The global spread of COVID-19 has challenged scientists to accelerate research and development in the race to find a safe and effective vaccine against SARS-CoV-2. Among the front-runners are the mRNA vaccines developed by Pfizer and its German partner BioNTech and by Moderna Therapeutics and the National Institutes of Health.
On 9 December 2020, Health Canada authorized use of the Pfizer-BioNTech vaccine for people who are 16 years of age or older under the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19 (the “Interim Order”). Canada was the third country to approve the Pfizer-BioNTech vaccine, following Bahrain and the United Kingdom. Subsequently, the United States and the European Union also approved the Pfizer-BioNTech vaccine.
On 23 December 2020, Health Canada authorized use of the Moderna vaccine for people who are 18 years of age or older under the Interim Order. Canada was the second country in the world to approve the Moderna vaccine, following only the United States’ approval on 18 December 2020.
mRNA vaccines are a brand new class of vaccines and will likely revolutionize the future of vaccine science. Prior to the Pfizer-BioNTech vaccine and the Moderna vaccine, mRNA vaccines had not been validated for human use. Development of the foundational enabling technology for mRNA vaccines began years ago and Canadian IP has played and continues to play a pivotal role in fueling the development of this exciting new class of vaccines.
mRNA Vaccine Technology
mRNA vaccines contain a synthetic RNA construct that is programmed to encode specific protein(s) that mimic the target viral protein(s). Once the synthetic RNA construct enters into the cytoplasm of a cell, the cell uses the construct as a template to make multiple copies of the encoded protein(s). The body then responds to the encoded protein(s) by generating antibodies and/or cytotoxic T lymphocytes (“CTL”) directed against them. As Health Canada explains, the synthetic RNA construct essentially functions as a “recipe, telling the cells of the body how to make [certain] protein(s) [to trigger an immune response].” Because RNA does not integrate into chromosomal DNA of human cells, mRNA vaccines eliminate the potential safety concerns relating to insertional mutagenesis associated with DNA vaccines.
The Pfizer-BioNTech vaccine and the Moderna vaccine are the first-ever mRNA vaccines to receive regulatory approval for human use. However, the development of mRNA vaccines that culminates in their success began decades ago. For example, as early as 1990, intramuscular injection of RNA expression vectors was shown to induce production of targeted proteins in muscle cells. In 1993, a liposome-entrapped mRNA vaccine in mice was shown to induce a virus-specific CTL (immune) response. After years of advanced research, various mRNA vaccine platforms have been developed to render a synthetic RNA construct more translatable, stable, and non-toxic. Also, previous studies of SARS-CoV and MERS-CoV, which belong to the same cluster of betacoronoviruses as SARS-CoV-2, have paved the way for COVID-19 mRNA vaccine technology.
The full genome sequence of SARS-CoV-2 is understood to encode four major structural proteins: spike, membrane, nucleocapsid, and envelope. The spike protein functions to allow the virus to dock to the host cell and fuse membranes. The spike protein has been an important target for antibody neutralization and vaccine development. Both the Pfizer vaccine and the Moderna vaccine contain synthetic RNA programmed to encode specific antigens that mimic certain epitopes (antibody binding sites) of the spike protein to trigger an immune response.
mRNA vaccines will likely change the future of vaccine science. For one thing, the mRNA vaccine manufacturing process is essentially chemistry-based. Once the full genomic sequence of a virus is available, candidate mRNA vaccines can be designed and synthesized in a few days, rather than months (as it is in the case of a conventional vaccine containing viral proteins or disabled forms of the virus). For context, Moderna finalized the sequence for its mRNA-1273 vaccine within mere days of Chinese scientists having published the genomic sequence of SARS-CoV-2. Two months later, Moderna started a safety phase I clinical trial to test its mRNA vaccine.
Additionally, mRNA vaccines are modular in nature and sequence-based. Theoretically, mRNA vaccines can be designed to encode any protein(s) to thereby quickly respond to a plethora of medical conditions and future pandemics. The flexibility to encode any protein(s) is potentially important to deal with new variants, e.g. mutated variants now coming out of the United Kingdom and South Africa or which may arise in future. Once the genomic sequence of a variant is known, candidate mRNA can be readily modified, although safety and efficacy testing likely remains necessary.
Novel mRNA Vaccine IP: Multiple Layers, Multiple Players, and Some Canadian Connection
Pfizer-BioNTech and Moderna are probably on track to obtain broad IP protection for their specific synthetic mRNA constructs and use of their vaccines. However, the mRNA vaccine patent landscape is likely to involve multiple layers and multiple players, as development of the foundational enabling technology began years ago.
For example, Vancouver-based Acuitas Therapeutics licensed its lipid nanoparticle delivery system in the development of the Pfizer-BioNTech vaccine. The lipid nanoparticle system enables reliable delivery of the synthetic mRNA construct(s) to the interior of target cells. The lipid nanoparticle system stems from research pioneered by Dr. Pieter Cullis and colleagues at the University of British Columbia.
Another company that holds rights that are potentially relevant to the mRNA vaccine arena is Arbutus Biopharma Corp., a Canadian biopharmaceutical company with expertise in liposomal drug delivery and RNA interference. Moderna previously licensed lipid nanoparticle technology held by Arbutus through Acuitas, and more recently, Moderna has been tied up in some administrative proceedings in the US in which it has challenged Arbutus’ patents. While there is no litigation between the two and no allegation that Moderna’s COVID-19 vaccine infringes Arbutus’ patent rights, at the very least in the early days of its development, Moderna also looked to Canadian technology to enable the delivery of mRNA vaccines.
In a further Canadian connection, CanSino Biologics Inc., a Chinese vaccine company, earlier this year partnered with Vancouver-based Precision Nanosystems to purportedly develop another mRNA vaccine. CanSino owns Chinese Patent No. CN 111218459 relating to Ad5-nCo, a COVID-19 vaccine that is based on human type 5 replication defective adenovirus. The fact that it has partnered with another company to also potentially develop an mRNA-based vaccine suggests it sees the value of this new technology.
It will be interesting to watch the mRNA vaccine patent landscape and assess the scope of Pfizer-BioNTech’s and Moderna’s patent protection for their COVID-19 vaccines. At least some of Pfizer-BioNTech and Moderna’s patent applications relating to their COVID-19 mRNA vaccines may have been filed less than 18 months ago and have not yet been laid open for public viewing. For now, one of Moderna’s patent families, including PCT application WO 2017/070626 may provide some insight into its mRNA vaccines. This patent family relates to respiratory virus RNA vaccines and methods of using the vaccines. Two of BioNTech’s patent families may provide some insight into the Pfizer-BioNTech vaccine. A first patent family includes PCT applications WO 2016/045732 and WO 2016/046060, which relate to aaqueous lipid and/or liposome formulations with an increased chemical stability that can be used to deliver compounds including mRNA. A second patent family includes PCT applications WO 2017/059902 and WO 2017/060314, which relate to stabilization of mRNA and an increase in mRNA translation.
Some Concluding Remarks
The COVID-19 experience shows the potential for collaboration among governments and private companies that aim to develop vaccines at lightening-fast speed. IP protection, including patent rights, would be a helpful tool to facilitate such collaboration to tackle other diseases and encourage innovation and investment in this area. It is also important to consider the intersection between public health and patent protection to ensure that IP rights do not become a barrier to innovation and access to affordable medical products.
**This article was originally published by The Lawyer’s Daily (www.thelawyersdaily.ca) a division of LexisNexis Canada Inc.