US government rights in patents on Molnupiravir, based upon funding of R&D at Emory University

(For more resources, please see our page on molnupiravir.)

Molnupiravir, the oral pill that is showing promising results as a potential treatment for covid-19, was invented at Emory University with U.S. government funds. After more than six years of non-clinical testing, Emory licensed molnupiravir to Ridgeback Biotherapeutics to continue its development as a potential treatment for covid-19. The discovery and further research efforts made at Emory between 2013 and 2020 benefited from an estimate of $35 million dollars in government support. As a consequence of these investments, the U.S. government has rights in key molnupiravir patents.

This blog overviews the role of the U.S. government in the research and development leading to molnupiravir, as well as co-owner of key patents directed to this drug.

Emory conducted extensive non-clinical testing

Emory scientist George Painter started working on molnupiravir-like compounds in 2013 after he was approached by the Defense Threat Reduction Agency (DTRA). The DTRA was looking for a way to fight Venezuelan equine encephalitis, a deadly disease that causes brain swelling. Painter and colleagues at the Emory Institute for Drug Development (EIDD) screened for libraries of known antiviral drug compounds and identified a potential candidate named EIDD-1931. To improve in vivo pharmacokinetics, they created a prodrug based on the chemical structure of EIDD-1931. That prodrug,  originally called EIDD-2801, is now better known as molnupiravir.

From 2013 to 2020, EIDD researchers conducted extensive non-clinical testing to investigate EIDD-1931 and molnupiravir as potential treatments for infectious diseases. Among other findings, their experiments demonstrated that EIDD-1931 is effective in protecting mice from lethal Venezuelan equine encephalitis and inhibit Middle East respiratory syndrome CoV (MERS-CoV) with minimal cytotoxicity. EIDD scientists also showed that molnupiravir has broad anti-influenza virus activity in cultured cells and mice. Based on these findings, Emory decided to focus on molnupiravir as a clinical candidate. However, although they were primarily interested in influenza, Painter and other colleagues at Emory also believed that molnupiravir could treat coronaviruses.

When the covid-19 pandemic hit, the Drug Innovation Ventures at Emory (DRIVE) was getting ready to file an Investigational New Drug (IND) application to test molnupiravir in humans. At the time, their disease target was still influenza. However, as the urgent need for covid-19 therapeutics became evident their focus quickly shifted to SARS-CoV-2. But DRIVE concluded that they lacked the resources to scale up for covid-19 clinical trials, and in March 2020 Emory licensed molnupiravir to Ridgeback to continue its development. With Emory paving the way with extensive non-clinical data, Ridgeback was able to quickly receive FDA approval for testing in humans. The non-clinical testing led by Emory was a significant contribution, particularly because some have been skeptical about the safety profile of drugs in the same class as molnupiravir. Less than two months later Ridgeback entered into a collaboration with pharmaceutical giant Merck, which took over the clinical development and manufacturing of molnupiravir.

U.S. federal agencies funded the research made at Emory

In a recent interview, Ridgeback co-founder Wendy Holman stated that their company asked for but “never got government funding […]” to build manufacturing capacity around molnupiravir. Although she was specifically referring to manufacturing subsidies, that statement appears to be part of an effort to minimize the extensive U.S. government funding towards molnupiravir. Her company have also been omitting the role of the U.S. government for instance in press releases, where they have instead added phrases like “[s]ince licensed by Ridgeback, all funds used for the development of molnupiravir have been provided by Merck and by Wayne and Wendy Holman of Ridgeback.”

Simply stating that Ridgeback and Merck have been developing molnupiravir with their own funding neglects the fact that when both companies entered the picture Emory had already spent over six years researching this drug with U.S. government money. The first steps in the development of molnupiravir relied upon millions awarded by U.S. federal agencies to Emory. In particular, Emory benefited from four contracts awarded by the DTRA and the National Institute of Allergy and Infectious Diseases (NIAID). These contracts were: HDTRA113C0072 worth $499,792, awarded in September 2013; HDTRA115C0075 worth $9,766,440, awarded in September 2015; HHSN272201500008C worth $3,360,106, awarded in June 2015 by the NIAID; and 75N93019C00058, awarded in September 2019 by the NIAID with a value of $15,891,151 at signing.

While those four contracts had a combined value of $29,517,489, the development of molnupiravir also benefited from additional funding through other sources. In fact, according to journal articles reporting findings about this drug the non-clinical experiments were also funded with several NIH grants including 5U19AI109680, 1U19AI142759, 5R01AI132178, R01AI108197, F31AI133952, T32AI112541, and DK065988. Probably taking those grants into account, George Painter himself estimates that in the 2013-2020 period federal agencies invested $35 million to research molnupiravir.

The U.S. government has rights in molnupiravir patents

One consequence of the extensive funding from federal agencies towards molnupiravir is the fact that the U.S. government has rights in key patents related to this drug.

Emory has five published U.S. applications directed to derivatives of n4-hydroxycytidine, the molnupiravir parent compound. Table 1 below summarizes those U.S. patent applications. The five applications name Emory scientist George Painter as one of the co-inventors. The Painter et al. applications disclose compound formulas, manufacturing processes, and methods of using certain n4-hydroxycytidine derivatives to treat diseases. One of the Painter et al. applications specifically discloses molnupiravir in one of the claims. That patent application also claims methods of treating “a human coronavirus infection” using molnupiravir.

Another application, 20210252033, discloses methods of using molnupiravir to treat SARS-CoV-2 specifically. That application, first filed in February 2020, is still pending.

Table 1. Emory U.S. patent applications directed to N4-hydroxycytidine derivatives 

All of the applications listed in Table 1 acknowledged government funding, either at the time of filing or via a subsequent amendment. Specifically, each of the Painter et al. applications acknowledge one or several of the contracts awarded by the DTRA and the NIAID. Moreover, on May 18, 2020, Emory executed respective confirmatory licenses to the DTRA and NIAID stating that the compounds and methods claimed in the 20200276219 application are subject inventions under 35 U.S.C. 200, et seq, the legal provisions pertaining to the Bayh-Dole Act. This means that the U.S. government co-owns molnupiravir and has rights to demand availability at a reasonable price.

The Biden Administration has leverage to address excessive pricing 

Perhaps one of the reasons why Ridgeback  is minimizing the role of the U.S. government in the development of molnupiravir is to avoid demands to make the drug available at a reasonable price. That kind of move has worked for companies like Novartis in the past. Yet, as a promising oral pill with many potential generic suppliers, the availability and affordability of molnupiravir will likely face intense scrutiny in the upcoming months.

Harvard and King’s College researchers Melissa Barber and Dzintars Gotham recently estimated the cost of production for molnupiravir. Based on a previously developed algorithm and public information they concluded that the cost of producing molnupiravir’s active pharmaceutical ingredients, including a 10% profit margin, is $19.99 a course.

In June 2021, Merck announced an agreement to supply the U.S. government approximately 1.7 million courses of molnupiravir for approximately $1.2 billion. KEI has obtained a copy of this contract, which is discussed in another blog published today. According to the contract, the U.S. government will pay $712 dollars per unit of molnupiravir, about 35 times the cost of production as estimated by Barber and Gotham.

With government rights in all of the Emory molnupiravir patent applications published to date, the Biden Administration has leverage to ensure that the prices for molnupiravir are reasonable. This is true even if Merck or other parties receive additional patents, because the U.S. government can use the world wide royalty free right in the granted patents in any compulsory licensing case under 28 U.S.C. 1498, to limit the liability of the U.S. government to compensate patent holders.

This leverage can be used to negotiate a better price in future supply agreements.