Chiron Corporation

Cetus Oncology Corporation

Cytel Corporation

Michael Kriegler

Carl F Perez

Kirston E Koths

Robert F Halenbeck

David A Jewell

Danute E Nitecki

Robert J Bayer

James C Paulson

Francis P McCormick

Mary M Bendig

S Tarran Jones

Margaret J Polley

Michael Nunn

Jan Tuttleman

Robert W Chestnut

Methods and materials are disclosed for the production of purified, active recombinant human neutrophil protease, PR-3, via activation of a pro-form herein referred to as proPR-3. Human PR-3 is useful for discovering inhibitors of excessive release of mature, active TNF&agr;. Also disclosed are methods for the identification of inhibitors of the conversion of the pro-form of TNF&agr; to its mature active form.

Recombinant PR-3 and assays employing the same

Recombinant PR-3 and compositions thereof

A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.

Infective protein delivery system

The present invention relates to compositions and methods for treating inflammation and other pathological conditions using novel blocking P-selectin antibodies that inhibit adhesion of leukocytes to activated platelets and/or to activated vascular endothelium in vivo. Both murine and humanized antibodies are provided.

Method for detecting the presence of P-selectin

Compounds having proteolytic inhibitory activity useful for treating diseases, particularly as applied to the treatment of sepsis, AIDS or autoimmune diseases, resulting from a decrease in the circulating level of mature protein hormones derived from the proteolytic cleavage of prohormone precursors such as 26 kDProTNF, and methods for identifying compounds having the desired inhibitory activity are provided.

Compositions for the inhibition of TNF hormone formation and uses thereof

Recombinant host cells encoding TNF proteins

TNF deletion muteins

Tumor Infiltrating Lymphocyte (TIL) cells transformed with exogenous DNA encoding tumor necrosis factor (TNF) prohormone variants are disclosed. Among such variants are the TNF .gamma. sig construct, which facilitates expression of the mature TNF polypeptide, and the noncleavable cytotoxic prohormone variants TNF.DELTA.(1.fwdarw.12) and TNF(1+12). The transformed TIL cells are useful in antitumor therapy.

Human til cells expressing recombinant TNF prohormone

Gene fusion encoding a hypersecretor protein

Methods and materials are disclosed for the production of purified, active recombinant human neutrophil protease, PR-3, via activation of a pro-form herein referred to as proPR-3. Human PR-3 is useful for discovering inhibitors of excessive release of mature, active TNF.alpha.. Also disclosed are methods for the identification of inhibitors of the conversion of the pro-form of TNF.alpha. to its mature active form.

Assay method for screening for inhibitors of proTNF conversion

Antibodies to P-selectin and their uses

Cleavage site blocking antibody that binds to prohormones, preferable Tumor Necrosis Factor, thereby preventing the formation of prohormone fragment(s) by proteolysis of the prohormone, and uses of the antibody including prophylactic and therapeutic methods to treat disease, and diagnostic assays for determining the amount of the prohormone and prohormone fragments present in a patients body.

Antibody methods for the treatment of a hormone-mediated disease

Assay method for the detection of 26kd TNF prohormone

Cleavage site blocking antibody to prohormone proteins and uses thereof

Growing community of inventors

San Francisco, CA, United States of America

Michael Kriegler