Since the emergence of the biggest global pandemic for more than a generation, research teams around the world have been working tirelessly to identify a treatment and vaccine for the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). In this article, we discuss some of these approaches, the significant progress made to date in the fight against COVID-19 and how companies and governments are taking unprecedented approaches to protecting their intellectual property in this time of crisis.
Library screening and re-purposing drugs
Pharmaceutical companies and research institutes are screening libraries of known compounds for their ability to specifically target the SARS-CoV-2 virus. For example, GSK has made compounds available from its library for screening for activity against COVID-19, and has also joined a collaborative research effort called the ‘COVID-19 Therapeutics Accelerator’, which was set up by The Wellcome Trust, the Bill & Melinda Gates Foundation and Mastercard, to identify potential treatments for COVID-19, accelerate their development, and prepare for the manufacture of millions of doses for use worldwide. In addition, Scripps Research has leveraged ReFRAME, which is one of the world’s leading drug repurposing collections that was established in 2018 by Calibr (the drug development division of Scripps Research), and has teamed up with scientists across the world to screen over 14,000 compounds in the hope of finding biological activity against the SARS-CoV-2 virus.
There is also hope that an existing anti-viral treatment already on the market can be re-purposed to combat COVID-19. The advantage of using an ‘off the shelf’ treatment, of course, is that the side effects and safety profiles, at least when used for their labelled treatments, are well-known and understood and should therefore provide a much quicker way to find an effective antiviral therapy.
A number of clinical trials are already underway testing the efficacy of existing drugs against SARS-CoV-2 virus. For example, the World Health Organisation (WHO) and its partners have launched the so-called ‘Solidarity’ international clinical trial for COVID-19 treatments. Four treatments are being currently studied by ‘Solidarity’, namely:
- Remdesivir, which has been used for Ebola treatment
- Lopinavir/Ritonavir, which is a licensed treatment for HIV
- Chloroquine and hydroxychloroquine are very closely related and used to treat malaria and rheumatology conditions respectively
- Interferon beta-1, which is used to treat multiple sclerosis
SARS-CoV-2 monoclonal antibodies
In the context of the treatment of viral infections, monoclonal antibodies bind directly to a viral antigen, such as a surface coat protein of the virus, and activate the immune system of the infected individual or directly block the action of the virus within them. Prior to the COVID-19 outbreak, there were a number of monoclonal antibody therapies being trialled, including antibodies to HIV, Ebola and Influenza.
While there has been only one monoclonal antibody approved for prophylactic treatment of viral infections (i.e. Palivizumab for the treatment of respiratory syncytial virus infections), monoclonal antibodies dominate the pharmaceutical market, with seven of the top ten best selling drugs of 2018 being monoclonal antibodies. Therefore, it is no surprise that many researchers are focusing their attention on antibodies specific for SARS-CoV-2 virus for treating COVID-19. For example, in the UK, AstraZeneca has joined forces with the Government and academia in the pursuit of coronavirus-neutralising antibodies, again highlighting the collaborative approach that many large pharmaceutical companies are taking at this time to find an effective therapy. The other benefit of having a highly specific SARS-CoV-2 monoclonal antibody is that it could also be used to detect the virus in patients and diagnose COVID-19, as well as to treat them.
Academics at Imperial College London are leading the development of a monoclonal antibody-based therapy and detection platform in a collaboration with the University of Kent, Hong Kong University and the National Institute for Biological Standards and Control, and they have recently received significant funding from the UK Medical Research Council. The exciting aspect of this work is that the antibodies may be able to diagnose and treat a wide variety of different coronavirus infections, and not just COVID-19, potentially providing a safeguard against future pandemic coronaviruses1.
While all of the above approaches may provide some relief, the ultimate goal for controlling the disease and protecting the world’s population from future waves of the virus is through vaccination. At the time of writing, there are currently six vaccines in clinical evaluation and about 70 in pre-clinical evaluation.
Many of the big players in the pharmaceutical industry are working to develop an effective vaccine, including Johnson & Johnson, Sanofi and GSK. However, some of the highest profile vaccine research in the UK is being carried out by teams at Imperial College London and The Jenner Institute at Oxford University, who have both received significant grants from the UK Government to progress their work, with Imperial College London receiving £22.5 million to fast-track the development of their coronavirus vaccine, and Oxford receiving £20 million.
Imperial College London’s novel vaccine utilises self-amplifying RNA, which works by injecting new genetic code into a muscle, instructing it to make a protein that is present on the surface of the coronavirus, to trigger a protective immune response. Work so far has shown that animals given the vaccine are able to produce neutralising antibodies against SARS-CoV-2. The team at Imperial College London is developing the vaccine and will test whether it can produce the same response in humans, which could ultimately protect against COVID-19. Clinical trials in humans are expected to start in June 20202.
Oxford University’s vaccine is based on an adenovirus, ChAdOx1, which is a weakened form of the common cold virus that infects chimpanzees. They have engineered the adenovirus vector to carry genetic material encoding the SARS-CoV-2 Spike protein, which is a protein found on the surface of the virus. The Oxford team speculate that exposing a patient’s body to the viral coat protein in this way will elicit an immune response producing antibodies, which will help stop the SARS-CoV-2 virus from entering human cells and prevent infection. Clinical trials have already begun on Oxford University’s vaccine called ‘ChAdOx1 nCoV-1’.
