Calls For COVID Patent Waivers Persist As Pooling Initiatives Plough Ahead

The formulas for various COVID-19 vaccines remain shrouded in intellectual property protections – one of many factors preventing them from being manufactured in developing nations. Those in favor of upholding IP say that scrapping patents could stifle future innovation, but their opponents believe preserving COVID-19 related IP rights is limiting access to lifesaving medical tools.

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In October 2020, the Indian and South African governments called upon the World Trade Organization to suspend certain obligations of the agreement on Trade-Related Aspects of Intellectual Property Rights, to allow open access to the patents on COVID-19 products related to prevention, treatment and containment of the disease for the duration of the pandemic. This, they argued, would help to facilitate access to vaccines and therapeutics for the global population – not just for wealthy countries which could afford to import the products, or those with the ability to manufacture them locally. The rapid upscale of local production, they said, would be critical to ensure wider access to affordable and effective medicines.

Heading into 2022, the waiver proposal has yet to come to fruition, even after the submission of a revised draft in May 2021 that narrowed it down to cover “health products and technologies” relating to COVID-19 prevention, treatment and containment, after the original proposal was judged to be too broad.

The US ruffled feathers after the Biden administration declared support for waiving IP protections for COVID-19 vaccines, a stance it continues to uphold while many other jurisdictions – including the EU, UK and Canada – stand in opposition. (Also see "US COVID Vaccine Patent Waiver Is Big, Symbolic Blow For Pharma, But The Fight Is Just Beginning" - Pink Sheet, 5 May, 2021.) Despite these declarations, the US has done little to change the situation and the Office of the US Trade Representative has not taken any steps to push the waiver through.

Medicines for Europe legal affairs and trade director Sergio Napolitano told In Vivo: “There are two ways to solve an issue of access to certain products in a certain country. You can either donate the products, which is something that all pharmaceutical companies do regularly, or you actually engage to put in place policies that would stimulate the manufacturing of those products in that region.”

While those in favor of patent waivers say that scrapping IP rights for COVID-19 products will help secure access to lifesaving therapies in the developing world, others argue that waivers alone will not facilitate global access and that methods like patent pooling, tiered pricing and donations are more effective.

Many pundits also maintain that waiving COVID-19 patents could stifle future innovation, as firms may be reluctant to invest in critical research and development in the future if they fear IP rights could once again be scrapped.

The Case For A Vaccine Patent Waiver

The WTO’s TRIPS agreement commits members to guaranteeing a minimum level of IP protection on new inventions – such as COVID-19 vaccines and treatments – and can include measures such as 20-year patents and safeguards on copyrights, trade secrets and industrial designs.

Waiving parts of the agreement – specifically sections one, four, five and seven of part II of the agreement and the enforcement these sections under part III of the agreement – in relation to eligible COVID-19 products could help to facilitate their production in lower income and less developed countries. Many regions have had to rely on donations from schemes like CoVax, having been unable to manufacture the jabs locally or purchase sufficient doses to vaccinate their population at scale.

Médecins Sans Frontières policy advisor Victorine de Milliano said: “If you implement the TRIPS waiver and you lift IP for diagnostics, tests and vaccines you remove the legal and policy uncertainties that are in place in order to diversify supply and allow collaborations and manufacturers in lower-middle-income countries (LMICs) to produce these medical tools.”

Under TRIPS, global governments do actually have the authority to produce a patented product without the rights to that patent during public health emergencies, via compulsory licensing. But this has not helped facilitate worldwide access to COVID-19 products. Compulsory licensing requires each individual country to seek specific exemptions for the multiple patents involved in each vaccine or antiviral and has generally been dismissed as an unworkable solution when it comes to effectively addressing pandemic-related IP barriers, although it has still been used in certain cases.

De Milliano said: “The global response to COVID-19 has been insufficient in terms of who has gotten access to vaccines and who is going to get access to treatments. We see severe inequity – 10% of people in lower income countries have had their first jab while people in higher income countries have had the opportunity to get three. It’s not a global response and it’s not the way to tackle a global pandemic.”

