Xoma Corporation

Other

International Genetic Engineering

Lynn S Grinna

Georgia Theofan

Arnold H Horwitz

David J Burke

Manik Baltaian

Thomas F Parsons

Arup Sen

Carol Hersh

Disclosed are novel bactericidal/permeability-increasing (BPI) protein products wherein cysteine residue number 132 or 135 is replaced by another amino acid residue, preferably an alanine or serine residue and/or wherein the leucine residue at position 193 is the carboxy terminal residue. Also disclosed are DNA sequences encoding methods for the production of the same in appropriate host cells, and stable homogeneous pharmaceutical compositions containing the analogs suitable for use treatment of gram negative bacterial infection and its sequelae.

Stable bactericidal/permeability-increasing protein products and pharmaceutical compositions containing the same

Disclosed are novel bactericidal/permeability-increasing (BPI) protein products wherein cysteine residue number 132 or 135 is replaced by another amino acid residue, preferably an alanine or serine residue and/or wherein the leucine residue at position 193 is the carboxy terminal residue. Also disclosed are DNA sequences encoding methods for the production of the same in appropriate host cells, and state homogeneous pharmaceutical compositions containing the analogs suitable for use treatment of gram negative bacterial infection and in sequelae.

Stable bactericidal permeability-increasing protein products and pharmaceutical compositions containing the same

Disclosed are novel hybrid fusion proteins comprising at their amino terminus, bactericidal/permeability-increasing protein or a biologically active fragment thereof and, at their carboxy terminus, at least one immunoglobulin heavy chain constant domain useful in treating bacterial infection. Also disclosed are DNA sequences encoding such proteins, recombinant methods for production of the proteins, and pharmaceutical preparations containing the recombinant products.

Methods for the preparation of positively charged proteins

Bactericidal/permeability increasing protein (BPI) and biologically active fragments, analogs and variants thereof are solubilized by lipid carriers including phospholipids, liposomes and nonionic detergents and stabilized against particle formation by poloxamer surfactants.

Bactericidal/permeability-increasing protein (BPI) compositions

Stable bactericidal/permeability-increasing protein products and

BPI-immunoglobulin fusion proteins

The present invention provides osteogenically active protein preparations comprising a heterodimer of P3 OF 31-34 subunit B and P3 OF 31-34 subunit D, which subunits are linked with at least one disulfide bond and methods for their preparation. The invention further provides cell lines transformed with nucleotide sequences encoding P3 OF 31-34 subunit B and P3 OF 31-34 subunit D and vectors comprising those sequences in operative association with an expression control sequence.

Heterodimeric osteogenic factor

Disclosed are improvements in methods for the isolation of endotoxin-binding proteins which are secreted by transfected host cells in appropriate cell culture media. In its preferred embodiment, the invention comprises addition of a cation exchange material to the media as the means of increasing the yield of recombinant endotoxin-binding proteins, such as bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein.

Methods for the preparation of endotoxin-binding proteins

Stable bactericidal/permeability-increasing protein muteins

The present invention provides an osteogenically active protein preparation characterized by a molecular weight of from about 31,000 to 34,000 daltons as characterized comprising a subunit identical to or homologous to a subunit in P3 OF 31-34, by non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis and by the characteristic of eluting from a reverse phase high performance liquid chromatography column equilibrated with buffers containing trifluoroacetic acid and acetonitrile by eluting within the concentrations of 35% to 45% acetonitrile. The invention further provides improved methods for isolating such preparations and genes encoding all or a portion of polypeptide subunits of dimers comprising the osteogenic protein preparation.

Growing community of inventors

Upperville, VA, United States of America

Lynn S Grinna