24 April 2019

CRISPR/Cas found the hosts

The decisive patent for the CRISPR/Cas system has been issued

Ivan Shunin, "The Attic"

A group of lawyers representing the interests of the Universities of California and Vienna, as well as Emmanuel Charpentier, have achieved recognition of the intellectual rights of their clients to the CRISPR/Cas genome editing system and technologies derived from it. The patent issued yesterday by the US Patent and Trademark Office (USPTO) establishes in the intellectual property of the California-Vienna Coalition methods and systems for changing DNA molecules both in living cells and in vitro using the CRISPR/Cas system in conjunction with one or more RNA guides. Such a formulation closes a very wide range of manipulations with the genome. This makes it possible, at least tentatively, to call Charpentier and Dudna the "legal mothers" of a biotechnological tool that has revolutionized modern biology and medicine.

The possibility of using the CRISPR/Cas system for targeted genome editing was first demonstrated in a 2012 paper by Jennifer Doudna and Emmanuel Charpentier. They showed that it is possible to synthesize a chimeric RNA guide that "recognizes" the gene needed by scientists and "leads" the Cas9 protein to it, which can cut a double strand of DNA.

The group of Dudna and Charpentier, having described in detail the mechanism of the system in bacteria and archaea, clearly showed that Cac proteins can be used to target the "shutdown" of almost any gene if equipped with an artificial RNA guide. In a demonstration experiment, they cut out the green fluorescent protein (GFP) gene from several plasmids in vitro. The article ended with the statement that the RNA-programmable Cas9 system could be used as an alternative to the then existing genome editors: TALENs and zinc fingers.

Six months later, Feng Zhang's group from the Broad Institute, who also studied the possibilities of Cas9, successfully applied the chimeric RNA guide method described by Dudna and Charpentier to edit eukaryotic cells: mice and humans.

At first, Charpentier and Dudna suggested that Zhang and George Church (who had also been actively involved in CRISPR systems all these years) create one company and thus collectively own the rights to it, but this project quickly failed. As a result, the "progenitors" of CRISPR-biotech created separate companies: some of them began to develop the medical application of the system, the other – to create CRISPR products for agriculture, animal husbandry and the chemical industry.

All this time, a legal war continued between the three closely related groups. The first group is the University of California (where Dudna works), the second is the Broad Institute (affiliated simultaneously with MIT and Harvard), the third concentrated around Charpentier. Many scientists turned out to be "played" for several groups at once: for example, Dudna is related to both the Broad Institute's Editas Medicine company and Caribou Biosciences, whose CRISPR license is "Californian".

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This is, for example, the scheme of transferring rights and licenses from original researchers to institutions in the case of several related commercial structures (ERS Genomics).

In 2018, the first round in the fight for a "fundamental" patent – for the technology of CRISPR intervention in eukaryotic cells - was left to Broad. This document blocked the claims of Dudna, Charpentier and their representatives to obtain a patent, which they were granted today. Now the lawyers defending the interests of the "California team" have achieved their goal. The fact that the USPTO is going to recognize the legality of the original patent of the California-Vienna coalition became known in February. Today the matter is brought to an end.

A dispute over a patent is not only a dispute for a lot of money. The echo of the revolution produced by the CRISPR/Cas system can be heard far beyond the laboratories. For at least five years, the whole world has been waiting for its creators to receive the Nobel Prize. But first we must finally figure out who is the right person to consider its creator. In the heat of the battle for billions and world fame, it is not so easy to make this decision, so the Nobel Committee apparently decided to wait for the end of the legal battle. Meanwhile, it flared up not only in the USA, but also spread to Europe, where patent offices not without pleasure noted the merits of other scientists who participated in the study of CRISPR-Cas9. In the patent issued today, in addition to Charpentier, Jennifer Dudna, Martin Jinek and Krzysztof Chylinski are also listed in the "inventors" column, also listed among the authors of the 2012 article

Now, after the American patent was granted to a trio consisting of the Universities of California and Vienna and Emmanuel Charpentier, the situation, on the one hand, has become clearer – but it still remains ambiguous. The grant of this patent does not take away existing patents from the Broad Institute, including the already mentioned patent for eukaryotic genome editing technology based on the CRISPR/Cas system and a number of patents for molecular diagnostics tools on the same "engine". What this means for the biotech business, which is not even up to its elbows in Crispr, but up to its ears, remains unclear. In general, right now there are 1796 patents mentioning the term CRISPR in the USPTO database. Whether they should now "bow down" to the broader California-Vienna patent, further practice will probably show.

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