Abstract: Expression vectors and transfection systems providing high expression of a desired polypeptide are provided. Also provided are methods of using the expression vectors and transfection systems and mammalian cells modified by these compositions and methods.
Abstract: Isolated nucleic acid molecules are disclosed, comprising an alphavirus nonstructural protein gene which, when operably incorporated into a recombinant alphavirus particle, eukaryotic layered vector initiation system, or RNA vector replicon, has a reduced level of vector-specific RNA synthesis, as compared to wild-type, and the same or greater level of proteins encoded by RNA transcribed from the viral junction region promoter, as compared to a wild-type recombinant alphavirus particle. Also disclosed are RNA vector replicons, alphavirus vector constructs, and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules.
Type:
Grant
Filed:
October 6, 1997
Date of Patent:
September 17, 2002
Assignees:
Chiron Corporation, Washington University
Inventors:
Thomas W. Dubensky, Jr., John M. Polo, Barbara A. Belli, Sondra Schlesinger, Sergey A. Dryga, Ilya Frolov
Abstract: The present invention has multiple aspects. In particular, in one aspect, the present invention is directed to a unit dose comprising 0.2 &mgr;g/kg to 36 &mgr;g/kg of a recombinant FGF or an angiogenically active fragment or mutein thereof. In another aspect, the present invention is directed to a pharmaceutical composition comprising an angiogenically effective dose of an FGF or an angiogenically active fragment or mutein thereof, and a pharmaceutically acceptable carrier. Typically, the angiogenically effective dose comprises 0.2 &mgr;g/kg to 36 &mgr;g/kg of an FGF of any one of SEQ ID NOS: 1-3, 5, 8-10 or 12-14 or an angiogenically active fragment or mutein thereof.
Type:
Grant
Filed:
October 13, 1999
Date of Patent:
September 17, 2002
Assignee:
Chiron Corporation
Inventors:
Martha J. Whitehouse, W. Michael Kavanaugh
Abstract: Methods for improving purification and quantification of platelet derived growth factor (PDGF) proteins having structural heterogeneity are provided. Preparation of substantially pure isoforms of these proteins is achieved using TSK sulfopropyl cation exchange chromatography and reverse phase high performance liquid chromatography. A reverse charged capillary zone electrophoresis method enables quantification of substantially pure isoforms of these proteins resulting from endoproteolytic post-translational modifications. Compositions of the invention are substantially purified isoforms of secreted PDGF proteins having structural heterogeneity, more particularly purified intact, single-clipped, and double-clipped isoforms of recombinant PDGF-BB. Pharmaceutical compositions comprising at least one of these substantially purified recombinant PDGF isoforms and methods for their use in promoting wound healing are also provided.
Type:
Grant
Filed:
April 14, 2000
Date of Patent:
September 10, 2002
Assignee:
Chiron Corporation
Inventors:
Michael Kunitani, An D. Tran, Hugh Parker
Abstract: Inhibitors, including antibodies, of IL8 binding to its receptors, that interact with the amino-terminal extracellular domain of the IL8 receptor and which compete with IL8 for receptor-binding, are disclosed. The inhibitors are useful modulators of IL8 receptor-mediated biological activity.
Type:
Grant
Filed:
September 14, 1993
Date of Patent:
September 10, 2002
Assignee:
Chiron Corporation
Inventors:
Patricia Tekamp-Olson, Guy Mullenbach, Mary Ellen Wernette-Hammond
Abstract: The present invention has multiple aspects. In particular, in one aspect, the present invention is directed to a unit dose composition comprising 0.2 &mgr;g/kg to 48 &mgr;g/kg of an FGF-2 of SEQ ID NO: 2, or an angiogenically active fragment or mutein thereof in a pharmaceutically acceptable carrier. In another aspect, the present invention is directed to a method for treating a human patient for coronary artery disease, comprising administering into one or more coronary vessels or a peripheral vein of a human patient in need of treatment for coronary artery disease a safe and angiogenically effective dose of a recombinant FGF-2, or an angiogenically active fragment or mutein thereof. The single unit dose composition of the present invention provides an angiogenic effect in a human CAD patient that lasts six months before re-treatment is required. In another aspect, the present invention is directed to a method of administration which optimizes patient's safety.
Abstract: A polypeptide containing an anchor region, a protease recognition site, and a detectable signal region can be produced recombinantly and directly attached to a solid support. The polypeptide is useful for screening protease regulators, especially protease inhibitors.
Type:
Grant
Filed:
October 17, 1997
Date of Patent:
August 20, 2002
Assignee:
Chiron Corporation
Inventors:
David Y. Chien, Mark J. Selby, Kevin Shoemaker, Robert L. Warne
Abstract: A human gene encoding a novel cyclin-dependent kinase termed hPFTAIRE and its expression products can be used to provide reagents and methods for detecting migrating or metastasizing cells. Compositions and methods for treating proliferative disorders and neoplasia are also provided.
