National Cancer Institute: Opportunity for a Cooperative Research and Development Agreement (CRADA) for the Research, Purification, and Further Development of a Factor(s) That Inhibits Human Immunodeficiency Virus (HIV) Replication

AGENCY:

National Institutes of Health, PHS, DHHS.

ACTION:

Notice.

The National Cancer Institute's Experimental Immunology Branch has identified a factor that is produced by leukocytes when exposed to influenza virus which inhibits HIV replication.

SUMMARY:

The National Cancer Institute (NCI) seeks a Cooperative Research and Development Agreement (CRADA) Collaborator to aid NCI in the further characterization and commercial development of a factor(s) that inhibits the replication of the Human Immunodeficiency Virus (HIV). NCI recently discovered that leukocytes stimulated with infectious or ultraviolet-inactivated influenza A virus produce a factor(s) that inhibits the replication of both CCR5- and CXCR4-tropic HIV-1 viral isolates. The factor(s) inhibits replication of the virus after viral binding but prior to reverse transcription. NCI has performed the initial characterization of the HIV-1 replication-inhibiting factor(s). The discovery of this factor(s) raises the possibility that immunization with recombinant influenza viral constructs and/or ultraviolet (UV)-inactivated influenza offers an immune-based therapeutic strategy that could be used to treat HIV-infected patients. NCI is looking for a CRADA Collaborator with a demonstrated record of success in protein purification and HIV therapeutics for the eventual use of this factor(s) in the clinical treatment of patients suffering from Acquired Immunodeficiency Syndrome (AIDS). The proposed term of the CRADA can be up to five (5) years.

DATES:

Interested parties should notify this office in writing of their interest in filing a formal proposal no later than May 26, 2000. Potential CRADA Collaborators will then have an additional thirty (30) days to submit a formal proposal. CRADA proposals submitted thereafter may be considered if a suitable CRADA Collaborator has not been selected.

ADDRESSES:

Inquiries and proposals regarding this opportunity should be addressed to Holly Symonds Clark, Ph.D., Technology Development Specialist (Tel. # 301-496-0477, FAX # 301-402-2117), Technology Development and Commercialization Branch, National Cancer Institute, 6120 Executive Blvd., Suite 450, Rockville, MD 20852. Inquiries directed to obtaining patent license(s) for the technology described in U.S. Provisional Patent Application Serial No. 60/162,262, filed October 29, 1999 for “Leukocyte-Derived Anti-Viral Factors” (Shearer et al.) (NCI), should be addressed to J.P. Kim, J.D., M.B.A., Technology Licensing Specialist, Office of Technology Transfer, National Institutes of Health, 6011 Executive Blvd., Suite 325, Rockville, MD 20852, (Tel. 301-496-7056, ext. 264; FAX 301-402-0220).

SUPPLEMENTARY INFORMATION:

A Cooperative Research and Development Agreement (CRADA) is the anticipated joint agreement to be entered into with NCI pursuant to the Federal Technology Transfer Act of 1986 and Executive Order 12591 of April 10, 1987 as amended by the National Technology Transfer Advancement Act of 1995. NCI is looking for a CRADA partner to aide NCI in the characterization and commercial development of the HIV replication-inhibiting factor. The expected duration of the CRADA would be from one (1) to five (5) years.

NCI has discovered a system in which leukocytes can produce an anti-HIV factor following exposure to an influenza virus. Specifically, NCI has found that the factor or factors secreted by the leukocytes inhibit retroviral replication prior to reverse transcription and formation of the provirus. The influenza virus to which the leukocytes are exposed causing them to generate anti-HIV activity include infectious influenza virus and UV-inactivated influenza virus. NCI has found that exposure of the leukocytes to the influenza virus can inhibit viral isolates that use different coreceptors for binding CD4.

The generation of the influenza-stimulated anti-HIV factor(s) can be mediated in the absence of CD4+ or CD8+ cells, and it does not appear to require the presence of both subsets. Thus, it is possible that the anti-HIV factor could be produced in patients exhibiting low CD4 counts. NCI has determined that the anti-HIV factor(s) presently claimed do not include several of the known chemokines or cytokines.

