Who owns CRISPR-Cas9?

    07/07/2015

    CRISPR

    A new revolution is sweeping through the world of genetic engineering and medicine called CRISPR-Cas9. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, or segments of DNA used by bacteria to cut out unwanted invading DNA from phages (viruses that invade bacteria). Cas9 (CRISPR associated protein 9) is a protein which aids the function of CRISPR to cut out undesirable foreign genes. A few years ago it was found that CRISPR-Cas9 could be engineered to edit the entire genomes of a panoply of organisms from bacteria all the way to mammals and humans, thus potentially curing many genetic diseases. It has been heralded as the technology that could cure anything from liver diseases to muscular dystrophy to HIV. The implications of this technology are so huge that Science magazine has recently dedicated a special edition to include all recent papers, commentaries and news articles about CRISPR.

    But who discovered it and who has the patent rights to it? In April 2014, a broad U.S. patent was awarded to Feng Zhang, a scientist at the MIT-Harvard Broad Institute who claims to have discovered the effectiveness of CRISPR-Cas9 on gene editing in human cells. Zhang filed his patent with a priority date of Dec 2012. Just a few months later, a Breakthrough Prize was awarded to Jennifer Doudna and Emmanuelle Charpentier from UC Berkeley and Vienna, Austria, for their contribution to the discovery of CRISPR. Doudner and Charpentier filed a patent with a priority date of May 25, 2012, which includes 155 claims, encompassing numerous applications of the system for a variety of cell types.

    All parties have founded startup biotech companies in the race to develop CRISPR as a viable clinical drug. Zhang co-founded Editas Medicine with Doudner before Doudner dropped out and went on to found Caribou Biosciences and Intellia Therapeutics. Charpentier is the founder of CRISPR Therapeutics but has now sold the rights for that company.

    Several challenges have arisen in lieu of these rival patent claims. Firstly, Doudner and Charpentier argue that they filed the patent documents for CRISPR before Zhang because they had an earlier priority date but Zhang was awarded the patent first. Zhang was awarded the broad patent because he had a laboratory notebook demonstrating his group was doing CRISPR genome editing in human cells before anyone else and also because he paid for an expedited patent review. Lawsuits are likely to be complicated and as Charpentier said, “It all sounds very confusing for an outsider, and it’s also quite confusing as an insider.”

    Furthermore, according to MIT technology review, “This isn’t the end of the patent fight. Although (Zhang) moved very swiftly, lawyers for Doudna and Charpentier are expected to mount an interference proceeding in the U.S.—that is, a winner-takes-all legal process in which one inventor can take over another’s patent.”

    Secondly, over 100 patents have already been filed by many scientists, including Zhang and Doudner, which make use of the CRISPR-Cas9 technology. This could land many scientists with patent infringements if CRISPR-Cas9 were ever licensed.

    Thirdly, the patent for CRISPR-Cas9 itself may be contentious since it uses DNA technology which has already existed in bacteria for millennia and can seem “obvious” for many scientists who can now easily use it in their laboratories. In a sense CRISPR was in fact “invented” by nature and not by any individual, so claiming a patent over the mechanism would be an act of god. Answering such an issue can be a headache not only for the legal field but also for bioethics philosophy.

    Some solutions to these challenges may lie in history. For example, when small interfering RNAs (siRNA) and when polymerase chain reaction (PCR) were first discovered similar debates arose in the science community about whether people could use the technology without a licence. With the discovery of recombinant DNA, Stanford University was assigned the Cohen-Boyer patent which allowed Stanford to non-exclusively hold the patent, enabling non-profit research institutes to use the technology without a licence. Stanford also developed a graduated royalty system with small companies to ensure some share of profits if companies used their technology effectively. For the discovery of siRNA, MIT was awarded the “Tuschl” patent, which also granted nonexclusive licences to companies selling the technology and allowed academic scientists to work on the molecules with no licence. Similarly, with the invention of the PCR, patents were adapted through a strategy known as “rational forbearance” to prevent researchers from being sued for patent infringement everytime they used the technology and to allow adaptive licences to be held by business partnerships.

    Perhaps ultimately the patent disputes for CRISPR-Cas9 will be sorted out by following one of the historical models of adapted patents for biomedical discoveries. However, since large-scale clinical trials using this technology are still a long way off it is hoped that this current dispute can be sorted out soon so that the safety of the CRISPR technology can be established.

    Reference:

    Shwerkow JS, Law, history and lessons in the CRISPR patent conflict, Nature.  Vol 33 (3): 256-257, 2015.

    Regalado A, Who Owns the Biggest Biotech Discovery of the Century? MIT Technology Review, Dec 4 2014.