ANTIGEN-BINDING MOLECULE CAPABLE OF BINDING TWO OR MORE ANTIGEN MOLECULES REPEATEDLY
The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.
1 .- 50 . (canceled)
51 . A method for producing a pharmaceutical composition comprising an antibody, the method comprising:
producing the antibody using nucleic acid comprising coding sequence encoding the antibody wherein.
(a) the produced antibody specifically binds to an antigen at a first pH that is in the range of pH 6.7 to pH 10.0, wherein the produced antibody is a molecule comprising an antigen-binding domain and an Fc domain that has FcRn-binding activity, and wherein the produced antibody binds the antigen through the antigen-binding domain;
(b) the produced antibody specifically binds to the antigen at a second pH that is in the range of pH 4.0 to pH 6.5;
(c) the binding activity of the produced antibody to the antigen at the first pH is greater than that at the second pH; and
(d) the produced antibody binds to the antigen in plasma in vivo and dissociates from the bound antigen under conditions present in an endosome in vivo; and formulating the produced antibody in a pharmaceutical composition.
52 . The method of claim 51 , wherein the antigen is a soluble antigen.
53 . The method of claim 51 , wherein the antibody is an IgG.
54 . The method of claim 51 , wherein the antibody is a chimeric antibody.
55 . The method of claim 51 , wherein the antibody is a humanized antibody.
56 . The method of claim 51 , wherein the antibody is a humanized IgG.