The use of biological methods (often genetic engineering and related advanced-molecular-biology applications) to produce products, processes, and related services. Generally, these are patentable under U.S. patent law.
The process of taking an invention or discovery to the marketplace. It involves working the idea into a business plan, consideration of protection options, and determining how to market and distribute the finished product.
intellectual property (IP) (close)
Creative ideas and expressions of the human mind that have commercial value and are entitled to the legal protection of a property right. The major legal mechanisms for protecting intellectual property are copyrights, patents, and trademarks. IP rights enable owners to select who may access and use their intellectual property and to protect it from unauthorized use.
A grant of permission to use an IP right within a defined time, context, market line, or territory. There are important distinctions between exclusive licenses and nonexclusive licenses. An exclusive license is “exclusive” as to a defined scope, that is, the license might not be the only license granted for a particular IP asset, as there might be many possible fields and scopes of use that can also be subject to exclusive licensing. In giving an exclusive license, the licensor promises that he or she will not grant other licenses of the same rights within the same scope or field covered by the exclusive license. The owner of IP rights may also grant any number of nonexclusive licenses covering rights within a defined scope. A patent license is a transfer of rights that does not amount to an assignment of the patent. A trademark or service mark can be validly licensed only if the licensor controls the nature and quality of the goods or services sold by the licensee under the licensed mark. Under copyright law, an exclusive licensee is the owner of a particular right of copyright, and he or she may sue for infringement of the licensed right. There is never more than a single copyright in a work regardless of the owner’s exclusive license of various rights to different persons.
patent (U.S.) (close)
A grant by the federal government to an inventor of the right to exclude others from making, using, or selling his or her invention. There are three kinds of patents in the United States: a standard utility patent on the functional aspects of products and processes; a design patent on the ornamental design of useful objects; and a plant patent on a new variety of a living plant. Patents do not protect ideas, only structures and methods that apply technological concepts. Each type of patent confers the right to exclude others from a precisely defined scope of technology, industrial design, or plant variety. In return for the right to exclude, an inventor must fully disclose the details of the invention to the public so that others can understand it and use it to further develop the technology. Once the patent expires, the public is entitled to make and use the invention and is entitled to a full and complete disclosure of how to do so.
Your source for expert commentary on IP management issues.
MIHR/PIPRA. 2007. Improved Production of a Natural Product Treatment for Malaria: One World Health, Amyris, and the University of California at Berkeley. In Executive Guide to Intellectual Property Management in Health and Agricultural Innovation: A Handbook of Best Practices (Krattiger A, RT Mahoney, L Nelsen et al.). MIHR (Oxford, UK), PIPRA (Davis, USA), Oswaldo Cruz Foundation (Fiocruz, Rio de Janeiro, Brazil), and bioDevelopments-International Institute (Ithaca, USA). Available online at www.ipHandbook.org.
Editors’ Note: This case study was prepared by MIHR members of the Technology Managers for Global Health (TMGH), a special interest group of the Association of University Technology Managers (AUTM) (see www.tmgh.org) and adapted for this Executive Guide. The original version was published as part of a collection of case studies: MIHR/TMGH. 2007. Academic Licensing to Global Health Product Development Partnerships (ed. U Balakrishnan). MIHR: Oxford, U.K.
© 2007. MIHR/PIPRA. Sharing the Art of IP Management: Photocopying and distribution through the Internet for noncommercial purposes is permitted and encouraged.
Improved Production of a Natural Product Treatment for Malaria: Oneworld Health, Amyris, and the University of California at Berkeley
In December 2004 the Bill and Melinda Gates Foundation1 awarded a five-year product development grant to the Institute for OneWorld Health (iOWH),2 a nonprofit pharmaceutical company, to create a unique three-way partnership between iOWH, a university (University of California at Berkeley),3 and a for-profit company (Amyris Biotechnologies, Inc.).4 The goal of this project5 is to significantly reduce the cost of artemisinin, a key precursor in the production of Artemisinin Combination Therapies (ACT), through synthetic biology, industrial fermentation, and chemical synthesis. Artemisinin is chemically converted to one of several derivatives and then combined with other drugs to make an ACT for the treatment of malaria.
Malaria is a parasitic blood disease that inflicts as many as 500 million people annually. About 1.5 million people die each year from the infection, primarily children in Africa and Asia. More than half of the deaths occur among the poorest 20 percent of the world’s population. Studies in Vietnam have shown that the botanically derived medicine, artemisinin derivatives, can reduce deaths from the illness by 97 percent. However, the current cost of a three-day course of drugs containing artemisinin is US$2.40, which places it out of reach for people in many nations where the disease is most prevalent. Reducing the price would make the treatment more widely accessible.
