Takeda Pharmaceutical Company Limited

Dyax Corporation

Nippon Zoki Pharmaceutical Co., Ltd.

Kusumam Joseph

Allen P Kaplan

The invention provides assay methods of detecting plasma protease CI inhibitor (C1-INH) that binds plasma kallikrein, Factor XII, or both, and uses thereof for identifying subjects at risk for or suffering from a pKal-me-diated or bradykinin-mediated disorder. Provided methods permit analysis of patients with plasma kallikrein-mediated angioedema (KMA), or other diseases mediated by pKal useful in the evaluation and treatment.

Evaluation, assays and treatment of pKal-mediated disorders

The invention provides assay methods of detecting plasma protease CI inhibitor (Cl-INH) that binds plasma kallikrein, Factor XII, or both, and uses thereof for identifying subjects at risk for or suffering from a pKal-mediated or bradykinin-mediated disorder. Provided methods permit analysis of patients with plasma kallikrein-mediated angioedema (KMA), or other diseases mediated by pKal useful in the evaluation and treatment.

Assays for determining levels of plasma protease C1 inhibitor

A activator for prekallikrein includes isolated, purified, or substantially purified heat shock protein 90, a phosphate ion, and mixtures thereof. The prekallikrein activator is part of an in vitro system for activating prekallikrein in the absence of FXIIa. The system includes the activator, high-molecular weight kininogen, and zinc ions. A method for activating prekallikrein to produce kallikrein in the absence of FXIIa includes mixing prekallikrein with the activator and a composition comprising high molecular weight kininogen and zinc ions. A method for evaluating the activity of a test drug for the production of kallikrein comprises activating prekallikrein and determining the kallikrein produced. The activity (promoting or inhibiting ability) of the tested drug against the production of kallikrein in the absence of FXIIa can be easily measured. The test drug may be an analgesic, anti-allergy, anti-inflammatory drug.

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Mt. Pleasant, SC, United States of America

Kusumam Joseph