(Bloomberg) -- Scientists have used the breakthrough gene-editing technology CRISPR to create advances in medicine and agriculture, from ways to eliminate sickle-cell anemia to growing mushrooms that resist browning.
But the battle over who will make money from it is just beginning.
On Monday, some of the most well-known research institutions in the world -- including University of California at Berkeley and the Broad Institute, which is affiliated with the Massachusetts Institute of Technology and Harvard University -- face off in an appeals court in Washington over the question of who invented and thus can profit from the technology.
CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, uses a defense mechanism employed by bacteria to target parts of a gene and cut them out like a pair of molecular scissors. It has already triggered a revolution in the world of genetics by making it easier to manipulate the building blocks of living organisms. The CRISPR breakthrough may one day lead to a Nobel Prize.
What’s unclear is who will reap the potential windfall on royalties for commercial applications in medicines, health treatments and improved foods.
“I’m a company and I want to practice CRISPR, who do I license, who do I pay?” said Kevin Noonan, a biotechnology lawyer with McDonnell Boehnen Hulbert & Berghoff in Chicago.
Universities and start-up companies primarily in the U.S. and China are ramping up research using CRISPR. Since 2013, patents have been sought on more than 2,500 CRISPR-related inventions, according to Swiss researchers.
One of them, CRISPR-Cas9, is a naturally-occurring enzyme used by bacteria to rid itself of viruses and was first discovered decades ago.
Researchers with UC Berkeley and the University of Vienna were first to find ways to guide those molecular scissors to targeted locations on the genome and say their work could be used for any living thing. They filed their patent application in 2012 and have called it “the discovery of the century.”
The Broad Institute in Massachusetts, set up by groups including MIT and Harvard to experiment with the human genome, said the UC Berkeley team only showed how the technology would work in a test tube. They said their research team proved CRISPR-Cas9 could work in plants and animals, including humans.
The arguments Monday before the U.S. Court of Appeals for the Federal Circuit involve the race to patent CRISPR technology. By paying an extra $70 fee, Broad got an accelerated review of its patent applications, which were issued while the application from UC Berkeley was still pending.
UC Berkeley objected, telling the patent office that its application covered all the work Broad claims to have invented. Last year, the patent office disagreed, saying the inventions were different enough that both could get patents. UC Berkeley appealed. A decision expected later this year.
UC Berkeley’s lawyer Donald Verrilli said in a statement on Monday that Broad’s team, led by Feng Zhang, were among six groups including UC that used “conventional, off-the-shelf tools to employ CRISPR-Cas9” in plant and animal cells.
UC Berkeley scientist and co-inventor Jennifer Doudna described the patent office ruling after it was released as saying “our patent will be for all tennis balls and Broad’s will be for green tennis balls.” The reason UC Berkeley objects is because those green tennis balls could be where the money is.
“Human therapeutics is really the money maker here,” said Michael Stramiello, a patent lawyer with Paul Hastings in Washington. “The parties involved would like to have a stake there. Certainly in California’s mind, it doesn’t really want to share rights there. If someone ends up with the lion share of rights, that’s extremely valuable.”
Just how valuable is yet unknown, but universities have been richly rewarded for ground-breaking ideas in medicine. Columbia University, where researchers in the 1980s developed a gene-splicing process fundamental to every biotechnology company, collected more than $600 million before its patent expired in 2003.
Proponents expect that CRISPR will change medical care in terms of genetic diseases, a fundamental evolution that will upend existing markets and create entirely new approaches to care that the current health system can’t anticipate.
If you can repair a defect with a one-time therapy, you wipe out the existing market for treating the condition and scale back related doctor and hospital visits. And if you can cut out a precise part of a gene, at some point you might be able to replace it with something else -- turning the infection-fighting T-cells into super soldiers that can eradicate cancer, for example. Researchers are looking at ways to alter mosquitos so they don’t carry malaria, treat eye disorders and even modify elephants to bring back woolly mammoths.
“At the end of the day, there’s so much potential with the CRISPR platform to treat so many diseases and have a tremendous effect on the patients,” said Samarth Kulkarni, chief executive officers of Crispr Therapeutics AG, which is developing a treatment for sickle-cell anemia.
Crispr, based in Zug, Switzerland, with operations in Cambridge, Massachusetts, was founded by Emmanuelle Charpentier, one of the inventors on the UC Berkeley side.
Companies are trying to stay out of the CRISPR patent dispute and avoid the types of litigation wars that enveloped advances in mobile phone technology.
DowDuPont Inc. is using CRISPR to develop corn and soybean crops that repel insects without chemical pesticides and tolerate herbicides for easier weed control, has licenses with both Broad and UCBerkeley.
Crispr and Intellia Therapeutics Inc. have licensed UC Berkeley’s technology, while Editas Medicine Inc. is using Broad’s inventions. The companies also have each sought patents on their own work.
The patent landscape is growing. IPStudies Sarl, a Switzerland-based research group, counted 2,519 CRISPR-related inventions, based on patents and published applications around the world. Applications generally are made public after 18 months.
100 Inventions Per Month
In 2012, the year UC Berkeley announced its discoveries, 71 CRISPR-related patents and applications were made public. Since the end of 2016, the group has identified about 100 new inventions being disclosed every month.
“From a technical standpoint, the CRISPR field has inspired many scientific teams worldwide,” said Corinne Le Buhan, a researcher with IPStudies. Most of the work is being done in the U.S. and China, while Europe “clearly lags behind,” she said.
One group is trying to develop a patent pool that would provide a sort of one-stop shop for anyone wanting to license basic technology, no matter which enzyme variant is used. MPEG LA LLC, better known for a licensing program related to video streaming, said it hopes to announce a CRISPR patent pool later this year.
“The market concerns I have heard is that the CRISPR patent landscape is very large, very confusing and difficult to navigate,” said Kristin Neuman, executive director for Biotechnology Licensing at MPEG LA. “It’s hard to figure out what rights they need to license, who they need to license.”
So far, the affiliated group of Broad, MIT, Harvard and the Rockefeller University are the only entities to publicly agree to join the MPEG LA pool. Neuman declined to name other companies, saying they were promised confidentiality or hadn’t yet fully signed on.
“The Broad Institute already licenses CRISPR-Cas9 non-exclusively for all applications, with the exception of human therapeutics, where we have significantly limited the exclusivity,” Issi Rozen, Broad’s chief business officer, said in a July announcement. “We look forward to working with others to ensure the widest possible access to all key CRISPR intellectual property.”
Fights between universities are rare, but is part of a growing trend of schools and institutes becoming more aggressive in trying to find ways to profit off their research. Universities are under pressure to get money from their patents because “there’s only so much you can charge for tuition,” Noonan said.
So far, the patent question hasn’t hindered work by companies like Crispr Therapeutics to develop new treatments.
“Our primary focus is to develop therapeutics, so I don’t let the intellectual property things distract from the mission,” Kulkarni said. Still, “it would be a shame if these IP wars get in the way. There is plenty of room for people to coexist.”
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