Novel heterodimeric proteins

Abstract

The invention provides novel heterodimeric proteins including heterodimeric antibodies.

1 .- 81 . (canceled) 
     
     
         82 . A heterodimeric antibody comprising:
 a) a first monomer comprising:
 i) a first variant human IgG1 Fc domain comprising amino acid substitutions T366S/L368A/Y407V, and 
 ii) a single chain Fv (scFv) region that binds a first antigen; 
   b) a second monomer comprising:
 i) a second variant human IgG1 Fc domain comprising amino acid substitution T366W, and 
 ii) a variable heavy chain; and 
   c) a light chain comprising a variable light chain and a constant light chain;   wherein said first and/or second variant Fc domain further comprises amino acid substitution(s) selected from the group consisting of 434A, 434S, 428L, 308F, 259I, 428L/434S, 259I/308F, 436I/428L, 436I or V/434S, 436V/428L, 252Y, 252Y/254T/256E, and 259I/308F/428L, and   wherein numbering is according to EU numbering.   
     
     
         83 . A nucleic acid composition comprising:
 a) a first nucleic acid encoding said first monomer of  claim 82 ;   b) a second nucleic acid encoding said second monomer of  claim 82 ; and   c) a third nucleic acid encoding said light chain of  claim 82 .   
     
     
         84 . An expression vector composition comprising:
 a) a first expression vector comprising said first nucleic acid of  claim 83 ;   b) a second expression vector comprising said second nucleic acid of  claim 83 ; and   c) a third expression vector comprising said third nucleic acid of  claim 83 .   
     
     
         85 . A host cell comprising the expression vector composition of  claim 84 . 
     
     
         86 . A method of making a heterodimeric antibody comprising culturing the host cell of  claim 85  under conditions wherein said heterodimeric antibody is expressed and recovering said heterodimeric antibody. 
     
     
         87 . A heterodimeric antibody comprising:
 a) a first monomer comprising:
 i) a first variant human IgG2 Fc domain comprising amino acid substitutions T366S/L368A/Y407V, and 
 ii) a single chain Fv (scFv) region that binds a first antigen; 
   b) a second monomer comprising:
 i) a second variant human IgG2 Fc domain comprising amino acid substitution T366W, and 
 ii) a variable heavy chain; and 
   c) a light chain comprising a variable light chain and a constant light chain;   wherein said first and/or second variant Fc domain further comprises amino acid substitution(s) selected from the group consisting of 434A, 434S, 428L, 308F, 259I, 428L/434S, 259I/308F, 436I/428L, 436I or V/434S, 436V/428L, 252Y, 252Y/254T/256E, and 259I/308F/428L, and   wherein numbering is according to EU numbering.   
     
     
         88 . A nucleic acid composition comprising:
 a) a first nucleic acid encoding said first monomer of  claim 87 ;   b) a second nucleic acid encoding said second monomer of  claim 87 ; and   c) a third nucleic acid encoding said light chain of  claim 87 .   
     
     
         89 . An expression vector composition comprising:
 a) a first expression vector comprising said first nucleic acid of  claim 88 ;   b) a second expression vector comprising said second nucleic acid of  claim 88 ; and   c) a third expression vector comprising said third nucleic acid of  claim 88 .   
     
     
         90 . A host cell comprising the expression vector composition of  claim 89 . 
     
     
         91 . A method of making a heterodimeric antibody comprising culturing the host cell of  claim 90  under conditions wherein said heterodimeric antibody is expressed and recovering said heterodimeric antibody. 
     
     
         92 . A heterodimeric antibody comprising:
 a) a first monomer comprising:
 i) a first variant human IgG4 Fc domain comprising amino acid substitutions T366S/L368A/Y407V, and 
 ii) a single chain Fv (scFv) region that binds a first antigen; 
   b) a second monomer comprising:
 i) a second variant human IgG4 Fc domain comprising amino acid substitution T366W, and 
 ii) a variable heavy chain; and 
   c) a light chain comprising a variable light chain and a constant light chain;   wherein said first and/or second variant Fc domain further comprises amino acid substitution(s) selected from the group consisting of 434A, 434S, 428L, 308F, 259I, 428L/434S, 259I/308F, 436I/428L, 436I or V/434S, 436V/428L, 252Y, 252Y/254T/256E, 259I/308F/428L, and 236A, and   wherein numbering is according to EU numbering.   
     
     
         93 . A nucleic acid composition comprising:
 a) a first nucleic acid encoding said first monomer of  claim 92 ;   b) a second nucleic acid encoding said second monomer of  claim 92 ; and   c) a third nucleic acid encoding said light chain of  claim 92 .   
     
     
         94 . An expression vector composition comprising:
 a) a first expression vector comprising said first nucleic acid of  claim 93 ;   b) a second expression vector comprising said second nucleic acid of  claim 93 ; and   c) a third expression vector comprising said third nucleic acid of  claim 93 .   
     
     
         95 . A host cell comprising the expression vector composition of  claim 94 . 
     
     
         96 . A method of making a heterodimeric antibody comprising culturing the host cell of  claim 95  under conditions wherein said heterodimeric antibody is expressed and recovering said heterodimeric antibody.