Microbial Screening System for Antiviral Agents Targeting PKR

Published in the Federal Register on Tuesday, April 1, 1997 [62 FR 15529]
National Institutes of Health

National Institute of Child Health and Human Development: Opportunity for a Cooperative Research and Development Agreement (CRADA) for the development of a microbial screen for anti-virals targeting PKR or inhibitors of PKR

AGENCY: National Institutes of Health, Public Health Service, DHHS

ACTION: Notice

SUMMARY: The National Institutes of Health is seeking one or more CRADA partners for further development and evaluation of a microbial screen in yeast to identify anti-viral agents that target regulators of and/or the PKR kinase. The National Institute of Child Health and Human Development has established a system in yeast to identify and characterize viral regulators of the PKR kinase, that should also be useful for identifying anti-viral agents that counteract the viral regulators. To expedite research and development of this system, the National Institutes of Health is seeking CRADAs with pharmaceutical or biotechnology companies in accordance with the regulations governing the transfer of Government-developed agents. Any proposal to use or develop this system will be considered.

ADDRESS: CRADA proposals and questions about this opportunity should be addressed to: Dr. Gordon Guroff, Deputy Scientific Director, National Institute of Child Health and Human Development, Building 49, Room 5A64, Bethesda, MD 20892 (301/496-4751).

DATE: CRADA proposals should be received on or before July 30, 1997 for priority consideration. However, CRADA proposals submitted thereafter will be considered until a suitable CRADA Collaborator is selected.

SUPPLEMENTARY INFORMATION: The protein kinase PKR is a component of the interferon-induced anti-viral defense mechanism in mammalian cells. Upon activation by binding double-stranded RNA in infected cells, the kinase down-regulates the cellular translational apparatus, and thus impairs viral protein expression. To overcome the inhibitory effects of PKR, viruses have developed efficient methods to prevent the activation or function of the kinase. A potential site of therapeutic intervention is to block viral inhibition of PKR.

The NICHD has developed a microbial system in the yeast Saccharomyces cerevisiae in which expression of PKR inhibits growth by down-regulating cellular protein synthesis. The toxicity of PKR in this system can be relieved by co-expression of viral regulatory factors including the vaccinia virus K3L protein. This simple microbial system should be amendable to high through-put screens to identify anti-viral agents that inactivate viral regulators of PKR, and thus restore PKR toxicity in this system. In addition, agents that act on PKR and reduce the sensitivity of PKR to viral regulatory factors could also be identified. This system should also be useful to identify regulators of PKR from other viruses, and then subsequently used to identify inhibitors of these newly identified viral regulatory factors.

In an effort to expedite research and development of new anti-viral agents targeting PKR, the National Institute of Child Health and Human Development seeks a CRADA partner(s) for joint exploration. Any CRADA proposals for use of this system will be considered.

The CRADA aims will include the rapid publication of research results consistent with protection of proprietary information and patentable inventions as well as the timely exploitation of commercial opportunities. The CRADA partner will enjoy the benefits of first negotiation for licensing Government rights to any inventions arising under the agreement and will advance funds payable upon signing the CRADA to help defray Government expenses for patenting such inventions and other CRADA-related costs.

The role of the National Institute of Child Health and Human Development will be as follows:
1. Provide the collaborator with the data on the system covered by the agreement.
2. Provide the yeast strains and plasmids covered by the agreement.
3. Continue studies on the system to optimize growth tests for screens.
4. Work cooperatively with the Collaborator to perform the necessary controls to validate results from screens.
5. Jointly identify additional PKR inhibitors, and establish necessary strains for anti viral screens.

The role of the Collaborator will be as follows:
1. Undertake studies to evaluate the usefulness of this system for high through-put screens.
2. Cooperate to identify additional PKR inhibitors that could be tested using this system.
3. Undertake studies using this system to identify agents that inactivate viral inhibitors of PKR.

Selection criteria for choosing the CRADA Collaborator(s) will include but are not limited to the following:
1. The ability to collaborate with the NICHD on further research and development of this technology. This ability can be demonstrated through experience and expertise in this and related areas of technology.
2. The demonstration of adequate resources to perform the research and development of this technology (e.g., personnel, expertise, and facilities) and accomplish objectives according to an appropriate timetable to be outlined in the CRADA Collaborator's proposal.
3. The level of financial support the CRADA Collaborator will provide for CRADA related Government activities.
4. The willingness to cooperate with the NICHD in publication of research results consistent with the protection of proprietary information and patentable inventions which may arise during the period of the agreement.
5. Agreement to be bound by DHHS rules and regulations regarding human subjects, patent rights, ethical treatment of animals, and randomized clinical trials.
6. Agreement with provisions for equitable distribution of patent rights to any inventions developed under the CRADA(s). Generally, the rights of ownership are retained by the organization which is the employer of the inventor, with an irrevocable, non-exclusive, royalty free license to the Government (when a company employee(s) is the sole inventor) or an option to negotiate an exclusive license to the company on terms that are appropriate (when the Government employee(s) are either sole or joint inventors).