CRISPR/Cas9: Legality and Biology Meet
Recently, the U.S. Patent and Trademark Office ruled in favor of the Broad Institute of MIT over UC Berkley in a row over the patent rights to the amazing Gene Editing Machine: CRISPR/Cas9. This is going to have consequences far and wide in terms of monetary compensation to use the technology in research, biomedical applications, medical clinical applications, agriculture, and the creation of superhumans. Okay, I’ll admit the last one is a bit of an overstatement, but there is already some research being conducted in human embryos (CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes). This dispute underscores the potential of this technology to have far-reaching consequences, and that the monetary rights conferred by patent control will be of the utmost importance.
The History of CRISPR-Cas9
Let’s begin by describing the story of CRISPR. It is a naturally occurring system that bacteria and archaea use to fight off infection by viruses. Simply, viruses infect bacteria with their DNA to make new viruses. Naturally occurring endonucleases such as Cas9 cleave the viral DNA, and these fragments are incorporated into the bacterial genome at the CRISPR locus. These are imprints similar to how our adaptive immune system works where exposure to an antigen, pathogen, or virus causes the immune system to recognize it and then save this information for later. This allows us to destroy the invader when it comes around the next time in a more efficient manner. Although we do not incorporate foreign genetic information into our genomes by this mechanism, CRISPR is likely the first evolutionary method of adaptive defense. In prokaryotes, when another virus of the same type comes along, they will come across the CRISPR/Cas9 system, and this allows the bacteria to destroy the target viral DNA much more easily than the first infection. This endows the future “progeny” of this originally infected bacteria with resistance to this type of virus. The featured figures here in this article breaks down the CRISPR/Cas9 system into an approachable and simple manner. If you want more information on the biology of CRISPR/Cas9, please, check out our Dr. D’s Discussions on the intricacies of the Gene Editing Machine.
Now, let’s break down the legal aspects to this story… The original paper published about using CRISPR/Cas9 as a gene editing machine was by UC Berkley in 2012, and a close follow-up by the Broad Institute in 2013 of the technology being utilized in human cells. This was followed by patent applications from both groups to gain control of the rights to the technology. Now, you may be thinking, why did the Broad Institute get the patent if they published second? Well, their legal team knew to use the fast track path to patenting and was awarded the patent rights in 2014. This is how the patent system in the U.S. works, but there are also some caveats to the published article in 2012 by UC Berkley. UC Berkley’s group led by Dr. Jennifer Doudna published an article in Science about the use of CRISPR in a prokaryotic organism, bacteria, where it was found and In Vitro (in a test tube). At the time of the patent and publication, Doudna’s group had not used the CRISPR system in human cells or animal cells, they characterized the system and developed the chimeric Guide RNA.
They applied for patents not only in prokaryotic organisms, but in eukaryotic cells as well. The judge ruled in favor of the Broad Institute based on the specific applications that were detailed within the Broad Institute’s patent, but also ruled that UC could receive the patents for “all cells”. This will need more time in the legal system to work out, but could indicate that a subcategory of cells could get a patent, but at the same time, the larger category could get one as well. This essentially means that bikes could be patented, but that tandem bicycles can also be patented at the same time. Mind boggling… It is possible that both of these institutions will split parts of whatever revenue comes from licensing. What is unclear is where will one patent’s reach end and another begins. Some of the confusion is centered around the fact that CRISPR is a naturally occurring system, so variations of and applications of the CRISPR system are what are up for debate and licensing. Furthermore, to what CRISPR is applied to, whether it be bacteria or human, mouse or agriculture, all of these applications individually could be patented, but also fall under the “all” claim by UC Berkeley.
This is probably not the end of the legal fight over CRISPR/Cas9, but there are other types of gene editing endonucleases (proteins that cut DNA such as Cas9) that are now coming to light and being patented, such as Cpf1. I for one am excited about the prospects of the CRISPR revolution in the biomedical sciences, but there is always another discovery right around the corner especially given the fact there are many naturally occurring gene editing systems in bacteria. We will keep you updated on the appeals process that UC will be going through, and we will also report on any new discoveries in the natural gene editing machines.