Anti-P-selectin antibodies and methods of their use and identification

Abstract

Antibodies are disclosed which bind specifically to P-selectin, block the binding of PSGL-1 to P-selectin, and cause dissociation of preformed P-selectin / PSGL-1 complexes. The disclosure identifies aheretofore unrecognized, near N-terminal, antibody binding domain (a conformational epitope) of P-selectin to which the antibodies (which may be chimeric, human or humanized antibodies for example) bind. Antibodies are disclosed which bind to the conformational epitope of P-selectin and which have a dual function in blocking binding of PSGL-1 to P-selectin, and in causing dissociation of preformedP-selectin / PSGL-1 complexes. Such dual function anti-P-selectin antibodies and binding fragments thereof may be used in the treatment of a variety of acute and chronic inflammatory and thrombotic disorders and conditions. Screening methods for identifying and characterizing such antibodies are also disclosed.

Description

[0001] This application is a PCT international patent application PCT / US2011 / 066470 with the filing date of December 21, 2011. The Chinese patent application number 201180068113.X that entered the Chinese national phase, the title of the invention is "Anti-P-selectin antibody and its use and identification Method" for divisional application. Technical field [0002] The present invention relates to antibodies and antibody fragments that bind to specific isotopes of P-selectin, and methods for their use and identification. Background technique [0003] In normal hemostasis and immune supervision, white blood cells circulate freely in the blood and respond to injury and infection through a continuous adhesion signal transduction process mediated by cell adhesion molecules (1-3). In inflammatory and thrombotic diseases, the process is dysregulated, can maintain the condition of white blood cells attacking their own tissues, and can cause serious and sometimes fatal complications. It...

AI Technical Summary

Problems solved by technology

[0023] As noted above, the interaction between sickled RBCs, platelets, leukocytes, and microvasculature in SCD is a P-selectin-dependent process that leads to vascular occlusion and painful crises

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