[Federal Register Volume 65, Number 59 (Monday, March 27, 2000)]
[Notices]
[Pages 16207-16209]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-7380]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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.

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    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

[[Page 16208]]

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.

[[Page 16209]]

    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.

    Dated: March 20, 2000.
Karen Maurey,
Deputy Chief, Technology Development and Commercialization Branch, 
National Cancer Institute, National Institutes of Health.
[FR Doc. 00-7380 Filed 3-24-00; 8:45 am]
BILLING CODE 4140-01-P