The University of California yesterday filed its opening brief with the U.S. Court of Appeals for the Federal Circuit in Washington, D.C., in support of its appeal of the U.S. Patent Trial and Appeal Board’s (PTAB) decision in the CRISPR-Cas9 interference. UC’s appeal seeks to reverse the PTAB’s decision finding no interference-in-fact between issued patents and an application of the Broad Institute, the Massachusetts Institute of Technology and Harvard on CRISPR-Cas9 gene editing in plant and animal cells and a patent application filed earlier by UC for gene editing in all environments, both cellular and non-cellular.
UC is joined in the appeal by the University of Vienna and Emmanuelle Charpentier, who, together with UC Berkeley’s Jennifer Doudna, turned an obscure system used by bacteria to defend themselves against virus infections into an easy-to-use gene-editing tool that has revolutionized biomedical research and fueled human hopes for gene therapy to cure disease. Doudna is a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute investigator.
In its Feb. 15 decision, the PTAB credited Doudna, Charpentier and their team for discovering and first successfully demonstrating the necessary and sufficient components to employ CRISPR-Cas9 to edit DNA. The PTAB, however, determined that UC’s claims to using CRISPR-Cas9 in all environments — including bacterial cells, eukaryotic cells (such as plant and animal cells) and outside of a cell — did not render obvious Broad’s claims to using CRISPR-Cas9 in eukaryotic cells. As a result, the PTAB found that UC’s application does not prevent researchers at the Broad Institute, who claimed to be the first to successfully employ the UC group’s discovery in eukaryotic cells, from seeking patents for use of the CRISPR-Cas9 system in that specific cellular environment.
“The PTAB’s ruling flies in the face of core legal principles that govern the interference-in-fact inquiry, and defies common sense,” according to the UC brief. “If uncorrected, that ruling threatens to allow Broad to arrogate to itself much of UC’s transformational invention without Broad demonstrating anything close to the genuine innovation that would justify finding its claims to be separately patentable. This court should not let such a profoundly erroneous and unjust result stand.”
In the appeal, UC argues that the PTAB used incorrect standards in assessing whether CRISPR-Cas9 gene editing in eukaryotes was an obvious extension of its core invention and the landmark June 2012 Science publication by the Doudna/Charpentier team describing that invention.
Citing previous court decisions, including those by the U.S. Supreme Court, UC’s lawyers argue that the correct standard is whether, given the teaching of its patent claims, the Science paper, and the standard laboratory techniques that were known and available to those ordinarily skilled in the art, researchers would have had a “reasonable expectation of success” in achieving gene editing in eukaryotes.
Instead, the PTAB concluded that the existence and availability of conventional techniques for applying bacterial gene-editing systems in eukaryotic cells did not “guarantee” success of that next step. In so doing, the PTAB discounted evidence that six different labs had quickly achieved eukaryotic editing using the information provided in the 2012 Science paper, including the Doudna/Charpentier team itself in work conducted before the Broad Institute filed for its patent.
The appeal asks the court to reverse the PTAB’s decision that the UC application and Broad Institute patents do not interfere, or to send the interference back to the PTAB for reconsideration of the issue using the proper criteria that have been applied in other cases. If it is established that the parties’ patent application and patents do interfere, the PTAB would proceed to decide which party is entitled to patents for use of CRISPR-Cas9 gene editing in plant and animal cells, as well as other environments.
Throughout the patent dispute with the Broad Institute, UC’s primary goal has been to establish the fact that Doudna, Charpentier and their team were the true inventors of the CRISPR-Cas9 gene editing technology, which in a mere five years has transformed plant and animal breeding, treatment for hereditary disease and strategies for combatting infectious disease and cancer.
“Ultimately, we expect to establish definitively that the team led by Jennifer Doudna and Emmanuelle Charpentier was the first to engineer CRISPR-Cas9 for use in all cell types including eukaryotic cells,” said Edward Penhoet, a special adviser on CRISPR to the UC president and UC Berkeley chancellor. Penhoet, a pioneer in the biotech industry who co-founded Chiron Corp. and served as its CEO for 17 years, is the associate dean of biology at UC Berkeley and a professor emeritus of molecular and cell biology.
The scientific community has acknowledged the pioneering nature of UC’s invention through numerous awards for Doudna and Charpentier, including the U.S. Breakthrough Prize, Japan Prize, Gruber Prize in Genetics and Canada Gairdner International Award.
UC has encouraged broad use of the CRISPR-Cas9 technology through an exclusive license with Caribou Biosciences Inc. of Berkeley, which has sublicensed the technology to many companies worldwide, including a sublicense to Intellia Therapeutics, Inc., for human therapeutic applications. Additionally, Dr. Charpentier has licensed CRISPR Therapeutics and ERS Genomics. And, UC has reserved for itself, and for other nonprofit institutions, the right to practice the patent rights for educational and research purposes.
UC and its partners, the University of Vienna and Emmanuelle Charpentier, have also received patents on the CRISPR-Cas9 technology outside the U.S., in countries such as the United Kingdom, China, Australia and from the European Patent Office.