It will be a clash of biological titans that could predict a Nobel Prize and bring a massive payday to the winner.
On Wednesday, the US Patent and Trademark Office will begin an “interference proceeding” that will determine whether the University of California or the Broad Institute and the Massachusetts Institute of Technology receive patents covering the use of CRISPR-Cas9, the genome-editing technology that is revolutionizing molecular biology.
CRISPR, which allows find-and-replace alterations of DNA, has sparked debates about designer babies, created visions of Zika- and malaria-carrying mosquitos being driven into extinction, resulting in cures for a host of devastating diseases, and…
Oh, let’s get real: The patent fight is about money. Here’s what you need to know:
What is happening this week?
A conference call. A panel of three USPTO judges, led by Deborah Katz, will hear a challenge to the patent office’s 2014 decision awarding a key CRISPR patent to Feng Zhang of the Broad and MIT rather than Jennifer Doudna of UC Berkeley.
The proceeding starts with calls among the judges and lawyers for each side in which they’ll discuss timetables for hearings, depositions, and potential witnesses. At issue is who first invented a way to use CRISPR-Cas9 to edit the genomes of cells in higher organisms. No one disputes that Doudna was the first to file for a patent on that invention (on March 15, 2013); Zhang filed seven months later (on Oct. 15).
Then why didn’t UC get the patent?
Because until the day after Doudna filed — March 16, 2013 — it didn’t matter who filed first; inventing first did. The United States changed its system to match that of other developed countries, but it doesn’t work retroactively.
The Broad, as the “junior party” (so deemed because it filed second), must show that Zhang invented genome-editing uses of CRISPR-Cas9 before Doudna did.
STAT is not so foolish as to take sides. The key paper from Doudna’s lab came out online in June 2012; it showed that the CRISPR-Cas9 system of enzymes and RNA cuts strands of DNA in a test tube at targeted sites.
In Jan. 2013, Zhang’s lab and that of George Church at Harvard Medical School reported using CRISPR-Cas9 not just to cut DNA but to edit it, and not in naked DNA but in genes in the cells of mice and humans. “Edit” means they substituted one sequence of DNA for what the cells had originally.
So didn’t Doudna beat Zhang by at least half a year?
She certainly reported some key results first. UC argues that Zhang’s achievement, extending test-tube results to cells in higher organisms, was “obvious,” and, thus, not deserving of the dozen or so patents the Broad was awarded. The Broad argues that if Zhang’s breakthrough was obvious, someone would have done it as soon as Doudna published her test-tube result — or that she would have done it herself as part of the 2012 paper.
Who’s favored to win?
Betting sites, for some odd reason, have not made a book on the CRISPR dispute the way they have on, for instance, who will win “The Bachelor.” But at least one legal blog gives Doudna the edge.
Patent attorney Eugene Quinn, founder of the IPWatchdog blog, points out that the senior/junior-party designation could prove crucial. “The rules are completely stacked against the junior party,” he told STAT. “In order for the junior party to prevail, they need to come up with proof that they conceived of an invention and reduced it to practice first.”
“If you can’t come up with evidence that proves your case, like a dated, witnessed, and signed lab notebook, you lose,” he said. “A tie will go to the senior party.”
In other words, advantage UC.
Does it matter who wins?
Appearances matter. The CRISPR saga has become entangled in gender politics, with some Doudna partisans saying it’s typical of science to slight women (her key collaborator was Emmanuelle Charpentier, now at the Max Planck Institute for Infection Biology in Berlin and Umeå University in Sweden).
When Broad director Eric Lander wrote a history of CRISPR earlier this year that critics thought downplayed Doudna’s and Charpentier’s work, he became a punching bag for, among other things, perceived sexism.
A win for Doudna would be a “Take that, Broad!” triumph. It would also cast Berkeley, which has a projected deficit this year of $150 million, as a David triumphing over Goliath’s hundreds of millions of dollars in grants and gifts.
How much money is at stake?
While most patents are dogs, some exceptional ones are financial gushers. Columbia University reaped $790 million in licensing revenue from one set of patents that allow scientists to insert foreign proteins into cells, and New York University has earned more than $1 billion from a patent underlying the arthritis drug Remicade.
Rather than waiting for years of royalties or licensing fees, universities can also cash in. Last week, for instance, UCLA sold its future royalty rights from the prostate cancer drug Xtandi for $520 million.
There’s no way to know what CRISPR patents might bring in licensing fees, royalties, or outright sale. But in a statement UC said that “IP licensing and our multifaceted relationships with industry benefit the campus by providing funds and other resources that support research and education, thus perpetuating a virtuous cycle of discovery, development, translation, and reinvestment into the research enterprise.”
Does the outcome matter to science?
Hard to tell. The Broad has made the technology covered by its 13 CRISPR patents free to academic researchers. On the commercial side, it has licensed patents exclusively to Editas Medicine (EDIT) for certain therapy-related uses, and to others for use on genes that Editas is not targeting.
Researchers could probably keep using CRISPR to make discoveries on the genetics of cancer, mental illness, muscular dystrophy, and other diseases, their progress unimpeded by any change in patent holders. In a statement, Broad spokesman Lee McGuire said the institute “will continue to widely share CRISPR genome-editing techniques,” and that it has already made CRISPR-Cas9 “available to the research community.”
But if an academic cuts a deal to sell a therapy or other product based on discoveries made with CRISPR, the patent holder will almost certainly demand royalties.
Does it matter to patients?
This is trickier. Three companies are using CRISPR to develop human therapies — Editas Medicine (cofounded by Zhang, Church, and others), CRISPR Therapeutics (cofounded by Charpentier, based on her share of the hoped-for UC patent), and Intellia Therapeutics (NTLA) (launched by Caribou Biosciences, which Doudna founded) — but it’s unclear whether biomedical technologies based on a disputed patent take longer to produce disease treatments.
One possibility is that any company with ties to the losing side would simply pay to license the winning side’s patent. Shaun Foy, a cofounder of CRISPR Therapeutics who served as the company’s first chief financial officer, said he expects the UC patent “will be the one standing, of course, and in that case people will need a license from us and their license from the Broad won’t be relevant.”
“Once you have a drug that can save lives, I don’t see anyone stopping the commercialization” based on a patent dispute, said Andre Choulika, CEO of Cellectis, which uses the genome-editing technology TALENS to develop cancer therapies.
That may be true eventually. But for now, it’s “important to have clarity on intellectual property for those companies to be successful,” including to raise capital from investors, said John Maraganore, CEO of Alnylam Pharmaceuticals (ALNY), a gene-silencing firm that was once embroiled in its own massive patent dispute. “It’s even more critical for pharmaceutical partners, which will view the uncertainty as a major overhang in working with the company.”
Will this be resolved on Wednesday?
Only if that’s when hell freezes over. Unless UC and the Broad settle, this could drag on for years. And the loser at the patent office can appeal, pushing a final resolution date back even further.
Elie Dolgin contributed reporting.