Abstract: 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.
Type:
Grant
Filed:
December 21, 2010
Date of Patent:
February 3, 2015
Assignees:
Selexys Pharmaceuticals Corporation, Oklahoma Medical Research Foundation
Inventors:
Scott Rollins, Richard Alvarez, Russell Rother, Rodger P. McEver, Ziad S. Kawar
Abstract: 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.
Type:
Application
Filed:
February 1, 2013
Publication date:
March 13, 2014
Applicant:
SELEXYS PHARMACEUTICALS CORPORATION
Inventors:
Rodger P. MCEVER, Richard ALVAREZ, Ziad KAWAR
Abstract: 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.
Type:
Grant
Filed:
November 30, 2007
Date of Patent:
February 19, 2013
Assignees:
Selexys Pharmaceuticals Corporation, Oklahoma Medical Research Foundation
Inventors:
Rodger P. McEver, Richard Alvarez, Ziad Kawar
Abstract: 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.
Type:
Application
Filed:
November 30, 2007
Publication date:
October 6, 2011
Applicant:
SELEXYS PHARMACEUTICALS CORPORATION
Inventors:
Rodger P. McEver, Richard Alvarez, Ziad Kawar
Abstract: 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.