[Updated 12/19/16, 5:33 p.m. ET. See below.] The two sides fighting over ownership of the landmark gene editing technology CRISPR-Cas9 are waiting for a decision from a panel of U.S. patent judges that could come early in the new year. Meanwhile, each side continues to make chess moves with their intellectual property.
The latest move was announced today. Editas Medicine (NASDAQ: EDIT) said it would pay a group of six academic centers including the Broad Institute, one of its top collaborators, for exclusive rights to a new system that might improve upon CRISPR-Cas9. Instead of using the enzyme Cas9 to snip out defective genes inside a cell, the new system uses the enzyme Cpf1. CRISPR-Cpf1 was first described in a paper published in the journal Cell last year, as Xconomy reported.
The paper’s authors, including the Broad’s Feng Zhang (pictured above at a 2014 Xconomy event), say that using Cpf1 could have benefits over Cas9 for a few reasons. It might lead to simpler designs and easier delivery into target cells, for example. Cpf1 also seems to cut DNA differently than Cas9, which could make it easier to insert a new gene after the old one is disabled. When developing human therapeutics, this could help researchers replace bad genes, not just knock them out. (To treat many diseases, it’s necessary not just to stop a defective gene from making a disease-causing protein, but also to provide the patient with a healthy version.)
These assertions still need to be tested in humans, not just petri dishes and lab animals. Editas made other assertions about Cpf1 in its release today: The enzyme is “structurally distinct” from Cas9 and has “independent intellectual property.” The court fight has focused specifically on the use of Cas9—which is just one of many enzymes that bacteria naturally use to ward off microbial attackers—and one close observer says Cpf1 should be beyond the scope of the drawn-out battle.
“Any other enzyme, Cpf1 for example, is not covered,” says Jacob Sherkow, who teaches intellectual property at New York Law School. “That’s great news for Zhang.” (Still in dispute, however, is how the court will rule upon the use of various types of Cas9 originating in different bacteria.)
The patent dispute centers around two groups of scientists. One is led by Jennifer Doudna of University of California, Berkeley and French microbiologist Emmanuelle Charpentier, who has assigned some of her rights to the University of Vienna. They converted the Cas9 found in the wild bacterium Streptococcus pyogenes into a more streamlined gene-editing tool and published the ground-breaking results in the journal Science in 2012.
The other group is led by Zhang, who is one of several Editas scientific cofounders. His lab’s work remains central to the company’s strategy. The Broad claims Zhang’s team was the first to make edits in eukaryotic cells (which include yeast, plant, and mammalian cells) with the CRISPR-Cas9 tool—an advancement that would give the Broad lucrative control over the use of CRISPR-Cas9 in human therapeutics and many other commercial uses. The Berkeley-led group says that was an obvious step and not worth granting a patent. (Here’s a summary of this month’s key hearing before the panel of judges at the U.S. Patent and Trademark Office.)
The Broad last week published a guide to its intellectual property licensing philosophy. When licensing to industry, the guide says, “non-profit institutions [like the Broad] should, in general, favor non-exclusive licenses over exclusive licenses.” However, there are times when exclusive licenses—such as those the Broad has issued to Editas—“may be appropriate because there is a clear case that it will better serve the public good.” In those cases, the Broad says it would license CRISPR technology to other companies to develop therapeutics in areas “not being pursued by the primary licensee after a defined period of time.”
The Cpf1 licensing news comes on the heels of Editas’s commercial rivals banding together last week to share intellectual property from UC Berkeley, the University of Vienna, and Charpentier herself, who owns rights because of patent laws in Sweden, where she conducted some of her work. The companies in this group—Intellia Therapeutics, Crispr Therapeutics, Caribou Biosciences, and ERS Genomics—said December 16 they would pool their resources to strengthen their shared rights and IP positions.
Sherkow says the broad cross-licensing should not have any bearing on the ongoing court fight. But it should clear up “some serious conflict between Doudna and Charpentier regarding their respective contributions,” he says. “It was unclear how those were going to be resolved.”
Doudna cofounded Caribou in 2011 to develop CRISPR-Cas9 technology across several fields, including medicine, agriculture, and industrial production. Caribou later granted Intellia an exclusive license to use its toolkit to develop human medicines. Charpentier, meanwhile, licensed her rights to Crispr Therapeutics, which is headquartered in Switzerland but mainly operates in Cambridge, MA.
Under the new agreement, Crispr Therapeutics and Intellia are not obliged to share with each other advances they have created on their own or with partners, according to Crispr Therapeutics CEO Rodger Novak. For example, each company is working on ways to deliver CRISPR-Cas9 into cells. The new agreement also does not restrict the companies from developing rival products. “Both companies have freedom to operate and can develop whatever product they intend to,” says Novak. “Since the applicability of the technology is so broad, we are currently not seeing the need to restrict ourselves.” Intellia officials were not immediately available for comment. [Updated with Novak comments.]
Editas, Crispr Therapeutics, and Intellia are all advancing CRISPR-Cas9 programs toward clinical studies, either on their own or with deep-pocketed biopharma partners. Editas has publicly set a goal of starting a rare eye disease trial this year. But the firm is likely quite a ways from testing Cpf1-based treatments in humans.
(Meanwhile, one group in China says it has begun a lung-cancer trial using live immune cells genetically altered with CRISPR-Cas9. In the U.S., a University of Pennsylvania research group could start an immune-cell cancer trial next year if the FDA allows.)
To license Cpf1 and other Cas9-related technology, Editas is paying the collective six institutions $6.25 million upfront, $10 million more in future cash or stock, and other potential milestones down the road. In addition to the Broad Institute, the recipients are Harvard University, MIT, the University of Iowa, Wageningen University of the Netherland, and the University of Tokyo.
Photo of Feng Zhang by Keith Spiro.