Last week, the US Patent and Trademarks office handed down a decision in one of the most high-profile patent cases of the century. In a one sentence ruling, an appeals board granted the rights to the powerful gene editing technology CRISPR-Cas9 to the Broad Institute of Harvard and MIT, while leaving the door open for rival CRISPR pioneer UC Berkeley to file a new patent to lay claim to those same discoveries.
Human embryonic stem cells. Image: Wikimedia
Why does this matter? While academic researchers can still use CRISPR for free, companies hoping to harness the gene editing tool to fight disease, solve agricultural problems, or for myriad other potential applications, may have to pay not one, but both institutions, a hefty fee. It's a decision has caused some to some to wonder whether the rights to such revolutionary technology don't really belong to a third party: the people.
On Thursday, the non-profit group Knowledge Ecology International plans to file a request to the Department of Health and Human Services asking the federal government to step in and ensure that CRISPR remains accessible to anyone who wants to use it. At the root of the petition is the question of whether one group can really own exclusive rights to technology that applies to not only all the genes in the human body, but every gene known to mankind.
"This is a fundamental technology," James Love, the organisation's executive director, told Gizmodo. "At the end of the day there's a legal obligation to make sure it's available to the public on reasonable terms."
The group's filing hinges on a 1980 law that says when research is funded by the federal government, as it was at both Berkeley and Broad, then the public can petition the government to "march-in" if patents are not being licensed on reasonable terms.
The petition is a long-shot. Since the law was enacted, the NIH (which HHS is part of) has held march-in hearings just four times. And while the threat of a march-in has at times inspired patent holders to make their inventions more widely available, the agency has never actually stepped in to officially intervene.
Still, Love is not the only one questioning whether the CRISPR patents are too broad.
The Bayh-Doyle Act, the same 1980 law Knowledge Ecology International is using to petition the government, was developed to allow universities to licence and patent anything invented using public funds. The idea was to decentralize control of federally-funded inventions, allowing universities to take control of their own work and for their inventions to more quickly make their way into the hands of the public. For the most part, this worked great when the patents were for things like a specific variety of cow without horns. But as science has advanced, so too has the scope of those patents. Now researchers are jumping at the chance to patent inventions with increasingly broad application, from synthetic genes to CRISPR, a technology with implications for every single known gene.
In the case of CRISPR, Berkeley and the Broad have both granted exclusive licenses for commercial human therapies to Caribou Biosciences and Editas Pharmaceuticals, respectively. But companies who wish to develop drugs or other human therapies using CRISPR will have to first go through Caribou and Editas for a sublicense, and pay their competitors a significant fee. That, in turn, has the potential to prevent those publicly-funded technologies form making their way to the public on the sort of "reasonable terms" the Bayh-Doyle Act demands.
"It has the potential to bottleneck innovation arriving at the market," Jacob Sherkow, a patent law professor at New York Law School, told Gizmodo. "Let's say you're a small biotech company and you want to develop a therapy for a specific gene. Currently, you basically have to go to a competitor and say, 'Mother, may I do this research?'"
Sherkow recently co-authored a paper in Science arguing that exclusive licensing could slow commercial innovation of CRISPR — which, if it it happened, would be a clear distortion of what the Bayh-Doyle Act intended.
This surrogate method of patenting has had a chilling effect on research before. In 1991, the University of Utah granted Myriad Genetics an exclusive licence to all discoveries relating to BRCA1 and BRCA2 genes, a common indicator for breast cancer. After completely halting research, Myriad eventually allowed academic research on the genes to continue. But the company also blocked the development of additional diagnostic tests for breast cancer. It took well over a decade and a Supreme Court ruling to open the market up to competitors.
In the aftermath of the last week's CRISPR patent decision, it is unclear what will happen to companies that have already licensed the technology from Berkeley. Berkeley may decide to appeal the ruling, seeking a patent for using CRISPR in all cell types, rather than just the cells of plants, animals and humans, as Broad has patented. Either way, the patent ruling may wind up requiring companies hoping to use CRISPR to licence the technology from both Broad and Berkeley. Sherkow said individual licenses will cost companies millions, which could deter smaller companies from pursuing work in CRISPR at all.
"Having for-profit companies manage this technology is going to stifle companies from doing important commercial work in this field," Sherkow said. "And we don't think there are safeguards to prevent that."
Love's group wants the NIH to ensure that CRISPR doesn't become another Myriad Genetics. A "march-in" could only happen after the agency conducts and investigation determining that the patent holders have, in one of four specific ways, failed to make their inventions readily available to the public. The NIH declined to comment specifically on the CRISPR case, other than to say it had not yet received the petition. But even discussing whether to march-in or not can sometimes be effective, as it was in 1997, when a company called CellPro petitioned four patents held by Johns Hopkins University. In that case the NIH decided against a march-in, but Hopkins loosened its patent agreement to make room for a competitor anyway. And while the NIH has in the past shied away from holding many such hearings, it has in some cases stepped in to negotiate more open access to inventions.
At the present pace of science, CRISPR-Cas9 will probably not wind up the be all, end all of genetic engineering. Already researchers have discovered many alternatives to it that may wind up being superior. But the battle for rights to it will likely not be the last major patent battle of our century, either. For the companies caught in the crosshairs, the Broad-Berkeley patent battle is sure to slow their work. The bigger question, though, is what other vital research might our beleaguered patent system slow in the future?