Abstract: The present invention is directed to novel adjuvant compositions, which target the cellular and/or humoral arms of immunity. According to an embodiment of the invention, an oil-in-water adjuvant composition is provided that comprises: (a) water; (b) a metabolizable oil comprising at least one branched or unbranched long-chain hydrocarbon moiety; (c) a steroid; and (d) a saponin.
Type:
Grant
Filed:
March 21, 2002
Date of Patent:
March 1, 2005
Assignee:
Chiron Corporation
Inventors:
Gary S. Ott, Derek O'Hagan, Manmohan Singh
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:
May 15, 1995
Date of Patent:
March 1, 2005
Assignee:
Chiron Corporation
Inventors:
Michael Houghton, Qui-Lim Choo, George Kuo
Abstract: This invention relates to human fibroblast growth factor (hFGF-21), and to variants thereof and to polynucleotides encoding FGF-21. The invention also relates to diagnostic and therapeutic agents related to the polynucleotides and proteins, including probes and antibodies, and to methods of treating liver disease such as cirrhosis and cancer, methods of treating conditions related to thymic function, and methods of treating conditions of the testis. The invention also relates to mouse fibroblast growth factor (mFGF-21), and to variants thereof and polynucleotides encoding mFGF-21.
Abstract: Highly purified preparations of TFPI or TFPI analogs can be prepared using a method that generally involves the following steps: (1) expression of TFPI or TFPI analog in E. coli, (2) isolation of refractile bodies, (3) dissolution of the refractile bodies and refolding of the expressed TFPI or TFPI analog, (4) SP-Sepharose fast flow (FF) chromatography, (5) a first concentration and diafiltration step, (6) Q-Sepharose high (HP) performance chromatography, (7) butyl hydrophobic interaction chromatography (HIC), (8) SP-Sepharose HP chromatography, and (9) a second concentration/diafiltration step. Less than about 12% of the TFPI or TFPI analog molecules in such preparations are modified TFPI or TFPI analog species (i.e., oxidized, carbamylated, acetylated, deamidated, aggregated, or misfolded species).
Type:
Application
Filed:
January 8, 2004
Publication date:
February 17, 2005
Applicants:
Chiron Corporation, Pharmacia & Upjohn Company
Inventors:
David Reifsnyder, Duane Inlow, Glenn Dorin, Patricio Riquelme, Cynthia Cowgill, Douglas Bolesch, Mark Gustafson
Abstract: The present invention involves methods and compositions for increasing the susceptibility of target cells to transduction by gene transfer vectors. Specifically, it is proposed that increasing intracellular permeability in epithelial tissue increases the percentage of input vector that will transduce that target tissue. Specific examples show that receptors for retrovirus are preferentially accessible on the basolateral surface of airway epithelia, and permeabilizing such tissues results in greater infection with retrovirus. This has important implications in gene therapy, for example, to treat cystic fibrosis with the CFTR gene.
Type:
Grant
Filed:
November 22, 1999
Date of Patent:
February 15, 2005
Assignees:
The University of Iowa Research Foundation, Chiron Corporation
Inventors:
Paul B. McCray, Jr., Guoshun Wang, Beverly Davidson, Mordechai Bodner, Steven M. Herrmann, Douglas J. Jolly
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:
August 2, 2002
Date of Patent:
February 15, 2005
Assignee:
Chiron Corporation
Inventors:
Derek O'Hagan, Gary Van Nest, Gary S. Ott, Manmohan Singh
Abstract: Chimeric oligonucleotide of the formula 5?-W—X1—Y—X2—Z-3?, where W represents a 5?-O-alkyl nucleotide, each of X1 and X2 represents a block of seven to twelve phosphodiester-linked 2?-O-alkyl ribonucleotides, Y represents a block of five to twelve phosphorothioate-linked deoxyribonucleotides, and Z represents a blocking group effective to block nuclease activity at the 3? end of the oligonucleotide, are described. These compounds exhibit high resistance to endo- and exonucleases, high sequence specificity, and the ability to activate RNAse H, as evidenced by efficient and long-lasting suppression of target mRNA. The oligonucleotides are preferably transfected into cells in formulations containing a lipid-peptoid conjugate carrier molecule of the formula L-linker-[N(CH2CH2NH2)CH2(C?O)—N(CH2CH2R)CH2(C?O)—N(CH2CH2R)CH2(C?O)]3—NH2, where L is a lipid moiety, including a steroid, and each group R is independently selected from alkyl, aminoalkyl, and aralkyl.
Type:
Grant
Filed:
April 3, 2001
Date of Patent:
January 25, 2005
Assignee:
Chiron Corporation
Inventors:
Michael A. Innis, Christoph J. Reinhard, Ronald N. Zuckermann
Abstract: A new receptor for fibroblast growth factor has been cloned and expressed. The recombinant receptor is useful for inhibiting FGF activity, and for screening compounds for binding activity similar to that of FGF. A soluble, truncated recombinant receptor is also prepared, and is capable of binding FGF.
Type:
Grant
Filed:
July 20, 2000
Date of Patent:
January 18, 2005
Assignee:
Chiron Corporation
Inventors:
Michael C. Keifer, Pablo D. T. Valenzuela, Philip J. Barr
Abstract: Chimeric proteins possessing Kunitz-type domain 1 of TFPI-2 and Kunitz-type domain 2 of TFPI are disclosed, as are muteins of TFPI and TFPI-2. Nucleic acid sequences, expression vectors and transformed host cells encoding and capable of producing the disclosed chimeric proteins and muteins are also disclosed. Finally, methods for prevention and treatment of septic shock using the chimeric proteins and muteins are disclosed.
