Patents Cannot Be Blamed for Inequitable Access to COVID-19 Vaccines

INTRODUCTION

The COVID-19 pandemic has been unique in many aspects. The speed of its spread over the globe, the death toll it causes, and the impact it has on the global economy are unrivalled in modern history, at least when the so-called Spanish flu is counted out. At the same time, science has never witnessed such a quick development of potent vaccines. The first COVID-19 cases were reported in Wuhan, China, on December 31, 2019. On January 12, 2020, Chinese researchers uploaded the SARS-CoV-2 genome to Genbank (NCBI Reference Sequence: NC_045512.2). On January 30, 2020, the Director-General of the World Health Organization (WHO) declared the outbreak of COVID-19 to be a public health emergency of international concern, and on March 11, 2020, the WHO characterized it as a pandemic. The first vaccines were available before the end of the year.

Ever since COVID-19 vaccines became a realistic option, part of the public discussion has been about a fair and sufficient distribution of the vaccine. Because COVID-19 is a global pandemic, the WHO has initiated the COVAX program, with the goal to accelerate the development and manufacture of COVID-19 vaccines and to guarantee fair and equitable access for every country in the world.

In October 2020, South Africa and India petitioned the World Trade Organization (WTO) to support their attempt to suspend patent protection for COVID-19-related drugs and technologies. Nongovernmental organizations (NGOs) like Doctors Without Borders have supported this initiative, inter alia, with a social media campaign. On December 10, 2020, the WTO, which is an international organization that administrates trade rules among its 164 member nations, discussed the proposal at its Council for Trade-Related Aspects of Intellectual Property Rights (TRIPS) meeting.

In May 2021, a revised proposal was submitted in which the focus shifted to “health products and technologies” for prevention, treatment, or containment of COVID-19. In the same month, the new U.S. administration under President Biden offered conditional support, yet only for “vaccines,” while Germany and some other European countries kept opposing the initiative.

There can be no doubt that a fast and equitable distribution of COVID-19 vaccines is the only key to overcoming this pandemic. Nothing is won if the Northern Hemisphere achieves a sufficiently high vaccination status, and eventually herd immunity, but the Southern Hemisphere lags behind. In other words: “How can anyone be safe until everyone is safe?” ¹

With the development of new variants with assumed higher infectivity, the call for patent waivers was again raised, e.g., by members of the European Parliament. ²

However, it may be a bit shortsighted to blame patents for the current disparities. Different authors have made clear that (1) insufficient know-how transfer and (2) supply chain problems, combined with (3) lack of production capacities, are the true reasons for this situation. ³ At least with regard to the first two reasons, Northern Hemisphere economies indeed have a strong responsibility, and also the WHO has addressed this issue by launching, in May 2020, the COVID-19 Technology Access Pool (C-TAP), which was initiated to “facilitate timely, equitable and affordable access of COVID-19 health products.”

Patent applications are usually published 18 months after filing. Because COVID-19 is such a young disease, patents which have specifically been filed to protect the actual vaccines have just been published but are not granted yet—and so can hardly be blamed for keeping vaccine manufacturers in less-developed countries out of the field.

However, background technologies have been developed earlier, so that their respective patent applications are already visible. Yet the idea that in order to be enabled to make a given vaccine, one would just need access to what is written in a patent is quite naive. Patents merely disclose key features, or even only individual building blocks, of a complex vaccine, and hence cannot serve as a blueprint for their manufacture.

FOCUS OF THIS STUDY

We have discussed the patent landscape of some COVID-19 vaccines recently. ⁴ In the present article, we investigate the patent situation for the first COVID-19 vaccine that went through full marketing authorization—BNT162b2 by BioNTech/Pfizer—and analyze whether the patent situation has an impact on the most important non-Western vaccine-producing countries (“countries of interest”), namely Brazil (BR), Egypt (EG), India (IN), Mexico (MX), Pakistan (PK), and South Africa (ZA). See Table 1 for information on major vaccine-producing companies in these countries and manufacturing agreements therewith. ⁵ In our analysis, we have intentionally left out Russia and China, because both countries are net exporters for COVID-19 vaccines, so do not seem to be blocked by third-party patents.

