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 on their invention the previous month.
Researchers hailed the publication as a major breakthrough. Scientists could now rewrite virtually any part of any genome with relative ease compared to existing methods. Scientists immediately recognized that CRISPR-Cas9 gene editing could have real-world applications for treating a wide range of diseases, from rare inherited conditions to common devastating diseases such as cancer or diabetes, as well as making advances in other fields such as agriculture, industrial biotechnology, animal health, and drug discovery.
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 Doudna and Charpentier, and made use of methods described in the Doudna-Charpentier patent application.
“Their paper immediately and dramatically transformed the field of molecular biology and genetics,” the Gruber Foundation said in awarding Doudna and Charpentier its 2015 Genetics Prize.
Yet despite widespread recognition from their colleagues, Doudna and Charpentier have found their innovative status 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 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. The Broad had filed its patent application more than six months after the Doudna-Charpentier team, and had been 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 first to present its story to government officials. 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 an “invention” worthy of its own patent.
The Doudna-Charpentier legal team requested that the USPTO conduct an “interference” proceeding to determine who was first to invent the CRISPR-Cas9 genome editing technology, which the USPTO Patent Trial and Appeal Board (PTAB) initiated in early 2016. But the Broad asked the PTAB to terminate the interference without deciding who was first to invent. The PTAB granted that request in early 2017. In making its determination, the PTAB inappropriately ignored the evidence that at least five other groups had implemented CRISPR-Cas9 in eukaryotic cells within a few months of the Science publication, and that the Broad filed its patent application after not only the Doudna-Charpentier team, but also after two other unrelated groups.
An appeal of the PTAB decision to terminate the interference is now before the U.S. Court of Appeals for the Federal Circuit (CAFC). The Doudna-Charpentier team has outlined for the court the legal errors that the PTAB committed in its analysis and decision. The CAFC can either reverse the PTAB decision, in which case the interference will resume, or remand the case back to the PTAB to correct its legal analysis and look at the evidence it ignored when making the decision to terminate the interference. Alternatively, the CAFC can affirm the PTAB decision, in which case a different interference may be initiated to determine who invented CRISPR-Cas9 gene editing in eukaryotic cells. Regardless of the appeal outcome, the Doudna-Charpentier team may obtain U.S. patents to CRISPR-Cas9 genome editing in all types of cells, as these claims were previously deemed allowable by the USPTO.
Meanwhile, outside of the United States where patents are awarded on a first-to-file basis, multiple countries have granted broad patents to the Doudna-Charpentier team 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.