Gene therapy is the latest in the line of tools in the hands of researcher to treat disease. Gene therapy involves modifying genes by disruption, correction or replacement. Gene therapy has witnessed both early successes and tragic failures in a clinical setting. However, the discovery and development of the CRISPR-Cas9 system has significantly improved the impetus and recover from its previously known shortcomings and adopt a viable therapeutic strategy. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats (hereinafter referred as CRISPR) adapting the immune system, is changing all sectors of life science and paving the way for personalized and customized medicine. The tool is also known as “molecular scissors,” and allow the researcher to cut DNA at a specific location and modify an existing gene segment.

CRISPR was discovered by Japanese scientists in the late 1980s, but its potential as a programmable gene-editing tool was only recognized in the last decade. This technology has the potential to edit genes in organisms in order to treat genetic diseases and defects. Researchers have used CRISPR-Cas9 to genetically modify mosquitoes so that they do not carry the malaria parasite, and to eliminate HIV in infected mice. CRISPR-Cas9 editing has also restored the efficacy of front-line chemotherapies for lung cancer.

CRISPR PATENT BATTLE

In May 2012, a team at the University of California, Berkeley (hereinafter referred to as ‘UC Berkeley’) led by Professor Doudna filed its first patent application for CRISPR-Cas9 in the U.S. patent office. A few months later, in December 2012, a research group at the Broad Institute affiliated with MIT and Harvard University (hereinafter referred to as the ‘Broad Institute’) led by Professor Zhang also filed its first patent application for CRISPR-Cas9. Upon discovering similar applications for the grant of patents, in 2016 UC Berkeley and the Broad Institute both launched priority proceedings at the US Patent and Trademark Office so that they would be granted the exclusive rights to CRISPR-Cas9 technology. The issue for determination was whether UC Berkeley’s patent application claiming the use of CRISPR-Cas9 in any living cell made the Broad Institute’s narrowly worded invention claiming the use of CRISPR-Cas9 in eukaryotic cells (i.e., animal and plant cells), obvious and thus invalid.

In an initial appeal on February 15, 2017, the U.S. Patent Trial and Appeal Board (PTAB) stated that there was no conflict between Broad Institute’s application and UC Berkeley’s application. This is because the respective researchers have qualified their respective inventions in different ways. The UC Berkeley researchers had described their invention in general terms, applying it to all kinds of DNA. In contrast, the Broad Institute team described its invention as a method for correcting DNA sequences in animal and plant cells. According to the PTAB, there was no “interference-in-fact” between the parties’ patent claims. Thereafter, UC Berkeley filed an appeal against the decision of the U.S. patent board, however that appeal was dismissed by a U.S. Court of Appeals. Finally, in 2018, UC Berkeley filed new U.S. patent applications including claims intended to create a new patent interference, specifically new claims directed to the use of CRISPR-Cas9 in eukaryotic cells.

On September 10, 2020, the U.S. Patent Trial and Appeal Board rejected UC Berkeley’s arguments and confirmed that Broad Institute had priority for the use of the CRISPR-Cas9 technique in animal and plant cells where arguably the greatest potential benefits of the technique lie. UC Berkeley, on the other hand, had priority in applying the technique to other cells, such as bacterial cells.

On October 7, 2020, the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to Professors Emmanuelle Charpentier and Jennifer Doudna for their immense contribution to the CRISPR‑Cas9 gene-editing technique.

At the European Patent Office, (hereinafter referred to as EPO), where a technical error resulted in Broad Institute’s patent applications having a later date than the patent applications of UC Berkeley. As a result, in Europe, the UC Berkeley group holds the rights to all of the first-generation patents with respect to CRISPR-Cas9.

Till the present date, no entity has been granted exclusive licenses for all CRISPR-Cas9 IP rights, and are held by either one research group or the other. While this is likely to have an impact on basic research using these techniques, any therapeutic or commercial opportunities will have to wait until the legal controversies are resolved.

CRISPR AND COVID-19

Lately, CRISPR has also proved useful in detection of pathological states  particularly in COVID-19. COVID-19 has been around for over two years now, however, its detection is still challenging. Recently, the stealth Omicron variant was reported. This variant is not identified in the regular RT-PCR test and therefore, false negatives have increased significantly. Complex chemical combinations and temperature cycling are used in the typical approach of applying the polymerase chain reaction (PCR) methodology. Professors Feng Zhang and Jennifer Doudna, who were engaged in a dispute of grant of patent to either of them, joined forces to combat COVID-19 in an attempt to save humanity by using  CRISPR system to directly identify the genetic material of viruses and their mutants.

Apart from the patent landscape's difficulty, one possible application of CRISPR-based technology that is on everyone's mind in the current global health crisis is its role in testing for and diagnosing infectious diseases. The most direct contribution of CRISPR to date may be in the fight against the global COVID-19 epidemic. CRISPR's potential applications and commercial value is potentially extremely high and it would be beneficial that all parties aligned together in the service of humanity.