IP Review Summer 2018

4 In the following years, the number of gene therapy trials grew rapidly. However, that all changed in October 1999 when an 18-year-old volunteer died from multiple organ failure after being administered a gene therapy to treat a genetic disease of his liver. His body experienced a severe immune reaction to the virus being used to carry the replacement gene into his body (referred to as a viral vector) which brought about the multiple organ failure. This tragedy dampened the enthusiasm around gene therapy and led to much stricter controls for researchers wishing to carry out human trials. In 2003, a further significant set-back occurred when a French patient, being treated for an immune disorder, developed a leukaemia-like condition as a direct result of the gene therapy treatment. The viral vector used in the therapy caused an unexpected mutation in an otherwise healthy gene which triggered the onset of the leukaemia in the patient. In addition to these unfortunate developments, there were problems getting different gene therapies to work effectively. For example, whilst researchers showed it was possible to deliver replacement genes to patients using gene therapy, it was very difficult to get the gene to function at a sufficiently high level so as to have a therapeutic effect on the disease. All these factors resulted in much of the research in this area being halted, especially by the big pharmaceutical companies. This left mostly academic researchers to progress the field during the 2000s. This is illustrated in Figure 1 below which shows the number of clinical trials approved year by year for gene therapies. As can be seen, the number of trials being approved peaked in 1999, after which there was a decline until 2003. In 2003, the first commercial gene therapy product Gendicide received a marketing authorisation in China for the treatment of cancers caused by a mutation in the p53 gene which suppresses tumour formation. This authorisation may have reinvigorated research into gene therapies as the number of clinical trials being approved again started to rise. However, with no further commercial successes, it was not long before the trials declined in number, bottoming out in 2011 to their lowest level since 1998. These trends are also supported by the number of gene therapy related patent applications being filed. As shown in Figure 2, the number increased rapidly between 1990 and 2000, after which there was a sharp decrease until 2003. In 2004, possibly following the authorisation of Gendicide, there was a rise in the number of patent applications filed. However, after this, the numbers again declined such that between 2006 and 2014 the number was around or just below 400 per year, less than half that seen during the peak in 2000. This shows that far less innovation was occurring in the ...The reinvention of human gene therapy IP review summer 2018 Gene Therapy Clinical Trials Approved Worldwide Figure 1