CRISPR Patent Battle Concludes: Feng Zhang's Broad Institute Prevails, UC Vows to Challenge

After more than a year of patent battles, Feng Zhang ultimately secured the CRISPR-Cas9 patent

After an intense patent battle, the final ownership of the CRISPR-Cas9 gene-editing technology, which has drawn significant attention from the scientific community, has been definitively settled. On Wednesday, the U.S. Patent Office announced the final result: the Broad Institute, affiliated with Harvard University and the Massachusetts Institute of Technology (MIT), emerged as the ultimate winner. This outcome deals a blow to the other party in the dispute—the University of California (University of California，(hereinafter referred to as UC), this must have come as a bolt from the blue.

Within the adjudication committee, three judges held veto power, and their determinations were deemed “undisputed facts.” In other words, these three judges were pivotal in deciding the ultimate ownership of the CRISPR patent technology. The ruling spanned 51 pages, elaborating in detail on the reasons for Broad’s victory. “Broad’s discovery holds significant implications for the entire industry,” stated Jacob Sherkow, a legal expert from New York Law School who participated in the patent case.

Although UC biologist Jennifer Doudna and her team have made DNA editing simple and feasible using CRISPR technology, this ruling suggests that the patent office does not view the technology as particularly groundbreaking. However, within the scientific community, UC’s technology holds distinct value: Doudna and another project leader, Emmanuelle Charpentier, have received numerous awards for their work. These include the 2015 Breakthrough Prize in Life Sciences (with a $3 million award), the 2015 Gruber Genetics Prize (with a $500,000 award), and the 2017 Japan Prize (with a $450,000 award).

The Patent Office stated that Broad’s invention involved using CRISPR technology to edit human and mouse cells, achieving success in higher-order cells. As this had not been accomplished previously, Broad’s findings were considered more milestone-worthy; therefore, the Patent Office determined that the patent should be awarded to Feng Zhang.

Previously, many discoveries made by molecular biologists, particularly gene-editing scientists, were hailed as groundbreaking. However, the Patent Office’s decision has undoubtedly provided an official definition of this CRISPR milestone: the CRISPR technology invented by Feng Zhang has fundamentally revolutionized our understanding of the blueprint of life and transformed humanity’s ability to modify living organisms. In the future, this technology holds immense potential for the medical field, not only by revolutionizing cancer treatment but also by enabling the cultivation of human-needed organs in animals.

This ruling has also sparked significant repercussions within the CRISPR technology industry. Companies that bet on the wrong side are currently in a state of distress, forced to confront intense intellectual property disputes. One such company is Berkeley-based Caribou Biosciences, which holds an exclusive license for the technology developed by Jennifer Doudna’s team. Another player, a Swiss CRISPR therapeutics company, derives its technology license from the University of Vienna—where Emmanuelle Charpentier previously worked—which, in a sense, aligns it with the UC camp.

On one side, there is gloom; on the other, jubilation. For the more than a dozen companies that have secured non-exclusive licenses from Broad, it is surely time to pop the champagne—among them GE Healthcare, the German pharmaceutical company Evotec, and the biggest winner of this round, Editas Medicine. Co-founded by Feng Zhang (with Jennifer Doudna also involved during her university years), Editas holds an exclusive license to the patent, which may make it the primary beneficiary of this ruling: Editas can not only apply Zhang’s CRISPR-Cas9 technology to disease treatment, but other companies must also go through Editas to obtain licenses for applying this technology in therapeutic contexts.

Reportedly, Editas’ closing stock price surged 29%, suggesting that many investors are likely beaming with joy today.

In response to the USPTO’s decision, UC promptly issued a press release. The overall tone appeared somewhat forced: as a result of this ruling, the patent applications filed by Doudna and Charpentier will be rejected. The statement noted, “In the foreseeable future, CRISPR gene-editing technology can be applied in all cell types. We will continue to seek robust evidence demonstrating that the Doudna/Charpentier team was the first to apply this technology across all cell types.” It further stated, “The Broad Institute’s patents pertain to the application of the technology in specific cell types, which is fundamentally different from the Doudna/Charpentier technology.”

UC has indicated that it is considering legal avenues to resolve the issue and has not ruled out the possibility of an appeal. Meanwhile, UC also extended an olive branch, stating, “Any CRISPR therapy intended for research into treating human diseases should be approved, rather than being restricted solely to Broad’s patents and companies previously licensed by UC.” Doudna asserted that CRISPR is a technology applicable to all cell types, including human cells.

Broad also responded to the patent ruling: “This further confirms that Broad and UC are distinct entities, with no interference between the two.”

The story begins with the patent litigation involving the University of California (UC). In 2012, the Patent Office rejected UC’s CRISPR-Cas9 patent application. Then, in 2014, it granted the patent to the Broad Institute. How could UC tolerate this? UC promptly filed a challenge with the Patent Office, essentially protesting: “What is going on? CRISPR-Cas9 belongs to us!”

The patent office accepted UC’s lawsuit, and the two parties have been litigating from January 2016 until yesterday...

