From Scientific Discovery to Global Impact and Nobel Prize: Vaccines, Patents, and the Story of Hepatitis B

World Hepatitis Day draws attention to one of the persistent challenges facing public health: viral hepatitis. Although effective means of prevention, diagnosis, and treatment are now available, hepatitis B and hepatitis C continue to cause severe illness and substantial mortality worldwide, primarily as a result of liver cirrhosis and liver cancer, which in many cases develop following infection by these viruses. Viral infections represent a broader medical challenge, as effective solutions remain unavailable for many of them.

Within this broader picture, the story of hepatitis B is exceptional. Although no approved vaccine yet exists for most viral diseases, hepatitis B is an example of a viral disease in which a scientific discovery, the development of a vaccine, and large-scale vaccination programs have succeeded in changing both the course of the disease and its global prevalence. This story brings together a brilliant scientist and a breakthrough discovery, patents, huge commercial success, dramatic effect of public health and a Nobel Prize.

For many years, hepatitis B was one of the most significant risk factors for severe liver disease. The vaccine changed that picture entirely: according to the World Health Organization, the proportion of children under the age of five living with chronic hepatitis B infection declined from approximately 5% in the pre-vaccine era to less than 1% in 2019, and was estimated at approximately 0.6% in 2024. In Taiwan, for example, a hepatitis B vaccination program led to a significant decline in the incidence of liver cancer among children.

 

An Unexpected Scientific Discovery

As is often the case with major scientific discoveries, Dr. Blumberg’s discovery occurred unexpectedly. Blumberg was studying genetic variation among populations and examining blood samples collected from people around the world. During one of these tests, a protein was identified that reacted with specific antibodies.

Further research revealed that the protein was correlated with liver disease. A series of scientific and clinical observations eventually led to its identification as a protein located on the surface of the hepatitis B virus. The protein was initially called the “Australia antigen,” because it was found in a blood sample taken from an Aboriginal Australian, and was later given the scientific designation HBsAg, or hepatitis B surface antigen.

This discovery led to the development of a test for detecting the presence of the virus in the blood and, ultimately, to a vaccine designed to induce the production of antibodies against that same protein.

The immense importance of Dr. Baruch Blumberg’s discovery and subsequent developments received international recognition when he was awarded the 1976 Nobel Prize in Physiology or Medicine.

 

From the Laboratory to the First Patent

At an early stage, efforts were made to protect the practical application of the discovery through patents. In 1969, Blumberg and his colleague Dr. Irving Millman, who were named as the inventors, filed a patent application covering a vaccine against viral hepatitis and the process for producing it.

The rights to the U.S. patent, titled “Vaccine against Viral Hepatitis and Process,” which was granted in 1972 as U.S. Patent No. 3,636,191, as well as corresponding patents in several European countries and Japan, were assigned to the Institute for Cancer Research in Philadelphia, which later became part of Fox Chase Cancer Center. The patent related to a vaccine based on the same protein.

Dr. Blumberg was also a co-inventor of a patent relating to the diagnosis of infection with the hepatitis B virus, U.S. Patent No. 3,872,225.

It is noteworthy that the patent application was not filed at a late stage, after the product had already been completed. Rather, it was filed while the scientific knowledge that would ultimately form the basis for the vaccine was still beginning to take shape. The early filing bore fruits since those patents formed the basis of a licensing agreement with Merck, signed in 1976, for the continued development and production of the vaccine, which gave large economic benefits to that company and the owners of the patents.

 

Sixteen Years from Discovery to Vaccine

Approximately 16 years passed between the 1965 discovery of the protein that led to the identification of the hepatitis B virus and the approval of the first vaccine in the United States in 1981. Additional years of vaccine development followed. This period illustrates just how long and complex the path can be from a scientific discovery to a commercially available vaccine. This long time period also demonstrates the huge expenses associated with such developments and emphasize the immense importance of patents as a key element in securing return on the huge investment of time, human capital and money.

 

Where Science and Intellectual Property Meet

As a third-generation of a family of patent attorneys who grew up in the world of intellectual property, and as someone whose academic studies led to a Ph.D. in biology, I view the development of the hepatitis B vaccine from two distinct but closely connected perspectives. I have navigated between these two worlds for nearly 40 years in my work as a patent attorney advising technology companies, innovators and technology transfer organizations (TTOs).

From the scientific perspective, I see the research, the biological mechanism, the technological challenge, and the depth of development required to transform a scientific idea into a genuine medical solution. This is a real challenge. During scientific research, it is easy to become overwhelmed by a vast body of findings and to overlook the critical piece of information that could change reality. I have great respect and appreciation for those investigators who are able to step back, recognize the significance of their findings, and understand their potential.

From the perspective of a patent attorney, the challenge is to protect innovation and build an intellectual property protection strategy through patents and other means. On the basis of that protection, innovators can preserve exclusivity over the results of their research and development, achieved through substantial investment of time, talent and money, and thereby create and maintain value and securing a return on those investments.

In medical development in particular, although not exclusively, patent protection must provide enforceable rights and be sufficiently broad to prevent competitors from easily designing around the patents.

Vaccines are among the clearest examples of this connection.