Abstract: Antimicrobial macrolide and ketolide compounds are provided having formulas XII: as well as pharmaceutically acceptable salts, esters or prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.
Type:
Application
Filed:
April 23, 2004
Publication date:
January 13, 2005
Applicant:
Chiron Corporation
Inventors:
Matthew Burger, Georgia Carroll, Daniel Chu, Xiaodong Lin, Jacob Plattner, Alice Rico
Abstract: Provided are affinity support materials having intermediate binding affinity for biological samples. Among the materials provided by the present invention are hydrophilic solid supports composed of hydrophilic ligands coupled to hydrophilic matrixes which are compatible with biological samples, for example, a cell line, a biological fluid such as blood, or a tissue cell lysate. The ligands may include affinity property groups and hydrophilic groups pendent from a backbone, and be configured to at least partially resolve components of a biological sample. Affinity supports in accordance with the present invention may be used in a variety of techniques and apparatuses to achieve improved separations of complex biological samples and thereby enhance the results of biological sample component fractionations, enrichments, purifications, expression product determinations and comparisons, and other biological sample processing techniques.
Type:
Application
Filed:
April 29, 2004
Publication date:
January 6, 2005
Applicant:
Chiron Corporation
Inventors:
Ronald Zuckermann, Eric Beausoleil, Matthew Wachowicz, Srinivas Kothakota
Abstract: A patient suffering from an endobronchial infection is treated by administering to the patient for inhalation a dose of less than about 4.0 ml of a nebulized aerosol formulation comprising from about 60 to about 200 mg/ml of an aminoglycoside antibiotic, such as tobramycin, in a physiologically acceptable carrier in a time period of less than about 10 minutes. Unit dose devices for storage and delivery of the aminoglycoside antibiotic formulations are also provided.
Type:
Application
Filed:
July 1, 2004
Publication date:
December 30, 2004
Applicant:
Chiron Corporation
Inventors:
Robert John Speirs, Barbara Ann Shaeffler, Peter Bruce Challoner
Abstract: Novel peptides that are capable of binding to uPAR and inhibiting the binding of an integrin and vitronectin are described. Also provided are nucleic acid sequences encoding the novel peptides. Methods for screening for small molecules, other peptides, or peptoids that mimic the antagonistic function of the peptides of the invention are described. The invention has applications in design of therapeutics for treating disorders characterized by upregulation of uPA and uPAR, and cancer and chronic inflammation, cell migration or uPAR: integrin binding interactions, and diagnostical applications to such disorders.
Type:
Application
Filed:
April 9, 2004
Publication date:
December 30, 2004
Applicant:
Chiron Corporation
Inventors:
Steven Rosenberg, Michael V. Doyle, Harold A. Chapman
Abstract: Methods and compositions are provided for the production of human manganese superoxide dismutase and a protocol for enhancing efficiency of expression. The gene encoding for human manganese superoxide dismutase was isolated and inserted into a vector in conjunction with a synthetic linker which provides for enhanced efficiency in translation.
E. coli strain HB101 containing the plasmid Nco5AHSODm was deposited at the A.T.C.C. on Oct. 3, 1986 and given Accession No. 67191.
Type:
Grant
Filed:
June 11, 2001
Date of Patent:
December 14, 2004
Assignee:
Chiron Corporation
Inventors:
Robert Alexander Hallewell, Graeme Ian Bell, Guy Towns Mullenbach
Abstract: The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.
Abstract: Compositions are provided which include hyaluronic acid derivatives in combination with vaccine antigens, and optionally adjuvants, for mucosal delivery. Also provided are methods of making the compositions, as well as methods of immunization using the same.
Abstract: This invention relates to mouse and human EGFH2, and to variants thereof and to polynucleotides encoding EGFH2. This invention also relates to therapeutic agents related to the polynucleotides and proteins.
Type:
Grant
Filed:
August 15, 2000
Date of Patent:
November 30, 2004
Assignee:
Chiron Corporation
Inventors:
W. Michael Kavanaugh, Hui Cen, Pauline Lee
Abstract: Immunoassays for detecting hepatitis C virus protein and immune complexes between hepatitis C virus protein and antibodies in biological samples, methods of screening blood products for hepatitis C virus, and kits employed therefor are provided.
Abstract: The present invention provides parenteral adjuvants comprising detoxified mutants of bacterial ADP-ribosylating toxins, particularly those from pertussis (PT), cholera (CT), and heat-labile E. coli (LT).
Type:
Grant
Filed:
March 18, 1998
Date of Patent:
November 16, 2004
Assignee:
Chiron Corporation
Inventors:
Gail Barchfeld, Giuseppe Del Giudice, Rino Rappuoli
Abstract: Methods are provided for obtaining measurable levels of a protein, nucleic acid molecule, or enzymatic product in a bodily fluid or cells of a human, comprising the step of administering to a human a recombinant retroviral preparation having a titer on HT1080 cells of greater than 105 cfu/ml, wherein the recombinant retroviral preparation is capable of directing the expression of a protein, nucleic acid molecule, or enzyme which generates an enzymatic product, such that measurable levels of the protein, nucleic acid molecule, or enzymatic product may be obtained in the bodily fluid or cells of the human.
Type:
Grant
Filed:
December 30, 1997
Date of Patent:
November 16, 2004
Assignee:
Chiron Corporation
Inventors:
Douglas J. Jolly, Stephen Chang, James G. Respess, Nicholas J. DePolo, David Chi-Tang Hsu, Carlos E. Ibanez, Judith Greengard, Lee Will