Abstract: Helicobacter pylori known to cause or be a cofactor in type B gastritis, peptic ulcers, and gastric tumors. In both developed and developing countries, a high percentage of people are infected with this bacterium. The present invention relates generally to certain H. pylori proteins, to the genes which express these proteins, and to the use of these proteins for diagnostic and vaccine applications. Specifically, molecular cloning, nucleotide, and amino add sequences for the H. pylori cytotoxin (CT), the "Cytotoxin Associated Immunodominant" (CAI) antigen, and the heat shock protein (hsp60) are described herein.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
June 20, 2000
Assignee:
Chiron Corporation
Inventors:
Antonello Covacci, Massimo Bugnoli, John Telford, Giovanni Macchia, Rino Rappuoli
Abstract: A novel kinase has been identified which phosphorylates I.kappa.B. Reagents which inhibit this kinase can be used as therapeutic tools to inhibit inflammation. The kinase can also be used as a target for drug screening to identify anti-inflammatory compounds.
Abstract: A family of cDNA sequences derived from hepatitis C virus (HCV) are provided. These sequences encode antigens which react immunologically with antibodies present in individuals with non-A non-B hepatitis (NANBH), but which are absent from individuals infected with hepatitis A virus, or hepatitis B virus, and also are absent in control individuals. The HCV cDNA sequences lack substantial homology to the sequences of hepatitis delta virus (HDV) and HBV. A comparison of the sequences of amino acids encoded in the HCV cDNA with the sequences of Flaviviruses indicates that HCV may be related to the Flaviviruses. The HCV cDNA sequences and the polypeptides encoded therein are useful as reagents for the detection and therapy of HCV. The reagents provided in the invention are also useful for the isolation of NANBH agent(s), for the propagation of these agents in tissue culture, and for the screening of antiviral agents for HCV.
Type:
Grant
Filed:
September 16, 1994
Date of Patent:
June 13, 2000
Assignee:
Chiron Corporation
Inventors:
Michael Houghton, Qui-Lim Choo, George Kuo
Abstract: The present invention relates to keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratonocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R-(SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.
Type:
Grant
Filed:
May 8, 1998
Date of Patent:
June 13, 2000
Assignee:
Chiron Corporation
Inventors:
Denis J. Gospodarowicz, Frank R. Masiarz
Abstract: Peptoids are provided which are polymers comprised of monomer units wherein the monomer units include at least some substitute amino acids and may include conventional amino acids. The peptoids can be synthesized in large numbers so as to provide libraries of peptoids which can be screened in order to isolate peptoids of desired biological activity. Although the peptoids may include amino acids, they preferably include only substituted amino acids and are designed in a manner so as to have a particular biological activity. Certain peptoids are designed to mimic as closely as possible the activity of known proteins. Other peptoids are designed so as to have greater or lesser activity than known proteins and may be designed so as to block known receptor sites and/or elicit a desired immunogenic response and thereby act as vaccines. In that the peptoids are comprised of substitute amino acids they can be designed to have structures which natural proteins cannot conform to.
Type:
Grant
Filed:
May 10, 1995
Date of Patent:
June 13, 2000
Assignee:
Chiron Corporation
Inventors:
Reyna J. Simon, Paul A. Bartlett, Daniel V. Santi
Abstract: Two Hepatitis C Virus envelope proteins (E1 and E2) are expressed without sialylation. Recombinant expression of these proteins in lower eukaryotes, or in mammalian cells in which terminal glycosylation is blocked, results in recombinant proteins which are more similar to native HCV glycoproteins. When isolated by GNA lectin affinity, the E1 and E2 proteins aggregate into virus-like particles.
Type:
Grant
Filed:
May 17, 1995
Date of Patent:
June 13, 2000
Assignee:
Chiron Corporation
Inventors:
Robert O. Ralston, Frank Marcus, Kent B. Thudium, Barbara A. Gervase, John A. Hall, Kim M. Berger, Qui-Lim Choo, Michael Houghton, George Kuo
Abstract: A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.
Abstract: The present application features nucleic acid, peptide and antibody compositions relating to genotypes of hepatitis C virus and methods of using such compositions for diagnostic and therapeutic purposes.
Type:
Grant
Filed:
May 16, 1995
Date of Patent:
June 6, 2000
Assignee:
Chiron Corporation
Inventors:
Tai-An Cha, Eileen Beall, Bruce Irvine, Janice Kolberg, Michael S. Urdea
Abstract: The present invention provides an improved ubiquitin fusion system for gene expression in yeast systems which allows for the regulatable high level production of heterologous proteins having destabilizing amino terminal residues. The ubiquitin fusion proteins expressed in yeast are cleaved precisely in vivo by an endogenous ubiquitin-specific hydrolase to yield heterologous proteins such as human alpha-1-antitrypsin, human gamma-interferon and human immunodeficiency virus integrase protein, all of which initiate with destabilizing residues. An expression vector containing a synthetic gene for monomeric yeast ubiquitin was constructed and expressed under the control of a glucose regulatable yeast promoter. Inclusion of unique restriction sites at the 3'-end of the synthetic ubiquitin gene allows for precise in-frame insertion of heterologous genes. The system can be used to increase expression of poorly expressed proteins and to produce proteins having selective amino-terminal destabilizing residues.
