Guest Post by Professor Jorge L. Contreras
The Patent Eligibility Restoration Act should be modified to prevent the reintroduction of patents on naturally-occurring genomic sequences that are isolated and purified in the lab, a change that will enable international pathogen research to continue while interfering little with private incentives to develop new biomedical technologies.
The Patent Eligibility Restoration Act of 2022 (PERA), introduced by Senator Thom Tillis (R-NC) in August 2022, is designed, among other things, to abrogate the Supreme Court’s patent eligibility decisions in Bilski, Mayo, Myriad and Alice. While Congressional action may be useful to clarify the confusing landscape of patent eligibility that has followed from these decisions, particularly in areas such as medical diagnostics, software and business methods, one piece of the eligibility puzzle that the Supreme Court got right, and which should not be changed, is Myriad’s holding that naturally occurring genomic sequences are ineligible for patent protection, even when “isolated and purified.”
In my book, The Genome Defense: Inside the Epic Legal Battle Over Who Owns Your DNA (New York: Algonquin, 2021), I discuss the Myriad case at length, focusing on its implications for human health and access to care. Like many others, I am concerned that PERA would make newly identified human genetic variants with significant health implications (e.g., this and this) patentable again, potentially removing them from the broad competitive market and placing them in the hands of the first research team that chances to identify them (a task that is, today, largely serendipitous and requires little innovative skill). I have previously discussed these concerns here. In this post, however, I focus on a different and less-discussed issue: the risk that non-human pathogenic genomic sequences (i.e., from viruses and bacteria) will be patented by non-U.S. institutions and used to delay the development of lifesaving diagnostics, vaccines and therapeutics.
When Patents Held Up Pathogen Research
Prior to the Myriad decision, research groups around the world were able to obtain patents on newly identified pathogen genomic sequences, including those of the H5N1 influenza strain and the SARS and MERS coronaviruses. As I discuss in this new article, these patents led to disputes and delays in research on the diseases and effective countermeasures. After Myriad, however, research groups appear to have stopped seeking patents on new pathogenic agents, as shown by the global experience with the Ebola and Zika outbreaks, leading to greater global cooperation and rapid responses by public health agencies and private developers of diagnostics, vaccines and therapeutics.
SARS-CoV-2: the Benefits of Patent-Free Pathogens
The genomic sequence of SARS-CoV-2 (the virus responsible for COVID-19) was first identified in early January 2020 by a team of researchers in China. On January 5, they uploaded the sequence to the publicly accessible GenBank database. Within days, diagnostic tests for the virus had been developed and a few months later, new vaccines against COVID-19 were being tested. As I have written previously, the unavailability of patents on genomic sequences, and the rapid uploading of the SARS-CoV-2 sequence to public databases, enabled researchers around the world to study the viral genome without fear of patent infringement and without the need to negotiate complex patent licensing agreements and pay royalties to the first researchers to determine its sequence. This open and unencumbered global research environment enabled scientists to identify and trace the spread of multiple pathogenic variants around the world, to understand the biological mechanisms of the virus, and to develop vaccines, diagnostics and therapeutics, all in record time.
PERA and U.S. Competitiveness
Senator Tillis, when introducing PERA, explained that a major goal of the bill is to enhance “the economic and global competitiveness of the United States”. He faults judicial decisions like that in Myriad for “undermining American innovation and allowing foreign adversaries like China to overtake us in key technology innovations.” Likewise, supporters of the draft legislation have enthusiastically proclaimed that it will “rev the US innovation engine once again”, warning that “[e]conomic growth, job creation, global competitiveness, public health and national security are all at risk until Congress repairs the law of patent eligibility that the Supreme Court has distorted.”
Yet, ironically, at least in the case of pathogenic sequences, PERA would work largely to benefit institutions in China and elsewhere, and could have adverse consequences for U.S. businesses and global public health.
Pathogens Usually Emerge, and are Sequenced, Outside the United States
Most serious pathogenic outbreaks result from the transmission of disease agents from animals to humans. These outbreaks originate in regions characterized by extensive animal husbandry, live animal markets, hunting or habitat loss. Within these parameters, the particular locale of a future outbreak is unpredictable. Recent infectious disease outbreaks have been traced, respectively, to China (SARS and H5N1), Saudi Arabia (MERS), Zaire and Congo (Ebola), Uganda and Brazil (Zika).
Likewise, once a pathogenic outbreak has entered human populations, the locations where its variants will emerge is also unpredictable. For example, the major variants of SARS-CoV-2 were first documented in China (original strain), the United Kingdom (alpha), South Africa (beta, omicron), Brazil (gamma), India (delta), Peru (lambda) and Botswana (omicron).
Today, genomic sequencing equipment is widely available at a modest cost. Researchers in 2021 estimated that the cost of sequencing a SARS-CoV-2 genome (only 1/100,000 the size of the human genome) is approximately $120, bringing it well within the reach of researchers in countries such as Gambia, which had, by mid-2021, sequenced more SARS-CoV-2 genomes than Germany.
It is also worth noting that countries, including the United States, that are parties to the World Trade Organization (WTO) Agreement on Trade Related Aspects of Intellectual Property (TRIPS) must give “national treatment” to applicants from all other member states. Thus, researchers from any TRIPS member country may apply for a U.S. patent and will be afforded the same rights as applicants from the United States. Indeed, for the past several years, most U.S. patents have been issued to non-U.S. applicants. In 2021, for example, of approximately 374,000 issued U.S. patents, nearly 200,000 (roughly 53%) were issued to foreign entities. This situation is not unique to the United States and is simply indicative of today’s global technology markets.
