CRISPR Technology: Officially Off-Limits?

By May Ho, Undergraduate Research Assistant, Karsan Lab, CBR

CRISPR, a technique that allows for precise gene editing, is taking the research world by storm. It has three components: a Cas9 enzyme that snips the DNA, a guide RNA that tells Cas9 where to snip, and the CRISPR sequence on the DNA that is recognized by the guide RNA. Because of its simplicity and remarkable precision, it has broad applications in biomedicine and beyond. For example, CRISPR-edited immune cells are already being used in clinical trials to treat cancer, and the technique can even create genetically engineered mosquitoes that may limit the spread of malaria. From these CRISPR technology success stories, an important question arises: Can further innovations take place now that CRISPR has been patented?

The patents to CRISPR-Cas9 were disputed between two separate teams: Jennifer Doudna of UC Berkley and Emmanuelle Charpentier at the University of Vienna; and Feng Zhang of the Broad Institute of MIT and Harvard.  In May 2012, Jennifer Doudna filed a patent on using CRISPR/Cas9 in all cells. Later that year, Feng Zhang filed his own patents on CRISPR-Cas9 gene-editing in eukaryotic cells, and he was granted a fast-track review of his patent application. However, in 2015, U.C. Berkley argued that Zhang’s patents should be retracted, since they overlapped with Doudna’s. Broad/Zhang recently emerged victorious from this battle, the court verdict declaring that they could keep their patents.

It is not exactly clear who first conceived of CRISPR. Doudna first published her findings in the August 2012 issue of Science, demonstrating that CRISPR could edit bacterial genes far better than pre-existing technologies. She challenged Zhang on the basis that his work in eukaryotic cells—published later that year—was merely an extension of hers.  However, Zhang argued that he conceived of CRISPR independently but waited to publish his results. Zhang showed that CRIPSR could work in human and animal cells—effectively establishing that CRISPR can be used to edit the genes of mice, monkeys, and humans. Compared to Doudna’s discovery in bacteria, his findings were far more lucrative, since he has demonstrated that CRISPR could be used in biological systems important for disease research.

It is certain that the verdict would influence researchers in both academia and industry. The only question that remains is in what way.

Some predict that there would be a series of innovation bottlenecks now that CRISPR-Cas9 is patented.  Scientists would hesitate to improve CRISPR for research in biotechnology if they are concerned about patent infringement. This sentiment is echoed by Aled Edwards of the University of Toronto, who believes that the patents will slow down innovation and CRISPR’s potential to create cures. His reasoning is partially based on a study conducted by the MIT economist, Heidi Williams, who measured the impact of patents on genes. Product development and scientific research on genes that were patented by Celera have been reduced by up to 30 percent compared to genes that were not patented.

Indeed, the CRISPR battle has already altered the direction of several biotechnology companies. Lengthy intellectual property disputes made Monsanto hesitant to create genetically-engineered plants with beneficial traits using CRISPR-Cas9 technology.

Noncommercial research involving CRISPR-Cas9 at universities can still proceed—but not without caveats. The leading institutions involved in the patent dispute have already offered free use of CRISPR-Cas9 technology for research purposes through non-profit organizations like Addgene. However, Broad has already granted its partner company, Editas, an exclusive license to develop human therapies targeting all segments of the human genome. Consequently, any down-stream research involving the use of CRISPR-Cas9 for the development of human therapeutics, in academia or industry, would fall under this exclusive license and would likely face difficulties progressing to full-fledged final products.

Unlike genes though, CRISPR has multiple components, complicating matters further. In September of 2015, Zhang announced that his team had developed a new system, CRISPR-Cpf1 that is superior to CRISPR-Cas9. The Cpf1 enzyme is in the same class of enzymes as Cas9 but is less prone to editing errors. Awarding Zhang a separate CRISPR-Cpf1 patent could encourage scientists to continue moving forward without concerns about CRISPR infringement claims. It might even accelerate the field as scientists discover better versions of CRISPR. Thus, scientists could potentially side-step any CRISPR-Cas9 patents and the verdict declaring MIT/Broad/Harvard as the winner could prove inconsequential as time goes on.

Until scientists discover better ways of executing the CRISPR technique though, any commercial scientific discoveries stemming from CRISPR-Cas9 would probably be slowed. For this reason, science patent experts have recommended that the institutions controlling patent rights to CRISPR should re-think their licensing approach. Any exclusive licenses concerning CRIPSR-Cas9 editing in the human genome should be drawn to specific genes to ensure that the capabilities of the revolutionary technique they have pioneered can be fully realized.

Further Reading

Boston College Intellectual Property & Technology Forum. The CRISPR Patent Battle: Who Will be “Cut” Out of Patent Rights to One of the Greatest Scientific Discoveries of Our Generation?

CBC News. The patent trap? Open science advocates want CRISPR technology to be free

Biotech Connection. CRISPR-Cas9 Genome Editing Technology (Part II): Ongoing Patent Battle and its Impact on the Biotech Industry

Nature Biotechnology. The emerging patent landscape of CRISPR–Cas gene editing technology

Science. CRISPR, surrogate licensing, and scientific discovery