The crux of the case centered on the claims in the University of California’s (UC) lawsuit, specifically whether the inventions of Doudna and Charpentier were substantially identical to those of Feng Zhang. Although the Broad Institute’s patent application was filed several months after UC’s, the Broad strategically paid an expedited examination fee—a modest sum that significantly accelerated the review process. As a result, the Broad was granted 13 relevant patents (with the remaining 30 patents uncontested by UC), thereby securing the CRISPR patents from the Patent Office. Also left behind in this outcome was the invention of Harvard geneticist George Church; the Patent Office criticized his innovation for having too narrow a scope (though the author wishes to express support for Dr. Church). In contrast, Zhang’s patents possess broad applicability, covering all mammalian cells.

UC dug up a 2012 report of its own, which roughly described how the teams of Doudna and Charpentier used CRISPR technology to trim DNA molecules in test tubes. Based on this “material evidence,” UC began taunting its haughty rival: “We achieved DNA editing inside eukaryotic cells (where DNA resides in the nucleus) first!” Zhang Feng and Church are merely continuations of Doudna’s scientific work. Although we did not complete the editing in living cells, we paved the way; anyone could have finished the subsequent steps.

In other words, UC contends that Doudna devised the recipe, while Zhang Feng merely refined and expanded upon it, which clearly fails to meet the criteria for patent eligibility.

Unfortunately, in the face of UC’s impassioned speech, the Patent Office did not care much.Thirteen months later, the examiners still did not agree with UC’s position. They held that performing multi-site editing in eukaryotic cells using CRISPR-Cas9 constitutes an invention, not something any layperson could accomplish. Consequently, they approved Zhang Feng’s patent application, determining that Broad’s patent does not infringe upon UC’s rights.

Although UC strove to maintain grace and restraint in its statement regarding the Patent Office’s final ruling, it may well have been devastated. The university now faces not only reputational damage but also significant commercial repercussions. If CRISPR proves valuable in treating genetic diseases and even cancer, offering hope to scientists and biotechnology companies, the technology could generate annual revenues in the billions. In agriculture, it can be used to engineer crops, boosting yields and improving food safety, which will also constitute a multi-billion-dollar market. It is all about money...

Although UC stated that it is currently weighing an appeal, IP experts have indicated that, given the high stakes involved, the likelihood of UC filing an appeal is low.

If UC wishes to appeal the Patent Office’s decision, it must take the case to the U.S. Court of Appeals for the Federal Circuit. Unfortunately, in recent years, the Federal Circuit has affirmed the Patent Office’s original rulings in more than half of all appeals. From 2012 to the present, the Federal Circuit has heard a total of 155 appeals, of which 120 resulted in affirmation of the original decision, 14 led to partial modifications of the judgment, and only 21 resulted in reversal.

Moreover, if UC decides to appeal, it may not be financially sustainable. In the previous litigation, Broad’s legal expenses were primarily covered by Editas, with $15 million already spent by the summer of 2016. Meanwhile, Caribou, UC’s financial backer, has already incurred $5 million in costs. It is unclear exactly how much money the two companies have poured into the case.

Amid a year-long protracted battle, as the dispute continued to deteriorate, the two companies engaged in intricate internal maneuvering alongside formal legal proceedings.

A former employee of Feng Zhang’s laboratory approached Doudna, claiming to possess confidential documents that could deal a severe blow to Zhang’s lab. The individual asserted, “Feng Zhang was able to successfully use CRISPR to edit mouse and human genes because he referenced Doudna’s 2012 paper.” In March, the University of California (UC) accused the Broad Institute of patent fraud, strongly condemning Broad for “concealing or distorting material information and intentionally deceiving the Patent Office,” and arguing that Zhang’s misconduct in this matter was sufficient to invalidate his experimental results. The Broad Institute refuted all allegations. Ultimately, due to UC’s lack of additional evidence, the Patent Office rejected the challenge.

Since last December, Broad has gradually gained the upper hand in this patent battle, bringing the CRISPR-triggered war to a near close. Although the two institutions have mostly engaged in verbal sparring, the three judges have expressed greater skepticism toward UC’s arguments than those of Broad. Meanwhile, Sherkow remarked on this protracted litigation: “In fact, UC is undermining itself.”

This patent war has led to hostile relations among major institutions. A year ago, Broad Institute President Eric Lander published an article on the history of CRISPR, prompting a direct rebuttal from Doudna, who stated that the article was factually inaccurate. AAAS CEO Rush Holt immediately stepped forward to support Eric, saying, “You’ve got to be kidding me.”

This inevitably brings to mind the patent disputes over integrated circuits in the last century. The integrated circuit can be regarded as the most important invention of the 20th century. Robert Noyce and Jack Kilby both developed different methods for manufacturing integrated circuits. Although Noyce’s technology was more widely adopted, the patent was ultimately awarded to Kilby.

Nevertheless, CRISPR technology represents a landmark breakthrough for the entire life sciences community. Many share my anticipation regarding the hope it offers for conquering diseases and the momentum it will inject into the industry.