| abstract |
The present invention provides for pH-dependent binding to an antigen such that the affinity for antigen binding at physiological pH (ie, pH 7.4) exceeds the pH of the endosome (ie, pH 6.0 or 5.5). It relates to an antibody having In other words, K D ratio or k off ratio of at pH 5.5 / pH 7.4 or pH 6.0 / pH 7.4 is 2,3,4,8,10,16,20,30,40 or more than 100, Or a range in between. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This is because when the antigen is one that undergoes antigenic mediated clearance (e.g., PCSK9), compares it with equivalent K D of an antibody having no binding of pH-dependent with pH 7.4, antibody half The phase can be increased. An antibody with pH-dependent binding can reduce the total antigen half-life if it undergoes reduced clearance when the antigen is bound to the antibody (eg, IL6). Antibodies with pH-dependent binding can also prolong the decrease in antigen not bound to the antibody. This may be important when antagonizing target antigens that are typically present at high levels (eg, IgE, DKK1, C5, and SOST). In addition, such antibodies can increase antigen half-life when the antigen is a receptor and the receptor has increased clearance when bound to the antibody (eg, a GMCSF receptor). [Figure 1] |