[Ip-health] US government rights in patents on Molnupiravir, based upon funding of R&D at Emory University

Luis Gil Abinader luis.gil.abinader at keionline.org
Mon Oct 4 10:25:46 PDT 2021


Link: https://www.keionline.org/36648

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

Posted on October 4, 2021 by Luis Gil Abinader

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, which has  successfully concluded
prosecution and is expected to be issued later this month with the U.S.
patent number 11,147,826, specifically covers molnupiravir in the allowed
claims. That patent 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

publication GOVT file date priority status patent id

20210252033 yes 2/8/2021 2/7/2020 pending –
20210060050 yes 7/6/2020 12/26/2014 pending –
20200276219 yes 12/7/2018 12/7/2017 issued 11147826
20190083520 yes 3/10/2017 3/10/2016 issued 10874683
20190022116 yes 12/16/2015 12/26/2014 abandoned –

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.


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