METTETAL II JEROME THOMAS,PONS JAUME,RAJPAL ARVIND,SHELTON DAVID LOUIS,CHABOT JEFFREY RAYMOND,CHAPARRO RIGGERS JAVIER FERNANDO,GOMES BRUCE CHARLES,LIANG HONG,MAYAWALA KAPIL
申请号：
CO12155949
公开号：
CO6592103A2
申请日:
2012.09.11
申请国别(地区):
CO
年份:
2013
代理人:
摘要：
The present Invention relates to Antibodies with Union of pH dependent Antigen so that the Affinity of Antigen binding at Physiological pH (i.e., ph 7.4) is greater than endosomal pH (IE pH 5.5 or 6.0). In other words, the proportion of the proportion of Ka KO / ph 7.4 pH 5.5 or 6.0 PH / ph 7.4 is over, ovar u00eda between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more.Such pH dependent Antibody Antigen dissociate preferentially in the endosome. This can increase the half-life of the Antibody with the Antibodies, compared with KD equivalent to ph 7.4 with any Union but pH dependent when the Antigen is one who suffers the Elimination mediated antigen (e.g., PCSK9).The Antibodies with pH dependent Union can decrease the half-life of total Antigen Elimination when the Antigen is reduced when bound to Antibody (e.g. 1Z4). The Antibodies with pH dependent Union may also Prolong the decrease in Antigen which is not bound to Antibody.This can be important when antagonized a Target Antigen typically present at high levels (For example, IgE, Dkk1, C5 and SOST). In addition, such Antibodies may increase the half-life of Antigen is an Antigen when the receiver and the receiver has increased Elimination when bound to Antibody (e.g. GMCSF receptor).La presente invención se refiere a anticuerpos con unión dependiente de pH a su antígeno de tal forma que la afinidad de unión al antígeno a pH fisiológico (es decir, pH 7,4) es mayor que a pH endosómico (es decir, pH 6,0 o 5,5). En otras palabras, la proporción de Ko la proporción de ka pH 5,5/pH 7,4 o a pH 6,0/pH 7,4 es más de, ovaría entre, 2, 3, 4, 8, 10, 16, 20, 30, 40, o 100 o más. Tales anticuerpos dependientes de pH se disocian preferencialmente del antígeno en el endosoma. Esto puede incrementar la semivida del anticuerpo, en comparación con los anticuerpos con KD equivalentes a pH 7,4 pero con ninguna unión dependiente de pH, cuando el antígeno es uno que sufre la eliminación mediada por antígeno (por ejemplo, PCSK9). Los
