CRISPR Dispute to Be Decided by Patent Office

As this magazine and others have detailed, CRISPR-Cas9—the powerful gene-editing technology being hailed as molecular biology’s “holy grail”—is the subject of a contentious dispute between the widely celebrated Jennifer Doudna at the University of California, Berkeley, and wunderkind Feng Zhang at the Broad Institute and MIT.

The central question: who invented it first?

Yesterday, that dispute became official in the eyes of the U.S. Patent and Trademark Office when an administrative patent judge officially declared an “interference” between Doudna’s pending patent application and a dozen of Zhang’s already issued patents. The interference proceeding sets up a legal showdown that may strip Zhang of his patents and see the two scientists deposed under oath.

Even among patent attorneys—generally, friends of the arcane and hypertechnical—interference proceedings are famous for their complexity. The U.S. patent office now grants patents on a “first to file” basis. But before 2013 this was not the case. Historically, U.S. patent law instead recognized that patent rights should go to whoever could prove they were “first to invent” an idea. Because there is a lag between when patent applications are filed and when they are issued—roughly, three years—this gave rise to the possibility that a later inventor could be awarded a patent before the patent office had time to process an earlier inventor’s application. In that circumstance, the later inventor’s patent “interferes” with the earlier inventor’s ability to rightfully obtain theirs.

This is precisely what occurred between Doudna and Zhang, whose patents are covered by the older rule. Doudna, with colleagues in Europe, filed a provisional patent application on her early iteration of the CRISPR editing technology on May 25, 2012; Zhang did the same on December 12, 2012. But Zhang’s attorneys requested that the patent office expedite its review of his application under a procedure—funnily named a Petition to Make Special—that allows inventors a quick up-or-down vote on simplified patent applications. As a result, Zhang was awarded his first patent on April 15, 2014, while Doudna’s patent application remained in limbo. Shortly thereafter, Zhang was awarded over a dozen patents on various forms of the technology.

Perhaps fearing that they were losing the great biotech patent race of the century, Doudna’s attorneys amended her application in order to directly conflict with Zhang’s patents. Specifically, Doudna’s attorneys claimed that her patent application covered gene-editing in mammalian cells—including humans—even though her original filing didn’t detail that aspect of the technology. Yesterday, to the delight of watchers of patent dockets everywhere, an administrative patent judge with a PhD in molecular biology, Judge Deborah Katz, officially declared the interference.

Despite these seemingly dry technicalities, the CRISPR patent dispute has been spiced with intrigue. During the examination of Doudna’s patent application, several unidentified third parties filed papers with the patent office seeking to block it, arguing that she was not the first to invent her CRISPR technique, while the Broad Institute unleashed its own volley of legal papers, lab notebooks, even copies of private e-mails between scientists. If Doudna’s original application did not command the focus of patent office supervisors when it was filed, it sure does now.

What comes next? A panel of three patent judges will get to decide who gets the patent rights to CRISPR-Cas9 editing in animal cells. Their decision is likely to center on a few core issues. One is whether Doudna’s original patent application really covered working with human cells. Another is the earliest date either scientist can prove they performed their breakthrough work.

Yesterday’s declaration of an interference proceeding already provides a few hints. First, it lists Doudna as the “senior party” and Zhang as the “junior party”—an initial determination that the administrative patent judge agrees that Doudna was the first inventor. This means that the burden of proof rests on Zhang, much like how, in a criminal trial, the government—not a criminal defendant—must prove its case beyond a reasonable doubt. Second, the declaration puts at issue all of the patent claims; none are left out. This suggests that the interference proceeding—assuming it retains its current scope—will be an all-or-nothing affair: Zhang will either get to keep all of his patents or lose all of them. This may mean that there is little room, legally, for the patent office to keep both sides happy. But as the dispute has shown us thus far, there is always room for surprises.

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