The Massachusetts Institute of Technology Broad Institute held on to its U.S. patent victory on the CRISPR/Cas9 front Monday when the U.S. Court of Appeals for the Federal Circuit agreed with a patent board that Broad's claims on using the gene-editing technology don't interfere with those of the University of California.
"This case turns in its entirety on the substantial evidence standard," according to the unanimous Federal Circuit decision written by Judge Kimberly Moore. That standard is whether a person of ordinary skill in the art would have had a reasonable expectation of success in applying the CRISPR/Cas9 system in eukaryotic cells.
The precedential decision affirmed the Patent Trial and Appeals Board's determination last year that there would have been no such expectation, given the differences between eukaryotic and prokaryotic systems. Thus, the Broad patents, which are limited to eukaryotic cells, don't interfere with UC's claims.
The dispute dates back to August 2012 when UC researchers published an article demonstrating that the isolated elements of the CRISPR/Cas9 system could be used in vitro in a noncellular experimental environment. Six months later, Broad researchers published an article describing the use of CRISPR/Cas9 in a human cell line. Both institutions sought patent protection. Broad limited its claims to use in eukaryotic cells, whereas the claims in UC's application do not refer to a particular cell type or environment, according to court documents.
CRISPR/Cas systems occur naturally in prokaryotes such as bacteria, but they have not been found to naturally exist in eukaryotes, such as plants and animals.
Citing PTAB's "exhaustive analysis" of the facts, including statements from UC's own experts about the obstacles of using CRISPR/Cas9 in eukaryotic cells, Moore said, "We conclude that substantial evidence supports the Board's finding that there was not a reasonable expectation of success" for using CRISPR/Cas9 technology the way the Broad Institute applied it.
At the same time, the Federal Circuit acknowledged that other evidence in the record could support UC's position that what Broad did was obvious, as the prior art contained a number of techniques that had been used to adapt other prokaryotic systems for use in eukaryotic cells.
"We are, however, an appellate body. We do not reweigh the evidence," the court said. "It is not our role to ask whether substantial evidence supports fact findings not made by the Board, but instead whether such evidence supports the findings that were in fact made. Here, we conclude that it does."
The Federal Circuit decision isn't necessarily the last word on the patents and applications involved in University of California v. Broad Institute. While UC can ask for the full Circuit to hear the case or appeal to the Supreme Court, CRISPR/Cas9 patents also could face validity challenges.
"We note that this case is about the scope of two sets of applied-for claims, and whether those claims are patentably distinct," the court said, adding that it was not ruling on the validity of any of the claims.
Earlier this year, the European Patent Office revoked a Broad Institute patent, EP 2771468 B1, on the basis that it lacked priority over novel art. The patent, which claims "engineering of systems, methods and optimized guide compositions for sequence manipulation" is one of the foundational CRISPR/Cas9 patents claimed by the Cambridge, Mass.-based institute. (See BioWorld, Jan. 19, 2018.)
The European decision is stayed while the Broad Institute appeals.
Split decision on Ampyra
In a second precedential opinion handed down Monday, the Federal Circuit split 2-1 in affirming a lower court decision that struck down four patents protecting Acorda Therapeutics Inc.'s Ampyra (dalfampridine) and opened the door for generic versions of the only drug approved in the U.S. for improving walking in people with multiple sclerosis.
The news sent Acorda's (NASDAQ:ACOR) shares reeling. Following its heaviest trading in three months, the Ardsley, N.Y.-based company closed the day at $20.80, down 24.5 percent from Friday's close of $27.55.
The majority opinion, written by Judge Richard Taranto, agreed with the district court that the patents, which would have expired in 2025 and 2027, were invalid due to obviousness. The patents claimed methods of administering a sustained-release formulation of the drug, maintaining specific 4-aminopyridine serum levels and indicating walking improvement.
In arguing against obviousness, Acorda cited the commercial success of the drug and the failure of other drug companies to address the long-felt but unmet need. But like the district court before it, the Federal Circuit noted the role played by a blocking patent in discouraging development of other drugs in the space. That patent, licensed exclusively to Acorda by Elan Corp. plc, expired in July.
"As to commercial success, the district court found that 'no one other than the Elan patentees and their licensees could have practiced the invention of the Acorda patents without facing liability for patent infringement. The risk of such liability would have provided an independent incentive for a patentee not to develop the invention of the Acorda patents, even if those inventions were obvious,'" Taranto wrote.
Judge Pauline Newman called such reasoning flawed in her dissent. "The consequences of this new legal theory are large. . . . Had the court's approach to the law of obviousness been in effect when Acorda took up the study of 4-aminopyridine after decades of failures by others, it is questionable whether this new treatment for multiple sclerosis would have been discovered and pursued. The loser is the afflicted public," Newman said.