By: Charlie Fehl
Last month, the legal future of the jack-of-all-trades gene editing technique CRISPR-Cas9 took significant shape. First reported as a bacterial defense targeted to specific gene loci by researchers based at University of California, Berkeley (Jennifer Doudna, Ph.D.), and Max Planck Institute for Infection Biology, Berlin (Emmanuelle Charpentier, Ph.D.), CRISPR-Cas9 combines the single gene selectivity of RNAi technologies with a bacterial enzyme—Cas9—able to catalyze double strand DNA (dsDNA) cleavage. Though this sounds disruptive and indeed normally is, dsDNA breaks can alternatively be “filled back in” with exogenous replacement DNA, potentially correcting mutations, inserting or removing harmful sequences, and even appending new domains and fusion proteins. For biotechnological applications, all components can conveniently be delivered on a single viral vector, rendering it useful for therapeutic applications.
Both biomedical research and industry took immediate note. Since the 2012 introduction of the CRISPR-Cas9 technique in bacterial systems, the Broad Institute in Boston, led by researcher Feng Zhang, Ph.D., was the first to optimize CRISPR-Cas9 for eukaryotic cells (a timeline exists here). This was an enormous advance to the technology, opening up the possibility for basic researchers to knock out or modify single gene functions in a highly modular fashion, unlike other heavily customized gene editing technologies like TALEN. The Broad Institute filed a patent on Zhang’s techniques for using CRISPR-Cas9 in eukaryotic cells, at odds with Berkeley’s general patent on the technique, which was filed first.
These conflicting patents thus spurred a hotly contested legal battle for the applications of CRISPR-Cas9 beginning in late 2014 when the Broad Institute patent was awarded. Attorneys at Berkeley sought a patent interference hearing, which was conducted last month by the U.S. Patent and Trade Office (USPTO). The Broad’s patents won what is considered a decisive victory over many of the more industrially applicable uses for the technology, such as biomedical gene editing in mammalian cells and crop engine
ering in plants. However, Berkeley retains the overall patent on the discovery of the technology itself.
This case reflects an interesting divide between a) the original discoverers of a chemical biology technique and b) the development of a particularly useful extension, namely into eukaryotic cells. However, the USPTO ruled in favor of the Broad Institute’s patent because the original bacterial biochemical characterization of CRISPR-Cas9 did not clearly suggest direct application in eukaryotic cells. Moving forward, this “oversight” could be an unfortunate consequence of humility wherein the authors may not have wished to claim too many hypothetical benefits from a novel technique. It remains to be seen what lessons basic researchers will interpret from this when protecting their discoveries.
As expected, companies banking on using CRISPR-Cas9 sustained market shocks due to uncertainty in patent regulation. Outside of the commercial realm, however, both institutions have made it clear that the two non-overlapping patents will not hinder basic research aims. This is an essential point, given the rapid adoption of this technique in almost all aspects of the life sciences. The future of gene editing is here to stay.
Charlie Fehl is a postdoc at the University of Oxford, where he studies carbohydrate biochemistry and biocatalysis with Benjamin G. Davis. He is interested in chemical biology tool development for pharmaceutical and biomedical applications.