Revolutionising Genome Editing With CRISPR/Cas9: Patent Battles And Human Embryos

A new genome editing technology - the CRISPR/Cas9 system - promises to revolutionize the way we modify genetic material in living cells, including how we treat disease. The battle over who owns and controls the technology in this exciting new area is fierce, with numerous patents being filed in multiple jurisdictions. Concerns have, however, been raised over the use of the CRISPR genome editing technology following news in April this year that a team led by Dr Huang Jienjin in Guangzhou, China, had used the technique on human embryos. This article considers the patent landscape for CRISPR, focusing in particular on the two original applications that cover this technology and who may stake a claim over its ownership. It then explores what may be protectable as a patent in Europe in the context of genome editing of human embryos and what regulations are in place to control what might be done, not only by way of research, but also in the clinic, with a focus on the position in the UK.

Background to the CRISPR system

The CRISPR/Cas9 technology, commonly referred to as simply CRISPR - which stands for clustered, regularly interspaced, short, palindromic repeats - was unearthed from the immune system of bacteria, which use it to identify and fight off invading viral infections. Researchers discovered DNA sequences associated with the bacteria's immune response, termed CRISPR, but until recently, were unable to establish their exact function. A hypothesis for the function of the CRISPR system was formulated once researchers noticed that CRISPR sequences are interspaced with DNA sequences that originate from invading viruses. The CRISPR system was therefore thought to be bacteria's way of integrating short sections of viral DNA into the bacterial genome and protecting the cell from later infections by the same virus.

This underlying technology has now been utilized as a 'programmable' tool to cleave any double-stranded DNA sequence. Whilst studies through loss of function are useful and indeed are the basis for many genetic studies, the accuracy of cleavage using the CRISPR system makes it easier to introduce selected DNA sequences or genes into a target genome using 'donor' DNA. Together with the vast amounts of information researchers have gleaned from mapping different genomes, this tool provides an exciting prospect for editing specific sites in a cell's genome.

The potential use of CRISPR technology is far reaching and has already spread across many sectors within the biotech sphere. In basic biology, the system can be used to study the behavior of cells, engineer model organisms and culture specific cell lines. Biomedical applications could hopefully result in a rise in novel therapies for human disease but it is the developments in human cells which are perhaps the most controversial: the ability to make highly targeted changes in the genome of any living cell, including human stem cells and human embryos.

The CRISPR patent landscape

The relative speed, precision and ease of use of the CRISPR system means that the technology is already being utilized in academic and commercial laboratories across the world.

There are two major players in the battle to secure rights to the CRISPR system. The first group is headed by Jennifer Douda, a Professor of Chemistry and Molecular and Cell Biology at the University of California, Berkeley, USA, who, in collaboration with Dr Emmanuelle Charpentier's group, published in August 2012 what is widely regarded as the first characterization of the function of Cas9 within the CRISPR system for introducing site-specific double-stranded breaks in target DNA [1]. Many papers have followed since then describing several applications of the technology, including from Feng Zhang's group at the Broad Institute of Harvard and MIT, USA [2]. Dr Zhang's group reported using several guide sequences to simultaneously edit a genome in eukaryotic cells, promoting the system's easy programmability and wide applicability.

While Doudna's and Charpentier's groups may have published first and have received a number of awards for their work in this field, it is Zhang who has been awarded the first patent on the basic CRISPR technology - US Patent No. 8,697,359, 'CRISPR-Cas systems and methods for altering expression of gene products' (the "Zhang patent") which was granted on 15 April 2015 and is owned by the Broad Institute. Nonetheless, the fight over the rights to control the technology is far from settled.

The waters quickly become muddied if we consider these patent filings in more detail. Despite the Broad Institute being granted the first US patent in relation to the general application of CRISPR, it is Doudna and Charpentier, amongst other inventors, who filed US patent application US 13/842,859 first (the "Doudna/Charpentier patent application"), with the University Of Vienna and The Regents Of The University Of California as the original owners.

The Zhang patent was filed on 15 October 2013 but it claims priority from four US provisional patent applications, the earliest of which was filed on 12 December 2012. The Doudna/Charpentier patent application was filed on 15 March 2013 and this application also claims priority from four US provisional patent applications, the earliest of which was filed on 25 May 2012, over 6 months before the first priority provisional patent application for the Zhang patent.

So why was Zhang's patent application granted first? Zhang's team opted for the accelerated examination procedure at the United States Patent and Trademark Office (USPTO), known as the Track One program [3], which...