Newsletter
New Era of Cancer Treatment: Patent War over Anti-Cancer Immunotherapy Strategies
The main conventional approaches to cancer treatment include surgical resection of lesions and chemotherapy or radiation therapy, which is toxic to both cancerous and normal tissues. Compared with conventional cancer therapies, novel types of cancer treatment focus more on precision medicine, targeting specific cells (cell markers, antigens), and how the components of the tumor microenvironment, such as regulatory T cells (Treg) and extracellular matrix (ECM), interact with cancer-associated fibroblasts (CAF). Therefore, these novel types of cancer treatment are more likely to bring about excellent therapeutic efficacy and reduce the occurrence of adverse side effects, such as off-target effects.
One of the highly-discussed topics concerning novel cancer treatments is Chimeric Antigen Receptor-T (CAR-T) cell therapy. Key CAR-T related patents include US6,319,494, US7,741,465, US7,446,190, US8,399,645 and so forth, wherein the CAR-T patented in US8,399,645 is structured as anti-CD19-4-1BB-CD3ζ. With respect to patent US8,399,645, the licensee Juno Therapeutics, Inc. launched an infringement lawsuit against Novartis, claiming that Novartis’s CAR-T product Kymriah® infringed on the patent at issue. In 2015, the two parties reached a settlement on the condition that Novartis agreed to pay Juno Therapeutics USD12.25 million and other royalties. In addition, news reports revealed that most CAR-Ts currently used by Chinese companies in clinical trials are CAR-Ts with the structure of 4-1BB-CD3ζ. Therefore, for China companies that intend to enter the U.S. market, authorization to practice patent US8,399,645 is a must before they produce, implement or sell CAR-T. Accordingly, it can be concluded that patent US8,399,645 has great commercial value.
Another highly-discussed topic concerning novel cancer treatments is immune checkpoint inhibitor therapies, in which the primary proteins to be targeted are CTLA4 (cytotoxic T-lymphocyte-associated protein 4), PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1). Key patents involving PD-1 inhibitors include US7,595,048, US8,728,474, US8,008,449, US8,952,136 and so forth. Among them, the scope of patent protection defined in independent claim 1 of US8,728,474 is rather broad, to the extent that any tumor treatment method will fall within the claimed scope as long as it involves administration of anti-PD-1 monoclonal antibody. This is because independent claim 1 of US8,728,474 neither limits the structural features of the PD-1 monoclonal antibody (e.g. the 6 CDRs of the light and heavy chains of the antibody) nor specifies the type of the tumor (e.g. specific cancers). In 2014, the patentee of US8,952,136 and its partner Ono/BMS filed an infringement lawsuit, claiming that Merck’s anti-PD-1 antibody (Keytruda®, Pembrolizumab) infringed on US8,728,474. Merck and Ono/BMS reached a settlement in 2017 with respect to all of their PD-1 antibody related patent lawsuits worldwide on the condition that Merck agreed to pay Ono/BMS a lump-sum payment of USD625 million and a certain percentage of global sales as royalties.
When getting involved in patent litigation, pharmaceutical companies should take various factors into systematic consideration (such as validity of the patent at issue, resource advantages/disadvantages of the parties, and market status, etc.) and take reasonable countermeasures. In the two cases identified above, the defendants each chose a quick end to their patent wars through settlement, possibly due to the reasons that (1) a patent lawsuit may last for years and incur considerable expense, and (2) an early end to a patent dispute can eliminate shipment uncertainty without further delay.