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Throw CRISPR into a pool

CRISPR-Cas9 is a research tool that should be shared through a patent pool

April 28, 2016 7:00 AM UTC

The scientists involved in disputes over CRISPR-Cas9 patents, and the institutions and companies they are affiliated with, should find a way to stop squabbling and start sharing. The best way forward is to create a patent pool, give free access to parties that contribute, and charge reasonable fees to entities wanting to license the patents.

In this case, the contributing parties would be the Regents of the University of California, the University of Vienna, the Broad Institute Inc. and the Massachusetts Institute of Technology, which are the assignees listed on the patents under dispute.

The idea is not to stop the inventors or universities from making money from their inventions. Rather, it's to stop them from paralyzing progress while they fight over who takes home all the winnings.

Agreeing to less than 100% of what is likely to be a very large pie shouldn't be a big ask. The CRISPR inventors, their investors, and the companies they have spun out - Editas Medicine Inc., Crispr Therapeutics AG, Intellia Therapeutics Inc. and Caribou Biosciences Inc. - still would have plenty of opportunities to reap profit from the discoveries. Every specific non-obvious gene therapy, cell therapy or other tailored invention using the technology could be patented, like any other medicine.

Anger management

The dispute centers on IP covering methods of use and composition of matter for the CRISPR gene editing technology, and is being fought in both the U.S. and Europe.

The Broad Institute of MIT and Harvard and MIT were issued the first patent under the accelerated review protocol, with claims based on the work of the Broad Institute's Feng Zhang showing the technique works in eukaryotic cells. The UC Regents have filed an interference in the U.S., claiming priority of work by Jennifer Doudna and Emmanuelle Charpentier that was filed and published before Zhang's study and described the technique for the first time, based on experiments in prokaryotic cells.

Doudna is a professor at University of California Berkeley. Charpentier, now at Umeå University and the Helmholtz Centre for Infection Research, performed her studies at the University of Vienna.

The fight has already proved ugly.

In December, Eric Lander, president and director of the Broad Institute, published a Perspective in Cell on the history of CRISPR that some critics have said is self-serving because it diminishes the role of Doudna and Charpentier in its discovery. Doudna and Charpentier hit back with publicly posted comments noting that the piece was "factually incorrect," and "incomplete and inaccurate."

The tone has spilled into the legal proceedings, where UC has accused Zhang of "inequitable conduct," arguing that he did not own or use one of the key molecular components of CRISPR in the experiments used to support his claims.

"Broad withheld or misrepresented material information with the intent to deceive the USPTO," the university stated in its motion. Other commentators have noted that goes a step beyond challenging the grounds on who is first to invent, entering terrain of invalidating the Broad's patent on the basis of misconduct.

In addition, Jacob Sherkow, associate professor of law at New York Law School, pointed out in a recent Comment in Nature, that the fight is unusual for being led by two research institutions although it's about "the industrial development of a foundational technology."

Henry Kissinger is reputed to have quipped that academic fights are vicious because so little is at stake.

This academic fight is different: a lot is at stake.

There is no doubt that CRISPR is a breakthrough - a fundamental tool that will advance human health and lead to unanticipated benefits to society. Obvious applications include altering genes in ways that address numerous intractable diseases.

There's also not much debate that CRISPR's potential can only be realized by the private sector. That's why restricting freedom to operate for researchers in industry will only slow the technology's transition from academic science to practical medicine.

It is impossible to know what discoveries aren't being made, or to quantify how much the search for new treatments is being slowed by IP disputes that take scientists out of their labs and into courtrooms, discourage collaboration and create barriers to commercializing new technologies. The fact that missed opportunities can't be counted doesn't mean they aren't real.

Not inventing the wheel

The problem isn't that universities and academics want to patent their discoveries. It's no exaggeration to say the 1980 Bayh-Dole Act in the U.S. made the biotech industry possible by giving universities the right to patent inventions discovered using government funds. Often, discoveries will only be commercialized if there's solid and exclusive IP.

The critical issue is how the patents are managed.

As a rule, universities overvalue their patents, driving away companies that might have commercialized technologies if they had been offered at a realistic price.

