by Brooke Hardison Wang
Collaborations, the transfer of technology, and other types of public-private partnerships are critical to the National Cancer Institute's (NCI) mission of fostering the best cancer research and promoting translation of that research from the bench to the bedside. NCI is the primary means of support for cancer research in America, with $3.8 billion spent in 2007 on cancer research at institutions across the country, and another one billion spent at NCI. NCI's intramural scientific program, which is housed primarily on its campuses in Frederick and Bethesda, Md., is uniquely positioned to explore innovative diagnostic and treatment development in areas such as orphan drugs or combination therapies—areas where industry and academic sectors often face difficulties due to concerns over marketability, intellectual property, competition and liability. NCI cannot do this research alone, however, particularly because the problems being addressed require special expertise and a multi-displinary approach. Partnerships have become an important component of America's investment in cancer research.
For industry partners, there can be many advantages to collaborating with NCI. NCI's scientists use cutting-edge technologies (functional imaging, genomics, proteomics and new approaches to drug development) to drive discoveries from the bench through clinical studies. NCI has resources that make it possible to conduct more extensive testing of new agents and products, and has experience in regulatory issues and the requirements involved in conducting clinical trials. In addition, NCI funds extensive clinical trial networks that allow larger studies to be conducted across the country, and NCI's large repositories make it possible to perform tests on a wide variety of tumor types and disease settings.
In order to promote collaboration and in response to concerns about U.S. competitiveness in the global economy, Congress passed two laws in 1980 that encourage government-owned and/or -funded research laboratories to pursue commercialization of their research results through collaboration with outside entities. These two laws are known as the Stevenson-Wydler Technology Innovation Act of 1980 (P.L. 96-480) and the Patent and Trademark Amendments of 1980 (P.L. 96-517), also known as the Bayh-Dole Act.
The Stevenson-Wydler Act allows NIH and other federal agencies to enter into license agreements with industry partners to promote development of technologies born out of NIH research. The act provides the American public with a financial return on their investment in the form of royalty payments and fees. The Stevenson-Wydler Act was expanded in 1986 to allow federal agencies to partner, not only in the dissemination of their results, but throughout the entire research process. (For more information on this type of partnership, see the paragraph on Cooperative Research and Development Agreements below.)
The Bayh-Dole Act was intended to address the barriers that can arise around intellectual property, or ownership, of the materials being developed. The Act promotes the advancement of both scientific and economic development by allowing the government to enable the transfer of federally funded technologies to the public by securing patent rights and licensing them to commercial entities. While the Stevenson-Wydler Act applies to collaborations between government scientists (i.e., federal employees) with outside agencies, the Bayh-Dole Act applies to extramural grantees and contractors, and allows the investigator's institution to retain the title (i.e., rights) to the government-funded invention. The grantee or contractor institution is charged with the responsibility to use the patent system to promote utilization, commercialization and public availability of the invention. If the institution is not interested in pursuing the technology, the government can elect to title the invention.
Collaborations between NCI-funded clinical cooperative groups and industry partners are directed by guidelines set through the NCI Cancer Therapy Evaluation Program, NCI-funded preclinical resources are managed by the Developmental Therapeutics Program, and collaborations between NCI intramural scientists and industry partners are managed through the NCI Office of Technology Transfer. There are several mechanisms through which the NCI, academic and industry partners work together. Some of the most common agreement types include:
- Cooperative Research and Development Agreement (CRADA). A CRADA allows an NCI-funded researcher to collaborate jointly with researchers in industry and academia to pursue a common research goal.
- Clinical Trial Agreement (CTA). CTAs are used when an NCI researcher, or NCI-supported extramural investigator, is conducting research on a new drug or device and that research is being done in collaboration with an industry sponsor.
- Confidential Disclosure Agreement (CDA). A CDA is used to exchange confidential information. The agreement specifies how the information may be used and addresses situations in which the information must be shared such as under court order or the Freedom of Information Act. This agreement makes no promises about inventions made through use of this information.
- Material Transfer Agreement (MTA). MTAs are used by NCI and other academic and for-profit organizations to send or receive research materials (such as cell lines, monoclonal antibodies or mouse models) for use by scientists in another institution.
- License. Each year, hundreds of new inventions are made by scientists at NCI. The NIH Office of Technology Transfer transfers these inventions, through licensing, to the private sector for development that will benefit the public health.
Over the years there have been several advancements in cancer treatment that have resulted from successful partnerships with NCI. Examples include:
- Gardasil® human papillomavirus (HPV) vaccine, based upon technology from NCI, was licensed and developed by Merck & Co.
- Kepivance®, a drug used to treat oral mucositis (a common side effect of high-dose chemotherapy and/or radiation involving painful lesions in the mouth or throat), is based on keratinocyte growth factor, which was discovered by NCI researchers in 1989. In 1992, Amgen was granted an exclusive license to develop potential therapeutic applications for this growth factor.
- Velcade®, a proteasome inhibitor used for the treatment of multiple myeloma, was developed through collaboration between NCI and Millennium Pharmaceuticals, Inc.
- Laser Capture Microdissection (LCM), a method used for collecting selected cells for genetic or proteomic analysis, was conceived by researchers at NCI and one of its sister institutes, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The resulting technology has been used in approximately 1,000 LCM machines for breast, prostate and pancreatic cancer research.
- The Multi-Replica Blotting Kit, which allows simultaneous detection of up to ten different proteins from one gel, is based on layered expression scanning (LES) technology developed by NCI researchers. 20/20 GeneSystems, Inc., Rockville, Md., worked with NCI researchers to refine the LES system and commercialized the Multi-Replica Blotting Kit.
- Taxol®, an anti-cancer drug approved for the treatment of breast, ovarian, and lung cancer, as well as Kaposi's sarcoma, is based on a compound called paclitaxel, which was discovered from the bark of the Pacific yew tree by NCI researchers involved in screening natural products for anti-cancer activity. NCI researchers conducted preclinical and clinical testing, and worked with Bristol-Myers Squibb, New York, N.Y., to develop supplies of Taxol® for clinical development. The resulting treatment has been used by over one million patients.
"As we move to a more personalized era of oncology, it is clear that we will require multiple agents to target multiple pathways in the same patient. Facilitating that future will challenge how we think of competition, of intellectual property, and even the language of contracts. I believe NCI must step into those areas and become the facilitator between the public, private, and academic sectors." —NCI Director John E. Niederhuber, M.D. (Click image to enlarge)