The combination of unpredictable sites of pathogenic emergence, inexpensive genome sequencing and national treatment under TRIPS suggests that if U.S. patents become available for pathogenic sequences, the parties most likely to obtain these patents will originate outside of the United States in countries that are likely sites of disease emergence. It is doubtful that allowing pathogen patenting would result in more patents being issued to U.S. applicants. Rather, U.S. and other companies that wished to develop diagnostics, vaccines and other technologies dependent on those sequences would either be excluded from the market or required to pay unpredictable prices for a license to operate under those patents.
Countries That Are Willing to Hold-Up Research
In recent years, certain foreign governments have shown themselves willing to hold-up international disease research and response efforts in order to gain concessions and advantages for themselves under the banner of “access and benefit sharing” (ABS). The most prominent example of this tactic occurred in 2006-07, when the government of Indonesia refused to share samples of the H5N1 influenza virus strain with the World Health Organization until it obtained commitments regarding access to any resulting biomedical products. Similar tactics were adopted by other countries during the MERS, Ebola and Zika outbreaks, as documented here.
If countries are willing to hold-up international research and disease response in order to secure ABS benefits for themselves, then they are also likely to use patents to extract further concessions from the international community. Demands for ABS concessions are not necessarily unjustified in view of past exploitation of local resources by foreign firms in developing countries. Yet even if justified, these barriers to the international response to emergent disease outbreaks can negatively impact global health. Reintroducing pathogen patenting will give countries where diseases emerge yet another tool to hold-up critical international research and development to the detriment of all.
Patents are not Necessary to Incentivize Pathogen Sequencing
One of the principal functions of the patent system is to provide financial incentives for innovators to develop new technologies. Yet, this rationale does not support the issuance of patents claiming pathogen sequences. The identification of new pathogens during emergent disease outbreaks is rarely undertaken by private industry. Rather, this function is usually carried out by public health agencies and academic laboratories, typically in the locale of the outbreak, and which are supported by public funds. Thus, unlike the development of vaccines and therapeutics, the financial incentives offered by patent exclusivity are not necessary to incentivize these early stage research efforts.
There Are Ample Patentable Innovations Relating to Disease Response and Containment Beyond Pathogen Sequences
It is also unnecessary to patent underlying pathogenic sequences in order to protect novel and innovative technologies such as diagnostics, vaccines and therapeutics. A 2012 WIPO study identified more than 50,000 patents and published patent applications across 57 countries that claimed the active ingredients of pneumonia, typhoid and influenza vaccines, most without claiming the underlying pathogen. Even more opportunities for innovation exist with respect to therapeutics, which can adopt a broad range of approaches to combating infection. For example, Regeneron filed more than 100 patent applications around the world on its Ebola drug Inmazeb, though the viral sequence was freely available on GenBank.
The broad availability of patents for innovation around pathogenic disease outbreaks is amply demonstrated by the COVID-19 pandemic. Despite the absence of patents claiming the SARS-CoV-2 sequence or its many variants, the research institutions and private firms that developed COVID-19 diagnostics and vaccines obtained numerous patents on the innovative aspects of their products. For example, one 2020 study found that, with respect to mRNA vaccine technology alone, 56 different entities ranging from large pharmaceutical companies to small and medium-sized entities held a total of 119 different patent families. Perhaps the most convincing evidence that sizeable numbers of patents have issued in this space is the expanding universe of patent litigation among mRNA vaccine manufacturers, now dubbed the “COVID-19 Patent Wars”. All of these examples demonstrate that COVID-19 technology innovations, vaccines in particular, have been amply protected without the need for patents on naturally occurring pathogenic sequences.
But is this Threat Real?
An argument that may be made against the need to limit further pathogen patents is that the ability of patent holders to enforce their patents, especially during global health crises, is limited by law. For example, in the United States, a patent holder cannot obtain a permanent injunction preventing an infringer from practicing a patented invention unless it demonstrates that the public interest would not be disserved by the entry of the injunction. Likewise, the International Trade Commission, when assessing the appropriateness of an exclusion order barring the importation of infringing goods into the United States, must take into account “the effect of such exclusion upon the public health and welfare.” These limitations have greatly reduced (but not entirely eliminated) the number of injunctions and exclusion orders issued with respect to medical and health-related technologies.
These limitations suggest that, at least in the United States, the existence of patents claiming pathogenic sequences might not represent a significant threat to pathogen research or biomedical product development. However, the existence of patents on these basic research tools, no matter what the likelihood of eventual litigation outcomes, can chill research, impose delays and prompt the payment of unwarranted fees. Moreover, even meritless claims are costly to fend off in court and impose some level of risk on defendants, particularly in the U.S. where fee shifting is rare. Thus, while various litigation doctrines may tend to lessen the threat of pathogen patents in the U.S., that threat is not eliminated entirely and may still represent a significant cost and deterrent to firms engaged in research and development of pathogen-based biomedical products.
Don’t Let PERA Potentially Hold Up Research Efforts
For the reasons outlined above, PERA should be modified to ensure that naturally occurring genomic sequences – even once isolated – remain ineligible subject matter for patent protection. Preventing the reintroduction of pathogen patents will enable international pathogen research to advance rapidly while interfering little with private incentives to develop innovative new biomedical technologies. In contrast, opening the door to pathogen patents arguably will provide opportunities for individual countries where outbreaks emerge to hold up international research efforts for their own benefit, causing delays and barriers to the development of lifesaving diagnostics, vaccines and drugs.