[Federal Register Volume 69, Number 112 (Thursday, June 10, 2004)]
[Notices]
[Pages 32594-32595]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-13100]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

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

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

A Peptide That Elicits Neutralizing Antibodies Targeting the HIV Co-
Receptor CCR5

Drs. Hana Golding and Surender Khurana (FDA)
U.S. Provisional Application filed 09 Apr 2004 (DHHS Reference No. E-
150-2004/0-US-01)
Licensing Contact: Sally Hu; 301/435-5606; [email protected].

    This invention identifies a peptide sequence that closely mimics 
the conformational epitope in CCR5, recognized by the HIV neutralizing 
monoclonal antibody targeting the co-receptor, by using a random 
peptide phage display library. This peptide upon immunization of 
rabbits generated antibodies that bind to the HIV-1 co-receptor CCR5 
resulting in blocking HIV transmission to target cells, including 
peripheral blood lymphocytes from human and monkeys. Thus, such 
antibodies could be directly used for preventing mother to child HIV 
transmission, for therapy of HIV-1 infected individuals, and may also 
have particular value when used in combination treatments with other 
antiviral therapies directed at viral targets, such as protease and 
reverse transcriptase. The peptide sequence can be used for potential 
vaccine development. This peptide can also be used for screening of 
human antibody phage display libraries to isolate human monoclonal with 
HIV entry-blocking potential. In addition, the peptide and antibodies 
recognizing it can be used as research tools for increasing the 
understanding of the mechanisms by which HIV, CCR5 and the HIV 
receptor, CD4, interact, and in general to understand mechanisms of HIV 
infectivity.

Inhibition of HIV Replication in Resting CD4+ Lymphocytes by Murr1

Gary J. Nabel et al. (NIAID)
U.S. Provisional Application No. 60/523,683 filed 21 Nov 2003 (DHHS 
Reference No. E-042-2004/0-US-01)
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    This technology describes the inhibition of HIV-1 growth in resting 
CD4+ T cells by Murr1, a highly conserved protein. This finding 
therefore could be used to prolong the asymptomatic phase of HIV 
infection. HIV-1 infects both proliferative and quiescent CD4+ T cells, 
although the virus replicates poorly in the latter. It has been 
demonstrated that Murr1 restricts HIV-1 replication by inhibiting basal 
and cytokine nuclear factor (NF)-[kappa]B activity. Short interfering 
RNAs (siRNAs) experiments that used specific Murr1 siRNAs resulted in 
lower levels of I[kappa]B-A and higher NF-[kappa]B activity and HIV-1 
replication. These results allude to the potential for a more effective 
HIV therapeutic that uses Murr1 to regulate viral replication. A Murr1 
anti-viral drug that can block viral replication in quiescent 
lymphocytes and latent cells with provirus might increase the number of 
patients that remain in the HIV-1 asymptomatic phase and thus lower the 
number that progress to the AIDS state.
    This technology is further described in Ganesh et al., Nature (18/
25 December 2003), 426(6968): 853-857.

Mechanisms for Improving the Breadth of the Immune Response to Diverse 
Strains and Clades of HIV

Gary J. Nabel et al. (NIAID)
U.S. Provisional Application No. 60/503,509 filed 15 Sep 2003 (DHHS 
Reference No. E-335-2003/0-US-01)
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    This technology describes a multiclade Env vaccine candidate that 
elicited neutralizing antibodies to a diverse group of primary HIV-1 
isolates as compared to antibodies generated from immunization with 
single clade vaccines. The immunogens of the vaccine included V3 loops 
from clades A, B, and C and had the cleavage site, fusion peptide, and 
interhelical regions deleted. Competition studies suggested that the 
neutralization activity is directed toward shared, conserved epitopes 
other than the V3 loop. Also described in this technology are 
immunogens involving deletion of the V3 loop that generated more potent 
neutralizing antibodies, suggesting that the highly conserved 
subregions within V3 may be relevant targets to elicit neutralizing 
antibody responses and increase the immunogenicity of HIV/AIDS 
vaccines. Such selective deletions in the V3 loop are effective in 
combination with deletions of other V loops. Immunogens with deletions 
of the V regions in general (V1--V4), including combinations of 
deletion immunogens, were also shown to elicit potent neutralizing 
antibodies. Previous studies of the cell-mediated immune response in 
mice using the multiclade vaccines of this current technology have 
shown that they induce Env-specific CD4 and CD8 immune response to

