The Patent Landscape Behind COVID-19 Vaccines

Development of vaccines to prevent COVID-19 has become a fascinating story, especially for those with any interest in life sciences. The speed in development and diversity of strategies that have arisen all around the world involve a vast patchwork of private companies, public institutions, and private-public partnerships such as CEPI (the Coalition for Epidemic Preparedness Innovations) and Gavi, a Geneva-based vaccine procurement organisation. However, most of the novel vaccines are being built using previously developed vaccine platform technologies. By vaccine platform technologies we refer to those techniques or methods that typically comprise multiple components or a common “recipe” and are used or have been proposed to be useful for producing more than one different vaccine1. Some platform technologies are older than others. For example, viral vectors carrying an antigen of choice have been used for longer and are more established than nucleic acidbased vaccines. In the development of Covid-19 vaccines, there has been a surprising uptake in the use of relatively new vaccine platforms. The choice of the less-tested platforms likely stems from the fact that the more traditional vaccine platforms have not been particularly successful in attempts to develop vaccines against coronaviruses, and also because many of the novel strategies promise a faster development timeline compared to the traditional platforms.

Given that most of the newer vaccine platforms, or at least some components of them, will have been developed within the past 20 years, many of them are likely to be still covered by patent protection. In this article, we took a look at the patent landscape covering some of the platform technologies that are being exploited by researchers in the race to develop an effective COVID-19 vaccine.

The WHO reported that as of July 14, 2020, there were 23 vaccines in clinical development and 140 vaccines in preclinical research2. Of this total of 163 vaccine candidates, 51 are reported as being developed using previously used platforms for vaccines against non-coronavirus targets. That leaves 112 vaccines that use a platform that has not previously been used for any approved vaccine. For the vaccines in clinical development, the number of vaccines that have been developed using a completely novel approach is surprisingly high, at roughly 50% (11/23). It is worth noting that vaccines that have been in development based on recent next-generation vaccine platform technology against other coronaviruses, such as SARS or MERS, have not yet resulted in clinically successful vaccines.

On the topic of platform technologies, the EPO has recently published a variety of search statements to help in identifying the most relevant documents in various technical fields3. This is fairly similar to the WIPO coronavirus search tool that we described in our previous article4 , however the EPO tool includes a specific section that is focussed only on vaccines. The vaccine platform categories listed are fairly broad, but include some of the specific platforms we will look at here, such as virus-like particles, nucleic acid based vaccines, nanoparticles and adjuvants used in formulating the vaccines.

New Patent Coverage? Based on prior experience in patent filings for vaccines at the time of epidemics, it is clear many patents have been and will be filed for the new COVID-19 vaccines. We cannot yet evaluate most of the claims that have been filed to cover the novel vaccines themselves or see by whom they have been filed, because patent applications are typically published no earlier than 18 months from the filing.

Having said that, the first patent application that specifically covers a COVID-19 vaccine was reportedly published on June 2nd, 2020 by China National Intellectual Property Administration5. The application No. CN202010193587.8 was only filed on March 18th by the Institute of Military Medicine, Chinese Academy of Military Sciences in conjunction with CanSino Biologics, a Chinese vaccine manufacturer. The patent application seems to describe the use of a human replication-deficient adenovirus as a vector encoding a specific S-protein sequence antigen. The description set forth that the claimed S-protein encoding nucleic acid sequence was optimised by reducing the content of rare codons to 3%, increasing the content of high-frequency codons to 81%, and increasing the GC content to 58%. The description further notes that the homology of the engineered S-protein antigen coding nucleic acid sequence with the original S-protein gene sequence was

The following table provides a look at some of the patent families covering components of platforms that are being used to develop candidate COVID-19 vaccines:

70.4%. The published claims as filed and re-produced in the INSERT as they were translated in the ESPACENET database, are illustrative of the types of claims one can anticipate to be included in other applications. The claims cover an isolated and optimised nucleic acid sequence for the specific antigen6, a specific vector or delivery method or vehicle delivering the antigen as a vaccine, and methods of use of the antigen as a vaccine, as well as methods of making the vaccine. The Chinese media reported that the Chinese Patent Office (CNIPO) granted the patent on August 17th , 2020, and it was issued on September 11th , 2020 as CN111218459B with claims that were identical to those published with the application. Interestingly, the claims are limited to use of spike protein of SEQ ID NO: 1 only.7 We anticipate the claims in patent filings for other specific COVID-19 vaccines to be relatively narrow in order to establish novelty over the early platform technology filings. This is clear, not only from the published Chinese patent application claims but also from our review of the patents covering the basic platform technologies, where other specific follow-on patent filings directed towards the use of the platform in making vaccines for preventing/treating other diseases have been filed.

The global story of the struggle in developing a vaccine against coronaviruses in general, and for COVID-19 specifically, should provide a backdrop for establishing inventiveness/non-obviousness that the patent offices around the world could acknowledge. However, establishing inventiveness/non-obviousness of any specific vaccine will also likely require some results that show that the particular approach surprisingly results in producing antibodies, and preferably neutralising antibodies against the SARS-CoV-2 virus.

