he exclusive licenses granted to three for-profit companies on key discoveries about the revolutionary genome-editing technology CRISPR-Cas9 threaten to “bottleneck” its use “to discover and develop useful human therapeutics,” patent experts argued in a paper published on Thursday.
What the exclusive licenses have done “is give an entire industry to … companies that will never be able to fully exploit it,” Jorge Contreras of the University of Utah, a co-author of the paper in Science, said in an interview. “And that may hold back the development of therapies.”
Exclusive licenses are not unusual in biotech, nanotechnology, or other cutting-edge fields, Contreras said. “What leaped out at us was not the exclusivity per se but the fact that the licenses granted to Editas Medicine and Caribou Biosciences are for every gene in the human body and every gene known to humankind.”
Editas, based in Cambridge, Mass., was co-founded by Feng Zhang of the Broad Institute of MIT and Harvard. Although the Broad has granted nonexclusive licenses for noncommercial use of CRISPR and for the development of CRISPR-based research tools, it has granted an exclusive license for the development of human therapies to Editas, which was co-founded by Zhang.
Similarly, Caribou Biosciences, based in Berkeley, Calif., was co-founded by Jennifer Doudna of the University of California, Berkeley. UC filed for patents on her CRISPR discoveries, and although they have not yet been issued, UC granted exclusive rights to them to Caribou, whose spin-off Intellia Therapeutics focuses on human uses. Crispr Therapeutics holds exclusive licenses for discoveries made by Doudna’s colleague, Emmanuelle Charpentier.
On Wednesday, the US patent office ruled that CRISPR patents issued to the Broad for Zhang’s CRISPR discoveries, covering its use in human cells, do not overlap with UC’s applications for CRISPR patents on all kinds of cells. That was a blow to UC, and means that the Broad can keep its patents. UC is confident it will finally be awarded those it applied for. Some outside experts, however, question whether that will happen.
Regardless of the outcome of the continuing patent bloodbath, there is no doubt that the Broad and possibly UC will hold CRISPR patents. Their decisions to issue exclusive licenses to what Contreras and his co-author, patent expert Jacob Sherkow of New York Law School, call “surrogate companies” are drawing criticism over whether they impede the development of the many human therapies, from curing sickle cell disease and Duchenne muscular dystrophy to treating cancer, that CRISPR could make possible.
Next week, the non-profit group Knowledge Ecology International, which focuses on social justice, plans to ask the federal government to develop a policy on when it will “ensure that the licensing of [the CRISPR] patents is as open and non-discriminatory as possible.” Under a 1980 law, if research was funded by the federal government, as both Zhang’s and Doudna’s was, the public can petition the government to step in if patents are not being licensed on reasonable terms.
That reflects the concern raised by Contreras and Sherkow. “We understand the profit motive. We understand that companies need an incentive to do R&D and to take experimental therapies through expensive clinical trials,” said Contreras. “But there is no possible way one small company, like Editas or Caribou, is going to be able to raise the money for and come up with an R&D plan for all known diseases.”
A Broad spokesman said that “for human therapeutics, we concluded that exclusivity is necessary to driving the level of investment needed to develop the technology.”
Rachel Haurwitz, president and CEO of Caribou, told STAT that “given the rapid and thrilling pace of CRISPR discoveries,” it is hard “to argue that the licensing of patent rights by academic institutions has had a negative impact on research.”
Editas and UC did not immediately respond to requests for comment. But Editas co-founder George Church of Harvard Medical School, whose lab showed in 2013 that CRISPR can be used to edit human genomes, said he believes the exclusive licenses “have the potential” to impede research into therapeutic genome editing.
“Even if all three of the companies [that currently hold exclusive licenses on CRISPR] survive and thrive,” he said at the annual meeting of the American Association for the Advancement of Science in Boston, “it’s probably not enough.”
According to the Broad’s license to Editas, the company has the first “right to exclusively use [CRISPR-Cas9] technology on targets of its choosing for the development of genomic medicines.” Other companies can apply to license CRISPR to use in genes that Editas is not targeting, but such a company would have to “provide a bona fide development plan,” after which Editas can then decide if it wants to go after that gene after all.
That stipulation, said Contreras, gives Editas too much control over what CRISPR-based therapies go forward.
“Why would a company come up with a development plan knowing that the Broad would take it to Editas, which can then say, well, we want to do that,” said Contreras.
In a recent paper, Stanford University law professor Lisa Ouellette argues that exclusive licenses are not always necessary to spur commercial develop of biotech research.
The foundational patents issued to Stanford for gene splicing, or recombinant DNA, starting in 1980 were not licensed exclusively, Ouellette pointed out. Yet they created the entire biotechnology industry. “Exclusivity wasn’t necessary to develop the technology,” including for the many human therapies developed by recombinant DNA, she said in an interview. “If the licenses had been exclusive it would have hampered the development of biotech.”
Is there any chance the government would exercise its legal right to require a university to license publicly-funded research to additional companies? “The federal government,” she said, “has never exercised that right.”
Contreras also doubted the government would act to keep CRISPR-based therapy development moving ahead. “That would be nice but will never happen,” he said. “Even in cases where drugs [developed with federal funding] were not being produced due to licensee failures, it didn’t.”