The Scripps Research Institute

Other

Scripps Clinic and Research Foundation

Richard J Ulevitch

Peter S Tobias

John C Mathison

Ann M Moriarty

Didier J Leturcq

Samuel D Wright

Theo Kirkland

Kim D Janda

Vladimir Kravchenko

Jiahuai Han

Jerome Pugin

Zhuang-Jei Li

Yong Jiang

Douglas N Mintz

Curtis B Wilson

Thomas E Karplus

The invention is directed to methods of inducing apoptosis, arresting cell cycle, or inhibiting cellular proliferation, or any combination thereof, in a tumor cell, by administration of an effective amount of an N-acyl homoserine lactone analog (AHL), optionally in conjunction with a tumor modulating agent such tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) to the patient. Novel bioactive analogs of an N-acyl homoserine lactone are also provided.

Trail enhancers for the selective killing of cancer cells

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.

Assay systems utilizing a reporter construct based on p38 phosphorylation of myocyte enhancer factor 2 (MEF2) transcription factor are provided. The reporter construct and methods of use are provided, as well as methods of treatment of inflammatory and muscular disorders associated with MEF2-regulated gene expression.

Assay systems and methods for measuring P38 map kinase, and modulators

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.

Growing community of inventors

Del Mar, CA, United States of America

Richard J Ulevitch