Abstract: An analyzer for performing automated assay testing. The analyzer includes a storage and conveyor system for conveying cuvettes to an incubation or processing conveyor, a storage and selection system for test sample containers, a storage and selection system for reagent containers, sample and reagent aspirating and dispensing probes, a separation system for separating bound from unbound tracer or labeled reagent, a detection system and date collection/processing system All of the sub-units of the machine are controlled by a central processing unit to coordinate the activity of all of the subunits of the analyze. The analyzer is specifically suited for performing heterogeneous binding assay protocols, particularly immunoassays.
Abstract: Recombinant protein complexes having human Factor VIII:C activity are expressed in a eukaryotic host cell by transforming the host cell with first and second expression cassettes encoding a first polypeptide substantially homologous to human Factor VIII:C A domain and a second polypeptide substantially homologous to human Factor VIII:C C domain, respectively. In the present invention, the first polypeptide may be extended having at its C-terminal a human Factor VIII:C B domain N-terminal peptide, a polypeptide spacer of 3-40 amino acids, and a human Factor VIII:C B domain C-terminal peptide. Expression of the second polypeptide is improved by employing an .alpha..sub.1 -antitrypsin signal sequence.
Type:
Grant
Filed:
May 16, 1995
Date of Patent:
May 9, 2000
Assignees:
Chiron Corporation, Novo Nordisk A/S
Inventors:
Barbara Chapman, Rae Lyn Burke, Mirella Ezban Rasmussen, Jan Moller Mikkelson
Abstract: A conductivity sensor for measuring hematocrit and a sensor housing for a blood analysis instrument using the conductivity sensor are described. The conductivity sensor includes a seven-electrode conductivity measurement cell in which three symmetric pairs of electrodes are arranged on opposite sides of a central electrode. The central electrode is connected to an AC source and the outermost pair of electrodes, which provide a return path for the current, are maintained at a ground or reference potential. The two inner pairs of electrodes measure the voltage drop along the current flow path. This arrangement confines the measurement current and potential within the sensor chamber, thereby preventing the sensor from interfering with other electrochemical sensors that may be provided in the blood analysis instrument. The sensor housing provides a linear arrangement of flow cells defining a fluid flow path through the housing.
Abstract: Methods for enhancing the immune response to vaccination in animals, including humans, comprise administering interleukin-2 (IL-2) as part of the vaccination regimen, preferably for 5 to 14 days post-vaccination. In addition, compositions for enhancing the immune response of an animal to a vaccine employ IL-2 as an active ingredient, preferably human IL-2.
Type:
Grant
Filed:
August 31, 1998
Date of Patent:
May 9, 2000
Assignee:
Chiron Corporation
Inventors:
Michael V. Doyle, Arthur D. Newell, Jack H. Nunberg, Thomas J. White
Abstract: Embodiments of the present invention feature methods and compositions for controlling the translation of viral peptides and proteins from viral nucleic acid, with particular applications to pestivirus and HCV. The methods and compositions feature control elements of the 5'UT region of the viral genome.
Type:
Grant
Filed:
May 12, 1995
Date of Patent:
May 2, 2000
Assignee:
Chiron Corporation
Inventors:
Jang H. Han, Richard R. Spaete, Byoung J. Yoo, Byung S. Suh, Mark J. Selby, Michael Houghton
Abstract: The invention provides for use of selective inhibitors of GSK3 for treatment of diseases that are mediated by GSK3 activity, including non-insulin dependent diabetes mellitus (NIDDM) and Alzheimer's disease. Also described are methods of identifying inhibitors of GSK3 activity. The selective GSK3 inhibitor can be a peptide, peptoid, small organic molecule, or polynucleotide.
Abstract: Methods for preventing or treating an antibody-mediated diease in a patient are presented, the methods comprising administration of a monoclonal antibody capable of binding to a human CD40 antigen located on the surface of a human B cell, wherein the binding of the antibody to the CD40 antigen prevents the growth or differentiation of the B cell. Monoclonal antibodies useful in these methods, and epitopes immunoreactive with such monoclonal antibodies are also presented.
Abstract: The invention provides for use of selective inhibitors of GSK3 for treatment of diseases that are mediated by GSK3 activity, including non-insulin dependent diabetes mellitus (NIDDM) and Alzheimer's disease. Also described are methods of identifying inhibitors of GSK3 activity. The selective GSK3 inhibitor can be a peptide, peptoid, small organic molecule, or polynucleotide.
Abstract: The claimed invention provides methods of detecting and typing HCV using type specific and type-cluster specific epitopes. The claimed invention also provides peptides having type specific and type-cluster specific epitopes.
Abstract: Novel compositions are provided that are derived from antigen-binding sites of immunoglobulins having affinity for cancer antigens. The compositions exhibit immunological binding properties of antibody molecules capable of binding specifically to a human tumor cell expressing an antigen selected from the group consisting of high molecular weight mucins bound by 2G3 and 369F10, c-erbB-2 tumor antigen, an approximately 42 kD glycoprotein, an approximately 55 kD glycoprotein, and the approximately 40, 60, 100 and 200 kD antigens bound by 113F1. A number of synthetic molecules are provided that include CDR and FR regions derived from same or different immunoglobulin moieties. Also provided are single chain polypeptides wherein V.sub.H and V.sub.L domains are attached by a single polypeptide linker. The sFv molecules can include ancillary polypeptide moieties which can be bioactive, or which provide a site of attachment for other useful moieties.