On Wednesday, October 25th, the Cambridge, MA-based medical research center The Broad Institute filed a brief with the Court of Appeals for the Federal Circuit in response to an appeal filed by the University of California stemming from patent interference proceedings playing out at the Patent Trial and Appeal Board (PTAB). The Broad Institute’s filing is the latest salvo in a patent battle which has played out between developers of a gene editing technology which could prove to be very important to the future of fighting disease in humans.
The Broad Institute’s brief asks the Federal Circuit to determine whether substantial evidence supports the PTAB’s finding that a person of ordinary skill in the art (POSA) in 2012 would not have had a reasonable expectation of success in engineering prokaryotic-based CRISPR-Cas9 systems to function in eukaryotic cells, such as human mammalian cells. CRISPR-Cas9 is a gene editing technique which involves the analysis of clustered regularly interspaced short palindromic repeats (CRISPR) arrays in DNA sequences created by viruses; these DNA sequences are then targeted and disabled by an enzyme known as CRISPR-associated protein 9 (Cas-9).
The University of California initiated the patent interference proceedings, which determine whether a filed patent application has priority over another patent application with interfering claims, in January 2013 to challenge a Broad Institute patent covering a CRISPR-Cas9 implementation. The PTAB decided the interference proceedings in January 2016, determining that research published by University of California professors in 2012 was not proof that a POSA would have a reasonable likelihood of success in engineering CRISPR systems to work in eukaryotic cells; the 2012 paper disclosed experiments of CRISPR in an in vitro test-tube environment.
The Broad Institute argues that substantial evidence exists which supports the PTAB’s findings in the patent interference proceedings. It identified five different categories of evidence and alleges that the University of California has failed to demonstrate that the categories shouldn’t have been given weight. After the publication of the 2012 CRISPR-Cas9 research paper, statements made by UC professors who contributed to the paper expressed uncertainty that the in vitro CRISPR-Cas9 results could be reproduced in eukaryotic cells. UC had tried to argue that the work of research groups after the 2012 paper was evidence of a reasonable expectation of success but while PTAB found that there was motivation to research the subject, there was no proof of a reasonable expectation of success of CRISPR-Cas9 in a eukaryotic environment. The Broad Institute also argued that the substantial difference between eukaryotic and prokaryotic, or cells without a nucleus, environments, as well as failures encountered in prior art attempts to adapt prokaryotic systems to eukaryotes, further support the PTAB’s finding of no interference of UC’s technology with Broad’s patent.
The University of California’s appeal argued that the PTAB had committed three legal errors in performing its interference-in-fact analysis. First, UC argued that the PTAB had applied an incorrect legal standard by requiring certainty of success prior to experimentation. Although the PTAB had acknowledged that there need not be absolute predictability for a finding of obviousness, statements made by an expert witness for UC led the panel to find that there was belief that the CRISPR-Cas9 system contemplated by UC might fail in eukaryotes, thus failing to provide a reasonable expectation of success. Next, UC argued that the PTAB improperly required as a matter of law that UC’s prior art teach specific instructions for the use of the system in eukaryotic cells. The Broad Institute’s brief notes that the PTAB never required that as a matter of law and that UC was attempting to recast a fact finding as a matter of law. Also, UC had argued that the PTAB erred in not considering an unpublished patent application filed by a third party. UC had submitted the unpublished patent application as evidence because it possibly interfered with its own patent rights as well as Broad Institute’s, but the PTAB found that the activities of an unrelated third party didn’t qualify UC to participate in patent interference proceedings against Broad. The unpublished patent application was also filed a little more than two weeks too late to qualify as prior art under 35 U.S.C. § 102(e).
The Broad Institute’s brief also responds to allegations made by the University of California on appeal that the PTAB failed to consider evidence and arguments in two areas. Broad argues that the PTAB did not err in failing to consider an argument on evidence of simultaneous invention and secondary considerations because UC failed to make such an argument to PTAB on the evidence presented. UC also argued to the Federal Circuit that the PTAB failed to consider prior art dated after December 12th, 2012, but Broad again alleges that UC made no such argument to the PTAB based on prior art after that date.