NCI predicts that the influenza-stimulated anti-HIV factor(s) offers the following advantages: 1. The anti-HIV activity appears to be independent of the presence of both CD4+ and CD8+ cells and of ability to generate strong T cell proliferative responses to flu, as well as of influenza-stimulated production of the Th1 cytokine, IFN-gamma. 2. Influenza-stimulated peripheral blood mononuclear cells (PBMCs) from HIV+ patients can generate anti-HIV activity that is as potent as cells from HIV-donors, and this activity appears to be independent of a patient's T helper responses to influenza. 3. Flu-stimulated anti-HIV-1 activity is broadly reactive in that it inhibits HIV-1 isolates that use different coreceptors for entry, and is therefore not a beta-chemokine. 4. NCI's demonstration that inhibition occurs prior to HIV reverse transcription distinguishes it from the CD8 anti-viral factor (CAF), which inhibits at transcription. 5. The fact that UV-inactivated flu can stimulate anti-HIV activity indicates the potential clinical feasibility of immunizing HIV+ patients. NCI believes that the utilization of an attenuated form of live influenza virus might represent the best form of immunization to HIV-1.

The described methods are the subject of U.S. Provisional Patent Application Serial No. 60/162,262, filed on October 29, 1999 by the Public Health Service on behalf of the Federal Government. Furthermore, the initial report and characterization of the invention is described in: J. Virol., in press, May 2000.

Under the present proposal, the goal of the CRADA will be to enhance the development of the influenza-stimulated, anti-HIV factor(s) in the following areas:

1. Further purification and characterization of the factor(s).

2. Determination of the factor's mechanism of viral replication inhibition.

3. Determination as to whether or not the factor(s) is unique by cloning and sequencing the gene.

4. Utilization of the SIV/macaque model to determine efficacy of flu-based therapy.

5. Development of clinical trials to test the efficacy of the flu-based therapy.

Party Contributions

The role of the NCI in the CRADA may include, but not be limited to:

1. Providing intellectual, scientific, and technical expertise and experience to the research project.

2. Providing the CRADA Collaborator with information and data relating to the influenza-stimulated, anti-HIV factor(s).

3. Planning research studies and interpreting research results.

4. Carrying out research to validate the anti-viral activities of the influenza-stimulated factor(s).

5. Publishing research results.

6. Developing additional potential applications of the factor(s).

The role of the CRADA Collaborator may include, but not be limited to:

1. Providing significant intellectual, scientific, and technical expertise or experience to the research project.

2. Planning research studies and interpreting research results.

3. Providing technical and/or financial support to facilitate scientific goals and for further design of applications of the technology outlined in the agreement.

4. Publishing research results.

Selection criteria for choosing the CRADA Collaborator may include, but not be limited to:

1. A demonstrated record of success in the areas of protein purification, characterization and therapeutic development.

2. A demonstrated background and expertise in immunological sciences and AIDS therapeutics.

3. The ability to collaborate with NCI on further research and development of this technology. This ability will be demonstrated through experience and expertise in this or related areas of technology indicating the ability to contribute intellectually to ongoing research and development.

4. The demonstration of adequate resources to perform the research and development of this technology (e.g. facilities, personnel and expertise) and to accomplish objectives according to an appropriate timetable to be outlined in the CRADA Collaborator's proposal.

5. The willingness to commit best effort and demonstrated resources to the research and development of this technology, as outlined in the CRADA Collaborator's proposal.

6. The demonstration of expertise in the commercial development and production of products related to this area of technology.

7. The level of financial support the CRADA Collaborator will provide for CRADA-related Government activities.

8. The willingness to cooperate with the National Cancer Institute in the timely publication of research results.

9. The agreement to be bound by the appropriate DHHS regulations relating to human subjects, and all PHS policies relating to the use and care of laboratory animals.

10. The willingness to accept the legal provisions and language of the CRADA with only minor modifications, if any. These provisions govern the distribution of future patent rights to CRADA inventions. Generally, the rights of ownership are retained by the organization that is the employer of the inventor, with (1) the grant of a license for research and other Government purposes to the Government when the CRADA Collaborator's employee is the sole inventor, or (2) the grant of an option to elect an exclusive or nonexclusive license to the CRADA Collaborator when the Government employee is the sole inventor.