CRISPR-cas9 technology is arguably the most significant development biotechnology has seen in the last half century. The implications of this breakthrough are vast, but how scientists will be able to use this technology all rests on the outcome of what may be the most unusual, and intensely fought patent battles of recent times.
In the red corner…
The story begins in 2012 with two teams of scientists, one at the University of California, Berkeley, and the other at the Broad Institute at MIT and Harvard. Jennifer Doudna and Emmanuelle Charpentier filed their patent application early in 2012 after they had conducted successful research which demonstrated how CRISPR technology could be used to edit DNA in prokaryote cells (e.g. bacteria). However, while they were waiting to be awarded their patent for their groundbreaking work which won them the “Spanish Noble Prize” as it’s known (the €50,000 Princess of Asturias Award of Technical and Scientific Research), another team headed by Feng Zhang at the Broad Institute at MIT and Harvard were working on something similar.
Later in 2012 Zhang’s team sent their patent application after they had successfully developed a way to use CRISPR technology in eukaryote cells, like human cells for example. In a move that’s completely legal the Broad Institute paid to expedite the review of their patent. This resulted in Zhang’s team being the first to receive a patent for editing cells with CRISPR, which they were awarded in April of 2014. At this point Doudna and Charpentier still had their patent pending, Zhang’s team had one the patent race even though they filed their application after Doudna and Charpentier.
Prokaryote vs eukaryote
Following the Broad Institute being awarded their patent, Berkely partitioned for a Patent Interference, taking the issue of who invented the technology to federal patent judges. The case gets complicated in that its focus has shifted to not who developed the cell editing technology first, but to who developed the technology for use within eukaryote cells. The reason being is that the development of applications in eukaryote cells, human cells, will be much more lucrative than applications for prokaryote cells. For example, there is the potential to eradicate genetically transmitted disease in humans with the development of the use of CRISPR gene editing in eukaryote cells. Whereas prokaryote use is limited to editing of bacterial cells, which while useful holds nothing of the gravity of human gene editing.
Berkeley make the case that in Doudna and Charpentier’s paper they make reference to the technology’s potential use in eukaryote cells. While the Broad Institute argue that Zhang’s development of the technology is novel, that there is no simple transition from prokaryote use to eukaryote. They even highlight that in Doudna and Charpentier’s paper they claim that they are uncertain that their technology would be transferable to use in eukaryote cells.
A member of Zhang’s team defects to Berkeley
In an interesting turn of events, a couple of months before the hearing took place a previous member of Zhang’s team accused the Broad Institute ofmisleading the patent office. Shuailiang Lin, a former junior scientist working with Zhang allegedly sent an email to Doudna, in which he claimed that he had evidence to prove that before Doudna’s paper was published Zhang’s team were only experiencing a stream of failures with their CRISPR work. It was only in light of her published research explaining how to use CRISPR in prokaryotes that Zhang’s team achieved success with eukaryotes.
However, the Broad Institute have hit back and claimed that at the time Lin sent the email to Doudna he was in a rush to renew his visa, after being rejected for a new position with them. They speculate that Lin’s motivations were linked to finding a work placement with Doudna, rather than revealing the truth.
Who is tipped to win?
Already a number of organisations have already made their allegiances with one side or another, having licensed the right to use CRISPR with their chosen predicted winner. However, it’s not clear at this point who will emerge victorious. It seems that it all rests on whether Berkeley can prove that the technology that they developed for use in prokaryotes was clearly readily usable for applications in eukaryotes. In the case that the Broad Institute wins then Berkeley have the option of then taking the matter to federal court. However, it is unlikely that judges in a federal court will have a strong scientific background, making the option unappealing as well as expensive.
Interestingly a bill called “first to file” has been passed since proceedings began which, if it had been in place beforehand Doudna and Charpentier would have been named as outright owners of the technology and the patent. In brief the bill states that whoever submitted the patent application first is the owner, hence “first to file”.
What does this mean for the future of CRISPR technology?
The outcome of this patent battle could have implications beyond that of who gets to go down in the history books as being the creator of this groundbreaking technology. For example, since proceedings began Zhang’s team have been awarded a number of patents off the back of the one that they already have. If they were to loose this battle then all inventions linked to the initial patent may be in jeopardy.
The case continues…
We may have to wait a while longer to see the outcome of this battle. A few days ago both sides made their case at the hearing, however there’s much more to come. Berkeley has asked that headline-making Harvard biologist George Church be subpoenaed, as they believe that he has the power to undermine key assumptions being made by the Broad Institute. Regardless of the outcome, this is certainly a story to follow.
My grateful thanks to Sarah Moore for help in writing the majority of this article