How Cooperative Agreements Drive Breakthroughs at NCATs

By: Krishna Balakrishnan, PhD, MBA, and Ami D. Gadhia, JD, LLM, CLP

The National Institutes of Health (NIH) is a unique biomedical institution that is both a granting agency that funds external research and a research enterprise that carries out in-house research. Very few institutions have the funding to accomplish health initiatives through grants and contracts, as well as the internal scientific expertise to conduct original research themselves. This unique vantage point allows the NIH to make maximum synergistic use of the most consequential laws enacted in the U.S. in the early 1980s, including the Bayh-Dole Act, the Federal Technology Transfer Act, and the Small Business Innovation Act.

Within NIH, the National Center for Advancing Translational Sciences (NCATS) presents another rarity: Seventy percent of the center’s internal work is inherently collaborative. By joining forces with outside collaborators, NCATS can carry out scientific work that neither party could do on its own. The collaborative culture at NCATS and the specialized granting mechanisms available within the NIH help NCATS achieve its mission of advancing the medical translational science field in broad, far-reaching strokes. NCATS not only innovates in the scientific field but also explores and practices innovation in technology transfer and translational science practices by establishing novel and creative ways of partnering.

Among the various funding mechanisms used by NIH, the Cooperative Agreement (CA) grant mechanism, and particularly the U mechanism, allows for remarkable flexibility in assembling diverse teams of scientists to define and advance newly emerging fields. Since the establishment of NCATS as a separate center within NIH in 2011, CA grants have gained so much popularity within NCATS that they account for approximately 50% of its active grant awards. The CA grant stipulates that a collaborative agreement needs to be executed before the grant can be funded.

The Office of Strategic Alliances (OSA) at NCATS is a central player in effectuating the synergy between the internal research at NCATS (the Intramural Research Program) and the external institutions funded by NIH (or Extramural Research). Several agreements are available to support these collaborations, such as the inter-institutional agreement (IIA), research collaboration agreement (RCA), cooperative research collaboration agreement (C-RCA), or a cooperative research and development agreement (CRADA). An IIA is the agreement by which joint IP is managed. The RCA, C-RCA, and CRADA are collaborative agreements that require research plans. Depending on the goals of the collaboration, any of these agreements can be used alone or in combination.

Prior to entering a collaborative agreement, the parties may need to exchange confidential information via a confidential disclosure agreement. If the parties want to outline their working relationship with broad goals to effectuate their understanding, then they may put in place a memorandum of understanding or a Letter of Intent. And where clinical research may be conducted, then a clinical research agreement is appropriate.

One example of a partnership between an academic center, the NCATS Extramural Program, and the NCATS Intramural Program that utilized a Cooperative Grant Mechanism and the C-RCA involved the 3-D Tissue Bioprinting Program. Cell-based laboratory tests and animal models are not always predictive of the efficacy or toxicity of potential therapeutics in humans. Recent scientific advances have given rise to the field of 3-D bioprinting of living tissues, a very complex platform that sorely needs the close interplay of the NCATS intramural scientists’ expertise on a platform technology and the academic collaborators’ knowledge about the disease model. The cooperative grant mechanism stipulated the need for a collaboration agreement between NCATS and the academic collaborator to be included in the grant to ensure that technology transfer and IP provisions would be agreed upon before the grant work began. Can the same model of collaboration and teamwork between NCATS and academic scientists be extended to the commercial sector? This is where the second set of landmark laws from the 1980s comes into play. The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs are also funding mechanisms used by the NIH and other federal agencies. The SBIR program was established under the Small Business Innovation Development Act of 1982 (Public Law 97-219), and STTR followed suit in 1992 (Public Law 102-564, Title II). These programs are one of the largest sources of early-stage funding available to eligible U.S.-based small businesses. Just like the CA grant mechanism described earlier, the small business programs also allow small business partners to work collaboratively with NCATS through the cooperative agreement (U) grant mechanism. Under the “U” mechanism, NCATS can support high-priority research areas that require substantial involvement from NIH scientific staff. The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed to perform the project under the U mechanism. Before, during, and after the award, the U.S. government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project. Awardees will retain custody of and have primary rights to the data and resources developed under these awards, subject to government rights of access consistent with current policies at the Department of Health and Human Services, Public Health Service, and NIH.

Collaborations form the backbone of translating research findings into treatments for human diseases. This article provided an overview of NCATS’ translational goals and explained how collaborations between NCATS scientists and academic/industry scientists achieved goals that cannot be achieved in isolation. NCATS uses other mechanisms to accelerate biomedical product development and train its next generation of translational scientists. The overall mission of NCATS is to develop more drugs for all people more efficiently. To do so, we have to make sure that no valuable scientific discovery is left midway on its translational journey, staring at the valley of death.