HETERODIMERIC HUMAN IgG1 POLYPEPTIDES WITH ISOELECTRIC POINT MODIFICATIONS
The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.
1 .- 27 . (canceled)
28 . A heterodimeric protein comprising:
a) first monomer comprising a first human antibody heavy chain constant domain that is a variant human antibody heavy chain constant domain comprising one or more amino acid substitutions selected from the following amino acid substitutions: G137E, G138S, S192N, L193F, I199T, N203D, K214T, K222T, 221-225 DKTHT to VE, H268Q, K274Q, R355Q, N384S, K392N, V397M, Q419E, and K447del, according to EU numbering; and
b) a second monomer comprising a second human antibody heavy chain constant domain.
29 . A heterodimeric protein comprising:
a) a first monomer comprising a first human antibody heavy chain constant domain that is a variant human antibody heavy chain constant domain comprising amino acid substitutions selected from the following amino acid substations: Q196K, P217R, P228R, N276K and H435R, according to EU numbering; and
b) a second monomer comprising a second human antibody heavy chain constant domain.
30 . A heterodimeric protein according to claim 28 , wherein the amino acid substitutions of the first human antibody heavy chain constant domain comprises K274Q, R355Q, Q419E, and K447del.
31 . A heterodimeric protein according to claim 29 , wherein the amino acid substitutions of the first human antibody heavy chain constant domain comprises P217R, P228R, and N276K.
32 . A heterodimeric protein according to claim 29 , wherein the amino acid substitutions of the first human antibody heavy chain constant domain comprises Q196K and N276K.
33 . The heterodimeric protein according to claim 28 or 29 , wherein the second human antibody heavy chain constant domain is a wild type human antibody heavy chain constant domain.
34 . The heterodimeric protein according to claim 28 or 29 , wherein the second human antibody heavy chain constant domain is a variant human antibody heavy chain constant domain comprising amino acid modifications as compared to a wild type parent human antibody heavy chain constant domain.
35 . The heterodimeric protein according to claim 34 , wherein said first and second human antibody heavy chain constant domains further comprise amino acid substitutions 428L and 434S.
36 . The heterodimeric protein according to claim 28 or 29 , wherein the first and second human antibody heavy chain constant domains each comprise a CH 1 -hinge-CH 2 -CH 3 domain.
37 . The heterodimeric protein according to claim 28 or 29 , wherein the first and second human antibody heavy chain constant domains each comprise a CH 2 -CH 3 domain.