Bayh-Dole at 40: Accomplishments, Challenges, and Possible Reforms.

Over forty years have passed since the enactment of the Patent and Trademark Amendment (Bayh-Dole) Act, which authorized institutions to patent inventions arising from federally-funded research. Although some experts have heralded the Bayh-Dole Act as ushering in a new era of technological advances, others have been less sanguine about its impact. In recent years, the rising price of prescription drugs and the patenting of COVID-19 therapeutics and vaccines developed with substantial federal government support have rekindled the debate whether companies should receive more restricted rights to such products. In this article, we trace the history leading to the enactment of the Bayh-Dole Act and critically assess its strength and weaknesses as well as unresolved questions concerning its scope. Based on this analysis, we propose reforms to better align the Bayh-Dole Act with public values and health outcomes, including clarifying the scope of government use rights, making it easier to invoke march-in rights for failure to meet health and safety needs, increasing transparency in how patents are licensed, and testing different approaches to foster the development and application of inventions.

US public investment in development of mRNA covid-19 vaccines: retrospective cohort study.

OBJECTIVE: To estimate US public investment in the development of mRNA covid-19 vaccines. DESIGN: Retrospective cohort study. SETTING: Publicly funded science from January 1985 to March 2022. DATA SOURCES: National Institutes of Health (NIH) Report Portfolio Online Reporting Tool Expenditures and Results (RePORTER) and other public databases. Government funded grants were scored as directly, indirectly, or not likely related to four key innovations underlying mRNA covid-19 vaccines-lipid nanoparticle, mRNA synthesis or modification, prefusion spike protein structure, and mRNA vaccine biotechnology-on the basis of principal investigator, project title, and abstract. MAIN OUTCOME MEASURE: Direct public investment in research and vaccine development, stratified by the rationale, government funding agency, and pre-pandemic (1985-2019) versus pandemic (1 January 2020 to 31 March 2022). RESULTS: 34 NIH funded research grants that were directly related to mRNA covid-19 vaccines were identified. These grants combined with other identified US government grants and contracts totaled $31.9bn (£26.3bn; €29.7bn), of which $337m was invested pre-pandemic. Pre-pandemic, the NIH invested $116m (35%) in basic and translational science related to mRNA vaccine technology, and the Biomedical Advanced Research and Development Authority (BARDA) ($148m; 44%) and the Department of Defense ($72m; 21%) invested in vaccine development. After the pandemic started, $29.2bn (92%) of US public funds purchased vaccines, $2.2bn (7%) supported clinical trials, and $108m (<1%) supported manufacturing plus basic and translational science. CONCLUSIONS: The US government invested at least $31.9bn to develop, produce, and purchase mRNA covid-19 vaccines, including sizeable investments in the three decades before the pandemic through March 2022. These public investments translated into millions of lives saved and were crucial in developing the mRNA vaccine technology that also has the potential to tackle future pandemics and to treat diseases beyond covid-19. To maximize overall health impact, policy makers should ensure equitable global access to publicly funded health technologies.

Trust and Regulation: Assuring Scientific Independence in the FDA's Emergency Use Authorization Process.

Since 2004, the Food and Drug Administration (FDA) has had the authority to allow access to unapproved medical products via the Emergency Use Authorization (EUA) pathway during times of emergency. It was rarely used until the COVID-19 pandemic, when concerns arose regarding the role of political pressure in the FDA's issuance of some EUAs, such as for hydroxychloroquine. Although US government officials should be responsive to the public, democratic accountability must be balanced against the need for thoughtful science-based decisionmaking. Inadequate agency independence can diminish public confidence in government leaders and the FDA. To consider whether reform of the EUA process might be appropriate, we considered three possible sources of inspiration for balancing independence and accountability in government scientific decisionmaking: models in other countries, in other U.S. agencies, and within the FDA itself. Strategies used in these settings include: (1) expanding the role of advisory committees, (2) increasing transparency of the agency's decisionmaking process and supporting rationale, and (3) improving management of internal agency disagreement. Such reforms could improve public trust in public health regulation both related to and separate from future emergencies.