 

Vaccines Cannot Be Developed Without Patent Protection

Vaccines have been among the leading contributors to the dramatic improvement in public health and life expectancy over the past century, alongside sanitation, antibiotics, preventive medicine, and improved living conditions. In recent years, we have all seen the importance of vaccines as a central component in controlling the COVID-19 pandemic and reducing severe illness and mortality.

Developing a vaccine is an immense scientific, regulatory, and commercial undertaking. It requires basic research, technological development, preclinical studies, large-scale clinical trials, regulatory approvals, the establishment of manufacturing capabilities that comply with regulatory requirements, quality control, global distribution, and, often, rapid adaptation to changing medical circumstances. The cost of developing a vaccine can reach hundreds of millions of dollars or more.

In many cases, the path from research to an approved and accessible product is led by commercial companies: pharmaceutical companies, biotechnology companies, platform companies that develop foundational technologies capable of being used repeatedly to create different products, and also startups that develop unique technologies and later enter into collaborations, licensing arrangements, or acquisition transactions with larger players.

In the medical field generally, and in vaccine development in particular, it would not be possible to raise the enormous amounts required for research and development without adequate patent protection. Companies in the medical field, even if large and with large cash reserves, will not undertake the substantial investments required for development or enter into agreements to acquire rights in a technology without the expectation of strong patent protection.

The author of this article was involved in a due diligence study for a global pharmaceutical company that was considering acquiring rights to a drug from another company, for hundreds of millions of dollars. The study identified significant doubts on the ability to obtain patent protection for the drug, and these doubts prevented this deal from closing.

What is true for large companies is even more so for smaller companies: without patent protection, companies may be unable to raise required capital, form collaborations, execute licensing deal, attract interest of strategic partners, or build a commercial model around high-risk medical technology.

 

Not One Patent, but a Portfolio of Patents

Medical developments, including vaccines, are mostly not protected by a single patent but rather through multiple layers of patent protection.

In the case of a vaccine, patent protection may relate to the immunizing substance itself, the method used to manufacture it, the formulation in which it is administered, the adjuvant (a substance added to certain vaccines to enhance the immune response to the vaccine antigen), the mechanism or device used to deliver it into the body, dosing and administration regimens, or sometimes a broader technological platform that may later be adapted for additional diseases.

 

Hepatitis B vaccines provide a good example of these layers of protection.

The first hepatitis B vaccines were based on extracting the HBsAg protein from the human plasma of individuals carrying the virus. Recombinant vaccines were later developed, in which the immunizing protein is manufactured through genetic engineering. This process enables controlled, consistent, and scalable production without dependence on a human plasma source.

The recombinant vaccine developed by Merck & Co., Recombivax HB®, was approved in the United States in 1986, followed by that of GlaxoSmithKline (GSK), Engerix-B®, in 1989.

These developments, including the production of HBsAg in yeast, recombinant DNA molecules encoding the protein, manufacturing processes, purification methods, and yield improvements, were covered by numerous patent rights. As a result, when the original patent expired in the United States in 1989 (at a time when the U.S. patent term was 17 years from the date of grant) and in other countries in 1990, patent protection covering more advanced developments remained in force for additional years. Those patents did not protect the results of the original scientific research itself. Rather, they protected the inventions required to transform the vaccine into a biotechnology product capable of being manufactured at scale.

 

The HPV Vaccine Tells a Similar Story

Another example of a successful vaccine originating in academic research is the technology underlying the vaccine against the human papillomavirus, or HPV. The academic research was conducted by scientists at the at the U.S. National Cancer Institute (NCI) who studied the molecular biology of HPV and developed virus-like particles capable of serving as a vaccine without presenting any risk of causing the disease, unlike the attenuated viruses used in many other vaccines. The NCI protected these developments through patents that were subsequently licensed to two global pharmaceutical companies, Merck and GSK.

The two companies developed and market vaccines protected by these patents: Merck’s Gardasil®, which has been marketed since 2006, and GlaxoSmithKline’s Cervarix®, which has been marketed since 2009. Clinical studies demonstrated that Gardasil® is fully (100%) effective in preventing persistent infection and precancerous lesions caused by two HPV strains responsible for approximately 70% of cervical cancer, as well as high effectivity in preventing other diseases caused by HPV.

According to Merck’s financial reports, Gardasil® generated average annual sales of approximately $6 billion between 2019 and 2025, reaching peak sales of approximately $8.5 billion in 2025. The licensing agreements generated substantial income for the NCI through milestone payments and royalties on sales.

This is a clear example of how patents can enable scientific research to be translated into investment, product development, and market development, together generating tangible economic value.

 

And This is at the Heart of The Matter: Innovation Does Not End with Discovery

In medicine and the life sciences, a strong patent is a central part of a company’s business story. It can affect the success of fundraising efforts, company valuation, the outcome of commercial negotiations, the completion of licensing transactions, the likelihood of strategic collaborations, market entry, and, more broadly, a company’s ability to create value from the results of its research.

 

World Hepatitis Day is intended to raise awareness of viral hepatitis and accelerate efforts relating to prevention, diagnosis, treatment, and access to medical services. The World Health Organization has established a clear objective: to eliminate viral hepatitis as a public health threat by 2030. In this context, the story of hepatitis B vaccines illustrates that medical innovation does not end with a scientific discovery. It also depends on the ability to transform that discovery into an accessible, patent-protected, adequately funded, and scalable solution.