"In January 2013, Zhang's team published a paper in Science showing how Crispr-Cas9 edits genes in human and mouse cells. In the same issue, Harvard geneticist George Church edited human cells with Crispr too. Doudna's team reported success in human cells that month as well, though Zhang is quick to assert that his approach cuts and repairs DNA better.
That detail matters because Zhang had asked the Broad Institute and MIT, where he holds a joint appointment, to file for a patent on his behalf. Doudna had filed her patent application—which was public information—seven months earlier. But the attorney filing for Zhang checked a box on the application marked “accelerate” and paid a fee, usually somewhere between $2,000 and $4,000. A series of emails followed between agents at the US Patent and Trademark Office and the Broad's patent attorneys, who argued that their claim was distinct.
A little more than a year after those human-cell papers came out, Doudna was on her way to work when she got an email telling her that Zhang, the Broad Institute, and MIT had indeed been awarded the patent on Crispr-Cas9 as a method to edit genomes. “I was quite surprised,” she says, “because we had filed our paperwork several months before he had.”
The Broad win started a firefight. The University of California amended Doudna's original claim to overlap Zhang's and sent the patent office a 114-page application for an interference proceeding—a hearing to determine who owns Crispr—this past April. In Europe, several parties are contesting Zhang's patent on the grounds that it lacks novelty. Zhang points to his grant application as proof that he independently came across the idea. He says he could have done what Doudna's team did in 2012, but he wanted to prove that Crispr worked within human cells. The USPTO may make its decision as soon as the end of the year.
America Needs to Figure Out the Ethics of Gene Editing Now
By Nick Stockton
Read This Before You Freak Out Over Gene-Edited Superbabies
By Nick Stockton
Ebola Survivors May Be The Key To Treatment—For Almost Any Disease
By Erika Check Hayden
The stakes here are high. Any company that wants to work with anything other than microbes will have to license Zhang's patent; royalties could be worth billions of dollars, and the resulting products could be worth billions more. Just by way of example: In 1983 Columbia University scientists patented a method for introducing foreign DNA into cells, called cotransformation. By the time the patents expired in 2000, they had brought in $790 million in revenue.
It's a testament to Crispr's value that despite the uncertainty over ownership, companies based on the technique keep launching. In 2011 Doudna and a student founded a company, Caribou, based on earlier Crispr patents; the University of California offered Caribou an exclusive license on the patent Doudna expected to get. Caribou uses Crispr to create industrial and research materials, potentially enzymes in laundry detergent and laboratory reagents. To focus on disease—where the long-term financial gain of Crispr-Cas9 will undoubtedly lie—Caribou spun off another biotech company called Intellia Therapeutics and sublicensed the Crispr-Cas9 rights. Pharma giant Novartis has invested in both startups. In Switzerland, Charpentier cofounded Crispr Therapeutics. And in Cambridge, Massachusetts, Zhang, George Church, and several others founded Editas Medicine, based on licenses on the patent Zhang eventually received.
Thus far the four companies have raised at least $158 million in venture capital."