Imagine, if you will, the archetypal example of a scientist. Clad in a stained lab coat or surrounded by dusty chalk boards, they spend long hours uncovering knowledge, unconcerned with profit or fame. This image may be inspiring, but is increasingly inaccurate. With the advent of massive biotech and pharmaceuticals firms, along with newfound attention from Wall Street, biomedical research has been influenced considerably by the intersection of business and academic interests. To see a clear example of this, one need look no further than the fierce battle waged in recent years over the CRISPR patents. But what do these patents concern? And why have so many high-profile scientists fiercely fought for their ownership?
CRISPR is a bacterial “immune system” of sorts that allows the cell to respond to attacks from invading bacteriophages, or viruses that exclusively prey on bacteria. By isolating small pieces of viral DNA and integrating these pieces into the bacteria’s genome, the bacteria can recognize the virus if it attacks again by identifying the integrated DNA sequence and destroy it before it causes damage. Scientists had the astonishing revelation that this system, and the identification and targeting of specific DNA sequences it entails, could be utilized in order to achieve a level of precision in genetic engineering never before thought possible. The technology is incredibly flexible, allowing researchers to target and edit any position of the genome.
Among the many questions associated with the advent of CRISPR technology, the most pressing one is: who owns CRISPR?
Among the many questions associated with the advent of CRISPR technology, the most pressing one is: who owns CRISPR? The winner the ownership of CRISPR will almost certainly revolutionize biomedical research, but several top scientists have had a variety of contributions to the technology. This has fueled a fierce, public debate over who ought to be awarded the CRISPR patents.
While many researchers have played indispensable roles in the development of CRISPR technology, two parties have emerged as the dominant competitors over the patent rights. Jennifer Doudna and Emmanuelle Charpentier, of UC Berkeley and the Max-Planck Institute respectively, have engaged in bitter debate with Feng Zhang of the Broad Institute (which is dually controlled by Harvard and MIT). While Doudna and Charpentier uncovered the fundamental science behind the technology before Zhang, Zhang is the one who first applied CRISPR in human cells. Of course, the ability to edit the human genome is the key to developing therapeutic applications and achieving unimaginable levels of fame and wealth.
The debate regarding CRISPR’s rightful owner began in 2012, when the team of Doudna and Charpentier filed a patent for the canonical form of CRISPR, CRISPR Type II utilizing the Cas9 nuclease. Zhang followed suit, filing for a similar technology in eukaryotes only. To complicate matters further, while Zhang filed his patent 9 months after Doudna did, he applied for a “fast-track” patent approval process that ensured that his patent was granted first despite having filed it later. From this point onward, UC Berkeley and the Broad Institute (representing the interests of their member scientists) began waging a legal battle over the rightful owner of patents.
In January of 2016, this conflict culminated with an official intervention by the United States PTO, or Patent and Trademark Office. The PTO’s arbitration process, a special “interference proceeding” which examines the validity of competing patent applications, continued throughout most of 2016. UC Berkeley argued that Doudna’s patent should hold precedence over Zhang’s, as it was filed before and was the first to demonstrate the validity of CRISPR technology. The Broad Institute, on the other hand, claimed that the application of CRISPR in eukaryotes merits a separate patent by itself. After months of debate, on February 15th, 2017 the PTO ruled that Zhang’s introduction of CRISPR into eukaryotic cells represents a novel advance and is thus patentable. It is not that the allowance of Zhang’s patent means that Doudna’s must be revoked, but rather that the two patents can coexist and do not interfere with each other.
While the patent debate has mostly been settled in the United States, there is still contention in Europe (which falls under the jurisdiction of the European Patent Office). In January of 2018, the EPO revoked a key patent filed by the Broad Institute in 2013 due to an issue with an earlier 2012 patent filed in the United States. The 2012 patent, which was mentioned in the European patent application as a way of proving that the Broad Institute’s technology predates that of competing groups, listed Luciano Marraffini, an American researcher at The Rockefeller University, as a co-inventor. But he was not listed on the European application, violating inventor listing rules and thus preventing the Broad Institute from using its 2012 patent as a method of claiming an earlier filing. This issue, combined with resistance from Charpentier, could undermine many of the Institute’s key patents and lead to Doudna having a dominant position in the CRISPR European patent space.
Even as the CRISPR patent debate continues, researchers have begun their foray into industry by founding and collaborating with companies in order to utilize the technology. Firms such as Doudna’s Caribou Biosciences, Zhang’s Editas Medicine, and Charpentier’s CRISPR Therapeutics have sprung up, representing a trend towards commercialization with profound implications for the field of gene editing and biomedical research as a whole. Over the next few years, we can expect to see a dramatic rise in the number and size of companies utilizing CRISPR as the technology becomes increasingly mainstream. Thus, ownership of the relevant patents is an extremely pertinent issue that must be addressed as the industry grows.