That doesn't mean all taxpayer-funded research should be made available for low or no cost. But the CRISPR dispute raises the risk that an IP landgrab by the pioneers' startups ultimately could severely limit access to a tool that could help create a wide range of medical solutions expected by taxpayers who funded the basic research.

Of course, defining a tool can be a muddy issue: one scientist's tool is another's ticket to the world of entrepreneurship. CRISPR, however, is arguably similar to PCR, cell lines, and other inventions that are widely considered tools that should be shared in the interests of advancing science.

The CRISPR pioneers have already been rewarded with valuable monetary and non-monetary currency: recognition in the form of cover stories and accolades in single-name journals, prestigious prizes, academic security and funding. Now they, and the academic institutions with economic interests in their patents, should find a way to share the fundamental IP, and then compete with the rest of the field to use it to create new products.

A patent pool could be the vehicle. Allowing the CRISPR innovators to access the patents on equal terms avoids the need for time-consuming negotiations over licensing or royalty terms, or the winner-take-all verdicts that courts can impose.

Given the acrimony in the CRISPR case, a neutral mediator such as NIH could play an active role in creating and managing the pool. Where international entities belong to the pool, neutral mediators from those terrains could be used.

Funders of science, including NIH and the philanthropic organizations that are becoming ever more influential, also have a role to play in persuading the CRISPR patent holders to adopt a more sensible course, as does the scientific community. Scientists are acutely conscious of their reputations, so pressure from colleagues could help tip the balance when decisions are made about attempting to maximize profits from the patents or acting in the interest of medical progress.

The concept of using patent pools in the public interest isn't new.

In 1917, the Wright brothers, Glenn Curtiss and other aircraft pioneers were asserting their patent rights so aggressively that they had made it almost impossible for any company to combine the technologies needed to advance airplane manufacturing. Like CRISPR, inventors were free to experiment with the technologies in their own workshops, but they couldn't incorporate them into commercial products without paying crippling royalties. Then-assistant secretary of the Navy, Franklin Roosevelt, successfully championed the creation of an aviation patent pool, the Manufacturers Aircraft Association, that slashed the royalty payments on airplane patents. Citing wartime necessity, Congress gave FDR a big stick, the right to obtain patents by eminent domain, that persuaded feuding parties to throw their patents into the pool.

More recently, public and private entities have worked together to create patent pools.

The Medicines Patent Pool, set up in 2010 to increase access to patents for HIV/AIDS drugs, has seen several pharmas and NIH contribute key patents. Last year, the organization expanded its scope to include HCV and tuberculosis.

Other patent pools have been formed covering green fluorescent protein (GFP) and the genome sequence of the severe acute respiratory syndrome (SARS) virus.

While each case has its own nuances, they - together with examples from the tech world - provide models to draw from.

Parties in the gene editing field have already broken ground in organizing meetings to get international agreement on the best way to ensure the technology is used ethically. There's no reason they can't take that same momentum to settle their commercial differences.

Companies and Institutions Mentioned

The Broad Institute of MIT and Harvard, Cambridge, Mass.

Caribou Biosciences Inc., Berkeley, Calif.

Crispr Therapeutics AG, Basel, Switzerland

Editas Medicines Inc. (NASDAQ:EDIT), Cambridge, Mass.

Helmholtz Centre for Infection Research, Braunschweig, Germany

Intellia Therapeutics Inc., Cambridge, Mass.

Massachusetts Institute of Technology (MIT), Cambridge, Mass.

Medicines Patent Pool, Geneva, Switzerland

National Institutes of Health (NIH), Bethesda, Md.

New York Law School, New York, N.Y.

Umeå University, Umeå, Sweden

University of California Berkeley, Berkeley, Calif.

University of Vienna, Vienna, Austria

Targets and Compounds

Cas9 - CRISPR-associated protein 9

References

Koch, S. "CRISPR burn." BioCentury Innovations (2016)

Lander, E. "The heroes of CRISPR." Cell (2016)

Martz, L. "Plenty of CRISPR pie." BioCentury Innovations (2015)

Sherkow, J. "CRISPR: Pursuit of profit poisons collaboration." Nature (2016)