If you’re reading this article, you likely already know about the CRISPR patent dispute. You may have a decent handle on the technology, or have read others’ work about the case, or have heard about the atmospherics of the hearing that was held last Tuesday, December 6, at the United States Patent and Trademark Office (PTO). But even with that background, its important for all of us—novice and expert alike—to take a step back and go over the basics of what the CRISPR patent dispute is really all about.
Before we even get to the question of what, precisely, was invented, it’s important to understand what a patent actually is. Surprising to many scientists, a patent is not a right to use one’s own invention—you have that whether you file for a patent or not—but rather, the right to exclude others from using an invention without the patent holder’s permission. This is a pretty powerful right—it’s one of the many reasons patents can be so valuable—and so it comes with limits. Patents only last from when they are issued by the PTO until twenty years after the date they were originally filed. And in exchange to receive a patent, inventors must thoroughly disclose how their inventions work. Attorneys refer to patents as “intellectual property” for a reason: like real property, patents can be licensed, sold, and even mortgaged.
But defining the word “inventor” can be difficult. Is an inventor the first person, anywhere in the world, to have come up with the invention—as its Latin root venire, or “come forth,” suggests? Or is an inventor, at least for legal purposes, the first to disclose an invention in a patent application? Prior to 2013, the United States was unique in awarding patents to the first true inventor, irrespective or whether he or she filed a patent application.
To that effect, 2012 saw two sets of inventors filed patent applications covering various uses of CRISPR: Jennifer Doudna and Emmanuelle Charpentier of U.C. Berkeley and the University of Vienna, respectively, in May 2012; and Feng Zhang of the Broad Institute of MIT and Harvard in December 2012. Even though it appeared that Doudna and Charpentier were both the first to invent an engineerable form of CRISPR and the first to file a patent application covering it, Zhang’s patent application was reviewed by the PTO faster—and as a consequence was granted before Doudna and Charpentier’s application was issued. This odd sequence of events set up a special, and rare, procedure at the PTO known as an “interference”: a trial to determine who the first true inventor of the claimed technology was.
The interference has been going on since January of this year. And during that time, attorneys for both sides have spent their time trying to convince a three-judge panel of the scientific and legal landscape of the dispute. The heart of that dispute centers on whether Doudna and Charpentier’s original patent application disclosed enough information to enable an ordinary molecular biologist to use the technology in eukaryotic cells, i.e., the cells of higher organisms. If it did, then it appears that Doudna and Charpentier are entitled to broad patents covering CRISPR in any cell system. If the patent application did not disclose sufficient information to use Doudna and Charpentier’s invention in eukaryotes, then Zhang is entitled to keep fourteen of his patents covering his iteration of CRISPR.
Last Tuesday, the interference reached a critical phase: public oral arguments before the three-judge panel. For interferences, these are exceedingly rare, and so the arguments themselves became a media event. During the arguments, the two each side focused on a single argument important to their respective cases. The Broad Institute asked the panel to declare that there was “no interference in fact.” That is, the Broad claims that Zhang’s patents don’t actually interfere with Doudna and Charpentier’s pending patent application; Zhang’s patents should be considered separately patentable inventions.
If the panel agrees, then Zhang would control a number of patents covering eukaryotic applications of CRISPR—such as human gene-editing. Doudna and Charpentier, by contrast, would be stuck with a patent for using CRISPR for bacteria, a far less lucrative piece of intellectual property. Berkeley argued that the proper way to define the invention was not distinguishing between pro- versus eukaryotes, but simply the RNA molecule used to effectuate the system, namely, a single guide RNA or sgRNA in any cell type. This is because, they argue, translating Doudna and Charpentier’s invention from bacteria to eukaryotes was a simple task, one in which ordinary molecular biologist could readily do. If Berkeley succeeds on this argument, Doudna and Charpentier would get a broad patent covering virtually every use of CRISPR—all the while stripping Zhang of his patents.
During the arguments, however, the judges had difficulty believing the ease of moving CRISPR from bacteria to eukarya. The judges pointed out that other systems—including other CRISPR-based systems—had difficulty translating to eukaryotic cells. And they noted that contemporaneous experiments in the area did not mean that scientists knew CRISPR was going to work in eukaryotes, or that could easily get it to work. By contrast, the Broad’s attorney seemed to persuade the judges—or least keep them silent to hear—that Zhang’s eukaryotic work was a separate invention.
A decision is likely due in the early part of 2017. That decision could play out a few ways. First, the judges could simply declare either Broad or Berkeley the winner, whereby the losing party will certainly appeal its case to the U.S. Court for the Federal Circuit. The judges could also render a split decision, awarding some applications of the technology, like using CRISPR with certain enzyme analogs discovered by Zhang, to Broad while giving the rest to Berkeley. Lastly, the judges could determine that both inventors essentially invented the same thing and begin a second phase of the interference proceeding, known as the “testimonial phase.” In that instance, the judges will need to take a harder look at things like lab notebooks and deposition testimony from Doudna, Charpentier, and Zhang. While the interference, thus far, has been largely civil and free of surprises, that’s where things could rapidly get ugly.