She continued: “We see lifting intellectual property barriers as a necessary measure, but going hand in hand with the other measures such as companies openly sharing their technology – it’s not that if one thing happens the other one shouldn’t happen. We are in year three of the pandemic right now, we need all hands on deck at this point.”

Global Vaccine Rollout Limited By Manufacturing Capacity, Not Patents

While numerous lower-income nations and organizations like MSF stand in favor of the TRIPS waiver, others argue waiving the patents would not make a material difference to COVID-19 vaccine access in the short-term.

“Patents aren’t impeding the vaccine rollout,” said Reddie & Grose partner Neil Thornton, a lawyer who specializes in patent law across the biotechnology and pharmaceuticals sector. “Patents aren’t involved in the accelerated manufacture and production of vaccines. The limiting factors for their production are supply of materials, manufacturing capacity, specialist equipment, trained personnel and infrastructure.”

The argument that LMICs generally lack the manufacturing capacity to produce their own vaccines, regardless of IP access, has been repeated frequently since the waiver was first proposed. (Also see "Is Moderna Finally Ready To Make A ‘Big Commitment’ On Not-For-Profit COVID-19 Vaccines?" - Scrip, 23 Apr, 2021.)

Alongside failing to achieve the expressed intentions of the waiver, the pro-patent camp fears that an IP waiver could stifle future innovation in the pharmaceutical industry. In future, pharmaceutical companies might not invest in creating therapies for public health emergencies if their IP could be suspended and they do not see a return on their investment.

But these arguments are not without their counterpoints. A December 2021 study by MSF found that there were 120 pharmaceutical manufacturers across Asia, Africa and Latin American with the technical requirements and quality standards necessary to manufacture mRNA vaccines, indicating that LMIC manufacturing capacity is being understated in discussions relating to COVID-19 vaccine patents.

The two mRNA vaccines from Moderna and Pfizer/BioNTech are still largely manufactured in high-income Western countries, with the exception of one full manufacturing license that BioNTech has with Fosun in China.

“We need to be making billions more doses in order to vaccinate the world,” MSF said. “The most effective way to do so would be by diversifying and expanding the manufacture of mRNA vaccines. Unlike older (pre-2020) vaccine technologies which are cell-based, mRNA vaccines are made through biochemical rather than biological processes. This makes for a simpler system of production, and one that is more predictable and easier to transfer to other manufacturers than previous vaccine technologies.”

It is worth noting, however, that this list represents a baseline scan focusing purely on technical feasibility, rather than will or capacity. “The companies identified by us will need to conduct their own ‘gap’ analysis before venturing into mRNA technology,” MSF said. “Not every company in this list of 120 might necessarily want to start making mRNA vaccines: there are multiple factors to take into account, such as the ability to access the required investment, the strength of the drug regulatory authority in the country of manufacture, and, finally, the prospect of a strong business case.”

The arguments that vaccine patents could stifle future innovation in the pharmaceutical industry have also faced criticism, since COVID-19 vaccine research and development was heavily subsidized by taxpayers rather than funded out of pocket by manufacturers.

The candidate developed in the UK by AstraZeneca and the University of Oxford was around 97% publicly funded, while BioNTech received $445m in funding from the German government to assist with COVID-19 vaccine development and the US National Institutes of Health has joint ownership of the Moderna vaccine patent due to its fundamental role in the candidate’s creation, which was supported by $6bn in public funds.

Patent Pooling Provides An Alternative Approach

Even placing these concerns aside, patent waivers still may not be the best way to facilitate greater access to COVID-19 vaccines in LMICs. Patent pooling, where originators are able to maintain their IP but make arrangements to share it directly with third parties, could ultimately provide a more effective solution.

Thornton said: “Patent waivers would mean that companies might end up making vaccines independently, without collaborating with the companies that already know how to do it. They will need to show they meet the same quality and safety regulations. This will take longer and be far more expensive than if a license was granted and the know-how provided.”