Artemisinin is currently extracted from the worm-wood plant, which is supplied by farmers in Vietnam and China (and more recently, Africa). Seasonality and availability of the plant contribute to the high price of the drug. The Gates-funded project hopes to eliminate the need for plant extraction by utilizing a platform technology of synthetic biology developed by Dr. Jay Keasling at the University of California (UC), Berkeley.6 The goal is to lower the cost of artemisinin-containing drugs ten-fold by producing a consistent, reliable, high-quality supply of artemisinin in microbes.
The US$42.6 million grant was divided among the three partners: US$8 million to UC Berkeley for continued basic research, US$12 million to Amyris for applied research on the fermentation and chemical processes, and US$22.6 million to iOWH to perform the required regulatory work and lead the implementation of the product development strategy for the developing world. UC Berkeley’s role focuses on the engineering of drug-precursor-producing microbe. Amyris’ efforts span engineering of the production microbe to optimizing the semisynthesis of the drug through fermentation and novel downstream synthetic chemistry. The role of iOWH includes developing a commercialization strategy based on a thorough understanding of the worldwide regulatory requirements and an analysis of the current ACT manufacturing supply-chain and distribution models. This one grant enables activities in all three areas of development and creates an integrated team, each of the partners applying its expertise to streamline translation from bench to bedside.
To ensure accessibility and affordability, the partners have committed to reduced returns in the malaria field. UC Berkeley has issued a royalty-free license to iOWH and shall grant royalty free licenses to Amyris for IP that is developed during the collaboration for the treatment of malaria in the developing world with the goal of significantly reducing the price of ACT products, and reducing the use of artemisinin mono-therapies per the World Health Organization’s recommendations for uncomplicated malaria.
This arrangement has benefits for all the parties. The university benefits from the research funding as well as from any royalties that may be realized on profit earned from sales by Amyris in areas outside of malaria in the developing world. As a for-profit company, Amyris can apply the innovations developed for the artemisinin project to other projects that rely on the same platform technology. As a nonprofit pharmaceutical company, iOWH is able to make malaria treatments more affordable for people in the developing world.
Partners in this project are:
The Bill and Melinda Gates Foundation provided the funding for the project.
The preferred and most effective treatments for malaria today are artemisinin-based combination therapies (ACT). Artemisinin, a complex natural product known as an herbal remedy for thousands of years, is typically derived from the wormwood plant. Plant sources of the chemical are variable and crop shortages contribute to increased cost. Chemical synthesis of the molecule would require 30 to 40 steps and is therefore impractical on a commercial scale.
Dr. Jay Keasling, a UC Berkeley professor of chemical engineering, developed a process of “synthetic biology” to produce an artemisinin precursor through a multistep process in bacteria.7 The precursor can then be chemically converted to artemisinin through synthetic chemistry developed at Amyris. Producing the drug precursor in microbes would lead to a more consistent and reliable supply and therefore reduce the cost of production.
The synthetic biology platform may also be used to produce other drugs, nutraceuticals, and flavors and fragrances.
Progress, Current Status, and Goals
During the five-year granting period, which began in 2005, the partners would carry out the following activities shown in Figure 1.
UC Berkeley researchers are working to identify the genes involved in the artemisinic acid biosynthetic pathway in the wormwood plant, Artemisia annua. Using their expertise in synthetic biology, they are inserting this biosynthetic pathway into microbes to create hosts that manufacture this direct precursor to artemisinin. Optimizing artemisinic acid production in these host cells is being achieved through cutting-edge techniques in metabolic engineering, in collaboration with scientists at Amyris Biotechnologies.
Amyris Biotechnologies is collaborating with the Center for Synthetic Biology to build a better microbe. Amyris will optimize the microbial strain developed with UC Berkeley for commercial production. In addition, Amyris will develop a fermentation and purification process for the precursor. Simultaneously, Amyris is developing a scaleable, inexpensive chemical process to convert the precursor to artemisinin.
OneWorld Health is the product development lead and has responsibility for directing this collaborative effort. In addition, the organization is leading the project’s regulatory and commercialization strategies and is conducting a risk-benefit analysis surrounding the use of artemisinin derivatives in malaria-endemic regions.
Agreements between the partners include the following:
All referenced Web sites were last accessed between 1 and 10 October 2007.
7 Martin VJ, DJ Pitera, ST Withers, JD Newman and JD Keasling. Engineering a Mevalonate Pathway in Escherichia Coli for Production of Terpenoids. Nature Biotechnology. 21 July 2003. (7): 796–802.