CRISPR patent showdown heating up

The patent war over who owns the rights to the revolutionary gene-editing technology CRISPR/Cas-9 is heating up, with patent examiners in the US issuing an interference memo, which paves the way for proceedings to begin, in what New York Law School Professor Jacob S. Sherkow is calling a "monumental event for patent attorneys, molecular biologists, the PTO, and the world". Broadly speaking, the University of California is taking on the Broad Institute in a 'patent interference' lawsuit with the US Patent and Trade Office, in a "winner takes all" style proceeding, the outcome of which is expected to put vast sums in existing licensing agreements and investment at risk. As we reported in November 2015, the situation is not much clearer in Europe, where oppositions have started to be filed against the CRISPR/Cas-9 gene editing system in Europe, following the grant of a patent to the Broad Institute, MIT and Harvard College on 11 February 2015, with nine parties registering their opposition, initiating a process that is expected to take at least five years to resolve. One aspect to note in this case is the pace of change in the gene-editing sector, which is so high that by the time the patent disputes are resolved, the industry may have moved on to the next latest and greatest technology.

Jacob S. Sherkow

Without question, this year’s—and potentially, this century’s—biggest biotech story is the rise of CRISPR, arguably the most precise and flexible gene editing technology yet to be created. As others have reported at length, two research teams—Jennifer Doudna’s lab at UC Berkeley, and others, and Feng Zhang’s lab at the Broad Institute and MIT—are engaged in a patent dispute over fundamental aspects of the CRISPR technology. (And to be clear—it’s Doudna’s and Zhang’s attorneys running this show—not the scientists.) On December 21st—after months of waiting—that patent dispute heated up substantially. The primary examiner responsible for Doudna’s patent application, Michelle K. Joike, along with an interference specialist (likely Brandon Fetterolf) issued an Initial Interference Memo, a recommendation that the Patent Trial and Appeals Board (the PTAB) conduct a procedure known as an “interference proceeding” between Doudna’s and Zhang’s patent applications (no PDF currently available). This has the potential to decide who owns the core CRISPR intellectual property, possibly stripping Zhang of his near-dozen patents, and shaking up hundreds of millions dollars of investment in their respective companies. It also may see Doudna and Zhang deposed and cross-examined on the priority and scope of their inventions. Needless to say, this is a monumental event for patent attorneys, molecular biologists, the PTO, and the world.

The origins of the dispute began with Doudna’s original patent application (No. 13/842,859), filed on March 15, 2013—a day before the PTO’s first-to-file rules came into effect—but given a priority date of May 25, 2012. That original application contained 155 broad claims to the CRISPR technology, but described only “genetically modified cells that produce Cas9,” the enzyme critical to the CRISPR reaction, and “Cas9 transgenic non-human multicellular organisms.”

On October 15, 2013, Zhang filed his own patent application (No. 14/054,414)—months after the first-to-file rules came into effect—but claiming a December 12, 2012 priority date under the old first-to-invent rules. Concurrent with his application, Zhang also filed an Accelerated Examination Request (also known, somewhat comically, as a Petition to Make Special), a request that the PTO make an up or down decision on an inventor’s application so long as it’s short (no more than three independent claims), directed to a single invention, and under the condition that the inventor won’t argue the patentability (or lack thereof) of individual claims during prosecution (i.e., that the inventor agrees to an all-or-nothing decision on his application). Zhang’s patent application, unlike Doudna’s however, specifically contemplated adapting CRISPR in eukaryotic cells. The PTO accepted this accelerated timeline and issue Zhang his first CRISPR patent on April 15, 2014. Thus—even though Doudna had both an earlier invention date and filing date—Zhang won the initial patent race, and with specific claims covering profitable eukaryotic applications.

Meanwhile, Doudna’s patent application languished at the PTO. For most of 2014, Doudna’s patent attorneys resolved to correct technical deficiencies in the ownership of the patent application, complicated by Doudna’s co-inventor Emmanuelle Charpentier’s agreements with several European institutions and her initial representation by different attorneys. In addition, on September 5, 2014, a mysterious third-party submitted a 66 page report of prior art—including one of Zhang’s patents—in an effort to sink Doudna’s application.

Doudna’s attorneys then attempted to get the PTO to more aggressively prosecute her patent application. Over the next few months, they met with Examiner Joike and amended Doudna’s claims, on January 8, 2015. The amendment was striking—it cancelled all 155 of Doudna’s previous claims, and replaced them with only nine claims covering the broadest applications of using CRISPR as a gene editing tool—including, presumably, eukaryotic applications. But this, too, spurred a response from a mysterious third party, who submitted more literature—including UC Berkeley press releases—to sink Doudna’s application.

