U.S. Patent and Trademark Office will hold hearings to determine whether University of California Berkeley, or Broad Institute of Harvard and MIT, should receive patents for new genomic engineering technique

In the race to master gene-editing in ways that will advance genetic medicine and patient care, one of the hottest technologies is CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. But now a patent fight has the potential to complicate how pathologists and other scientists use this exciting technology.

This dispute over the CRISPR patent—a tool that has been hailed as one of the biggest biotech breakthroughs of the decade—will likely be settled in the coming months by the United States Patent and Trademark Office (USPTO).

The USPTO will be reviewing key patents awarded for what is called CRISPR/Cas9. The technology is already generating novel therapies for diseases, which should create new opportunities for pathologists and medical laboratories.

Millions of Dollars and High Prestige at Stake

This landmark discovery, however, has scientists from the Broad Institute of Harvard and MIT, and from the University of California Berkeley, embroiled in a legal battle over which institution gets to hold the patent for the invention. The winning institution may not only gain prestige but also potentially earn millions of dollars from licensing the technology, which Science Daily dubbed “programmable DNA scissors” for researchers and biotechnology companies.

“This is an absolutely humungous biotech patent dispute,” stated Associate Professor of Law Jacob Sherkow, JD, MA, BSc, of New York Law School in an article published in the journal Nature. “We’re all waiting with bated breath,” Sherkow said.

History of the Patent Dispute

The patent dispute dates back to 2012. That year, a team of researchers led by Berkeley’s Jennifer Doudna, PhD, a Professor of Molecular and Cell Biology and Chemistry and an Investigator at the Howard Hughes Medical Institute (HHMI), and Emmanuelle Charpentier, PhD, now at the Max Planck Institute for Infection Biology in Berlin, discovered a programmable RNA complex in the bacterial immune system that guides the cleaving of DNA at targeted sites. They published their findings in the journal Science in August 2012 and filed a patent application on March 15, 2013.

In February, 2013, a second team of researchers, led by bioengineer Feng Zhang, PhD, an Investigator at McGovern Institute, Assistant Professor at MIT, and a Core Member of the Broad Institute, published a breakthrough paper in Science that reported the first successful programmable genome editing of mammalian cells using CRISPR-Cas9. Because the Broad Institute paid for an accelerated review of its patent application, it was awarded the first of its CRISPR patents in April 2014.

‘First to File’ versus ‘First to Invent’

While patents today are awarded based on “first to file,” the law in 2013—when Doudna’s CRISPR application was filed—required patents to be decided based on the “first to invent,” rule. For that reason, University of California Berkeley is challenging the USPTO’s awarding of CRISPR patents to Broad Institute.

Jennifer Doudna, PhD (left), a Professor of Molecular and Cell Biology and Chemistry and an Investigator at the Howard Hughes Medical Institute (HHMI), and Feng Zhang, PhD (right), Assistant Professor at MIT and a Core Member of the Broad Institute, both claim they were the first researcher to ‘invent’ critical aspects of the new CRISPR gene-editing technology now in patent dispute. (Photo copyright: STAT, AP, and Katherine Taylor, Boston Globe.)

Jennifer Doudna, PhD (left), a Professor of Molecular and Cell Biology and Chemistry and an Investigator at the Howard Hughes Medical Institute (HHMI), and Feng Zhang, PhD (right), Assistant Professor at MIT and a Core Member of the Broad Institute, both claim they were the first researcher to ‘invent’ critical aspects of the new CRISPR gene-editing technology now in patent dispute. (Photo copyright: STAT, AP, and Katherine Taylor, Boston Globe.)

According to an article published in STAT, the USPTO has scheduled oral arguments for Nov. 17, 2016, in an “interference proceeding,” during which a panel of administrative patent judges will determine which research team was the first to invent the CRISPR technique.

Biotech Companies Seek to Leverage CRISPR Tech

CRISPR/Cas9 technology allows scientists to precisely and efficiently edit genes in organisms of all sorts, giving it the power to transform both medicine and agriculture. However, an article published in Quanta Magazine noted that scientists in Japan are predicting that CRISPR also will be used “in the immediate future” to alter the genes of human embryos.

Because of CRISPR’s potential to be used on human embryos, Doudna was among a group of biologists who last year called for a worldwide moratorium on CRISPR use until its safety could be assessed, as Dark Daily reported in July, 2015.

According to an article in Nature, Broad Institute will continue to make CRISPR/Cas9 reagents available to researchers and has given no indications it will pursue licensing fees from academics.

Biotech companies, however, are looking to leverage the CRISPR technology, and all three leading CRISPR researchers have ties to CRISPR/Cas9 startups, as follows:

• Zhang remains on the leadership team of Editas Medicine in Cambridge, Mass., which he co-founded with Doudna and others in 2013.

• Doudna is now affiliated with Intellia Therapeutics in Cambridge, Mass., and is a co-founder of Caribou Biosciences.

• Charpentier has co-founded CRISPR Therapeutics in Basel, Switzerland.

“The intellectual property in this space is pretty complex, to put it nicely,” stated Rodger Novak, MD, a former pharmaceutical industry executive who is now CEO of CRISPR Therapeutics, in an article published in MIT Technology Review. “Everyone knows there are conflicting claims,” Novak concluded.

Clinical laboratory executives and pathologists have seen patent-holders reap substantial licensing fees from the diagnostic uses for certain patented technologies. One familiar example is the polymerase chain reaction (PCR) patent held by Roche during the 1990s. Medical laboratories using assays that incorporated PCR technology paid billions of dollars in licensing fees to Roche.

Andrea Downing Peck

Related Information:

Programmable DNA Scissors Found for Bacterial Immune System

Bitter Fight Over CRISPR Patent Heats Up

A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity

Multiplex Genome Engineering Using CRISPR/Cas9 Systems

The Gene Hackers

In the CRISPR Patent Fight, the Broad Institute Gains Edge in Early Rulings

Control of CRISPR, Biotech’s Most Promising Breakthrough Is Up for Grabs

The CRISPR Patent Fight Has Begun–And It’s Not Pretty

Who Owns the Biggest Biotech Discovery of the Century?

Breakthrough DNA Editor Born of Bacteria

Top Biologists Call for Moratorium on Use of CRISPR Gene Editing Tool for Clinical Purposes Because of Concerns About Unresolved Ethical Issues