HETERODIMERIC HUMAN IgG1 POLYPEPTIDES WITH ISOELECTRIC POINT MODIFICATIONS

Abstract

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.