday was electric. At least it was to roughly 100 members of the bar, the media, the investment community, and the lay public who lined up for hours to score a place in a 69-seat hearing room at the U.S. Patent & Trademark Office to hear lawyers argue the biggest biotech patent case in memory.

The occasion was oral arguments before a three-judge panel in a patent “interference” case that is likely to decide who controls the foundational, and lucrative, patents covering the gene-editing method called CRISPR-Cas9.

CRISPR is a new kind of molecular scissors useful for genetically modifying everything from lab mice to wheat plants. But almost since its inception, CRISPR has been roiled by an inventorship dispute between the University of California, Berkeley, and the Broad Institute of MIT and Harvard.

The facts are that Berkeley was first to file a patent application describing the CRISPR system in its fundamental form and its function in bacteria, based on work by Jennifer Doudna and Emmanuel Charpentier. But it was the Broad Institute that succeeded in winning more than a dozen patents covering CRISPR’s use to edit the DNA of higher organisms like humans, plants, and animals—known as “eukaryotes”—where gene editing is most valuable.

The hearing was the first, and potentially last, public session in the interference process. Despite its wide-ranging scope, and hundreds of pages of legal motions already filed, arguments lasted a brisk 45 minutes and consisted mainly of scientific and legal arcana regarding whether Doudna’s development of CRISPR editing in bacteria should give Berkeley rights over its use in all cell types, or whether the Broad’s demonstration of the technology in human cells was a “non-obvious” advance and its own invention.

Attorney Todd Walters, representing the University of California, Berkeley, focused on the apparent ease with which several research laboratories extended Doudna’s invention to human cells. In fact, following her seminal Science paper in the summer of 2012, six teams succeeded within months in making the technology work in human cells, including that of Feng Zhang of the Broad Institute. “There’s no special sauce here,” Walters told the judge.

Attorney Steven Trybus, representing the Broad, argued that Zhang’s work in human cells, published in early 2013, was an appreciable advance. He noted that moving biotechnology systems from bacterial cells to human ones is consistently fraught, and that an ordinary molecular biologist would have had “no reasonable expectation of success.” To highlight this point, Trybus showed the judges statements Doudna made in media interviews in 2012 saying that she believed efforts to use CRISPR in human cells would be difficult.

Guessing case outcomes based on what questions judges ask is notoriously difficult. But Judge Deborah Katz, a Ph.D. molecular biologist, probed Berkeley’s attorney about whether anyone could really have had an “expectation” CRISPR would work in human cells or whether scientists’ experiments evinced a mere “hope of success.”

Since it was instituted in January, the patent interference has had the flavor of a winner-take-all contest, and the sides have not shown any appetite to settle. That means the impact of the judges’ decision—expected in early 2017—could be tremendous. The Broad Institute could lose a large part, or all, of its enormous patent estate to Berkeley. Or Berkeley could go away completely empty handed. Both sides have already entered extensive commercial agreements with biomedical startups and agricultural companies like DuPont and Monsanto. All these agreements hang in the balance.

Jacob S. Sherkow is an associate professor at the Innovation Center for Law and Technology, New York Law School.