BACKGROUND TECHNOLOGIES

In a first step, we were able to identify a set of international patent applications—assigned to BioNTech or third parties—that cover background technologies as well as individual elements of BNT162b2. We have then analyzed whether these international patent applications have national counterparts in the countries of interest.

TECHNICAL CHARACTERISTICS OF BNT162B2

BNT162b2 is well described in literature. ⁶ It is an mRNA vaccine having the following technical characteristics.

PATENT APPLICATIONS PROTECTING COVID-19 MRNA VACCINES PER SE

In a second step, we identified patent applications that protect COVID-19 mRNA vaccines per se. As said, patent applications are usually published within 18 months after filing. Because the genome of SARS-CoV-2 was made publicly available on January 12, 2020, the earliest possible date for which the publication of a patent application directed at a COVID-19 vaccine per se could be expected was July 12, 2021. ¹¹

METHODOLOGY AND RESULTS

Based on the above technical considerations, we identified a series of third-party international patent applications (also called “PCT applications”) that cover the respective technologies. These applications are shown in Table 2.

Patents and patent applications have a territorial (and sometimes, like in Europe, a superterritorial, yet still regionally confined) effect only. Hence, in order to block a domestic industry from producing a vaccine, the respective patent applications must at least have pending national counterparts in that respective jurisdiction, if not granted national counterparts.

The process of entering the so-called national phases, which lead to the pending national counterparts, requires that the respective patent applicant actively initiate such national phases. Until the applicant decides to enter national phase in a given country, the patent application will not take any legal effect therein.

Because internet-based patent databases like INPADOC provide insufficient coverage for some of the countries of interest, we obtained information directly at the respective patent offices. It should not be left unnoted that some of the patent applications shown in Table 2—or, more precisely, individual national phases thereof—are subject to legal disputes. ¹² However these disputes do not affect the freedom of third parties to operate in the above-mentioned countries of interest.

As Table 2 shows, for most of the key features of BNT162b2 encompassed by international patent applications, no pending national counterparts exist in the countries of interest. Hence, patent owners have simply no legal means to block the respective domestic industries from using the respective technologies.

As regards patent applications protecting COVID-19 mRNA vaccines per se, we identified three patent families, assigned to Moderna, CureVac, and BioNTech. Moderna missed the above key date by less than three weeks, as it filed a priority application on January 28, 2020; i.e., 16 days after the SARS-CoV-2 genome was published. The application essentially comprises the spike protein sequence as translated from the published SARS-CoV-2 genome, plus the 2P mutant that could be derived from the earlier work performed by the NIH, labelled SEQ ID NO: 29.

CureVac came slightly later and filed its priority application on February 2, 2020, while BioNTec filed on April 22, 2020. It is not really surprising that all three applications cover similar subject matter, with all of them claiming the exact same mRNA sequence encoding for the 1273 aa long spike protein comprising the K968P and V969P substitutions.

See Table 3 for an overview. All three patent families are still in what is called “the international phase,” so national counterparts—in particular, in the countries of interest discussed herein—are not yet to be expected (see Table 3 for the respective deadlines). Even when national phases have been entered, the examination and eventual grant of these patent applications may still take anywhere between two and five years.

It needs to be noted that Moderna already has a corresponding U.S. application pending (Pub. no. US2021228707A1) which received notice of allowance on August 27, 2021, with the following independent claim:

1. A messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) that comprises a nucleotide sequence having at least 80% identity to the nucleotide sequence of SEQ ID NO: 28 and encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 29.

Because Moderna, CureVac, and BioNtech use mRNA encoding for the exact same spike protein including the 2P substitution, there is a likelihood that even in view of the degeneracy of the genetic code, said patent claim also covers BNT162b2.

