Immunologist Tasuku Honjo celebrates his receipt of the Nobel Prize in 2018 with his wife, Shigeko Honjo.
Kyodo via AP Images
By Dennis Normile
In another high-profile case of a Japanese scientist fighting for a share of the profits generated by a key discovery, Nobel laureate Tasuku Honjo last Friday announced he plans to sue Osaka, Japan–based Ono Pharmaceutical for 22 billion yen ($200 million) he believes he should get for supporting the drug firm in a patent dispute.
The 78-year-old Kyoto University immunologist shared the 2018 Nobel Prize in Physiology or Medicine with James Allison, of the MD Anderson Cancer Center at the University of Texas, “for their discovery of cancer therapy by inhibition of negative immune regulation.” Both discovered ways to remove brakes on the immune system that prevent it from attacking tumor cells, although they identified different mechanisms. Honjo’s discovery focused on a molecule expressed in dying T cells, which he called programmed death 1, or PD-1. Later, he and others found the molecule could be harnessed for cancer therapies.
In the years since the discovery, competing groups have developed PD-1–related drugs for treating cancer. Ono co-owns key patents with Honjo. The Japanese company worked together with Bristol Myers Squibb to develop Opdivo, which was approved in both Japan and the United States to treat metastatic melanoma in 2014. That same year, Merck won approval for Keytruda, an anticancer drug that also targets PD-1 receptors.
Ono and Bristol Myers Squibb sued Merck for patent infringement. Honjo traveled to the United States to appear as an expert witness in court and provided other support for the suit. In 2017, Merck agreed to pay $625 million in patent royalties, as well as a portion of Keytruda’s sales revenue between 2017 and 2026, to Ono and its partners.
Honjo says his efforts related to the case were not anticipated in his original compensation agreement with Ono, so he says the company promised him 40% of any settlement. Honjo says he has not received his share of the payment. After 3 years of fruitless negotiations with the company, he has decided to take the matter to court.
An Ono public relations official says the company has no comment.
The stage for this dispute was set in the early 2000s when Honjo wanted to patent his PD-1 discovery for use in treating cancer. At the time, Japanese universities, including Kyoto, “didn’t have any management capacity or the knowledge to apply for patents; they didn’t even have money to support applications,” he says. So he turned to Ono. “They did not do anything scientifically, [but] they helped me to apply for a patent,” Honjo says.
Since then, Japan’s universities have gotten more sophisticated in handling intellectual property, though their experience doesn’t match that accumulated by U.S. universities, he says. And corporations in Japan are still taking advantage of the situation, he asserts. “We believe this lawsuit is not only for my own case, but also to support many other scientists in academia,” Honjo says. He has pledged to donate his share of any settlement to Kyoto University for a fund to support young investigators.
This is not the first time a Japanese Nobel laureate has become embroiled in litigation over compensation for their prize-winning work. In the early 2000s, materials scientist Shuji Nakamura took his former employer, Nichia Corporation, to court claiming he had not been properly compensated for developing a blue light-emitting diode (LED). At the time, Japan’s patent laws allowed employees named as inventors to cede rights to their employers for reasonable compensation without providing any guidance to the meaning of reasonable. In 2004, a Japanese court noted that Nichia had earned more than $1.1 billion in profits from the blue LED and awarded Nakamura a stunning $180 million. Nichia appealed and in 2005 Nakamura accepted a $9 million payment to settle the matter. By that time, he had moved to the University of California, Santa Barbara. He shared the 2014 Nobel Prize for Physics “for the invention of efficient blue light-emitting diodes” with two other Japanese scientists.
“Nakamura’s challenge resulted in a great improvement [to the status] of scientists employed by companies, but that didn’t affect the balance between industry and academia,” Honjo says.
Although Honjo and Ono are now opponents in the new case, they are allied with Bristol Myers Squibb in yet another ongoing battle over patents related to PD-1. In May 2019, a U.S. court ruled that six U.S. patents covering PD-1 based cancer treatments originally granted to Honjo and Ono should be revised to include two researchers, Gordon Freeman and Clive Wood, at the Dana-Farber Cancer Institute. The court found the three scientists collaborated extensively and are joint inventors of the six patents. Honjo and his partners have appealed the ruling.
Source: Science Mag