On September 10, 2018, the U.S. Court of Appeals for the Federal Circuit (CAFC) handed down a long-awaited decision in a patent interference case pitting researchers from the Massachusetts Institute of Technology (MIT) and Harvard University’s Broad Institute against researchers from the University of California, Berkeley (UC) and the University of Vienna, Austria. At issue were competing patents concerning a breakthrough gene-editing technology known as CRISPR-Cas9. The CAFC’s ruling, which upheld a 2017 decision by the US Patent and Trademark Office (USPTO) affirming the Harvard and MIT patents, was heralded as a blow to the scientists of the University of California, Berkeley and University of Vienna, Austria.
The high profile dispute between the two groups of researchers and academic institutions revolved around intellectual property patent rights underpinning the commercialization of products developed through the use of the CRISPR-Cas9 system. CRISPR (Clustered Regularly Interspersed Palindromic Repeats ) is a technology that allows scientists to edit genomic sequences with a high degree of precision by manipulating the biological equivalents of molecular scissors, functioning in tandem with assorted enzymes, referred to as Cas (CRISPR-associated systems) enzymes.
The CRISPR-Cas9 system, the focus of the recent litigation, was initially invented by researchers led by Drs. Jennifer Doudna of the University of California, Berkeley and Emmanuelle Charpentier, formerly of the University of Vienna, Austria and now at the Max Planck Institute for Infection Biology in Berlin, Germany. Applications of the CRISPR technology, from correcting and alleviating diseases in humans to increasing agricultural crop outputs, as well as yet unknown uses have all been touted since this technology became widely known and available starting in 2012.
The financial and reputational stakes for both sides are significant. On the one hand, are potentially many billions of dollars’ worth of licensing fees in play, given the enormous range of potential applications in the medical and agricultural fields and beyond. There are also bragging rights and coveted present and future accolades from the global scientific community to be gotten. Both would enhance the prestige of the teams of researchers and greatly raise awareness of their pioneering work – work that produced a discovery that the scientists from the University of California at Berkeley and the University of Vienna, Austria have called “the discovery of the century.” 1
Shares in Crispr Therapeutics, co-founded by Emmanuelle Charpentier and shares of Intellia Therapeutics , co-founded by Jennifer Doudna – both of which licensed the University of California Berkeley inventions – dropped by as much as 5.3 percent and 2.5 percent, respectively after the decision was handed down. Meanwhile, shares in Editas Medicines Inc., which licenses the Broad and MIT inventions, jumped by as much as 6.8 percent before pulling back. 2
But interestingly, the CRISPR technologies that power all three of these companies, as well as countless others may already be obsolete. Indeed, the pace of discovery in the CRISPR field has only accelerated since the current patent fight began back in 2014. CRISPR systems that are more promising and more targeted in terms of their biological specificity and function have emerged in the last few years, lessening the primacy of and reliance on the CRISPR-Cas9 system. 3 Thus, investors wanting to enter the CRISPR space or entities wanting to leverage their particular “flavor” of CRISPR technology may want to ponder these particular developments as they evaluate their long-term strategic business goals and considerations.
Another “wrinkle” in the CRISP narrative is that performing gene editing in cells’ genomes using the CRISP-Cas9 system may inadvertently increase the risk of producing altered cells which, rather than being used to treat disease, might in fact trigger cancer. 4 Two recent studies published in Nature Medicine show that when the CRISPR-Cas 9 system is deployed inside two different kinds of human cells – retinal cells and pluripotent stem cells, respectively – it subsequently activates a gene called p53, which either repairs the DNA break or causes the targeted cell to self-destruct. Hence, cells that survive the CRISP-Cas9 editing event do so because of their altered p53 gene, which abrogates the cell’s inherent repair or death machinery. This phenomenon appears to be a hurdle that scientists are taking seriously. As one report points out, this p53 problem “might affect other products that companies hope to develop via gene correction.” 5 It would also be a potential problem when using the CRISPR-Cas9 system on stem cells. 6
While the CAFC’s decision in the legal fight over the intellectual property surrounding the CRISPR-Cas9 system may be nearing its end, the evolution of the science underlying CRISPR technologies ensures that we haven’t heard the last of this truly groundbreaking and trailblazing discovery. As one legal scholar noted, “This is still an incredibly important case for the present…but it may not be an incredibly important case for the future.” 7
1 Susan Decker and Tatiana Darie, “Gene-Editing Patent Challenge Rejected by U.S. Appeals Court”, https://www.bloomberg.com/news/articles/2018-09-10/gene-editing-patent-challenge-rejected-by-u-s-appeals-court (last viewed, September 28, 2018).
3 Megan Molteni, “Crispr’s Epic Patent Fight Changes the Course of Biology,” https://www.wired.com/story/crisprs-epic-patent-fight-changed-the-course-of-biology/ (last viewed September 28, 2018).
4 https://www.kqed.org/futureofyou/442526/major-hurdle-for-crispr-edited-cells-might-cause-cancer-find-two-studies; see also Sharon Begley, “A serious new hurdle for CRISPR: Edited cells might cause cancer, two studies find.” https://www.statnews.com/2018/06/11/crispr-hurdle-edited-cells-might-cause-cancer/).
7 George Dvorsky, “Appeals Court Upholds CRISPR Patent, Potentially Ending Bitter Dispute”, https://gizmodo.com/appeals-court-upholds-crispr-patent-potentially-ending-1828948320 (quoting Jacob S. Sherkow).