The National Cancer Institute (NCI), Center for Cancer Research (CCR), Laboratory of Cell Biology, The Chemical Immunology Section (CIS) plans to enter into a sole source contract with Therimmune Research Corp., 620 Professional Drive, Gaithersburg, MD 20879 for the continued services of Jim A. Turpin, Ph.D. TRC will provide a wide range of antiviral evaluations tailored to meet the needs of the Government. The evaluations to be provided include, but are not limited to, range of action assessments using a wide range of HIV-1 clinical isolates with defined genetic and phenotypic characteristics, such as resistance to one of more (multidrug-resistant) clinically relevant antivirals, activity against subtype representative virus and co-receptor specific viruses. Mechanism of action studies are required to verify the specificity of NCp7 inhibitors for their proposed antiviral target, such as biochemical assays for the inhibition of reverse transcriptase, protease and integrase enzymes, and cell-based assays to assess inhibition of virus attachment and entry. The mechanism of action studies will also include evaluation specific for the effect of NCp7 inhibitors on virus and cells. This can include determining the virucidal activity of inhibitors on cell-free virus and/or alterations in the infectivity of viruses released from HIV-1 infected cells. This type of study can also include assessment of the specific effects of the inhibitors by Western blotting on virion-associated and cell-associated virus proteins. These findings will serve to identify the diagnostic and characteristic abnormalities induced by NCp7 inhibitors on virus and on cells infected with HIV-1. Further studies will include in vitro models developed specifically by Dr. Turpin for the assessment of NCp7 inhibitors. This includes assessing their effect in chronically and latently infected cell lines and primary cells and in unique cell-to-cell transmission models developed specifically for the Laboratory of Cell Biology. These studies will also include models developed by Dr. Turpin which are specific to Zn finger inhibitors. Dr. Turpin is an expert in the field of NCp7 Zn finger inhibitors and his expertise includes practical laboratory knowledge on the effects of these inhibitors on infected and uninfected cells, and their positioning for advancement to in vivo animal studies. This expertise has been used in the last year to design a unique HIV-1 cell-to-cell transmission inhibition assay that offers a new avenue for the identification of inhibitors for this mode of HIV transmission and identification of new approaches to develop combination antiviral therapies using Zn finger inhibitors. It is anticipated that an award will be made for one year plus two optional years. This is not a request for competitive quotation. However, if any interested party believes it can meet the above requirement, it may submit a statement of capabilities. The statement of capabilities and any other information furnished must be in writing and must contain material in sufficient detail to allow the NCI research to determine if the party can perform this requirement. An original and one copy of the capability statements must be received in the contracting office by 3:00 p.m. EDT, on September 4, 2002. All questions must be in writing and can be faxed to (301) 402-4513 or emailed to [email protected] . It is the vendor's responsibility to call (301) 402-4509 to insure that questions have been received. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. No collect call will be accepted.

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