Incyte Pharmaceuticals, Inc.

Invitron Limited

Randal W Scott

Marian N Marra

Craig G Wilde

Jeffrey J Seilhamer

Joseph E Griffith

Christopher P Prior

Stephen A Duffy

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

A method and system for quantifying the relative abundance of gene transcripts in a biological sample. One embodiment of the method generates high-throughput sequence-specific analysis of multiple RNAs or their corresponding cDNAs (gene transcript imaging analysis). Another embodiment of the method produces a gene transcript imaging analysis by the use of high-throughput CDNA sequence analysis. In addition, the gene transcript imaging can be used to detect or diagnose a particular biological state, disease, or condition which is correlated to the relative abundance of gene transcripts in a given cell or population of cells. The invention provides a method for comparing the gene transcript image analysis from two or more different biological samples in order to distinguish between the two samples and identify one or more genes which are differentially expressed between the two samples.

Comparative gene transcript analysis

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

A method and system for quantifying the relative abundance of gene transcripts in a biological sample. One embodiment of the method generates high-throughput sequence-specific analysis of multiple RNAs or their corresponding cDNAs (gene transcript imaging analysis). Another embodiment of the method produces a gene transcript imaging analysis by the use of high-throughput cDNA sequence analysis. In addition, the gene transcript imaging can be used to detect or diagnose a particular biological state, disease, or condition which is correlated to the relative abundance of gene transcripts in a given cell or population of cells. The invention provides a method for comparing the gene transcript image analysis from two or more different biological samples in order to distinguish between the two samples and identify one or more genes which are differentially expressed between the two samples.

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

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

Methods and pharmaceutical compositions for treatment of inflammation and arthritis using protease nexin-I as an active ingredient are disclosed.

Pharmaceutical dosage unit for treating inflammation comprising protease

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.

Novel antimicrobial peptide

Practical amounts of tissue plasminogen activator (tPA) whether secreted by cells naturally producing it or prepared by recombinant means can be solubilized by providing, in aqueous medium at pH 5-14 8 a solubilizing amount of a basic amino acid optionally and preferably, in the presence of a citric acid moiety. The ability to solubilize tPA at concentrations of up to 50 mg is significant as an aid in permitting smaller volumes for purification and permitting single injections of the drug as opposed to intravenous administration.

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Cupertino, CA, United States of America

Randal W Scott