Abstract: Novel Hepatitis C E1 and E2 truncated polypeptides and complexes comprising these polypeptides, are disclosed. The polypeptides are C-terminally truncated to remove all or a portion of their membrane spanning domains. Hence, the polypeptides are capable of secretion when expressed recombinantly.
Abstract: Compositions are provided which include biodegradable microparticles with entrapped or adsorbed antigens, in combination with submicron oil-in-water emulsions. Also provided are methods of immunization which comprise administering to a vertebrate subject (a) a submicron oil-in-water emulsion, and (b) a therapeutically effective amount of a selected antigen entrapped in a microparticle.
Type:
Grant
Filed:
May 2, 2000
Date of Patent:
October 23, 2001
Assignee:
Chiron Corporation
Inventors:
Derek O'Hagan, Gary Van Nest, Gary S. Ott, Manmohan Singh
Abstract: The present invention relates to a hybrid protein comprising the Pseudomonas aeruginosa outer membrane protein I (OprI) which is fused with its amino terminal end to the carboxy-terminal end of a carboxy-terminal portion of the Pseudomonas aeruginosa outer membrane protein F (OprF), as well as to monoclonal or polyclonal antibodies against this hybrid protein. Both, the hybrid protein and the antibodies directed to the hybrid protein confer protection against an infection by Pseudomonas aeruginosa to laboratory animals or man.
Type:
Grant
Filed:
March 10, 1999
Date of Patent:
October 9, 2001
Assignee:
Chiron Behring GmbH & Co.
Inventors:
Bernhard Knapp, Klaus-Dieter Hungerer, Michael Bröker, Bernd-Ulrich von Specht, Horst Domdey
Abstract: An adjuvant composition, comprising a metabolizable oil and an emulsifying agent, wherein the oil and the detergent are present in the form of an oil-in-water emulsion having oil droplets substantially all of which are less than 1 micron in diameter. In preferred embodiments, the emulsifying agent is also an immunostimulating agent, such as a lipophilic muramyl peptide. Alternatively, an immunostimulating agent separate from the emulsifying agent can be used.
Type:
Grant
Filed:
April 7, 1995
Date of Patent:
October 9, 2001
Assignee:
Chiron Corporation
Inventors:
Gary Van Nest, Gary Ott, Gail Barchfeld
Abstract: Compositions and methods are provided for endopeptidases and their production, and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides. These compositions and methods utilize recombinant PACE 4 and 4.1, mammalian endopeptidases that are specific for dibasic amino acid sites. Therapeutic compositions and methods employing PACE 4 or 4.1 or their inhibitors are also provided.
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 26, 1994
Date of Patent:
August 14, 2001
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: 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 &agr;1-antitrypsin signal sequence.
Type:
Grant
Filed:
May 16, 1995
Date of Patent:
May 8, 2001
Assignees:
Chiron Corporation, Novo Nordisk A/S
Inventors:
Barbara Chapman, Rae Lyn Burke, Mirella Ezban Rasmussen, Jan Moller Mikkelson
Abstract: EGF muteins in which the histidine at position 16 is replaced with a neutral or acidic amino acid exhibit activity at pHs lower than obtainable with wild type EGF.
Type:
Grant
Filed:
March 20, 1996
Date of Patent:
February 20, 2001
Assignee:
Chiron Corporation
Inventors:
Guy T. Mullenbach, Jeffrey M. Blaney, Steven Rosenberg
Abstract: Novel Hepatitis C E1 and E2 truncated polypeptides and complexes comprising these polypeptides, are disclosed. The polypeptides are C-terminally truncated to remove all or a portion of their membrane spanning domains. Hence, the polypeptides are capable of secretion when expressed recombinantly.
Abstract: Methods for purifying authentic, properly folded IGF polypeptides from yeast transformants are disclosed. The methods include a refolding step and provide for high yields of authentic IGF from a variety of yeast strains.
Type:
Grant
Filed:
December 15, 1997
Date of Patent:
September 12, 2000
Assignee:
Chiron Corporation
Inventors:
Cynthia Cowgill, Louis Juarbe, Patricio Riquelme, Glenn Dorin, Christopher M. Bussineau, Robert D. Kudrna, Ausman G. Otzurk
Abstract: This invention relates generally to the field of immunology, in particular that of antibodies and antibody productions. More specifically, this invention relates to bispecific antibodies, the hybrid hybridomas which produce them, the parent hybridomas, the production and selection of the hybridomas and hybrid hybridomas, and the purification of the bispecific antibodies. Specific examples relate to bispecific monoclonal antibodies which recognize both the human multi-drug resistance antigen, P-glycoprotein and human Fc.gamma. receptor III (hFc.gamma.RIII). These bispecific antibodies are useful in killing cancer cells.
Abstract: The present invention relates generally to modified secreted viral proteins, to the genes which express these proteins and to antibodies produced against such proteins, and to the use of these materials in diagnostic and vaccine applications. In particular, the present invention describes deletion of the transmembrane region only and retention of at least part of the cytoplasmic domain itself or fusion with at least part of an alternate cytoplasmic domain. The result will generally be the secretion of proteins which are normally membrane-bound (nonsecretory). This invention greatly increases the efficiency of secretion of the derivative protein. Specific viral proteins of interest include, but are not limited to, those from CMV, HSV, EBV, VZV, HCV, HIV, and influenza.
Type:
Grant
Filed:
July 29, 1994
Date of Patent:
August 8, 2000
Assignee:
Chiron Corporation
Inventors:
Rae Lyn Burke, Karin Hartog, Carol Pachl
Abstract: A noncloning method for expressing a gene of interest in a mammalian host cell is disclosed. The invention utilizes three basic individual elements: (1) a promoter element; (2) at least one gene of interest; and (3) a selectable marker cassette which includes in 5' to 3' order, an internal ribosome entry site ("IRES"), at least one gene coding for a selectable marker, and a transcription termination sequence. The three individual elements are cotransfected into a mammalian host cell where they become operably linked such that expression of the selectable marker gene(s) necessarily requires coexpression of the gene of interest.
Abstract: Novel polypeptides called signaling inositol polyphosphate 5-phosphatases are described called SIP-130, SIP-125, and SIP-N. SIP-130 is capable of binding to aPTB domain of SH2 and collagen containing protein (SHC). Also provided are polynucleotide sequences encoding the novel polypeptides, as well as vectors and host cells containing the polynucleotides. Further provided are modulators including agonists and antagonists of the novel polypeptides for use as therapeutics, including antibodies, polypeptides, small molecules, and polynucleotides and methods of using the therapeutics in treatment of diseases associated with abnormal cell growth. Methods of making the polypeptides, polynucleotides, vectors, host cells, antibodies, and small molecules are also provided. Gene delivery vehicles including SIP and SIP activity-modulating polynucleotides are described.
Type:
Grant
Filed:
November 19, 1998
Date of Patent:
July 18, 2000
Assignee:
Chiron Corporation
Inventors:
W. Michael Kavanaugh, David Pot, Lewis T. Williams
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: 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: 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: 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: 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: 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.