Trials are currently taking place across the UK, including Oxford, Southampton, Bristol and London and are expected to run for the next six months. Industrial partners will be vital in progressing and producing the vaccine and Oxford University and AstraZeneca have announced an agreement for the global development and distribution of Oxford University’s recombinant adenovirus vaccine3.
Patents and COVID-19
Many of the drugs being tested for efficacy against COVID-19 are under patent protection and any newly developed vaccine or therapy would also be eligible for patent protection. It is also possible to protect a new medical use of a known and patented composition by second medical use claims, or their equivalent, in most jurisdictions. Therefore, many patent applications may have been, or will be, filed to COVID-19 therapies and related technologies.
The patent system provides a way by which companies can attempt to make worthwhile all of the time and financial investment they have put into developing their new drug. Patents encourage innovation, resulting in the development of new therapies, which is of benefit to all.
However, at times of crises such as this, when fast and cost-effective access to effective drugs will be needed to fight COVID-19, there will be pressure on the pharmaceutical industry to provide access to these therapies at a reasonable cost and also to collaborate in an effective manner.
Many jurisdictions have a mechanism that enables access to intellectual property in public health emergencies known as ‘compulsory licences’. These enable drug-makers to legally manufacture and sell patented dugs during public health emergencies. These often require the drug-makers to pay the patent holder a fair and reasonable market price for the drug. A number of countries have passed new compulsory licencing legislation since the start of the COVID-19 outbreak, including Canada, Germany and France, all of which appear to make the issuance of a compulsory licence quicker and easier, seemingly pre-empting future issuances of compulsory licences if an effective treatment is discovered.
However, at the time of writing, Israel is the only country to issue a COVID-19 related compulsory patent licence, to Lopinavir/Ritonavir (brand name Kaletra®) owned by AbbVie. This may be due to the uncertainty of the efficacy of current treatments and, if a patented therapy is shown to have proven efficacy, more countries may start to introduce compulsory licences.
Costa Rica’s president, Carlos Alvarado Quesada has called for a voluntary global pool of existing and future intellectual property rights to COVID-19 treatments, to provide free access or licensing on affordable and reasonable terms, and this idea has already been endorsed by WHO Director-General Tedros Adhanom Ghebreyesus. In light of this unprecedented crisis, many companies have already adopted a collaborative attitude when it comes to enforcing patent rights and have voluntarily waived their intellectual property rights in order to make their products more easily available. For example, on 20 March 2020, AbbVie stated that, due to the coronavirus pandemic, it will stop enforcing its patent rights in respect of Kaletra®, including the generic supply of the treatment for HIV.
Remdesivir is a drug developed by Gilead Sciences Inc. and is one of the existing anti-viral treatments that has shown most promise for treating COVID-19. Having initially obtained orphan drug designation in the US, which would have entitled Gilead to a seven-year market exclusivity period among other advantages, it has now requested that the orphan drug status is rescinded after public criticism of the move.
In 2016, Gilead filed a patent application (WO 2017/049060) directed to the use of Remdesivir for the treatment of arenaviridae and coronavirus infections, including Acute Respiratory Syndrome coronavirus (SARS) and Middle East Respiratory Syndrome coronavirus (MERS). On 6 February 2020, Gilead began working with the Chinese Healthcare Department to conduct clinical studies into the effectiveness of Remdesivir for treating COVID-19 patients and offered to provide free Remdesivir in these trials. It was therefore surprising that, in March 2020, The Wuhan Institute of Virology of the Chinese Academy announced that it had filed a patent application on 21 January 2020 for the use of Remdesivir specifically to treat SARS-CoV-2 infections.
While Gilead has published patent applications directed to coronavirus, the use of Remdesivir to specifically target SARS-CoV-2 infections is still at least prima facie patentable, in that it would constitute a further medical use of Remdesivir to treat a novel coronavirus species that is not disclosed in any of Gilead’s earlier patent applications. There has been a suggestion that The Wuhan Institute’s filing was a tactical move for use as a bargaining chip with Gilead during their cross-licensing negotiations and to ensure access to the drug. However, compulsory licensing mechanisms could enable access to Remdesivir anyway (if needed) and this has been seen by many as a provocative move that could, in fact, hamper the collaborative effort that has been seen so far.
Nearly every big player in the pharmaceutical industry has announced collaborations with industry, academia and governments in the race to find a coronavirus treatment or vaccine, and many have already stated that they do not intend to profit from this work. For example, GSK has released a statement that it does not expect to profit from its portfolio of collaborations for COVID-19 vaccines during this pandemic. The thought of governments across the world issuing compulsory licences and companies halting the enforcement of their patents and opening up their libraries and drugs to the research world may have seemed far-fetched just a few months ago. However, these are unprecedented times.
As treatments and vaccines are developed, it will be interesting to see how intellectual property rights holders will ensure access to their technologies and how governments will balance the public need with patentee’s interests. However, with governments, academia and industry all joining forces on an unprecedented scale in the fight against COVID-19 and working to the goal, we hope that the correct balance will be struck, human ingenuity will prevail and we will eventually have a treatment and/or a vaccine that will be accessible to all.