Hence, it will not surprise if this case gives rise to legal disputes. In fact, tensions between NIH and Moderna have already been reported, because NIH claims it contributed to development but has not been named as coapplicant. ¹³

Also, it should be noted that a granted U.S. patent has no blocking effect in any countries outside of the United States.

Further, an opinion issued by the European Patent Office (EPO) exists which was provided on behalf of the World Intellectual Property Organization (WIPO), which administrates international patent applications. In said opinion, the subject matter of the claims of Moderna's international patent application were deemed to lack an inventive step, in view of the published SARS-CoV-2 genome and the prepublication of the 2P substitution motif by NIH. ¹⁴ In national phases, most patent offices refer to such opinion, meaning that Moderna's national phase filings will experience considerable headwind.

CONCLUSION

Patent applications which do not exist in a given country do not have to be waived. Hence, simply and plainly, third-party patents cannot be blamed for the fact that in the key countries discussed herein, the domestic industry has not yet started to develop and/or manufacture BNT162b2m or a similar mRNA-based vaccine.

This finding does not, of course, deliver a complete absolution for vaccine manufacturers in the Northern Hemisphere. As discussed already, what is needed is (1) an increased know-how transfer, not only for developing, manufacturing, and approving the vaccine per se, but also, where necessary, for the upscaling of production capacities; (2) the lifting of all export bans regarding vaccine ingredients as well as vials, etc.; and (3) financial aid, too.

The fact that the new U.S. administration seems to support the patent waiver initiative leaves a bitter taste, in view of the fact that the U.S. had a de facto export ban in place not only for COVID-19 vaccines but also for seemingly trivial components, such as syringes and needles. ¹⁵

Interestingly, the WHO, in its above-mentioned C-TAP initiative, stated that one reason why it decided to advance immediately the know-how transfer of mRNA vaccines would be that “many technical features thereof are free of Intellectual Property Rights in many countries of the world.” ¹⁶ In particular, in the mRNA technologies, we are all reaping the harvest of innovations that were brought to fruition with venture capital funding by investors—who see patent protection as insurance that they will have at least a chance to recoup the resources they have advanced.

One should not be distracted by the fact that some vaccines, including BNT162b2, have been developed with record speed, and feature so far unseen efficacy.

First, BNT162b2 is the result of 20 years of continuous development of mRNA vaccines. The idea to use mRNA for vaccination was for the first time tested and described by Ingmar Hoerr, who founded CureVac in 2000. ¹⁷

Second, even in modern times, vaccine development is far from being a safe bet, yet it continues to be a risky business, as exemplified by the disappointing results of CureVac's CVnCoV, ¹⁸ Sanofi's VAT00008, ¹⁹ or Merck‘s V590 and V591. ²⁰ These failures resulted in considerable financial losses for the respective companies and their shareholders.

Abolishing the prospect of receiving exclusivity, for a limited amount of time, in return for taking such risk would severely discourage innovation—and this is the last thing we need in these times.

As reported recently, ²¹ Pfizer and BioNTech announced that they signed a letter of intent with the Biovac Institute in South Africa's Cape Town to transfer technology, install equipment, and develop manufacturing capability to produce BNT162b2. When fully ramped-up, vaccine production is said to exceed 100 million doses, to be distributed exclusively within African countries. The raw material for the vaccines will be imported from Europe and the first doses will be produced in 2022.

While this may come too late for so many, it should be noted that India's government in March 2021 suspended exports of ChAdOx1, which India's Serum Institute had licensed from AstraZeneca, to African countries under the global vaccine distribution initiative COVAX. The ban is due to the catastrophic increase of COVID-19 cases in India, ²² so as to secure sufficient supplies for the Indian population. It is, therefore, somehow understandable, yet has already been blamed as “vaccine nationalism.” ²³

However, the ban leaves many African countries without the long-awaited vaccines, and patents are hardly to be blamed for the resulting shortage—despite the respective allegations raised by the Indian government in its October 2020 WTO petition.