In the United States and other countries, the academic and private sectors have a long history of positive and productive interaction with the biotech industry. Key scientific developments from academia, pioneering companies and risk-taking investors have created an industry that is now one of the most important in the world. What drives this interaction? In a word, synergy.
A nonprofit academic institution trains students for future roles in biotechnology; performs leading-edge life sciences research; has specialized research facilities and equipment; and engages locally, regionally and globally in the economy. Using funding from government agencies, foundations, companies and other external sources, academic institutions add to the base of scientific knowledge in biotechnology and make discoveries with significant impact and commercial promise. However, an academic institution does not make and sell products or generate profits. It can take an innovation only so far, after which it needs a partner with the resources, expertise, market and knowledge application skills to go further. Two examples of successful collaboration between academic institutions and private companies, both of which resulted in regulatory approval for COVID-19 vaccines, are described in Box 6.1 and Box 6.2.
The seminal work for the mRNA vaccine platform used by both the Pfizer/BioNTech and Moderna vaccines was performed in the laboratories of Dr Drew Weissman and Dr Katalin Kariko at the University of Pennsylvania (Penn).
Penn exclusively licensed the Weissman/Kariko mRNA platform patents to a small company, Cell Script, in 2016. Cell Script sublicensed the mRNA platform to Moderna in June 2017 and BioNTech in July 2017.
In October 2018, BioNTech signed a collaboration and exclusive license agreement with Penn which included a USD 5 million research budget and license terms that included USD 44.4 million in milestone payments, a low single digit royalty rate and a percentage of sublicensing income.
Also in 2018, Pfizer executed an exclusive license agreement with BioNTech for the mRNA platform patent rights that it either owned or controlled. The Pfizer/BioNTech agreement is reported to contain USD 185 million in upfront payments, USD 72 million in cash and USD 113 million in equity.
The Pfizer/BioNTech vaccine received emergency use authorization (EUA) on December 11, 2020 and full regulatory approval on August 23, 2021, making it the first USFDA-approved COVID-19 vaccine.
Moderna received its full regulatory approval in January 2022.
While academic institutions generally license platform technology on a nonexclusive basis so that the platform can be widely used, in this situation the exclusive licensee issued more than one sublicense, thereby allowing the platform technology to be more broadly used and provide greater public benefit. In the case of COVID-19, this resulted in vaccines being produced more quickly and on a larger scale.
Prior experience and work with other coronaviruses such as SARS (severe acute respiratory syndrome) in 2002 and MERS (Middle East respiratory syndrome) in 2012 at the University of Oxford provided a foundation for the development of a COVID-19 vaccine. Long-term support from the UK Vaccines Network (a partnership between the UK Medical Research Council and Department of Health and Social Care) led to the development of the viral vector vaccine platform and optimized manufacturing methods which provided a substantial head start for the COVID-19 vaccine work.
In early 2020, Vaccitech, a spin-off of the Jenner Institute, and the University of Oxford co-invented a vaccine for COVID-19 using the ChAdOx platform. This platform is based on an adenovirus which can be modified to make one or more antigens – proteins specific to a pathogen (such as SARS-CoV2) or cancer. The ChAdOx vector particles are formulated into a vaccine or immunotherapy to deliver the genetic blueprint for the antigen into the cells of the body and induce an immune response.
The Jenner Institute and Oxford Vaccine Group of the University of Oxford granted AstraZeneca an exclusive license to ChAdOx1 nCoV-19 in April 2020 to develop and distribute the resulting vaccine worldwide. License terms for supplying downstream (post-pandemic) commercial markets were subject to a separate agreement.
Clinical trials began in April 2020 and regulatory approval was obtained in November 2020. The ability to store the vaccine in a normal refrigerator allowed it to be administered in a broad range of global health settings. AstraZeneca pledged to sell the vaccine at a not-for-profit rate for the entirety of the pandemic and entered into several licensing agreements with large manufacturers, including the Serum Institute of India.
Through consistent funding from programs such as Europe’s Horizon 2020 research funding program with its focus on international cooperation, China’s Innovation Funding Program, which provides funding and financial incentives in China for European innovation stakeholders, and India’s “Startup India Seed Fund Scheme” to name a few, public and private organizations have been able to develop foundational technologies that are ultimately used to develop life-saving therapeutics.
The characteristics and strengths of a biotech company complement what academia can offer. Often, a company can neither afford nor justify the immense cost and risk of basic biological research and the complex infrastructure that supports it. It can, however, track and assess discoveries and inventions coming out of laboratories. The company can option or license a promising invention and use its own or an investor’s financial assets to further develop the idea. If the license is from an academic institution, ideally through an industry-supported research or consulting arrangement, the licensee can benefit from further studies by and continued interaction with the investigators who developed the invention and recruit key members of the scientific team when they complete their PhD studies. The company can fund clinical trials at the originating institution or a network of medical centers and hospitals. These aspects are similar in many regards to licensing between private institutions, whether a research organization or another company, where agreements such as those between Pfizer and BioNTech
The marriage of academic and biotechnology industry resources and strengths had led to, and continues to lead to, far-reaching developments in the biotechnology sector that have improved the human condition. These collaborations include, for example, the development of the prostate-specific antigen diagnostic test, the discovery of the gene for cystic fibrosis, a synthetic process to produce Taxol and the development of Xtandi, a life-extending therapy for prostate cancer patients. Figure 6.1 illustrates the Taxol development timeline in more detail, while Box 6.3 outlines the development of Xtandi.
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The patentable technology that became the blockbuster prostate cancer drug Xtandi was developed by University of California Los Angeles (UCLA) researchers Mike Jung and Charles Sawyers and their co-inventors. UCLA filed the first of a series of patents in 2004 and granted an exclusive license to Medivation in 2005. The timeline below shows the major events around Xtandi starting with the grant of this exclusive license. USFDA approval for the first approved indication for Xtandi was obtained in the third quarter of 2012 and was followed by regulatory approval in other major territories. In 2021, the first generic counterpart of Xtandi was approved.
August 2005 – Exclusive license
May 2012 – NDA filed
August 2012 – FDA approval
June 2013 – EC (European Commission) approval, first indication
March 2014 – Japanese Regulatory approval, first indication
November 2016 – Pressure on US Government to exert "March in Rights"
November 2016 – India denies Xtandi patent
November 2019 – China National Medical Products Admin (NMPA) approval
May 2021 – First generic approval
An alliance agreement between the University of Pennsylvania and Novartis yielded an on-campus research center and two USFDA approved personalized cell-based therapies (Box 6.4).
2012 – Penn and Novartis sign a global research and license agreement around chimeric antigen receptor (CAR) technologies.
2016 – As provided under the 2012 agreement, the Center for Advanced Cellular Therapies is built on a Penn campus.
2017 – USFDA approves a personalized cellular therapy (Kymriah) for the treatment of acute lymphoblastic leukemia in patients under the age of 25 years.
2018 – USFDA approval for the use of Kymriah for non-Hodgkin lymphoma.
2019 – Alliance agreement ends. A new narrowly focused agreement, which includes four clinical trials, is executed.
Patented technologies, whether developed in universities or public or private institutions, are utilized to attract companies/investors to further their R&D. In addition, startup companies are ordinarily formed based on some invention developed by an investigator in a university. The startup usually in-licenses the patent asset to a company, which uses its patent assets to attract investors or established companies to raise the funds necessary for moving products through the development and regulatory processes.