He added: “These vaccines are complex, multi-component products, involving many different materials and processes, which are covered by several different patents, often with multiple companies owning patents on different aspects of the technology. Production of a vaccine needs collaboration between all these companies, providing opportunities for cross-licensing their patents and technology so they all benefit from a commercial deal.”

Passing on patents for complex products like vaccines without any extra support from the originator will most likely be insufficient for the vast majority third party manufacturers to step in and adequately replicate them. Vaccines are highly complex biological products and their production is dependent on specific manufacturing processes and practices which are not always disclosed in a patent. While a waiver would allow a third party to use the ‘recipe’ for a vaccine, it would not give them access to all the information needed to manufacture the product to the required standard.

In contrast, a patent pooling arrangement could allow manufacturers across lower-income nations access to the IP behind COVID vaccines and the support of a technology transfer from the originator to train the companies in producing the products. Without such an arrangement they would have to either work out the manufacturing process themselves through trial and error, a laborious and expensive process which many companies may shy away from.

That said, one company has now been successful in such an endeavor – and has established a patent pool to go with it. South African biotechnology company Afrigen has used a publicly available sequence of Moderna’s vaccine to make its own version of the product, which could be tested in humans before the end of this year. (Also see "Yes We Can: South African Scientists On Their Way With mRNA Vaccine" - Scrip, 8 Feb, 2022.)

Afrigen’s candidate is the first COVID-19 vaccine to be developed based on a pre-established product without the approval or involvement of the developer, as well as the first mRNA vaccine to be designed, developed and produced at scale in Africa.

The company has now signed an agreement with the Medicines Patent Pool to establish itself as a technology transfer hub for COVID-19 mRNA technology, receiving a €39m ($44.6m) grant to cover the work from 2021 to 2026.

As part of a consortium of manufacturers working to boost vaccine production in South Africa, and through a hub and spoke model, the project “aims to boost the vaccine manufacturing capacity of LMICs to respond more equitably to COVID-19 and future pandemics,” MPP said.

Afrigen managing director Petro Terblanche said: “The hub has been busy gearing up its Cape Town facility, recruiting staff, receiving training from international experts and partners such as Thermo Fisher Scientific and working with South Africa’s regulatory agency SAPHRA to ensure that once ready to produce, Afrigen meets all the prerequisite standards.”

LDC Controversy

Beximco’s antiviral launches have been aided by the TRIPS waiver, which exempts less economically developed countries, including Beximco’s native Bangladesh, from enforcing IP rights on pharmaceutical products. This has allowed the company to manufacture and sell generic versions of patented drugs both natively and to other LDCs that do not have a patent protection scheme in place.

Bangladesh’s status as an LDC has been criticized by some industry leaders, with Sanjiv Navangul – former chief of Janssen’s India business and current managing director and CEO of Baharat Serums and Vaccines Limited – tweeting: “Interesting that after eclipsing India in per capita income Bangladesh [is] still not ready to implement patent laws and has taken further extension to exempt them.”

But while Bangladesh’s per capita income rose to $2,227 in 2020-21 while India’s was $1,947 during the same period, in terms of absolute gross domestic product and other parameters India’s economy remains far ahead.

Bangladesh’s GDP at current prices is likely to rise to $565bn in 2026 from $355bn in 2021, while India’s is expected to increase from $2,946bn to $4,393bn in the same period.

 

MPP said that “Afrigen is already well on its way to setting up a state-of-the-art technology transfer and training hub for mRNA-based COVID-19 vaccines, including, as a first-generation vaccine, as a comparator and a relevant comparator for next-generation mRNA vaccines.” The technology transfer program “will provide sufficient transfer of know-how to allow recipient manufacturers to produce and release mRNA vaccines at scale to support clinical development, national/regional marketing authorization and WHO prequalification and sustainable supply to meet local and regional vaccine demand.”

The in-development product is also being designed to be better suited to at-scale production in LMICs, with developers aiming for greater thermo-stability of the vaccine to remove its reliance on cold storage. South African vaccine producer Biovac will be the first recipient of technology from the hub.

Patent pooling schemes such as this one have generally received more support from the global pharmaceutical industry than outright IP waivers.