Type:
Grant
Filed:
December 7, 1998
Date of Patent:
August 13, 2002
Assignee:
Chiron Corporation
Inventors:
Christoph Reinhard, David Pot, Altaf Kassam, Tasha Marenbach, Lewis T. Williams
Abstract: Methods and compositions are provided for producing recombinant AAV vector particles; comprising the general steps of (a) introducing into a host cell (i) pfloxAAV, (ii) a recombinant viral vector encoding plasmid, and (iii) a plasmid encoding herpesvirus, cytomegalovirus, or adenoviral functions, or a herpesvirus, cytomegalovirus, or, adenovirus itself, in order to produce flox AAV particles and recombinant AAV particles; and (b) introducing into a second host cell (i) the recombinant AAV particles and flox AAV particles of (a), (ii) a vector which directs the expression of Cre, and (iii) a vector which directs the expression of herpesvirus, CMV, or adenovirus helper functions, such that said recombinant AAV vector particles are produced.
Abstract: The present invention is based on the discovery of polynucleotides that represent novel genes that are differentially expressed in pancreatic disease, e.g., pancreatic cancer, dysplasia, pancreatitis, or diabetes. The invention features methods of identifying cells affected by such pancreatic diseases by detection of a gene product encoded by such differentially expressed genes, as well as methods of modulating expression of such gene products to effect therapy (e.g., to decrease growth and/or affect abnormal characteristics of cancerous or dysplastic pancreatic cells.
Abstract: Human hepatitis C virus (HCV) has been identified as the aetiological agent of non-A, non-B hepatitis (NANBH). HCV viruses display considerable genotypic and phenotypic heterogeneity. Thus, there is considerable need in the art for more sensitive reagents that facilitate the detection of HCV variants. The genome of hepatitis C virus (HCV) consists of seven functional regions: the core, E1, E2/NS1, NS2, NS3, NS4, and NS5 regions. An attempt was made to improve the sensitivity of anti-HCV assays by developing multiple copy epitope fusion antigens (MEFAs) which incorporate the major immunodominant epitopes from the functional regions of the HCV genome. These MEFAs are encompassed by the following generic structural formula: (A)x—(B)y—(C)z. This formula represents a linear amino acid sequence comprising multiple copies of one HCV epitope (A) linked to multiple copies of another HCV epitope (B) which in turn is linked to multiple copies of yet another HCV epitope (C).
Type:
Grant
Filed:
May 20, 1997
Date of Patent:
August 6, 2002
Assignee:
Chiron Corporation
Inventors:
Pablo D. T. Valenzuela, David Ying Chien
Abstract: Isolated nucleic acid molecules are disclosed. comprising an alphavirus nonstructural protein gene which, when operably incorporated into a recombinant alphavirus particle, eukaryotic layered vector initiation system, or RNA vector replicon, has a reduced level of vector-specific RNA synthesis, as compared to wild-type, and the same or greater level of proteins encoded by RNA transcribed from the viral junction region promoter, as compared to a wild-type recombinant alphavirus particle. Also disclosed are RNA vector replicons, alphavirus vector constructs, and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules.
Type:
Grant
Filed:
October 8, 1999
Date of Patent:
July 30, 2002
Assignees:
Chiron Corporation, Washingto University
Inventors:
Thomas W. Dubensky, Jr., John M. Polo, Sondra Schlesinger, Ilya Frolov
Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.
Abstract: A human gene termed CIF130 and its expression products can alter the spatial or temporal patterns of mitosis or cell cycle progression of a human cell. Methods of treating disorders involving alterations in the regulation of mitosis or cell cycle progression utilize the gene and its expression product. Genes whose expression is dependent upon CIF130 expression can be identified.
Abstract: The invention provides host cells comprising a translation operator sequence (TOP) and packaging elements. Also provided are viral vectors comprising a TOP operably linked to a transgene. Also provided are methods of using these host cells and viral vectors to produce recombinant virions.
Abstract: Novel pyridine and pyrimidine derivatives which selectively inhibit glycogen synthase kinase 3 are provided and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions which may be mediated by glycogen synthase kinase 3.
Type:
Grant
Filed:
June 18, 1999
Date of Patent:
July 9, 2002
Assignee:
Chiron Corporation
Inventors:
Dane A. Goff, Stephen D. Harrison, John M. Nuss, David B. Ring, Xiaohui A. Zhou
Abstract: The claimed invention provides methods of detecting and typing HCV using nucleic acid molecules encoding type specific and type-cluster specific epitopes. The nucleic acid molecules flanking regions encoding type specific or type cluster specific epitopes are useful in priming the polymerase chain reaction to determine the genotype an HCV isolate.
Abstract: A method for boosting an immune response against meningococcal capsular antigen is disclosed. The method entails administering a first glycoconjugate vaccine composition to a subject to provide an initial state of anti-meningococcal immunity, and then boosting the anti-meningococcal immunity by administration of a second, boosting vaccination. Also disclosed is the use of vaccine compositions in the preparation of anti-meningococcal medicaments. The use entails administering a first glycoconjugate vaccine composition to a subject to provide an initial state of anti-meningococcal immunity, and then boosting the anti-meningococcal immunity by administration of a second, boosting vaccination.
Abstract: Mammalian deep orange tumor suppressor genes are disclosed. Mammalian deep orange genes and proteins can be used as therapeutics, as diagnostic tools, and in making animal models. The genes can be used to identify a q13 region of a human chromosome 15 and a central region of a mouse chromosome 2.