[Federal Register Volume 67, Number 31 (Thursday, February 14, 2002)]
[Notices]
[Pages 6938-6940]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-3568]


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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 agencies 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

[[Page 6939]]

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.

Filtration of Red Blood Cells

    David F. Stroncek (CC), Susan F. Leitman (CC), Herb M. Cullis (EM), 
DHHS Reference No. E-339-01/0 filed 06 Nov 2001, Licensing Contact: 
Dale Berkley; 301/496-7735 ext. 223; e-mail: [email protected].
    The invention is a method for collecting whole blood using an 
oxygen permeable collection bag to prevent the polymerization of 
Hemoglobin S, so as to prevent clogging of leukocyte reduction filters. 
Red blood cell components collected for transfusion are prepared from 
whole blood collected by phlebotomy or apheresis from healthy 
volunteers. Before the manufacturing of RBC components is complete, the 
blood is passed through leukocyte reduction filters to remove 
contaminating white blood cells. Unfortunately, RBC components from 
healthy donors with sickle cell trait clog these filters. When this 
occurs, the RBC components cannot be processed further and must be 
thrown out. The invention takes advantage of the discovery that the 
obstruction of leukocyte reduction filters is due to the polymerization 
of Hemoglobin S in RBCs from people with sickle cell trait when the 
oxygen concentration is low. The invention demonstrates that collecting 
the blood in oxygen permeable containers prevents this polymerization, 
allowing for efficient high-speed filtration of collected blood.

Discovery of Novel Inhibitors of HIV-1 Integrase That Can Be Used 
for the Treatment of Retroviral Infection Including AIDS

    Terrence R. Burke, Jr., Xuechen Zhang, Godwin C. G. Pais, 
Christophe Marchand, Evguenia Svarovskaia, Vinay K. Pathak, and Yves 
Pommier (NCI), DHHS Reference No. E-317-01/0 filed 07 Dec 2001, 
Licensing Contact: Sally Hu; 301/496-7056 ext. 265; e-mail: 
[email protected].
    This invention provides azido group-containing diketo acids that 
can inhibit HIV-1 integrase in vitro efficiently while being highly 
selective for the strand transfer step of the integration reaction. 
Human Immunodeficiency Virus (HIV) and other retroviruses require three 
viral enzymes for replication: reverse transcriptase, protease and 
integrase. The prognosis of AIDS has been improved recently by the 
discovery and application of reverse transcriptase and protease 
inhibitors. However, a significant fraction of patients fail to respond 
to such treatments and viral resistance remains a major problem. 
Furthermore, anti-AIDS combinations are often not well tolerated. Thus, 
HIV integrase is a rational target for AIDS therapy because genetic 
studies demonstrated that the enzyme is essential for viral replication 
while being without a cellular equivalent. Therefore, specific 
integrase inhibitors should be effective and devoid of toxicity. Since 
this invention involves the discovery of novel HIV-1 integrase 
inhibitors that are derived from diketo acids with a different anti-HIV 
mechanism from that of reverse transcriptase and protease inhibitors, 
these azide group-containing compounds may represent potential new 
therapeutics for treatment of retroviral infections, including AIDS.

Strategies To Destabilize the Active HIV-1 Protease Dimer Resulting 
in Stable Monomer Formation

    John L. Medabalimi (NIDDK), Rieko Ishima (NIDCR), and Angela 
Gronenborn (NIDDK), DHHS Reference No. E-242-01/0 filed 23 Aug 2001, 
Licensing Contact: Sally Hu; 301/496-7056 ext. 265; e-mail: 
[email protected].
    Upon maturation from its precursor, the HIV-1 protease forms and 
exists mostly as a functional dimer. The present invention relates to 
compositions and methods for inhibiting activity of functional dimeric 
retroviral proteases. More specifically, the invention relates to 
defining specific interface regions critical for dimer formation and 
production of stable folded monomers. These monomers are inactive and 
some of these monomers can block functional protease dimerization. The 
invention also describes a method of designing folded protease monomers 
that are stable in solution at concentrations several-fold higher than 
encountered in nature (stable up to 0.6 mM for several weeks at 20 deg. 
C). Modifying the native protease monomer chain through substituting 
amino acids at the terminal regions brings about this stabilization. 
Knowledge of unique regions critical for the dimerization of the 
protease and the stable monomers may be used in the development of 
novel inhibitors targeting the protease, in the generation of 
clinically relevant antibodies and anti-idiotypic antibodies for the 
inhibition of functional protease activity, in the generation of a 
screening assay or kit that can be used to identify other similarly 
acting protease antagonists, in the preparation of vaccine 
formulations, and in the treatment of virally infected cells.

Novel Broadly Reactive HIV-Neutralizing Human Monoclonal Antibody 
Against Receptor-Induced Epitope on gp120

    Dimiter Dimitrov (NCI), Maxime Moulard (EM), Dennis Burton (EM), 
Yuuei Shu (NCI), Sanjay Phogat (NCI), and Xiadong Xiao (NCI), DHHS 
Reference No. E-130-01/0 filed 16 Oct 2001, Licensing Contact: Sally 
Hu; 301/496-7056 ext. 265; e-mail: [email protected].
    This invention provides a novel anti-HIV human monoclonal antibody 
named X5. The X5 antibody demonstrates promise over other conventional 
anti-HIV antibodies because this antibody presents a unique binding 
activity different than its counterparts. It has been established that 
the very initial stage of HIV-1 entry into cells is mediated by a 
complex between the virus envelope glycoprotein (Env) such as gp120-
gp41, a receptor CD4 and a co-receptor CCR5. The X5 antibody binds to 
an epitope on gp120 that is induced by interaction between gp120 and 
the receptor CD4 and enhanced by the co-receptor CCR5. The X5 antibody 
also shows strong activity at very low levels (in the range from 
0.0001-0.1 Mg/ml concentration in dependence on the isolate). Because 
it is a human antibody, it can be administered directly into patients 
so that it is an ideal candidate for clinical trials. It also can be 
easily produced because it was obtained by screening of phage display 
libraries and its sequence is known. Finally, since it has neutralized 
all virus envelope glycoproteins, including from primary isolates from 
different clades, that were tested against, the epitope is very 
conserved and resistance is unlikely to develop. Therefore, this 
antibody and/or its derivatives including fusion proteins with CD4 are 
good candidates for clinical development.
    Additional information on the current research in Dr. Dimitrov's 
laboratory may be found at http://www-

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lecb.ncifcrf.gov/~dimitrov/dimitrov.html. 

    Dated: February 7, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-3568 Filed 2-13-02; 8:45 am]
BILLING CODE 4140-01-P