Genelabs Technologies, Inc.

Leland Stanford Junior University

Pathologica LLC

Pathlogica LLC

Kenneth G Hadlock

Gregory R Reyes

Steven K H Foung

Zhen-Yong Keck

Stephanie Yu

Steven Kh Foung

Hien Kim Do

Hope Lancero

Michael S McGrath

Michael S Mcgrath

Theresa P Chow

Chin-Joo Goh

The present invention provides methods for the regulation of osteopontin activity in a subject as well as for treating or preventing conditions associated with an increased activity of osteopontin activity in a subject.

Regulation of osteopontin

Conformational epitopes of the envelope proteins E1 and E2 of the Hepatitis C virus (HCV) have been identified and characterized using a panel of monoclonal antibodies derived from patients infected with HCV. These conserved conformational and linear epitopes of the HCV protein E1 or E2 have been determined to be important in the immune response of humans to HCV and may be particularly important in neutralizing the virus. Based on the identification of these conformational epitopes, vaccines containing peptides and mimotopes with these conformational epitopes intact may be prepared and administered to patients to prevent and/or treat HCV infection. The identification of four distinct groups of monoclonal antibodies with each directed to a particular epitope of E1 or E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen. Pharmaceutical compositions for prevention and treatment of HCV, comprising one or more the monoclonal antibodies, are provided.

Prevention and treatment of HCV infection employing antibodies directed against conformational and linear epitopes

Methods for treating viral infections using polyamine analogs, including mitoguazone (MGBG), are provided. In these methods, polyamine analogs destroy macrophages that act as viral reservoirs, facilitating the destruction of the viruses that dwell within the macrophages. Examples of viral infections that may be treated with the present methods include, but are not limited to, infections from human immunodeficiency viruses. These methods differ from previous methods of treatment using polyamine analogs, wherein the polyamine analogs were administered only as anti-tumor agents.

Methods for treating viral infections using polyamine analogs

Conformational epitopes of the envelope protein E2 of the Hepatitis C virus (HCV) have been identified and characterized using a panel of monoclonal antibodies derived from patients infected with HCV. These conformational epitopes have been determined to be important in the immune response of humans to HCV and may be particularly important in neutralizing the virus. Based on the identification of these conformational epitopes, vaccines containing peptides and mimotopes with these conformational epitopes intact may be prepared and administered to patients to prevent and/or treat HCV infection. The identification of four distinct groups of monoclonal antibodies with each directed to a particular epitope of E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen.

Prevention and treatment of HCV infection employing antibodies directed against conformational epitopes

Human monoclonal antibodies binding to epitopes common to type 1 and 2 HCV are provided, as well as conformationally conserved HCV E2 2a and 2b proteins. Compositions comprising the antibodies find use in diagnosis and therapy. The antibodies recognize conformational epitopes that are conserved across multiple genotypes of HCV. Thus the antibodies have the potential to be useful in the prevention and treatment of the majority of HCV infections. A subset of the antibodies (CBH-2, CBH-5, CBH-7, CBH-8C, CBH-8E, and CBH-11) have the ability to prevent the binding of HCV E2 proteins of multiple genotypes to human CD81, a possible co-receptor for HCV infection. A subset of the antibodies (CBH-2 and CBH-5) have been shown to inhibit the binding of HCV virions (as opposed to purified E2 protein) to human CD81. A further subset of the antibodies (CBH-4D, CBH4B, CBH-8C, and CBH-9) have been shown to prevent HCV envelope mediated fusion using an HCV psuedotype system.

Prevention and treatment of HCV infection employing antibodies that inhibit the interaction of HCV virions with their receptor

Method and assay kit for positively identifying HTLV-I and HTLV-II infection from human serum samples. The kit includes peptide antigens from the C-terminal regions of HLTV-I p19 and HTLV-II p21 gag proteins, and peptide antigens from the HLTV-I and HTLV-II env proteins immobilized on a solid support. After reaction of the serum sample with the solid support, an antibody-detection reagent in the kit is added to the support, to detect binding of human serum antibodies to each of the peptide antigens separately. The test allows positive identification of HTLV-I or HTLV-II when antibody binding to each HTLV-I or HTLV-II gag and env peptide antigen, respectively, is observed. Also disclosed is a kit for screening human sera for evidence of HTLV-I or HTLV-II infection.

HTLV-I/HTLV-II assay and method

Novel HTLV-I and HTLV-II peptide antigens are disclosed for use in diagnostics assays for screening and confirming HTLV-I and HTLV-II antisera. The peptides are derived from analogous regions of HTLV-I and HTLV-II gp46 envelope proteins, and are differentiated by their immunoreactivity with an HTLV-II specific monoclonal antibody and by HTLV-I and HTLV-II antisera. The peptides are also useful in vaccine compositions.

HTLV-I and HTLV-II peptide antigens and methods

HTLV-II peptide antigens

Novel HTLV-I and HTLV-II peptides are disclosed for use in diagnostic assays for detecting and confirming HTLV-I and HTLV-II infection in human sera. The peptides are derived from analogous regions of HTLV-I and HTLV-II gp21 envelope protein, and are diagnostic of HTLV-I or HTLV-II infection. The invention also includes an assay kit and method for detecting, and discriminating between, HTLV-I and HTLV-II infection in humans.

Growing community of inventors

San Francisco, CA, United States of America

Kenneth G Hadlock