Given how big a deal CRISPR-Cas9 gene-editing technology is to the near-term and long-term future of life sciences both commercially and academically—and how many billions or trillions of dollars it could be worth before something comes along to supplant it—it’s not surprising that with competing patent claims, the legal battle would be a bitter one. And bitter it was as the Broad Institute of MIT and Harvard in Cambridge, Mass., and the University of California, Berkeley (UC Berkeley) went to war over CRISPR in the patent law courts.
In the end, though, in mid-February, judges at the U.S. Patent and Trademark Office (USPTO) ruled that the technology for use of the technology in eukaryotic (complete human and animal cells, for example) belongs to the Broad Institute and not the University of California Berkeley.
The summary of the decision says: “Broad has persuaded us that the parties claim patentably distinct subject matter, rebutting the presumption created by declaration of this interference. Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment. Specifically, the evidence shows that the invention of such systems in eukaryotic cells would not have been obvious over the invention of CRISPR-Cas9 systems in any environment, including in prokaryotic cells or in vitro, because one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment. This evidence shows that the parties’ claims do not interfere. Accordingly, we terminate the interference.”
Of course, it’s not surprising the Broad Institute would agree with the USPTO ruling, and it says that the decision confirms that the patents and applications of Broad Institute and UC Berkeley do not interfere with each other because they are about different subjects.
“Broad Institute and collaborators were issued patents for methods for genome editing in eukaryotic (including human) cells, while UC Berkeley and collaborators applied for patents concerning CRISPR methods based on studies in cell-free systems that did not involve genome editing in eukaryotic cells,” the Broad Institute explained. “CRISPR research is a very large field that involves contributions from talented scientists around the world ... Over the next few years there will be many patents issued in the CRISPR field to many institutions. As of February 2017, the USPTO has issued 50 patents with claims to CRISPR and/or Cas9, including a robust portfolio of 13 CRISPR patents to the Broad Institute, MIT and affiliated groups for inventions from Dr. Feng Zhang and the Zhang lab.”
Also unsurprising is that UC Berkeley disagrees, noting in a blog post: “The PTAB [Patent Trial and Appeal Board] decision does, however, leave in place patents previously issued to the Broad Institute for use of CRISPR-Cas9 in human and other ‘eukaryotic’ cells. The University of California and its co-owners maintain that using the CRISPR-Cas9 system in eukaryotic cells is not separately patentable from using the system in other cell types, and for that reason disagrees with the PTAB’s decision. As such, the university and its co-owners will be considering all possible options for moving forward in the current legal dispute, including other legal challenges to the Broad Institute’s patents and the possibility of appealing the PTAB’s decision.”
In other words, UC Berkeley says that its patent should nevertheless cover the use of CRISPR-Cas9 in all cells—eukaryotic or otherwise. As noted in a Nature article about the decision, Jennifer Doudna of UC Berkeley, one of the inventors on that UC patent, compared it to a situation where someone was to license permission for someone to use green tennis balls, saying: “They will have a patent on the green tennis balls,” she said in reference to the Broad patents, and “We will have a patent on all tennis balls.”
In other words, it may yet turn out that in enforcing the patents, even if Berkeley’s current court loss holds up under a likely appeal effort soon, many companies could theoretically be forced to pay licensing fees to the Broad Institute and UC Berkeley to use CRISPR in human cells.
Nature also quoted patent lawyer Catherine Coombes, who in her opinion sees the decision as fair, explaining that the UC Berkeley invention would cover the design of the RNA molecule that guides the key step in CRISPR-Cas9 gene editing, directing the Cas9 enzyme to a specific site in the genome—but that getting the system to work in eukaryotes was an additional inventive step on the Broad Institute’s part.
So the battle, while over, isn’t really necessarily over. And unless the parties come to some kind of out-of-court agreement, it’s quite likely we will be seeing these matters argued again fairly soon.