The PD-1 antibody patent litigation, globally filed in
Japan, the United States and Europe, came to an end with a
Summary of the case
According to the press releases of Ono pharmaceutical and
Bristol-Myers Squibb, as well as others, the facts are as
Ono and Professor Tasuku Honjo (distinguished professor at
Kyoto University) are co-patentees of a patent for an invention
entitled "An immunopotentiative composition" (JP 4409430,
Patent No. 1), and a patent for an invention entitled
"monoclonal antibody" (JP 5159730, Patent No. 2).
Claim 1 of Patent No. 1 is as follows.
An agent for treatment of melanoma comprising a PD-1
antibody as an active ingredient, the agent having effect of
suppressing proliferation or metastasis of melanoma in
Claim 1 of Patent No. 2 is as follows.
An agent for treatment of cancer comprising a PD-1 antibody
as an active ingredient, the agent having effect of suppressing
proliferation of cancer cells in vivo (except for an agent for
treatment of melanoma).
On October 24 2016, Ono and Professor Honjo filed a lawsuit
seeking an injunction for patent infringement at the Tokyo
District Court on the basis of infringement of Patent No. 1 and
No. 2 against Merck Sharp & Dohme (MSD), which obtained a
manufacturing and marketing approval of Keytruda®
(pembrolizumab MK-3475) on September 28 2016.
The European and US patents corresponding to Patent No. 1
and No. 2 are licensed to Bristol-Myers Squibb (BMS), and
lawsuits based on such patents are pending in Europe as well as
in the US. Furthermore, Ono and BMS have announced that they do
not seek a judicial decision on sales suspension of
Keytruda® in these lawsuits, if the litigant parties make
an agreement to pay appropriate consideration including
royalties or if such order is made by the court, taking into
consideration the characteristics of this type of therapy
helping patients' lives. They will take such an approach in
this lawsuit as well.
On January 21 2017, Ono issued a press release stating that
Ono and BMS entered into a settlement and licence agreement
with Merck (US) and its associated companies.
They reached the following agreements:
Ono and BMS allow sales of Merck's Keytruda® after
recognising validity of their use patents and product
Merck makes an initial payment of $625 million to Ono and
BMS, and pays ongoing royalties on global sales of Keytruda of
6.5 % from January 1 2017 until December 31 2023, and 2.5 %
from January 1 2024 until December 31 2026.
The initial payment and royalties will be shared between BMS
and Ono in a 75/25 per cent allocation, respectively.
By this settlement, all global patent infringement
litigation against Merck's sale of Keytruda® was ended.
"Bristol-Myers Squibb and Ono's agreement with Merck
protects our scientific discoveries and validates the strong
intellectual property rights we secured as the early innovators
in the science of PD-1, a key mechanism in Immuno-Oncology that
has proven to have transformational impact in cancer care,"
says Giovanni Caforio, M.D., chief executive officer, BMS.
"Today's agreement is also a good decision for patients as it
supports the continuation of ongoing research and maintains
access to anti-PD-1 therapies for cancer patients around the
The attempt of cancer treatment to step on the accelerator
of immunity has not succeeded. In contrast, the cancer
immunotherapy with PD-1 inhibitors, which prevents the brakes
from being applied to immunity, is a breakthrough because it is
highly likely to be effective against various kind of cancers,
cancers are less likely to recur, since it is effective for a
long period after administration is stopped and its mechanism
is to activate the immune system without attacking cancer cells
directly, therefore side effects are less severe, if any.
After a generation of the therapy with PD-1 antibody, cancer
treatment has turned a significant corner. "We're at the point
where we've discovered the cancer equivalent of penicillin,"
says Dan Chen, head of cancer at Genentech (Andy Coghlan,
Closing in on Cancer, New Scientist, March 5 2016). A
generation of antibiotics overcame infections in the 20th
century, now in the 21st century, there is a possibility that
cancers will be cured by immunotherapy with PD-1 inhibitors.
Professor Honjo was awarded the Nobel Prize in Physiology or
Medicine 2018 due to this achievement.
This litigation was withdrawn about three months after
filing, and the trial did not proceed substantially. MSD has
not yet obtained a manufacturing and marketing approval for the
products with "unresectable advanced or recurrent non-small
cell lung cancer" effectiveness and efficacy among MSD's
products, and argued that since those with "unresectable
melanoma" effectiveness and efficacy have not yet been included
in the NHI price listing, there is no likelihood of
infringement, therefore, there is no benefit in a suit. MSD
argued that there is no urgency or necessity for the resolution
of the dispute by a lawsuit for demand of an injunction, since
Ono etc. have announced that they will not seek a judicial
decision on sales suspension of MSD's product, if appropriate
consideration is paid by MSD. This is a case where the
significance of pharmaceutical companies' existence, whose
mission is to save patients, was questioned in patent
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