Federal Circuit Affirms PTAB Finding That UC's and Broad's Foundational CRISPR Technologies Are "Patentably Distinct"

Sunday, September 16, 2018

Source: BioPharma Law

On September 10, 2018, the U.S. Court of Appeals for the Federal Circuit (CAFC), in University of California v. Broad Institute, Inc., affirmed the Patent Trial and Appeal Board’s (PTAB) earlier determination that there was no interference-in-fact between the University of California’s (UC) patents and those owned by the Broad Institute, MIT, and Harvard (collectively “Broad”), directed to CRISPR-Cas9 technology.  In so doing, the CAFC upheld the PTAB’s underlying finding that, “given the differences between eukaryotic and prokaryotic systems, a person of ordinary skill in the art would not have had a reasonable expectation of success in applying the CRISPR-Cas9 system in eukaryotes.”
 
In general, CRISPR-Cas9 is a targeted DNA-cutting system that occurs naturally in prokaryotes, and which has been used to edit the DNA of eukaryotic cells in recent years. In August 2012, UC published an article demonstrating that the CRISPR-Cas9 system could be used in vitro, i.e. in a non-cellular experimental environment. Within a few months of UC’s publication, several groups, including Broad, independently applied CRISPR-Cas9 in eukaryotic cells. Broad’s researchers described the use of CRISPR-Cas9 in a human cell line in a published article in February 2013. Both UC and Broad sought patent protection for their respective CRISPR-Cas9 technologies. Whereas UC filed its patent application with claims directed to methods of cleaving DNA using CRISPR-Cas9 without reference to a specific cell type or environment, Broad filed its patent applications with claims limited to the use of CRISPR-Cas9 in eukaryotic cells.
 
To determine whether the CRISPR-Cas9 claims of UC and Broad were “patentably indistinct,” and which party was the first to invent the claimed technology, the PTAB instituted an interference proceeding under pre-AIA 35 U.S.C. § 102(g) (since the applications were filed before enactment of the AIA). When determining whether claims are “patentably distinct,” the PTAB asks whether the subject matter of a claim of one party, if prior art, would have rendered obvious (or anticipated) the subject matter of a claim of the opposing party.
 
In examining the claims of UC and Broad the PTAB determined that no interference-in-fact existed because UC’s claim would not have rendered obvious or anticipated Broad’s claims. Broad provided extensive expert testimony about the differences between prokaryotic and eukaryotic systems and how those differences rendered the application of the CRISPR-Cas9 system in eukaryotic cells unpredictable. Moreover, Broad presented statements from UC inventors acknowledging doubts and frustrations about engineering CRISPR-Cas9 systems to function in eukaryotic cells and noting the significance of Broad’s success. Finally, the PTAB found that the developments of other gene editing systems were not particularly informative in assessing the reasonable expectation of success of CRISPR-Cas9 in plant and animal cells. In light of all this evidence, the CAFC concluded “that the Board’s fact finding as to a lack of reasonable expectation of success is supported by substantial evidence.”
 
In upholding the PTAB’s ruling, the CAFC rejected UC’s arguments that simultaneous inventions may serve as evidence of obviousness: “[t]he fact that six research groups succeeded in applying [CRISPR-Cas] in eukaryotic cells within a short period of time after [UC’s disclosure] is certainly strong evidence that there was a motivation to combine the prior art in this manner.” While the PTAB recognized UC’s evidence of simultaneous invention in this context, it concluded such evidence pointed to a motivation to combine the prior art references but not ‘necessarily’ an expectation of success. The CAFC thus affirmed the PTAB’s finding, but noted that the decision is limited to “the scope of two sets of applied-for claims,” and “is not a ruling on the validity of either set of claims.”
 
The decision has important implications for the CRISPR-Cas9 patent landscape as it upholds both UC’s and Broad’s patent claims to this foundational and potentially game-changing technology. Third parties that are active in the field may thus have to seek a license from both groups if they want to commercialize this technology. Moreover, since the intellectual property landscape of the CRISPR-Cas9 is so intertwined, even UC and Broad may have to cross-license the technology between themselves to continue research. While the CAFC’s affirmation of the PTAB’s earlier decision seems to provide a modicum of clarity to this complex landscape for those waiting on the sidelines to capitalize on the discovery, given the financial stakes involved and the flexibility of this technology, it is likely that further disputes over the foundational CRISPR-Cas9 innovation will likely continue for some time into the foreseeable future.
 
We will continue to monitor trends and disputes involving CRISPR-Cas systems and provide updates.

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