Too much of a good thing

In 2020, the Nobel Prize in Chemistry went to Emmanuelle Charpentier and Jennifer Doudna for the discovery of “genetic scissors” abbreviated CRISPR/Cas9. But this happy event is only the icing on the cake, under which real battles for the right of inventorship, ownership and control are hidden.

CRISPR-Cas9 is a breakthrough technology that allows parts of the genome to be edited by deleting, adding or changing regions of the DNA sequence.

The acronym CRISPR appeared in the late 1980s, when, during the study of archaebacteria that live in salt water, palindromic sequences in their genome were discovered. These sequences, about 30 nucleotides long, were repeated multiple times and separated from each other by unique regions of DNA of approximately the same length. At that time, no one understood what the function of these structures was, but they were titled CRISPR (Clustered Regularly Interspaced Palindromic Repeats). In 2002, along with CRISPR-arrays, structures similar to them were discovered in bacteria. A group of protein-encoding genes were called “in a very original manner” – CAS (CRISPR-Associated Genes).

Subsequent years of research showed that CRISPR fragments are found in the DNA of bacteriophages, i.e. viruses that infect and kill bacteria. It turns out that bacteria store DNA fragments of their worst enemies. It results in formulating the key assumption that CRISPR is the immune memory of bacteria, which stores information about the viruses that infect the bacteria. A bacterial cell that was infected with a bacteriophage and did not die cuts its genome into small fragments, embeds it in CRISPR arrays and passes this information on to its descendants, who become resistant to the bacteriophage. At this point Emmanuelle Charpentier and Jennifer Doudna came up with an idea to adapt this system to cut any DNA, which eventually was worth a Nobel Prize.

The DNA editing work done by Charpentier and Doudna is certainly seminal, but it was done in a test tube. Therefore, scientists faced a new ambitious task – to repeat the editing process in human cells. Feng Zhang of the Massachusetts Institute of Technology (MIT) has already solved this problem by optimizing DNA editing and making it compatible with living cells that have a nucleus.

Why has this technology become a breakthrough?

Potentially (we emphasize, potentially!) CRISPR-Cas9 could be used to cut out mutations of the human genome responsible for a whole host of diseases, such as sickle cell anemia, breast and ovarian cancer, or possibly HIV. Thus, one technology will become a tool of treating many diseases.

Naturally, when such a promising technology emerges, questions of inventorship, ownership and control are never far behind.

Today, it can be considered that three scientists – Emmanuelle Charpentier, Jennifer Doudna and Feng Zhang – were pioneers of CRISPR-Cas9. Each of them and the institutions they work for have created subsidiaries to commercialize the CRISPR-Cas9 system. Thus, the companies Caribou Biosciences and Intellia Therapeutics are associated with the team of Jennifer Doudna, CRISPR Therapeutics, ERS Genomics and Casebia Therapeutics were started by Emmanuelle Charpentier, and Editas Medicine belongs to Feng Zhang. Soon, competitive independent companies, such as Toolgen Inc (Korea), MilliporeSigma (formerly known as Sigma-Aldrich, now part of the Merck KGaA group), Vilnius University (Lithuania), Cellectis (France), and DowDuPont, stepped up.

Thus, one of the key players in this story is Feng Zhang and his employer – MTI, which until recently owned the European patent EP 2771468 B1 “Engineering of systems, methods and optimized guide compositions for sequence manipulation”. The patent was issued on February 11, 2015, and on March 15, 2021, it was terminated for lack of novelty.

In general, the patent EP 2771468 B1 was obtained through the international application with the number PCT/US2013/074819, and 12 US patent applications were listed as priority applications.

At the stage of submitting the international application MTI made an unfortunate slip.

The inventors in the US priority application and the granted European patent are different. Specifically, the inventors in EP 2771468 B1 are Feng Zhang, Le Cong, Patrick Hsu and Fei Ran. However, the group of scientists who worked on the CRISPR-Cas9 technology is much larger. In addition to the already mentioned authors, Naomi Habib, Luciano Marraffini, David Cox, Shuaillang Lin and Randall Platt and others were authors in the priority applications. Naturally, one of the researchers – Marraffini Luciano – and the Rockefeller Institute, where he worked, were very upset by this turn of events and decided to challenge the validity of the patent.

Critically, there were 4 US applications listed as priority applications with Luciano Marraffini as the inventor, but no legal transfer of rights from Marraffini to any of the authors of patent EP 2771468 B1 was executed. Thus, the European Patent Office debarred 4 applications the right to be priority applications and they became known prior art. In view of that, patent EP 2771468 B1 has lost novelty, which is one of the criteria for patentability.

No novelty – no patent.

No patent – free way for competitors.

The situation that has arisen with the MTI patent is very revealing – it is always necessary to legally formalize mutual relations. Work with professionals. Our scientific and patent department will not only secure your rights, but also plan and protect your ideas in any country of the world. We bring new products to the market and conduct direct prosecution in the countries of the European Union, Bulgaria, Ukraine, Azerbaijan, Armenia, Uzbekistan, Georgia, Kazakhstan, you can find out more on our website.

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