[[Page 32595]]

multiple clades. Thus, this technology offers promise in developing a 
globally effective HIV/AIDS vaccine, which must induce both cellular 
and humoral immunity to multiple strains from the various clades.
    This work is described, in part, in Z. Yang et al., J. Virol. 
(April 2004) 78(8): 4029-4036.

Methods for Inhibiting Proinflammatory Cytokine Expression Using 
Ghrelin

Drs. Vishwa D. Dixit, Dennis D. Taub, Eric Schaffer and Dzung Nguyen 
(NIA)
U.S. Provisional Patent Application filed 11 May 2004 (DHHS Reference 
No. E-016-2004/0-US-01)
Licensing Contact: Sally Hu; 301/435-5606; [email protected].

    Ghrelin, a recently described endogenous ligand for growth hormone 
secretagogue receptors (GHS-R), is produced from stomach serving as a 
potent circulating orexigen controlling energy expenditure, adiposity 
and GH secretion. We have discovered that ghrelin exerts anti-
inflammatory effects by inhibiting the secretion of both acute and 
chronic cytokines including IL-1, IL-6, TNF-[alpha], IFN-[gamma], IL-12 
p40, , chemokines, and CSFs in vitro in human cells as well as in vivo 
in mouse model of sepsis and inflammation. We also found that ghrelin 
directly controls human growth hormone and insulin growth factor 
expression by human immune cells. This invention is useful for 
treatment of various inflammatory disorders including inflammatory 
bowel disease, Crohn's disease, rheumatoid arthritis, multiple 
sclerosis, atherosclerosis, endotoxemia and graft-versus-host disease.

Stem Cell Factor (SCF) Stimulates Neural Stem Cell Migration to Sites 
of Brain and Spinal Cord Injury

Howard A. Fine et al. (NCI)
U.S. Provisional Application No. 60/525,760 filed 26 Nov 2003 (DHHS 
Reference No. E-035-2004/0-US-01) and U.S. Provisional Application 
filed 19 Apr 2004 (DHHS Reference No. E-035-2004/1-US-01)
Licensing Contact: Fatima Sayyid; 301/435-4521; [email protected].

    Endogenous neural stem/progenitor cells (NSPCs) have recently been 
recognized to hold the promise for therapeutics to combat 
neurodegenerative diseases, such as Parkinson's and Alzheimer's 
disease. Endogenous NSPCs have been shown to generate new functional 
neurons to replace the nerve cells that have been injured, lost, or 
destroyed in the diseases and recover brain functions. Such therapy, 
however, is limited due to lack of methods to mobilize endogenous NSPCs 
to the site of injury.
    The present invention relates to methods for recruiting large 
numbers of NSPC to the specific site of neurological injury through 
local injection of recombinant or genetic vector-derived Stem Cell 
Factor (SCF). The inventors have identified that SCF secreted by nerve 
cells in the site of injury leads to migration of endogenous NSPCs to 
the site of injury and their proliferation to form neurons. The 
inventors have shown that local injection of recombinant SCF at the 
site of brain or spinal cord injury induces increased migration of 
NSPCs to the site of injury. Therefore, this invention could have 
significant commercial application in the development of therapeutic 
interventions including cell-based therapies for neurodegenerative 
diseases.

    Dated: June 4, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-13100 Filed 6-9-04; 8:45 am]
BILLING CODE 4140-01-P