PTAB Ruling on CRISPR: No Interference

On Wednesday, February 15, 2017, the Patent Trial and Appeal Board (“PTAB”) ruled in favor of the Broad Institute of MIT and Harvard in a closely watched patent fight with UC Berkeley over the breakthrough CRISPR genome-editing technology.  The PTAB concluded that the Broad Institute’s later-filed patents for using CRISPR in eukaryotic cells did not interfere with Berkeley’s earlier-filed patent application that disclosed the use of CRISPR technology in vitro and claimed the use of CRISPR technology in general.

CRISPR (an acronym for “clustered regularly interspaced short palindromic repeats”) has been hailed as the “biggest biotech discovery of the century.” The interference proceeding between the Broad Institute and UC Berkeley has in turn been one of the most important patent office proceedings of the century.  A team of scientists led by Jennifer Doudna at UC Berkeley was the first to apply for a provisional patent application on a non-naturally occurring CRISPR system called CRISPR-Cas9 back in May 2012.  Doudna’s team published a paper on the use of the system to cleave a piece of DNA of choice in vitro (in a test tube) in June 2012.  Separately, Feng Zhang of the Broad Institute applied for a provisional patent application on the use CRISPR-Cas9 to cleave DNA of choice in eukaryotic cells—including human cells—in December 2012 and co-authored a seminal paper on that topic in January 2013.  Although its application was filed after UC Berkeley’s, the Broad Institute secured accelerated review and obtained issued patents, while UC Berkeley’s application is still pending. 

The PTAB declared an interference proceeding to decide which of the two parties gets to have a patent on CRISPR-Cas9.  Interference proceedings derive from pre-American Invents Act 35 U.S.C. § 102(g),[1] which states that if two parties claim patentably indistinct matter, a patent can only be awarded to the first inventor.  They typically involve disputes as to which of two parties was the first to invent.

Before the PTAB could decide who was the first to invent CRISPR, however, the Broad Institute filed a motion arguing that there was no interference to resolve.  Under the applicable regulations ( 37 C.F.R. § 41.203(a)), an interference (a.k.a. “interference-in-fact”) exists if “the subject matter of a claim of one party would, if prior art, have anticipated or rendered obvious the subject matter of a claim of the opposing party and vice versa.”  In other words, an interference-in-fact exists only if both inventions would have invalidated each other.  The Broad Institute argued that this test was not met because its invention, the use of CRISPR technology in eukaryotic cells, was not anticipated or rendered obvious by UC Berkeley’s claimed invention, the use of CRISPR technology in general.  At a hearing before the PTAB on December 6, 2016, the parties focused primarily on this issue.

In a 51-page decision, the PTAB sided with the Broad and determined, by a preponderance of the evidence, that there is no interference-in-fact.  Because that issue was determinative, the PTAB declined to decide the other issues and terminated the interference.  In sum, the Board found that:

Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment.  Specifically, the evidence shows that the invention of such systems in eukaryotic cells would not have been obvious over the invention of CRISPR-Cas9 systems in any environment, including in prokaryotic cells or in vitro, because one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment.

In finding no reasonable expectation of success that the CRISPR-Cas9 system would work in eukaryotic cells just because the same components worked in vitro, the PTAB focused on contemporaneous statements made by the UC Berkeley inventors at the time of their June 2012 paper, and on the opinions of the experts in the interference.  The PTAB pointed to statements made by UC Berkeley inventors Jinek and Doudna that although they were excited by the possibilities raised by their June 2012 paper, they were not sure if CRISPR, which is native to bacteria, would work in eukaryotic cells.  The PTAB also noted that even UC Berkeley’s expert had stated that there was “no guarantee” that Cas9 would work in a eukaryotic context.  UC Berkeley had argued that a number of research groups attempted to use CRISPR-Cas9 in eukaryotic cells after Doudna’s June 2012 was published.  But the PTAB found that this only showed a motivation to invent, not a reasonable expectation of success in actually doing so.  Specifically, the PTAB “agree[d] with Broad’s argument that a large reward might motivate persons to try an experiment even if the likelihood of success is very low.” 

Because PTAB concluded that the two inventions are patentably distinct, its decision means that both parties’ patent claims can potentially coexist.  In fact, Jennifer Doudna of UC Berkeley has already stated following the PTAB’s decision that she will be pursuing her claims in hope of getting an issued patent.  What becomes of the UC Berkeley patent application remains to be seen.  But the Broad Institute CRISPR patents have survived UC Berkeley’s challenge.