While the complete genetic sequence of SARS-CoV-2 was published on January 11, 2020, public information on the specific SARS-CoV-2 antigen(s) used in the vaccine development is limited8. Like the published Chinese patent application with claims that identify a specific sequence ID as the antigen, we anticipate that other patent applications are likely to be filed to cover the specific, effective antigenic fragment(s) and their potential modification(s) and/or combination(s). In view of the uncertainty in biology, we further envisage that the specific vector constructs and/or specific formulations that elicit in vivo neutralising effect on the SARS-CoV-2 virus could be patented. Furthermore, the development process of these vaccines may also uncover some unexpected tweaks to the existing platforms that may make the platform perform better for future projects and therefore provide patentable claims. Any such advances that may be utilised in some form for possibly speeding up other vaccine development or manufacturing, targeting new or previously difficult to target pathogens, and making potentially safer and/or more effective vaccines could lead to further patent filings. Such follow-on filings will create a larger portfolio of patent documents sitting over and around each platform technology, with specific filings directed towards use in preventing and/or treating COVID-19.

What about Freedom-to-operate? As with any technology that utilises multiple components covered by multiple patent claims, clearing the right to make, use and sell a product that utilises the components can become a challenge. While collaboration initially appeared to be the popular route for COVID-19 vaccine development, the potential for significant commercial gains has already begun to brew some patent battles.

For example, the much talked about mRNA-platform-based vaccine under development by Moderna is facing headwinds from Arbutus. Arbutus claims that the delivery system, based on lipid nanoparticles (LNP) that are essential for delivering Moderna’s vaccine, infringes patents covering the original LNP technology

CANSino Biologics patent application publication No. CN111218459A claims as published:

1. A polynucleotide for coding a Sprotein of the 2019 novel coronavirus is characterised in that the sequence of the polynucleotide is shown as SEQ ID

NO: 1. 2. A vector comprising the polynucleotide of claim 1 . 3. The vector of claim 2, wherein the vector is pDC316. 4. A human replication-deficient recombinant adenovirus capable of expressing the polynucleotide of claim 1. 5. The recombinant adenovirus of claim 4, wherein the recombinant adenovirus is derived from an admax adenovirus system. 6. The use of the recombinant adenovirus of claims 4 and 5 in the preparation of a vaccine for the prevention of 2019 novel coronavirus. 7. The method of claim 6, wherein the recombinant adenovirus is formulated as an injection, nasal drop, or spray. 8. The use of claim 7, wherein the recombinant adenovirus is prepared as an intramuscular injection. 9. A method of preparing a recombinant adenovirus according to claim 4 or 5, said method comprising the steps of: (1) constructing a shuttle plasmid vector comprising a polynucleotide encoding a 2019 novel coronavirus s protein; (2) transfecting the shuttle plasmid vector and the skeleton plasmid

of step (1) into the host cell; (3) culturing the host cell in step (2); (4) harvesting the human replication-deficient recombinant adenovirus released from the cells of step (3); (5) amplifying and culturing the recombinant adenovirus in step (4); (6) purifying the culture product in step (5). 10. The method of claim 9, wherein the vector of step (1) is pDC316. 11. The method of claim 9, wherein the backbone plasmid of step (2) is pBHGlox_E1, 3Cre. 12. The method of claim 9, wherein the cell of step (3) is an hek293 cell. 13. The method of claim 9, wherein the amplification culture method of step (5) is suspension culture. 14. The method of claim 9, wherein the purification method of step (6) is source 30q chromatography.

patents owned by Arbutus9 (see above table for some of the relevant LNP filings held by either party). While Moderna’s battle over rights to use the Arbutus LNP technology began before the development of COVID-19 vaccine by Moderna, there is no doubt the stakes have gotten significantly higher in light of the initial development successes of Moderna’s vaccine candidate.

We will continue to follow the developing landscape of COVID-19 vaccines once a more complete picture of the filings emerges. It will be fascinating to observe how much of the collaborative spirit remains when the intellectual property positions are clarified.

REFERENCES

1. https://www.centerforhealthsecurity.org/ourwork/pubs_archive/pubs-pdfs/2019/190423OPP-platform-report.pdf 2. https://www.who.int/publications/m/item/ draft-landscape-of-covid-19-candidate-vaccines 3. https://www.epo.org/news-events/in-focus/ fighting-coronavirus.html 4. http://www.hgf.com/updates/news/2020/06/alook-at-the-wipo-coronavirus-tools/; https:// patentscope.wipo.int/search/en/covid19.jsf 5. https://www.natlawreview.com/article/ chinese-patent-application-coronavirusvaccine-published 6. https://worldwide.espacenet.com/patent/ search/family/070813158/publication/ CN111218459A?q=CN111218459 7. https://www.chinadaily.com.cn/a/202008/16/ WS5f391566a31083481726099a.html 8. https://www.nature.com/articles/d41573-02000073-5 9. https://www.evaluate.com/vantage/articles/ news/patents-and-litigation/covid-19vaccine-battle-just-got-interesting

Dr. Leena Contarino

Leena is a member of the HGF Life Sciences Team and also a member of the HGF Microbiome IP Team. She advises clients in creating strategies to capture, protect and commercialise inventions mainly in the areas of biologics, including DNA, RNA, peptides, and proteins, such as antibodies and enzymes, as well as cells and microbes. She also has considerable experience in diagnostics utilising biomolecules, particularly for personalised medicine applications. Ellie Purnell

Ellie is a member of the HGF Life Sciences team and also a member of the HGF AgBio and Industrial Biotechnology teams. She has developed a breadth of experience extending across a variety of technologies in life sciences and has a keen interest in biochemistry, cell biology and plant sciences. Ellie has specific experience working with multinational clients in the antibody, microbiology and plant genetics sectors.