The fight to determine who invented fundamental parts of the CRISPR-Cas9 gene editing technology appears to be headed into a long, arcane battle, the likes of which would never be seen again in the U.S. patent system.
The move toward a so-called interference proceeding was signaled before the holidays by a slight change in the status of a key CRISPR-Cas9 patent application on the U.S. Patent and Trademark Office’s website. The note went practically unnoticed for a week because the PTO suffered a massive power outage that shut down its computer systems.
But on Dec. 29, Jacob Sherkow of the New York Law School, writing on the Stanford University Law School’s Law and Biosciences blog, noted the change.
The patent application submitted by University of California, Berkeley researcher Jennifer Doudna (pictured above) and colleagues—a key part of the patent dispute—is now classified under the status “Interference — Initial memorandum.”
What this means is the patent examiner in charge of the case, Michelle Joike, has finally recommended that the case get kicked upstairs, in a sense, to a court-like setting. This higher level of adjudication, known as interference in PTO-speak, only takes place when a challenger has made a strong argument that the PTO should reconsider a granted patent.
Doudna and company, in this case, are the challengers. The patents they want re-examined belong to the Broad Institute of MIT and Harvard and the principal Broad scientist Feng Zhang. The PTO granted Zhang and Broad the first-ever CRISPR patent in April of 2014, with a dozen more to follow.
The Doudna camp has been fighting that decision ever since, gathering evidence and testimony to bolster their case.
If an appeals board takes up Joike’s recommendation, each side would try to prove with lab notebooks, photographs, e-mail, and other evidence that it was the first to invent this new gene editing technology.
CRISPR-Cas9 has taken the biological research world by storm since Doudna and colleagues published a paper in Science in 2012 that described their work transforming a bacterial defense system into a gene editing tool. Some have called it the democratization of genetic alteration. The technique gives researchers an easy way to snip out genes in all kinds of organisms, giving rise to fears that so-called “designer babies” are just around the corner, or that a genetically altered creature will be released into the wild and create unalterable damage. Those concerns spurred an international summit last month that gathered scientists and bioethicists in Washington, DC.
There is great promise, too. Several companies with licenses to the competing Doudna and Zhang patents—and with other IP in their portfolios—are racing to move CRISPR-based therapies into clinical trials to treat genetic disease. The CEO of Cambridge, MA-based Editas Medicine—which has license to the Zhang patents—said in November that her company hopes to have a treatment for a rare form of blindness in the clinic by 2017.
Editas and other human therapeutics companies aim to edit somatic cells—not human eggs, sperm, or embryos—which means the changes could not be passed down to the patients’ offspring. A large part of the patent dispute hinges upon whose work first described a gene editing system that worked not just in test tubes or prokaryotic cells, such as bacteria, but also in eukaryotes—that is, more advanced life forms.
As the patent fight has simmered, many scientists have published work describing improvements and changes to the underlying CRISPR system. For example, several labs including Zhang’s described in September a new enzyme—the molecular scissors used to snip the DNA—called Cpf1 that, they say, when used with the CRISPR editing system could get around some of the problems with the Cas9 enzyme.
The PTO could not be reached over the holiday weekend for comment. But it seems as if the Doudna camp’s efforts to move the case to a court-like interference proceeding have worked. The appeals board must approve the examiner’s recommendation, but Sherkow, citing PTO sources, wrote in his blog post that the decision is “largely pro-forma.”
Another patent attorney with experience in interference cases agreed. “I’ve never seen an examiner recommend interference and not have it declared,” said Muna Abu-Shaar of Biospark Intellectual Property Law in Cambridge, MA. The appeals board could still say no, but because of a few factors, “the PTO would do the public a big disservice by not declaring the interference and sorting this mess,” Abu-Shaar said.
If it takes place, Doudna and Zhang might have to “take the stand, or at least testify under oath in a deposition,” Sherkow wrote.
Contacted over the weekend, Doudna wrote via e-mail, “I don’t know any more than you do right now regarding the PTO action, hoping for some insight as the case proceeds.”
Broad Institute spokesman Paul Goldsmith did not have an update, either.
As I wrote in late 2014, the CRISPR patent dispute between the Doudna and Zhang camps is being fought under old PTO rules, thanks to an overhaul of American patent law in 2011.
Under the old rules, the first person to prove his or her invention was rewarded with a patent. Under the new rules, the patent goes to whoever is first to file an application. Because of the slow pace of putting laws in place, the CRISPR case will be settled under the old rules, likely making it the last great “first to invent” fight in U.S. patent history, which admittedly excites patent specialists but not many others.
This is likely the last major interference case because the new patent rules have done away with the complex process. It seems no one involved in intellectual property will mourn. According to Sherkow, interference demands “an almost Soviet-style detail to bureaucratic rules that gives even seasoned patent prosecutors the shudders.”
The PTO must approve a settlement, making one less likely, wrote Sherkow. And if no settlement takes place, the outcome of the interference can be appealed up through the U.S. court system. In other words, the biotech patent fight of the century might feel like it lasted the better part of the century when all is said and done.