Merck + Co., Inc.

John L Humes

Richard A Mumford

Wilson B Knight

William A Hanlon

Malcolm MacCoss

William K Hagmann

Shrenik K Shah

Paul E Finke

Joshua S Boger

Mary Ellen Dahlgren

D T Davies

A immunoassay based on the detection of leukocyte-elastase produced fibrinogen cleavage peptides which allows the evaluation of the potency of compounds that inhibit formation of cleavage peptides in a variety of in vitro cell biological situations is provided. The assay may be employed to detect an endogenous leukocyte-elastase produced fibrinogen cleavage peptide signal in normal human plasma and at elevated levels in cystic fibrosis plasma and in rheumatoid arthritis synovial fluid samples. The assay procedure can be a single step assay which allows for the rapid and reproducible detection of specific cleavage peptides.

Assay for marker of human polymorphonuclear leukocyte elastase activity

N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.

Assay for evaluating inhibition of polymorphonuclear leukocyte elastase

Assay for evaluating inhibition of PMN elastase by N-substituted

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Berkeley Heights, NJ, United States of America

John L Humes