Selexys Pharmaceuticals Corporation

Oklahoma Medical Research Foundation

Richard Alvarez

Rodger P McEver

Ziad Kawar

Scott A Rollins

Russell P Rother

Ziad S Kawar

Rodger P Mcever

The invention features antibodies, e.g., chimeric and humanized antibodies, that recognize (i.e., bind) P-selectin. The P-selectin antibodies prevent P-selectin from binding to its cognate receptor. The P-selectin antibodies can be used to treat inflammatory and thrombotic conditions, e.g., sickle cell disease, pain crisis associated with sickle cell disease, deep vein thrombosis, asthma, rheumatoid arthritis, psoriasis, and ischemia reperfusion injury in a patient in need thereof.

Methods of treating sickle cell disease with anti-P-selectin antibodies

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

Anti-P-selectin antibodies

Methods of treating inflammatory or thrombotic conditions with anti-P-selectin antibodies

Anti-P-selectin antibodies and methods of using the same to treat inflammatory diseases

The present invention is directed to antibodies and binding fragments thereof, which bind with high affinity and specificity to human P-selectin glycoprotein ligand 1 (PSGL-1) and which block both selectin and chemokine binding to PSGL-1 expressed on leukocytes, lymphocytes and endothelial cells and thus which inhibit migration and/or rolling of these cells and to methods for screening for such antibodies and binding fragments thereof and to methods of therapeutic use thereof.

Methods of inhibiting the PSGL-1-mediated adhesion and chemokine-mediated migration with PSGL-1-specific antibodies

Growing community of inventors

Edmond, OK, United States of America

Richard Alvarez