Incyte Pharmaceuticals, Inc.

Invitron Limited

Marian N Marra

Randal W Scott

Craig G Wilde

Joseph E Griffith

Terje Espevik

James L Snable

In general, the invention features a recombinant endotoxin-neutralizing polypeptide (RENP) characterized by (i) an amino acid sequence, (ii) an amino acid sequence and structure that facilitates selective and specific binding to lipopolysaccharide and (iii) once bound to the lipopolysaccharide, provides endotoxin-neutralizing activity. Preferably, the RENP is composed of an amino acid sequence similar to, but not identical to, an amino acid sequence of BPI, LBP, or both. Preferably, the RENP contains an LPS-binding domain derived from the amino acid sequence of BPI, LBP, or both. Preferably, the RENPs are covalently bound to a molecule which enhances the half-life of the polypeptide. The RENPs of the invention can be used in pharmaceutical compositions for therapeutic and prophylactic regimens, as well as in various in vitro and in vivo diagnostic methods.

Recombinant endotoxin-neutralizing proteins

The present invention provides a composition comprising a BPI Protein and an anionic compound which composition exhibits (1) no bacterial activity and (2) endotoxin neutralizing activity. Also, this invention provides methods for using BPI Proteins.

Recombinant analogs of bactericidal/permeability increasing protein

The present invention provides a composition comprising a BPI Protein and an anionic compound which composition exhibits (1) no bactericidal activity and (2) endotoxin neutralizing activity. Also, this invention provides methods for using BPI Proteins.

Genetically engineered BPI variant proteins

Bactericidal/permeability-increasing protein (BPI) is useful to neutralize non-lipopolysaccharide compounds capable of stimulating TNF production and has application in vitro and in vivo for therapeutics and prophylactic treatment. This use of BPI can be combined with the administration of materials, such as an enzyme, microorganism, living cells or cell fractions, encapsulated in alginate gels.

Neutralization of non-lipopolysaccharide compounds by

The present invention provides a method for preventing endotoxin-associated shock in a subject which comprises administering to the subject an amount of a BPI protein effective to bind to endotoxin so as to prevent endotoxin associated shock in the subject. This invention further provides a method for treating a subject suffering from endotoxin-associated shock which comprises administering to the subject an amount of a BPI protein effective to bind endotoxin so as to treat the subject suffering from endotoxin-associated shock.

Recombinant, non-glycosylated bpi protein and uses thereof

Treatment of endotoxin-associated shock and prevention thereof using a

The present invention provides a composition comprising a BPI Protein and a lipid carrier. Additionally, this invention provides a method for solubilizing a BPI protein which comprises contacting the BPI Protein with a lipid carrier under conditions such that the BPI Protein is solubilized.

Pharmaceutical compositions comprising recombinant BPI proteins and a

This invention provides a purified polypeptide useful as an antimicrobial agent. This purified polypeptide has been derived from human granulocytes, and has a molecular weight of about 3,700 daltons and the N-terminal amino acid sequence val-cys-ser-cys-arg-leu-val-phe-cys-arg-arg-thr-glu-leu-arg-val-gly-asn-cy s-leu-ilu-gly-gly-val-ser-phe-thr-tyr-cys-cys-thr-arg-val. This invention also provides methods for producing this polypeptide, pharmaceutical compositions containing the polypeptide, and uses thereof.

DNA encoding novel antimicrobial polypeptide and methods for obtaining

Treatment of endotoxin-associated shock and preventation thereof using a

The present invention provides a method of inhibiting lipopolysaccharide (LPS)-mediated stimulation of cells. This method comprises contacting the cells, in the presence of a cell-stimulating amount of lipopolysaccharide, with Bactericidal/Permeability Increasing Protein (BPI) in an amount effective to inhibit cell stimulation.

Use of bactericidal/permeability increasing protein or biologically

This invention provides a purified polypeptide useful as an antimicrobial agent. This purified polypeptide has been derived from human granulocytes, and has a molecular weight of about 3,700 daltons and the N-terminal amino acid sequence val-cys-ser-cys-arg-leu-val-phe-cys-arg-arg-thr-glu- leu-arg-val-gly-asn-cys-leu-ile-gly-gly-val-ser-phe-thr-try-cys-thr-arg-va l. This invention also provides methods for producing this polypeptide, pharmaceutical compositions containing the polypeptide, and uses thereof.

Growing community of inventors

San Mateo, CA, United States of America

Marian N Marra