A Global Intellectual Property Waiver is Still Needed to Address the Inequities of COVID-19 and Future Pandemic Preparedness.

In October 2020, India and South Africa submitted a proposal to the World Trade Organization (WTO) to suspend IP on all COVID-19 vaccines, therapeutics, and diagnostics until widespread vaccination could help achieve immunity among people in low- and middle-income countries. After 18 months, the final WTO Decision substantially watered down the original text proposed by India and South Africa, limiting it only to patents on vaccines and the use of protected clinical trial data for regulatory approval. We address why an IP waiver under TRIPS consistent with the one originally proposed by India and South Africa is still needed to not only meet the ongoing inequities of COVID-19, but also to ensure the right precedent for future equitable pandemic preparedness and other crises affecting the global South. To meet the multilateral goals of the WTO, an IP waiver as proposed by India and South Africa is still needed to increase manufacturing capability for vaccines, therapeutics, and other COVID-19 health-related technologies.

Government Patent Use to Promote Public Health in the United States: Overcoming Nonpatent Exclusivities

GOVERNMENT PATENT USE One way to facilitate public access to high-cost medications is through government patent use.1 Given sovereign immunity-a legal doctrine immunizing the government from being sued without its consent-the federal government and its agents, such as generic drug manufacturers, have the ability to make or use patented inventions without the permission of the patent holder;in other words, protected by sovereign immunity, the federal government could use inventors' US patents without legal consequence (US patent rights do not apply overseas). [...]nonpatent exclusivities generally prohibit the approval of competing products only if they rely on data generated by another manufacturer. [...]the government or any third party could submit full new drug applications with original data.1,2 This strategy would not be able to circumvent Orphan Drug Act exclusivity for rare disease drugs because that act blocks the FDA from approving the "same drug" for the same disease or condition if it is a generic;however, because full trials would be needed, it might be feasible to pursue approval of a chemically distinct but therapeutically identical drug. [...]many agency actions are judicially reviewable under the Administrative Procedure Act (1946, Pub L No. 79-404)-a statute that waives the federal government's sovereign immunity. Fourth, Congress could amend the Federal Food, Drug, and Cosmetic Act (1938, Pub L No. 75-717) and the Public Health Service Act (1944, Pub L No. 78-410) to carve out exceptions to existing nonpatent exclusivities for government use.1,8 Although an exception exists for biologics the Public Health Service prepares when the biologic is unavailable from the license holder,9 this kind of authority could be expanded in terms of both to whom and to what it applies as well as under what conditions.

Premarket Development Times for Innovative Vaccines--To What Extent Are the Coronavirus Disease 2019 (COVID-19) Vaccines Outliers?

One reason expressed in surveys of people reporting coronavirus disease 2019 (COVID-19) vaccine hesitancy is how rapidly these vaccines have reached the market. To estimate the length of time the COVID-19 vaccine spent in research and development as compared to other novel vaccines, we apply previously established methods for estimating medical product development times, using the key associated patent filings cited by the manufacturer as the marker of when commercial development activity began. Applying these methods to a cohort of recently approved innovative vaccines and comparing them to the first-approved COVID-19 vaccine (BioNTech/Pfizer), we found key patent filings for the technology in this COVID-19 vaccine occurred 10.0 years prior to regulatory authorization. By this metric, the development timelines for innovative vaccines have been shortening since the 1980s, and the COVID-19 vaccine comfortably fits within this pattern. Vaccine development timelines have now even drawn to parity with many of the most commonly used drugs.

Characteristics of Clinical Trials Launched Early in the COVID-19 Pandemic in the US and in France.

Based on hierarchical classification and logistic regression of early US and French COVID-19 clinical trials we show that despite the registration of a large number of trials, only a minority had characteristics usually associated with providing robust and relevant evidence.