History of CRISPR-Cas9 Gene Editing

CRISPR-Cas9 evolved as part of a bacterial immune system that protects against viral infection. Jennifer Doudna, Emmanuelle Charpentier and their colleagues made the key discoveries that enabled CRISPR-Cas9 to be used for genome editing in any cellular environment.

In June 2012, biochemist Jennifer Doudna of the University of California, Berkeley, microbiologist Emmanuelle Charpentier then of Umeå University, Sweden, and their colleagues published a watershed article in Science describing a revolutionary genome editing technology called CRISPR-Cas9. The Doudna-Charpentier team had filed a patent application, owned by The Regents of the University of California, the University of Vienna, and Dr. Emmanuelle Charpentier (collectively, “CVC”), on their invention the previous month.

Researchers hailed the publication as a major breakthrough, as the technology suggested that any part of any genome could now be rewritten with relative ease compared to existing methods. Scientists immediately recognized that CRISPR-Cas9 genome editing could have real-world applications, from treating a wide range of diseases, including rare inherited conditions and common devastating diseases such as cancer or diabetes, to making advances in fields such as agriculture, industrial biotechnology, animal health, research tools, and drug discovery.


"Research groups rushed to use the method described in the article to edit DNA in a variety of cell types."

The Science article set off a burst of activity. Research groups rushed to use the method described in the article to edit DNA in a variety of cell types. Within seven months, six independent groups had published scientific papers and/or filed patent applications describing CRISPR-Cas9 genome editing in human and other mammalian cells. All of the papers cited the June 2012 Science publication by the Doudna-Charpentier team, and made use of methods described in the CVC patent application.

“Their paper immediately and dramatically transformed the field of molecular biology and genetics,” the Gruber Foundation stated in awarding Drs. Doudna and Charpentier its 2015 Genetics Prize.

Yet despite widespread recognition from the scientific community, Drs. Doudna and Charpentier found their status as innovators challenged on the legal front. In April 2014, a group based at the Broad Institute in Cambridge, Massachusetts, was awarded the first U.S. patent (owned by the Broad Institute, Inc., Massachusetts Institute of Technology, and the President and Fellows of Harvard College; collectively, the “Broad”) for editing eukaryotic cells (a category that includes all plants and animals, including humans) with CRISPR-Cas9.

The issuance of this U.S. patent came as a complete surprise since the patent granted before publication of the patent application. The Broad had filed its patent application more than six months after the CVC patent application was filed, and was the fourth group to file a patent application claiming the use of CRISPR-Cas9 genome editing in eukaryotic cells. But because the Broad expedited examination by the U.S. Patent and Trademark Office (USPTO), it was the first to present its story to the USPTO. According to the Broad, even though it had not faced any challenges in applying the Doudna-Charpentier team’s invention to eukaryotic cells and had not needed to invent any new techniques to do so, the use of CRISPR-Cas9 specifically in eukaryotic cells was a separate “invention” worthy of its own patent.

CVC requested that the USPTO conduct a patent interference proceeding to determine who was the first to invent the CRISPR-Cas9 genome editing technology. The interference proceeding was declared by the USPTO Patent Trial and Appeal Board (PTAB) on January 11, 2016 (Interference No. 106,048; the “’048 Interference”). However, the Broad asked the PTAB to terminate the interference, stating there was “no interference in fact” as the claims in the involved CVC patent application were different in scope compared to the claims of the involved Broad patents. The PTAB granted that request in early 2017 and discontinued the current interference without deciding who was the first to invent. Specifically, the PTAB found that the claim sets presented by the two parties were considered “patentably distinct” from each other because the CVC patent application’s claims were broader in scope and not restricted to the use of CRISPR-Cas9 in eukaryotic cells, whereas Broad’s claims were limited to use of CRISPR-Cas9 in eukaryotic cells.

CVC appealed the PTAB’s decision to terminate the interference to the U.S. Court of Appeals for the Federal Circuit (CAFC). On September 10, 2018, the CAFC affirmed the PTAB decision, resulting in the CVC patent application, which was previously considered allowable, being released from the interference and returned to the USPTO. This application has now been allowed and should grant as a patent in the near future. Irrespective of both the PTAB’s decision and the CAFC affirmance, CVC can obtain, and is aggressively pursuing, additional U.S. patents to CRISPR-Cas9 genome editing in all types of cells, including use in eukaryotic cells.


"Multiple countries, including the US and Europe, have granted broad patents to CVC for their CRISPR-Cas9 genome editing inventions, including the use in eukaryotic cells, affirming the team’s inventive contribution to this extraordinary technology."

Meanwhile, outside of the U.S., where patents are awarded on a first-to-file basis, multiple countries, including Europe, have granted broad patents to CVC for their CRISPR-Cas9 genome editing inventions, including the use in eukaryotic cells, affirming the team’s inventive contribution to this extraordinary technology. These jurisdictions rightly recognized the June 2012 Science paper, and the patent application that immediately preceded it, as the key catalysts that set off the current revolution in CRISPR-Cas9 genome editing.

The First Year of CRISPR-Cas9 Genome Editing

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Introduction to CRISPR/Cas9 Genome Editing

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