The U.S. Court of Appeals for the Federal Circuit has heard the oral arguments for the next round of the patent battle between the University of California Berkeley and the Broad Institute of MIT and Harvard. The hearing, which took place yesterday, granted Donald Verrilli from UC Berkeley and Raymond Nimrod from the Broad Institute roughly 15 minutes each to state their case for why a previous ruling in the Broad’s favour should be overturned or upheld, respectively.

The CRISPR patent battle has been on-going between the two organisations since 2015. UC Berkeley have argued that a patent filed by the Broad for using CRISPR in eukaryotic cells is a reasonable extension of their own patent covering the use of CRISPR in prokaryotic cells. As a result, they believe that Broad’s patent is invalid and should be repealed. Last year, the US Patent and Trademark Office (USPTO) ruled that the Broad’s work and subsequent patent required sufficient innovation to be considered its own invention and thus the patent should be upheld. UC Berkeley appealed that ruling in April 2017.

Yesterday’s oral arguments were the result of that appeal. UC Berkeley hoped to convince the court that the previous ruling by USPTO was not in keeping with relevant legal precedents and should, therefore, be overturned. Opposing them, the Broad Institute hoped to prove that the previous ruling was accurate and should be upheld.

As the party that filed the appeal, the responsibility of opening the arguments fell to Verrilli, UC Berkeley’s former Solicitor General and new Attorney. His argument broadly followed two central points:

  1. The Patent Trial and Appeal Board (PTAB) had focused too much on inventor statements (comments made by the researchers involved in CRISPR development at UC Berkeley and the Broad Institute).
  2. Other groups working on CRISPR were using the same techniques as those employed by the Broad, and as such, their work could not be considered transformative.

The first point was quickly met with some resistance from the judges involved, Chief Judge Sharon Prost and Judge Kimberly Moore.

“We think that the way that the PTAB cleared those statements is inconsistent with the law of the circuit with respect to the proper weight that ought to be given to inventor statements,” Verrilli said.

Chief Judge Prost responded that she was unclear on the point that Verrilli was making, stating, “An inventor statement may contemporaneously be a piece of evidence, and it is a piece of evidence weighed with all the rest of the evidence.”

Verrilli’s second point was accepted more readily, as he said, “The PTAB ruled that the evidence of what the six other groups did, not just that they succeeded, and not just how fast they succeeded, but how they succeeded, what techniques they used, was irrelevant to the question of reasonable expectation of success.”

His argument was that the PTAB should not have rejected this evidence when making their decision, as it proved that the work that the Broad researchers carried out was ‘obvious’ to people of ordinary skill in the art (i.e. people working within the field of genomics). If it can be proven that the Broad’s work was an ‘obvious continuation’ of UC Berkeley’s, then the patent could be considered invalid, as its contents would already be covered by the previous one.

Nimrod refuted Verrilli’s claims by stating that the Broad’s researchers at no point demonstrated a reasonable expectation of success and therefore the work they were performing could not have been an obvious continuation. To prove his argument, he referenced the three other RNA-based techniques that have been converted from use in prokaryotic cells to eukaryotic cells. In each of those three cases, the experiments needed to be changed significantly in order to work; the Broad researchers had no reason to believe that CRISPR would not be the same. As UC Berkeley did not provide researchers with the specific instructions they would need to perform CRISPR in eukaryotic cells, their patent should not be considered to cover this particular use.

Nimrod also argued that the PTAB had considered the inventor statements in a way that was consistent with previous rulings, and that the conclusions they came to were sound given the evidence available.

Once both sides had presented their arguments, Verrilli was granted a few minutes of rebuttal, during which he restated his own arguments. In particular, he focused on the fact that other research groups were carrying out the same techniques as the Broad Institute at the same time and thus there is no evidence that anyone believed unique conditions would be needed, as Nimrod had claimed. On this point, Judge Moore was very dismissive.

“And you know what they did with ribosomes and riboswitches?” She asked Verrilli. “I’ll tell you because I know you don’t. They started with conventional techniques and guess what? They didn’t work. It took years of innovation. That’s how science works, Mr Verrilli. You start with the conventional techniques and then when they don’t work, you spend the time, energy, and money coming up with a new technique.”

The ruling on this appeal is expected later this year.

 

Patent Dispute Timeline

May 2012 – UC Berkeley file a patent application that explicitly covers the use of CRISPR in non-eukaryotic cells.

June 2012 – Jennifer Doudna and Emmanuelle Charpentier at UC Berkeley publish their first CRISPR paper in Science, which reports CRISPR-Cas9 being used in prokaryotic cells as a gene editing tool.

December 2012 – Ahead of paper publication, the Broad Institute files for patent to cover the work being done with CRISPR in eukaryotic cells.

October 2013 – Feng Zhang and his team at the Broad Institute publish a paper in Nature Protocols that demonstrates the use of CRISPR in prokaryotic cells.

April 2014 – The US Patent and Trademark Office (USPTO) award a CRISPR patent to the Broad which covers the use of the tool in eukaryotic cells.

April 2015 – UC Berkeley alert the USPTO to their concerns and formally request that they review the situation. This is the start of the patent dispute.

January 2016 – The USPTO grants UC Berkeley’s request for a review and assemble a panel to manage the dispute.

December 2016 – The first round of oral arguments are made before the panel.

February 2017 – As previously expected, the panel vote in favour of upholding the Broad Institute’s patent. The ruling doesn’t negate UC Berkeley’s patent over use of CRISPR in non-eukaryotic cells, leading to the university releasing a press release that claims they have still come out on top.

April 2017 – UC Berkeley appeal the previous ruling.

October 2017 – The Broad Institute files their first arguments in preparation for the oral arguments, which took place yesterday.

April 2018 – The US Court of Appeals for the Federal Circuit hears the oral arguments for UC Berkeley’s appeal.