CRISPR (clustered regularly interspaced short palindromic repeats) gene-editing technology is considered as one of the biggest innovations of the century in the biotechnology field and has gained a lot of attention worldwide, especially in the US and Europe in the area of Intellectual Property Rights.
Research has shown that a protein named Cas9 found in the Streptococcus bacteria “CRISPR” immune system that works like scissors was used by the bacteria to alter the DNA of viruses which attacked the bacteria. Based on this finding, CRISPR Cas9 was developed to make cuts in any desired DNA sequence. This new technology was found to be better and cheaper than known gene editing techniques, and therefore generated a lot of interest worldwide in the area of gene editing tools by researchers, especially in the Pharma and Agricultural industries.
The patent landscape surrounding CRISPR technology is also attracting a lot of attention as this technology has generated a considerable amount of money for the innovators from big companies such as AstraZeneca, DuPont, Monsanto and as well as CRISPR start-up companies through patent licences.
In 2015, the University of California, Berkeley (UCB), requested a patent interference proceeding against patents granted to the Broad Institute of MIT and Harvard in relation to CRISPR technology. UCB’s patent applications described the basic structure of CRISPR-Cas9 and its use in any environment (including in “prokaryotic” cells), while the Broad Institute’s later patent applications described how to use the technology in “eukaryotic” cells. In 2017, the USPTO’s Patent Trial and Appeal Board (PTAB) gave a decision stating that there was no interference and granted the Broad Institute the rights to use the technology in eukaryotes.
In Europe, the situation is different and more complex since a number of patent applications have been filed in relation to CRISPR technology by different parties, including the Broad Institute of MIT and Harvard, University of California, Berkeley (UCB), ERS Genomics (a company started by Emmanuelle Charpentier (one of the inventors) to develop CRISPR-based therapeutics), Cellectis, and Sigma-Aldrich to name a few.
Most of the applications filed in relation to CRISPR technology are at different stages of examination, opposition and appeal proceedings before the EPO.
In May 2017, in contrast to the decision given in the interference proceedings in the United States, the EPO granted Emmanuelle Charpentier, the founder of ERS Genomics, her first European Patent (EP2800811) with very broad claims covering the use of CRISPR technology across prokaryotic and eukaryotic cells and organisms. If this patent is upheld, this would give Emmanuelle Charpentier the rights over use of CRISPR technology in both prokaryotic and eukaryotic cells. Of course, as expected, a number of Notices of Opposition have been filed against this patent and currently these oppositions are pending before the EPO’s Opposition Division.
Although EP 2800811 has, before grant, withstood at least seven “third party observations” which challenged the patentability of the claimed invention, it is expected that during the opposition proceedings, the patentee may be forced to narrow its claim to cover use of CRISPR technology only in prokaryotes. If not, the patentee may end up with broader protection covering the use of CRISPR technology in both prokaryotic and eukaryotic cells, which would be a big advantage for ERS Genomics.
While in the US, the Broad Institute was considered as the winning party since it obtained protection for use of the CRISPR technology in eukaryotes, in Europe the Broad Institute’s European Patent (EP 2,771,468) covering CRISPR/Cas9 technology was revoked by the EPO’s Opposition Division in its entirety after finding that the Broad Institute could not claim two key priority dates.
While the Broad Institute has announced its decision to appeal against the decision of the EPO, the outcome of any such appeal needs to be monitored carefully: many experts believe that the chances of the Broad Institute succeeding on appeal are slim.
Nevertheless, the Broad Institute has indicated that having its patent (EP 2,771,468) invalidated in Europe, will not cause them to lose their position at the leading edge of CRISPR research and licensing, since they have a large portfolio of patents covering this technology. In particular, they believe that more recent patent applications covering specific and different Cas proteins like Cpf1 will not be affected.
Although the Broad Institute thinks this does not have any impact on their business plans in relation to CRISPR technology, it is possible that the value of Broad’s basic patent portfolio may reduce and they may need to undertake cross-licencing with other big players such as UCB and ERS Genomics in order to fully use the basic technology in Europe. In July 2017, the EPO granted a French biotech company Cellectis the first patent to use CRISPR technology in T cells. In February 2018 Cellectis was also granted two US patents to use CRISPR technology to make CAR-T cells.
In February 2018, the EPO granted a second CRISPR/Cas9 patent to ERS Genomics, one month after revoking Broad Institute of MIT and Harvard’s patent relating to the technology.
There is no doubt that CRISPR technology has brought a significant change in the field of biotechnology in relation to gene editing tools, and researchers around the world have already started using CRISPR-Cas9 systems to edit genomes in the field of agriculture and medicine. In 2016, the U.S. National Institutes of Health approved the first clinical trials using CRISPR-Cas9 on cancer, and in the UK, the Human Fertilization and Embryo Authority (HFEA) has approved its use to permanently edit DNA in a human embryo.
The Intellectual Property around this technology is being closely watched by IP experts and investors as more and more companies have shown interest in obtaining rights to CRISPR technology for use in developing new therapies or products, and millions of dollars are expected to be generated through licenses.
However, the grant of patents in relation to CRISPR technology to some parties and refusal of patents to others may create a complex and unclear IP landscape, with overlap of rights. In the United States, UC Berkeley has filed an appeal against the PTAB’s decision in the interference proceedings, and in Europe, all patent applications relating to CRISPR technology are pending decisions from various proceedings including Examination, Opposition and Appeal, and therefore it is still not clear what rights each party will end up with.
As with all new technologies, more and more research and developments are being made around CRISPR technology resulting in new inventions and related IP rights.
As a result of this complex and unclear situation surrounding the patent rights, it appears that those who wish to use CRISPR technology may need to obtain multiple licences from different parties depending upon who gets what out of the pending patent rights.
We will keep you updated on further developments.