National Institutes of Health, Public Health Service, DHHS.
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 Start Printed Page 6939federally-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.
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@example.com.
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: firstname.lastname@example.org.
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@example.com.
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° 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: firstname.lastname@example.org.
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.Start Signature
Dated: February 7, 2002.
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]
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