While the world of biology might be filled with enthusiasm and optimism about CRISPR/Cas9 (commonly referred to simply as “CRISPR”) and its benefits, the world of bioethics is quite concerned with the implications of this DNA editing technology and its effect on humanity. Be that as it may, the corporate world is looking forward to embracing and exploiting this rapidly spreading and promising technology for a faster, easier, more precise and cheaper process of DNA editing. It is the ownership of CRISPR-related IP, in general and related patents, in particular, that will be the decisive factor in who will benefit, businesswise, from this, new life changing technology.
What is CRISPR?
While touted by some as the most-significant biotechnology advancement in decades, with expected billion-dollar revenues, the CRISPR/Cas9 has been mired in uncertainty for nearly four years. CRISPR/Cas9 stands for “Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9,” and is the name given to this revolutionary tool that enables faster, cheaper, easier processing of human genome alteration.
CRISPR’s inventors, Jennifer Doudna (from the University of California, Berkley) and Emmanuelle Charpentier, originally researched CRISPR when investigating the manner in which bacteria defend themselves against viruses. They discovered that the natural CRISPR/Cas9 bacterial defense system could be programmed to serve as a sophisticated genome-editing tool, enabling deletion or replacement of segments of DNA with unprecedented accuracy, speed, price and ease. The Doudna Group expanded their research to eukaryotic cells, but they were not alone in this quest. A team of researchers, led by Feng Zhang at MIT were also exploring these new possibilities and the potential implications of all aspects of this technology - from gene therapy to combating HIV and other diseases.
As with most groundbreaking technologies, especially those with clear commercial uses, the matter of patents soon became the focus of attention. In particular - who owns the right to patent this technology?
The battle over priority
While both the Doudna Group and Zhang Group successfully modified human eukaryotic cells using CRISPR in January 2013, in anticipation of their discovery, a first series of provisional applications were already filed in May 2012 by the Doudna Group and in December 2012 by the Zhang Group, followed by non-provisional applications in 2013. Understanding the commercial implications and the significant potential of the technology, Zhang accelerated the examination of their non-provisional application and were granted a first patent, in a series of more than a dozen, on the CRISPR technology; despite Doudna being the first to file a priority application. As the patent applications in question claim priority from applications filed prior to enactment of the AIA in March 2013, the question that arises in the CRISPR patent battle is: who was the first to invent the use of CRISPR in human eukaryotic cells. As one would expect, the parties’ positions on the issue are diametrically opposed.
Both sides have submitted numerous documents to the USPTO to support their priority over the other. For Zhang, these include a Declaration in which it has been argued that Doudna’s provisional applications did not sufficiently describe the use of CRISPR with eukaryotic cells, supported by lab records demonstrating that Zhang developed this system in early 2012, prior to the filing of Doudna's provisional application. In response, Doudna filed an amended set of claims with a broader application of CRISPR, as well as a declaration by Professor Dana Carroll, from the University of Utah, widely-considered a pioneer in the field of gene editing), asserting that Doudna’s provisional applications “clear[ly] disclos[e] use of the compositions in eukaryotic cells, [and] provide detailed descriptions of numerous steps that could be taken to apply the system to a eukaryotic cell environment”.
More importantly, however, the Doudna Group also filed a “Suggestion of Interference” (the proceeding commonly known as "interference") requesting the USPTO to determine who first invented the CRISPR technology.-. Interference is the procedure existing under the pre-AIA, “first-to-invent”, regime for determining priority in the event of patent applications with overlapping subject matter. On January 11, 2016, the USPTO agreed to hear Doudna’s challenge to Zhang’s patent for the CRISPR technology.
The CRISPR patent portfolios of both parties had been licensed to companies co-founded by the researchers, each of which raised tens of millions of dollars to fund research and development. However, these R&D endeavors, with their potential of generating cures of life-threatening diseases, are largely on hold, pending the resolution of this patent battle. It is now in the hands of the USPTO to determine who owns one of the most significant and potentially valuable – biotechnology patents in recent history.
The CRISPR-related patent battle at the USPTO, as important as it is, is not the only one and parallel patent battles to determine rights over the CRISPR technology are also in the European Patent Office and in other jurisdiction. The underlying law (and also procedure) in other jurisdictions is very different to that in the USPTO and the result may be that the eventual outcome could be different and even opposite to that in the US. This remains to be seen. As is common in patent battles with such high stakes, an out-of-court settlement can also not be ruled out.