Doudna’s attorneys then went for broke. On April 13, 2015, they amended Doudna’s application once again, cancelling all previous claims—164 to date—and replacing them with 82 new claims directed to “a desired cell type”—an effort to include both prokaryotic and eukaryotic cells. But more importantly, Doudna’s attorneys filed a 114 page Suggestion of Interference, claiming that ten of Zhang’s issued patents—despite their later priority date—were interfering with their patent application. Two days later, Antonio Regalado of the Technology Review quoted Paul Goldsmith of the Broad Institute saying that the Institute had made “repeated efforts and trips since the beginning of 2013 to resolve this situation outside the legal system.”

We—the world, patent academics, technologists—have been waiting on the interference request since then. And, on December 21st, the examiner corps recommended to the PTAB that it initiate such an interference proceeding, and changed the status of Doudna’s patent application accordingly. Frustratingly—and almost suspiciously (almost)—the PTO then experienced, on the following day, a massive, crippling power outage that frustrated public attempts to access any application’s docket. While the decision to institute an interference proceeding is ultimately up to the PTAB, one former PTO employee I have spoken with claims that the decision is largely pro forma and follows the examiners’ recommendations. The fight is on.

So: What happens now? Well, over the next few months we can expect a final decision from the PTAB on the interference decision, and an assignment by the Chief Judge of the PTAB, Nathan Kelley, of a three patent judge panel to hear the case. (Given the spate of hires of patent judges by the PTAB, and their technical specialization, it’s highly likely that all three will have some life science technical experience.) And then we can commence with what could be the last, great interference proceeding—ever—in the PTO.

This will be an event unto itself for two reason: First, because it will likely—or at least discourage—the possibility of a settlement between the parties. The interference declaration is a Rubicon, of sorts, beyond which the parties must compete for territory. They may settle, but interference settlements must be approved by the PTO and cannot be anticompetitive. The reasons for this are arcane but sensible—we don’t want patentees to collude to divvy up patents rights to which they are not otherwise entitled.

Second, because interference proceedings are famous for their formalistic complexity—an almost Soviet-style detail to bureaucratic rules that gives even seasoned patent prosecutors the shudders. With that said, the proceedings look somewhat like an actual trial, with the interference divided into two phases: the interlocutory phase and the testimonial phase. At the interlocutory stage, the three judge panel will set a motions calendar—a timeline for when the two parties—Doudna, the “senior party,” and Zhang, the “junior party”—can present initial briefs. Those initial briefs will likely include preliminary substantive statements about the patentability of the inventions at-issue, whether there is truly an interference in-fact, or whether the PTAB should redefine the scope of the interference. The PTAB may also consider motions as to why each why each party is entitled to certain priority dates—the determining factor in who will be awarded their respective patents if there is an interference in-fact. Those motions often come down to inventor testimony—notarized notebooks and the like—as well as affidavits called Rule 131 Statements (based on their governance under 37 C.F.R. § 1.131). Because Rule 131 statements may decide the interference proceeding outright, they have long been notorious in the patent community for encouraging inventor duplicitousness—“Of course I invented that two years earlier than I originally claimed!” Whether Doudna and Zhang—two of the most well-liked and seemingly honest scientists in any field—will engage in this priority dispute through Rule 131 Statements will be interesting. (To be clear: I’m not at all saying that Doudna or Zhang are going to lie, or that if they do file Rule 131 Statements, they’re lying. I’m only saying that the procedure has a bad reputation among patent attorneys. It’ll be like watching Nobel Prize winners defend themselves in traffic court.) In addition, the parties are entitled to limited discovery during the interlocutory phase—mostly, document discovery concerning priority dates, but notably inventor depositions and cross-examinations. That’s right: Doudna and Zhang may be required to take the stand. (Or, at least testify under oath in a deposition.)

After the interlocutory phase, the three panel will rule on any outstanding motions. At that time, the panel may decide the issue outright—by determining, for example, that there is an interference in-fact and that Doudna wins because she has priority—or, given conflicting evidence, move the proceeding to the next, testimonial phase. In that case, the parties file substantive briefs on the issues, somewhat like Supreme Court merits briefs. The panel then hosts oral argument, typically 40 minutes total, 20 minutes per side. If the CRISPR patent dispute does come to this, the oral argument should—in theory—be open to the public.

After all that, the three judge panel decides the interference issue and awards one (or none) of the parties his or her respective patents. And, as elsewhere with the PTO, the losing party may appeal a negative decision to the U.S. Court of Appeals for the Federal Circuit, stringing out the final determination of priority for years to come. Time will tell. But the biotech patent dispute of this century may last well into this century.

Jacob S. Sherkow is a former CLB fellow and currently an Associate Professor at New York Law School