CRISPR: A licence to heal

Few areas of emerging research have generated as much excitement in the life sciences community as CRISPR/Cas9, a gene-editing system which relies on the cas9 enzyme to alter DNA. But who invented it and who owns it?

Life sciences experts are convinced by the revolutionary technology’s ability to put gene-editing at the heart of healthcare, making the associated IP an extremely valuable asset. Claims of ownership are far from resolved and have been the subject of protracted legal battles in the US and Europe.

An impending interference proceeding at the US Patent and Trademark Office (USPTO) will be critical in determining who lands the US rights to a key branch of the technology. There are few more qualified to shed some light on the matter than Eric Rhodes, chief executive officer of ERS Genomics.

Based in Dublin, ERS licenses patent rights to CRISPR/Cas9 and is a key player in the CRISPR IP sphere.

“In its simplest terms, what CRISPR allowed us to do is modify DNA sequences within cells and organisms,” Rhodes says. While CRISPR is not the first genome-editing tool of this kind, its efficiency and ease of use set it apart, he explains.

The legal superstructure that has been constructed around CRISPR and its associated IP can appear at a glance to be as complex as the science itself. For a start, who invented the technology and who owns the basic foundational IP is the subject of protracted legal battles.

On one side, there is the University of California (UC), the University of Vienna, and Emmanuelle Charpentier; on the other, the Broad Institute, a collaboration between the Massachusetts Institute of Technology and Harvard University.

Each side owns its own patents, and each side has assigned those patents to a curated network of licensing companies that manages the rights to CRISPR for different applications. One of those companies is ERS Genomics, which was created by Charpentier to provide “broad access” to CRISPR/Cas9.

"There's always been the questions of whether, in addition to the UC portfolio, you also need a licence to the Broad Institute's patents." - Eric Rhodes, ERS Genomics

ERS doesn’t own the rights to the technology—the company has been assigned Charpentier’s patent rights for all applications of CRISPR/Cas9 other than as a human therapeutic.

While human therapeutics are arguably the “most important” application of CRISPR, Rhodes acknowledges, the applications covered by ERS’s licenses have groundbreaking potential.

CRISPR’s ease of use and efficiency, Rhodes says, have allowed gene-editing to broaden out into a range of applications that were previously too expensive or technically challenging.

These include areas such as livestock, plant agriculture, and veterinary medicine, and there could be direct benefits to human medicine as well. Rhodes cites one example of CRISPR being used to develop rodents with immune systems that mirror that of humans.

Licensing focus

Amid the ongoing battle between scientists and research institutions, all seeking to prove who first invented and developed the technology, ERS stands out as a key pillar in the CRISPR landscape, but one which does not engage in scientific research.

“We don’t have labs, we don’t do R&D—we do licensing,” Rhodes says. As the global battle for patent ownership shows, however, IP is arguably the most valuable asset associated with CRISPR.

“We take the patents and make the rights available,” he says. In Rhodes’ words, the company sees itself as simply “enabling” others to commercialise Charpentier and her co-inventors’ work and bring it to market.

ERS lives and breathes IP. In spite of this, however, it doesn’t have an in-house patent team of its own. Rather, it shares external counsel with some of the other companies in the UC network and works closely with in-house counsel at Caribou, Intellia, and CRISPR Therapeutics.

“We’re essentially five or six people; we have fewer internal resources compared to some of the human therapeutic focused companies,” Rhodes insists.

Close cooperation between this group is essential the context of the ongoing patent battle with the Broad Institute. The latest battleground between the factions is an interference proceeding instituted by the USPTO in June.

Under this interference the USPTO will rule on which side first invented CRISPR/Cas9 technology for use in eukaryotic cells (cells which have a nucleus enclosed inside a membrane).

It involves 12 patents and one patent application owned by Broad, and 10 patent applications from the UC side. Proceedings are still at an early stage, Rhodes says.

“What’s happening now is that the two sides are lining up to present arguments and motions,” he explains.

For example, Broad has filed a motion to have the proceeding declared invalid, and has been granted the opportunity to argue its case to the USPTO.

“Our expectation is that won’t happen,” Rhodes says. Assuming the proceedings go ahead in full, the second phase will involve the parties presenting detailed evidence, such as data and notebooks, for the USPTO to pore over.

Then will come what both sides hope will be a definitive decision. “We’re probably about two years away from the end of proceedings,” Rhodes advises.

Patent pool

All the while, UC has been building its patent portfolio. In September, the USPTO approved three more patents for applications of CRISPR/Cas9, with the total number of patents expected to reach 17 by the end of the year.

This marks a rapid expansion of the portfolio since the USPTO issued the first patent in June 2018. With each new granted patent, an ERS licensee gains access to the expanded patent pool, rather than the portfolio as it was when they signed.

Has the expansion in the portfolio, as well as the ongoing interference proceedings, necessitated a change in licensing strategy on ERS’s part?

“It has a little,” Rhodes says. “There’s always been the question of whether, in addition to the UC portfolio, you also need a licence to the Broad Institute’s patents.”

With the interference proceedings seemingly posing more of a risk to the Broad Institute’s established patent portfolio than UC’s—while ten of UC’s patent applications are involved in the proceedings, it is also examining 12 of Broad’s already granted patents—this arguably strengthens ERS’s position.

“At the moment you still need both licenses, but if UC prevails in the US, that might change,” he points out.

“We have to balance the risks in the licences we were putting in place,” he explains. With UC’s position in the CRISPR IP sector more established, and the Broad Institute arguably more vulnerable as a result of the interference proceedings, ERS’s position in licensing negotiations appears to have grown stronger.

“During all the negotiations we take into account the risk that’s being taken by the licensee, as well as the value of the patents. Given the shift in the balance of risk, and the growing patent portfolio, the cost of an ERS licence has increased,” Rhodes says.

Licence criteria

How do ERS’s licensing deals come about, and what does it look for in a licensing partner? Is its goal simply to license the IP as broadly as possible, as its mission statement suggests, or is it more selective?

“There isn’t a list of fixed criteria,” Rhodes says. Often, companies simply approach ERS with an idea to commercialise CRISPR in the hope it will be interested in a deal. But ERS has also approached companies who have “publicly” spoken about their plans for commercialising the technology, he says.

In terms of the kind of licensing partners ERS is looking for, Rhodes says the company has been flexible in its strategy.

“For the past three years, we’ve been focused very much on the pharmaceutical industry,” he says. During the past year or so, however, there has been something of a strategic shift towards veterinary medicine and so-called “green” chemistry. While a lot of these ideas are still in development, some products in these fields made under an ERS licence are “very close” to going to market, Rhodes says.

How did this strategic shift come about?

“More companies in these spaces started coming to us,” Rhodes says. Such exploratory discussions offer ERS a chance to speak with licensees and learn more about the potential applications of the valuable technology they control.

“We’ve seen what kind of opportunities there are,” Rhodes says. The process is a fluid one—on other occasions, he says, companies have approached ERS and asked it to present CRISPR’s potential applications to their own scientists.

For ERS and its partners, the technology is constantly pushing new boundaries in terms of how it can be applied.

“CRISPR has opened the eyes of a lot of people in new areas,” Rhodes says.

CRISPR/Cas9’s transformative impact on medicine and other areas has yet to be fully realised, but one area in which there might soon be more certainty is on who owns the rights to the technology in the US.

The interference proceedings at the USPTO will have a decisive role to play. For his part, Rhodes is confident that his side will prevail. Those with a stake in the wider UC portfolio will hope his confidence is well placed, and should pay close attention over the next two years.

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