公开(公告)号：EP2654781B1

公开(公告)日：2018-01-24

申请号：EP11851933.9

申请日：2011-12-21

申请人： Selexys Pharmaceuticals Corporation ,  Oklahoma Medical Research Foundation

发明人： ROLLINS, Scott ,  ALVAREZ, Richard ,  ROTHER, Russell ,  KAWAR, Ziad, S. ,  MCEVER, Rodger, P.

IPC分类号： C07K16/28 ,  A61P7/02 ,  A61P7/06 ,  A61P37/00

CPC分类号： C07K16/2854 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/71 ,  C07K2317/76 ,  C07K2317/92

摘要： 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 a heretofore 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 preformed P-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.

公开(公告)号：EP2654781A1

公开(公告)日：2013-10-30

申请号：EP11851933.9

申请日：2011-12-21

申请人： Selexys Pharmaceuticals Corporation ,  Oklahoma Medical Research Foundation

发明人： ROLLINS, Scott ,  ALVAREZ, Richard ,  ROTHER, Russell ,  KAWAR, Ziad, S. ,  MCEVER, Rodger, P.

IPC分类号： A61K39/00

CPC分类号： C07K16/2854 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/71 ,  C07K2317/76 ,  C07K2317/92

摘要： 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 a heretofore 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 preformed P-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.

摘要翻译： 公开了与P-选择蛋白特异性结合的抗体，阻断PSGL-1与P-选择蛋白的结合，并引起预先形成的P-选择蛋白/ PSGL-1复合物的解离。 该公开内容鉴定了抗体（其可能是嵌合型，人源化或人源化抗体）与其结合的P-选择蛋白的迄今为止未被认识的近N末端抗体结合结构域（构象表位）。 公开了结合P-选择素的构象表位的抗体，其具有阻断PSGL-1与P-选择蛋白结合的双重功能，并引起预先形成的P-选择蛋白/ PSGL-1复合物的解离。 这种双重功能的抗P-选择蛋白抗体及其结合片段可用于治疗各种急性和慢性炎症和血栓形成障碍和病症。 还公开了用于鉴定和表征此类抗体的筛选方法。