Chiron Corporation

University of California

G.d. Searle & Company

Robert A Hallewell

Guy T Mullenbach

Howard M Goodman

Steven Rosenberg

William J Rutter

Pablo D Valenzuela

Graeme Ian Bell

Jeffrey C Edman

Philip J Barr

Patricia A Tekamp-Olson

John Spencer Emtage

Anthony J Brake

Norman H Carey

William C Tacon

Manganese superoxide dismutase cloning and expression in microoganisms

Methods and compositions are provided for the production of human superoxide dismutase and a novel protocol for enhancing efficiency of expression. The gene encoding for human superoxide dismutase is isolated and inserted into a vector in conjunction with a synthetic linker which provides for enhanced efficiency in translation.,strain D1210 (pSODX8) was deposited at the A.T.C.C. on Sep. 27, 1983 and given Accession No. 39453. Yeast strain 2150-2-3 (pC1/1GAPSOD) and,strains D1210 (pSOD11) and D1210 (pS20R) were deposited at the A.T.C.C. on May 9, 1984, and given Accession Nos. 20708, 39679 and 39,680, respectively.

DNA construct comprising a vector for expression of human cytoplasmic Cu/Zn superoxide dismutase in E. coli and method of use of same

Manganese superoxide dismutase cloning and expression in microorganisms

Methods and compositions are provided for the production of human superoxide dismutase and a novel protocol for enhancing efficiency of expression. The gene encoding for human superoxide dismutase is isolated and inserted into a vector in conjunction with a synthetic linker which provides for enhanced efficiency in translation.

Isolated DNA sequence comprising DNA encoding human cytoplasmic Cu-Zn

Methods and compositions are provided for the production of human superoxide dismutase and a novel protocol for enhancing efficiency of expression. The gene encoding for human superoxide dismutase is isolated and inserted into a vector in conjunction with a synthetic linker which provides for enhanced efficiency in translation. E. coli strain D1210 (pSODX8) was deposited at the A.T.C.C. on Sep. 27, 1983 and given Accession No. 39453. Yeast strain 2150-2-3 (pC1/1GAPSOD) and E. coli strains D1210 (pSOD11) and D1210 (pS2OR) were deposited at the A.T.C.C. on May 9, 1984, and given Accession Nos. 20708, 39679 and 39,680, respectively.

Superoxide dismutase cloning and expression in microorganisms

Genetic modification of superoxide dismutase to increase expression in

DNA encoding human cytoplasmic Cu/Zn superoxide dismutase

Methods and compositions are provided for the production of human superoxide dismutase and a novel protocol for enhancing efficiency of expression. The gene encoding for human superoxide dismutase is isolated and inserted into a vector in conjunction with a synthetic linker which provides for enhanced efficiency in translation. E. coli strain D1210 (pSOD.times.8) was deposited at the A.T.C.C. on Sep. 27, 1983 and given Accession No. 39453. Yeast strain 2150-2-3 (pC1/1GAPSOD) and E. coli strains D1210 (pSOD11) and D1210 (pS2OR) were deposited at the A.T.C.C. on May 9, 1984, and given Accession Nos. 20708, 39679 and 39,680, respectively.

Superoxide dismutase (SOD) analogs whose amino acid sequence includes a heterologous peptide domain such as the RGDX tetrapeptide found in fibronectin or the LGGAKQAGDV decapeptide found in fibrinogen that enables the analog to bind to a moiety that is normally present at sites of desired SOD therapy. The domain is incorporated into the SOD sequence in a manner in which it is available to interact with such moieties but does not destroy the enzymatic activity of the molecule. The inclusion of the domain enables the analog to more readily access the target tissue upon which it is to act and/or increase the corporeal half-life of the molecule.

Superoxide dismutase analogs having novel binding properties

A DNA expression vector is described which is derived from the highly efficient trp operon. The expression vector provides for the direct expression of an inserted gene or cDNA. Using the expression vector described herein, it is possible to obtain the protein coded by the gene or cDNA directly and not as a fusion protein. The expression vector comprises the promoter, operator and leader ribosomal binding site of the trp operon.

DNA expression vector suitable for direct expression of a foreign gene

Recombinant Cu/Zn superoxide dismutase (SOD) polymers having an extended in vivo half-life composed of SOD monomers covalently coupled to each other, carboxy terminus to amino terminus, by a polypeptide spacer such as a fragment of the hinge region of an immunoglobulin.

Superoxide dismutase polymers

Methods and compositions are provided for the production of human copper/zinc superoxide dimutase (SOD) polypeptides in microorganisms. Bacterially produced human CuZn SOD polypeptides are provided. E. coli strain D1210 (pSODX8) was deposited at the A.T.C.C. on Sept. 27, 1983 and given Accession No. 39453. Yeast strain 2150-2-3 (pCl/1GAPSOD) and E. coli strains D1210 (pSOD11) and D1210 (pS2OR) were deposited at the A.T.C.C. on May 9, 1984, and were given Accession Nos. 20708, 39679 and 39680, respectively.

Polypeptides of human copper/zinc superoxide dimutase

A DNA expression vector which contains the trp promotor is described. The expression vector provides for the overproduction of .beta.-lactamase. Insertion of a gene or cDNA into the .beta.-lactamase gene of the expression vector results in the over-production of a fusion protein comprising a part of the .beta.-lactamase as the N-terminal end and the protein coded for by the inserted DNA as the C-terminal end. Using the expression vector described herein, it is possible to obtain large amounts of the fusion protein. A fusion protein containing the surface antigen of Hepatitis B virus and a vaccine containing this fusion protein are also described.

Amplified expression vector

Methods and compositions are provided for high level production of foreign proteins in yeast. The system is exemplified by production of .alpha..sub.1 -antitrypsin in yeast strain AB110, derived from yeast strains 2150-2-3 and AB103.1. S. carlsbergensis/S. cerevisiae hybrid strain AB110 containing plasmid pCl/1GAPATi9 was deposited at the A.T.C.C. on May 9, 1984, and given Accession No. 20709.

Expression of .alpha.-1 antitrypsin in yeast

Proteinaceous composition are provided which inhibit naturally occurring serine proteases. Particularly, an amino acid sequence analogous to human .alpha..sub.1 -antitrypsin is modified at the active site while maintaining protease inhibition. The methionine at the active site is substituted with an oxidatively stable amino acid, while other amino acids may also be changed, added or deleted, particularly at the termini. The yeast strains AB103.1 (pCl/PH05ATi(Val) and AB110 (pCl/1GAPATi(Val) were deposited at the A.T.C.C. on June 18, 1984 and given Accession Nos. 20711 and 20712, respectively.

Growing community of inventors

San Francisco, CA, United States of America

Robert A Hallewell