Posted By Jey Kumarasamy
Meet CRISPR, a revolutionary gene editing tool of “unprecedented precision, efficiency and flexibility”. MIT Technology Review has called it “the biggest biotech discovery of the century.” And its scientific and commercial potential has made it “one of the hottest investments” in the biotechnology industry.
CRISPR is based on a naturally-occurring, defense mechanism found in a wide range of bacteria to combat virus DNA. It uses the protein Cas9 and a “tailored guide RNA sequence to cut and splice material from or into the DNA helix.” Potential areas of application include agriculture, industrial biotechnology and, of course, the treatment of human diseases.
No one disputes that CRISPR is a groundbreaking invention. Instead, the most salient issue is regarding who owns the patent rights to the technology. Two research teams are currently involved in a high-stakes patent dispute in the US. On one side, there is Jennifer Doudna and her team at the University of California, Berkeley. On the other, there is Feng Zhang and his team at the Broad Institute, a Massachusetts-based research centre partnered with the Massachusetts Institute of Technology and Harvard University. Both scientists claim to have invented CRISPR first.
Jennifer Doudna (left) and Feng Zhang (right) are the two leading scientists involved in the US patent dispute over CRISPR (Source: STAT)
First-to-invent versus first-to-file system
Before getting into the details of this particular legal dispute, there is some important background information we need to understand.
Until very recently, the US was the last country in the world to employ a first-to-invent system rather than a first-to-file system. In a first-to-invent system, the patent to an invention disputed by two parties would be given to the one who could prove that they were the first to invent it. This was accomplished through a process called “interference proceedings”.
On March 16, 2013, the US switched to a first-to-file system where priority is given to the first inventor to file a patent application, thereby eliminating the need for interference proceedings. This change was part of the America Invents Act.
Patent applications
The chronology of events is critical to this dispute.
The Berkeley team was first to initiate their patent application for the CRISPR technology in May 2012. The Broad team followed with their own provisional patent application in December 2012. Under the current first-to-file system, the story would likely end here. But since both these applications have a priority date earlier than March 16, 2013, they fall under the older first-to-invent regime.
The Broad team, unlike the Berkeley team, had requested that its application be expedited under the USPTO Track One program. Therefore, they were granted the patent in April 2014 before the Berkeley team’s application had even been reviewed. Another difference was that the Broad application specifically considered application of the technology in eukaryotic cells, which tend to be found in more complex organisms (e.g. humans), as opposed to prokaryotic cells that have a simpler structure (e.g. bacterial cells). While their patent application was being reviewed, Zhang submitted a personal declaration arguing that it was not obvious from the Berkeley team’s earlier filings that the technique could also be applied in eukaryotic cells.
In April 2015, the Berkeley team amended their application to include both eukaryotic and prokaryotic cells. They also requested for a patent interference by filing a “Suggestion of Interference” against several Broad patents, including the one mentioned above. The USPTO granted their request in January 2016.
Interference proceeding
Patent interference proceedings are considered to be highly technical. Ultimately, a panel of three USPTO patent judges will decide which team gets patent rights to the technology. Each party may submit evidence, in writing or in the form of oral arguments, to establish that they invented the CRISPR application to gene editing first. Oral hearings have been scheduled for November 17, 2016.
In addition, the panel determined the Berkeley team to be the “senior party” and the Broad team to be the “junior party” based on the filing dates. In interference proceedings, the burden of proof lies on the junior party. Therefore, the Broad team will need to convince the panel that the patent office was correct to grant them their CRISPR patents.
It seems that it may take a couple years before a decision is finally rendered. Even then, many expect that the losing party will appeal the decision because of the “high financial stakes.”
Furthermore, this may be a sneak peek of what is to come in other jurisdictions around the world. In Europe, for instance, the Broad team “fast-tracked several of its applications at the European Patent Office (EPO), and has been awarded several patents so far.” The Berkeley team has also filed a patent application but it is still pending. Last year, nine parties came forward to launch an opposition procedure against the first European CRISPR patent awarded to the Broad team. This dispute may also take years before it is resolved.
Conclusion
It will probably be quite a while before we know how this story ends. As mentioned, CRISPR has been described by some as the “the biggest biotech discovery of the century.” This alone suggests that there is sufficient financial incentive for the players involved to slog through this patent battle.
Meanwhile, the uncertainty over who owns the patent rights to this technology does not seem to have slowed down investment in CRISPR-related research and development. A few months ago, Editas Medicine, a Massachusetts-based biotechnology firm co-founded by Zhang, raised US$94 million on its IPO. Other biotechnology firms that are seeking to use the CRIPSR technology to develop successful human therapeutics include Crispr Therapeutics and Caribou Biosciences (co-founded by Doudna).
As for why the scientific community does not seem to be waiting for the legal dispute to be resolved first, Robin Feldman, a professor at the UC Hastings Law School, sums it up quite well: “The patent system lumbers on. But innovation is on its own timeline.”
A summary of how the CRISPR technology is used to edit a gene (Source: Business Insider)
McGill Journal of Law and Health 