Napolitano said: “In relation to COVID vaccines, Medicines for Europe supports initiatives that will stimulate voluntary licensing, where you negotiate a license with the IP owner alongside a technology transfer – whereas, when a government says ‘Okay, you can start producing this product from tomorrow,’ you can do it legally because you have the waiver or compulsory license, but you may not have the know-how internally.”

Patent Pooling Proves Itself In Antivirals Space

The vaccine patent wars sit in stark contrast to the way the generics industry has launched antiviral medicines for COVID-19. Vaccines are normally developed and marketed by the originator company, and it is much rarer to have a generic vaccine than a generic antiviral product. However, the arrangements made to facilitate antiviral developments could act as a blueprint for the sharing of vaccine IP, both for Afrigen and for others in the future.

Within weeks of the approvals of Merck & Co.’s molnupiravir and Pfizer’s Paxlovid (nirmatrelvir and ritonavir tablets, co-packaged for oral use), generics manufacturers across the globe had commenced production of their own generic versions to bolster global access to the treatments. (Also see "Generics Industry At The Forefront In War Against COVID-19 In 2021" - Generics Bulletin, 14 Jan, 2022.)

Beximco Pharmaceuticals came blazing ahead of its competitors, launching the world’s first molnupiravir generic, Emorivir, in November. (Also see "Beximco Launches World’s First Molnupiravir Generic" - Generics Bulletin, 9 Nov, 2021.) The firm later closed 2021 by launching the first generic Paxlovid, known as Bexovid. (Also see "Beximco Delivers First Cut-Price Generic Paxlovid" - Generics Bulletin, 4 Jan, 2022.) Beximco was also responsible for the first generic launch of intravenous antiviral remdesivir in May 2020. (Also see "Beximco Launches First Remdesivir Generic" - Generics Bulletin, 21 May, 2020.)

Access to COVID-19 drugs has also been bolstered by the MPP, which has signed deals with both Merck and Pfizer for their oral antivirals, facilitating their supply to low- and-middle-income countries.

MPP has now signed sublicensing agreements with 27 generics manufacturers based across 11 countries to supply generic molnupiravir to 105 LMICs. (Also see "Molnupiravir To Reach 105 LMICs Through MPP Agreement" - Generics Bulletin, 21 Jan, 2022.) Under the terms of the agreement with Merck, MPP was permitted “to further license non-exclusive sublicenses to manufacturers and diversify the manufacturing base for the supply of quality-assured or World Health Organization-prequalified molnupiravir to countries covered by the MPP License, subject to local regulatory authorization.”

Neither Merck, nor Ridgeback Biotherapeutics to which molnupiravir is licensed or Emory University where it was invented, will receive royalties for the sale of the drug while COVID-19 is classified as a public health emergency by the WHO.

MPP’s agreement with Pfizer will see the drug licensed to 95 countries representing about 53% of the world’s population, including all LMICs and some upper-middle income countries in sub-Saharan Africa. (Also see "Pfizer And MPP Sign Deal For Generics Of COVID-19 Candidate Paxlovid" - Generics Bulletin, 17 Nov, 2021.)

Under this deal, Pfizer will not receive any royalties on sales in low-income countries. It has also waived royalties on sales in all countries covered by the agreement while COVID-19 retains WHO emergency status. The company has said it will sell the supply it produces using a tiered pricing approach based on the income level of each country.

Pharma firms concerned about protecting their IP may well be breathing a sigh of relief. With the number of patent pool agreements relating to COVID-19 products slowly growing, it would not be unreasonable to bet that this is the trade format that will facilitate supply of vaccines and antivirals to LMICs for the foreseeable future.

Thornton said: “Without the patent system, everyone would keep everything as a trade secret. The patent system provides an incentive to publish what the invention is in return for a monopoly to stop others using it for a limited period of time. But it also facilitates collaboration and technology sharing.”

He noted: “Patents also help in that they provide an understanding of who owns what and facilitates the process to happen. If we didn’t have patents, I don’t think we would have the vaccine solutions we have now.”