On September 10, 2018, the Federal Circuit affirmed a decision by the Patent Trial and Appeal Board (PTAB) determining that there was no interference in fact between the University of California's ("UC") U.S. Patent Application No. 13/842,859 and multiple patents and applications owned by the Broad Institute, MIT and Harvard College (collectively "Broad Institute") that claim technologies related to the CRISPR-Cas9 gene-editing technology.

The CRISPR-Cas9 system is used to cut targeted DNA sequences, thereby allowing scientists to add, modify, or delete pieces of genetic material within an organism. Adapted from bacteria, the CRISPR-Cas9 system has been used to study mechanisms of disease and is currently being explored for possible applications in the treatment and prevention of various diseases in humans. It consists of three components, a crRNA molecule that targets a particular DNA sequence; a tracrRNA molecule that pairs with the crRNA molecule to form a functional guide RNA; and the Cas9 protein that interacts with the crRNA and tracrRNA and cuts DNA at the target location.

In 2012, researchers at the University of California, in collaboration with the University of Vienna and Emmanuelle Charpentier, demonstrated that the elements of the CRISPR-Cas9 system could be used in vitro. The following year, Broad Institute researchers published their results, showing the use of CRISPR-Cas9 in a human cell line. Both parties sought patent protection for their discoveries, and an interference was declared by the PTO. Notably, UC's patent application claimed a method of cleaving nucleic acid using the CRISPR-Cas9 system, but did not specify the cell type or environment in which the system functioned. In contrast, Broad Institute sought claims that limited the use of the CRISPR-Cas9 system to eukaryotic cells. During the interference, Broad Institute argued that its claims were patentably distinct from UC's claims because one skilled in the art would not have possessed a reasonable expectation that the CRISPR-Cas9 system would work in eukaryotic cells based on UC's disclosures, including the 2012 article, which did not report any experimental results using eukaryotic cells.

The PTAB determines whether an interference exists by applying a two-way test in which it asks whether the claims of one party, if prior art, would have anticipated or rendered obvious the claims of the other or vice versa. Here, the PTAB agreed with Broad Institute and held that UC's claims did not render Broad Institute's claims obvious. More specifically, the PTAB held that, given the mixture of evidence in the record, including evidence of the difficulties associated with applying prokaryotic systems to eukaryotic cells, one skilled in the art would not have reasonably expected the CRISPR-Cas9 system to work in eukaryotes.

On appeal, UC argued that the PTAB adopted too rigid a test for obviousness when it looked for specific instructions in the prior art and erred in its treatment of evidence relating to simultaneous invention. The Federal Circuit disagreed with UC on both points. The Federal Circuit found the PTAB's factual findings supported by substantial evidence, going so far as to say "[t]his case turns in its entirety on the substantial evidence standard." 

Regarding UC's first argument, the Federal Circuit noted the record contained evidence from witnesses for both parties that indicated the function of CRISPR-Cas9 in eukaryotes was unpredictable and could not be determined absent attempts to apply the system in eukaryotes. Evidence also demonstrated that similar prokaryotic systems could not be implemented in eukaryotes without tailoring the particular conditions of their use. In other words, a skilled artisan would not have reasonably expected the CRISPR-Cas9 system to work in eukaryotes based on the in vitro research performed by the UC scientists or based on related systems that had been disclosed in the art. And, although the prior art described mechanisms, i.e., provided general instructions, for implementing the CRISPR-Cas9 system in eukaryotes, the lack of specific instructions here combined with the prior failures supported the PTAB's finding of no interference in fact.

The Federal Circuit similarly found no error in the PTAB's evaluation of evidence relating to simultaneous invention. The court held the PTAB correctly recognized that simultaneous invention may be evidence of the level of skill in the art and objective evidence that persons of ordinary skill in the art recognized a problem and a solution to the problem. However, evidence of simultaneous invention, alone, cannot support an obviousness determination. More specifically, while simultaneous invention may show there is a motivation to combine prior art, it does not necessarily demonstrate an expectation of success. In this case, the balance of evidence, including the explicit statements of different inventors and the prior failures in the art, supported the PTAB's determination that UC's patent application did not render Broad Institute's claims obvious.

Practice Tip:  Although this case is not particularly notable for its application of the law of obviousness, it provides a good example of a case in which the outcome on appeal was driven "in its entirety" by the standard of review. The Federal Circuit reviews the PTAB's factual findings for substantial evidence. Thus, when appealing from the PTAB, it may be more important to identify gaps or discrepancies in the PTAB's findings or identify a pure error of law than it is to assign errors to the PTAB's application of facts to law.

Regents of the University of California v. Broad Institute, Inc., 2017-1907 (Fed. Cir. Sept. 10, 2018)

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