Powerful Technique Promises to Revolutionize Biotechnology
A powerful technique promises to revolutionize biotechnology. With the clumsy name of CRISPR-Cas9, this method enables rapid and convenient editing of genes with potential applications for medicine, agriculture, and other technologies. The Federal Circuit recently resolved a dispute over patent rights to this gene-editing method.[1] The competing parties were a group in Boston (The Broad Institute, MIT, and Harvard) (“Broad”) and the University of California at Berkeley and others (“UC”).
Because the inventions were made before the American Invents Act (AIA) took effect, the dispute was resolved under the pre-AIA “first-to-invent” rule as an “interference.” If two parties claim the same or patentably indistinct inventions (the claims “interfere”), then under the pre-AIA 35 U.S.C. § 102(g), a patent may be awarded only to the first inventor.
Broad claimed methods of editing the genome of eukaryotic cells (including animal, human, and plant cells), while the claims in UC’s applications, with an earlier invention date, were based on studies in cell-free systems from prokaryotic cells such as bacteria, and did not claim editing genomes in eukaryotic cells.[2] Since the claimed inventions are not identical, whether the two groups of inventions interfere depended on whether the claims to the CRISPR-Cas9 methods in eukaryotic cells would have been obvious from the UC methods in cell-free systems from prokaryotic cells. The PTAB and then the Federal Circuit found that there was no “interference-in-fact”—that Broad’s methods of editing eukaryotic genes were not obvious from UC’s test-tube methods. That is, even if UC’s claims were considered as prior art, they would not have rendered Broad’s claims obvious. Because they are patentably distinct, each party is eligible for patents on its own inventions.
Obviousness requires finding that a person of ordinary skill in the art would have been motivated to combine or modify the teachings in the prior art and would have had a reasonable expectation of success in doing so. In re Stepan Co., 868 F.3d 1342 (Fed. Cir. 2017). The PTAB found that a person of ordinary skill in the art would not have had a reasonable expectation of success in applying UC’s CRISPR-Cas9 system to eukaryotic cells. To determine whether there would have been a reasonable expectation of success, the PTAB considered scientific evidence of fundamental differences between prokaryotic and eukaryotic cells that would weigh against an expectation that a prokaryotic system could be adapted to function in eukaryotic cells. There was extensive evidence of obstacles and failures encountered in initial attempts to adapt prokaryotic systems to eukaryotes. Contemporaneous statements, actions, and failures by other researchers who sought to engineer CRISPR systems to work in eukaryotic cells demonstrated that, while they were motivated to try, they had no reasonable expectation of success. There were also statements by the UC inventors acknowledging doubts and frustrations about engineering CRISPR-Cas9 systems to function in eukaryotic cells and noting the significance of Broad’s success. For example, one of the named UC inventors, Dr. Jennifer Doudna, acknowledged a “huge bottleneck” in making genetic modifications in animals and humans, and stated “there was a problem. We weren’t sure if CRISPR-Cas9 would work in eukaryotes.” Thus, the PTAB concluded that even though there was motivation to try to apply the UC method to eukaryotic cells, there was not the reasonable expectation of success required for a finding of obviousness.
One factor that can show obviousness of an invention is simultaneous invention by several independent inventors. UC presented evidence that within months after their publication of the CRISPR-Cas9 method in vitro, six research groups independently successfully applied CRISPR-Cas9 in eukaryotic cells. Although recognizing this as evidence of motivation to apply CRISPR-Cas9 to eukaryotic cells, the PTAB concluded and the Federal Circuit affirmed that simultaneous invention did not establish a reasonable expectation of success given the specific facts and context of the art at the time.
Resolution of the patent rights to CRISPR-Cas9 opens the way to licensing of this technique to many in the biotechnology industry who plan to apply this method to develop new products and technologies.
[1] University of California et al. v. Broad Institute, et al., No 2017-1907 (September 10, 2018).
[2] “Eukaryotic” cells are cells that contain a nucleus and organelles, and are enclosed by a plasma membrane. Organisms that have eukaryotic cells include protozoa, fungi, plants, and animals. “Prokaryotic” cells include cells such as bacteria, which lack a nucleus.
