| abstract |
Antibodies which specifically bind to P-selectin are disclosed, block the binding of PSGL-1 to P-selectin, and cause cleavage of the generated P-selectin / PSGL-1 complexes. The invention identifies an hitherto unidentified, near the amino terminus, antibody binding region (a stereotaxic epitope) of the P-selectin to which the antibodies (which may be chimeric, human, or humanized antibodies, for example) bind. Antibodies that bind to the P-selectin stereotaxic epitope and which have a dual function in preventing the binding of PSGL-1 to P-selectin and in causing the cleavage of the generated P-selectin / PSGL-1 complexes. These dual-function anti-P-selectin antibodies and their binding fragments can be used for the treatment of various acute and chronic inflammatory and thrombotic disorders and diseases. Screening methods for the identification and characterization of these antibodies are also disclosed. |