The Scripps Research Institute

Other

Peter S Tobias

Richard J Ulevitch

John C Mathison

Ann M Moriarty

Didier J Leturcq

Samuel D Wright

Theo Kirkland

Jiahuai Han

Douglas N Mintz

Jerome Pugin

This invention provides hybridoma cell lines producing monoclonal antibodies which inhibit CD14 mediated cell activation. Monoclonal antibodies produced by these cell lines also are provided. The antibodies are useful for the detection of the presence of cell surface and soluble CD14 in a sample. Chimeric and CDR grafted antibodies generated from the above monoclonal antibodies are further provided. Pharmaceutical compositions containing the above biological compositions are provided. These are useful to treat and prevent disorders with CD14 mediated cell activation, such as sepsis.

Hybrid cells producing monoclonal anti-CD14 antibodies

The present invention concerns a method of treating LBP-mediated LPS-induced myeloid cell activation comprising administering a therapeutically effective amount of an anti-LBP monoclonal antibody molecule. A therapeutic composition comprising anti-LBP antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

Monoclonal antibodies immunoreactive with lipopolysaccharide binding protein (LBP) and methods of their use

The present invention concerns a method of treating sepsis comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CD14 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

Methods and compositions for ameliorating the symptoms of sepsis

Methods and compositions for inhibiting CD14 mediated cell activation

The present invention concerns a method of treating bacteremia, sepsis and other forms of toxemia caused by Gram-positive bacteria and mycobacteria comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CD14 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

Use of antibodies to block the effects of gram-positive bacteria and mycobacteria

The present invention concerns a method of treating sepsis comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CDl4 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

A lipopolysaccharide binding protein is disclosed as are an assay method, polypeptides and antibodies related to that binding protein. The binding protein: (a) is present in impure form in acute phase serum, but is substantially absent from normal serum; (b) binds to Gram-negative bacterially secreted lipopolysaccharide in vitro in the serum of the animal treated; (c) retards in vitro binding of the lipopolysaccharide to high density lipoprotein present in the normal serum of the animal host; and (d) immunoreacts with antibodies raised to a polypeptide having the amino acid residue sequence, from left to right and in the direction from amino-terminus to carboxy-terminus, or ##STR1## wherein each of said parenthesized amino acid residues is an alternative to the immediately preceding residue in said sequence.

Acute phase protein modulating endotoxic activity of

The present invention provides a first polypeptide fragment of lipopolysaccharide (LPS) binding protein (LBP) which binds to lipopolysaccharide, but prevents the LPS:LBP complex from either transferring LPS to CD14 or promoting the formation of an LPS:CD14 complex and a second polypeptide fragment of LBP which binds to CD14 receptor to inhibit binding of LPS:LBP complex to the CD14 receptor. Also included are methods of ameliorating symptoms of sepsis in a subject by administration of a LBP polypeptide of the invention, or administration of antibody to LBP polypeptide or anti-idiotype antibody.

Polypeptides of lipopolysaccharide binding protein

Monoclonal antibodies immunoreactive with lipopolysaccharide binding

The present invention concerns a method of treating CD14-mediated host inflammatory response to LPS often associated with sepsis comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CD14 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

The present invention describes a rapid method for the identification of compounds/reagents which inhibit lipopolysaccharide (LPS) binding to LPS binding protein (LBP), and kits for practicing the method.

Methods for identifying inhibitors of LPS-mediated LBP binding

Antibodies that bind to a lipopolysaccharide binding protein, LBP, which is present in acute phase serum of an animal host, but is substantially absent from the normal serum of the host and antibodies that bind to LBP, are described.

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San Diego, CA, United States of America

Peter S Tobias