De-immunised anti-erbb3 antibodies

Abstract

Provided herein are antibody molecules that bind specifically to ERBB3 and related nucleic acid molecules, vectors and host cells. Also provided herein are medical uses of such antibody molecules.

1 . A nucleic acid molecule encoding the heavy chain variable (VH) region amino acid sequence and the light chain variable (VL) region amino acid sequence of an anti-ERBB3 antibody or an antigen-binding portion thereof, wherein
 (a) the VH region amino acid sequence comprises HCDR1 of GFTFSDYSMS (SEQ ID NO: 24), HCDR2 of VSTISDSGTYTYYPDSVKG (SEQ ID NO: 25) and HCDR3 of EWGDYDGFDF (SEQ ID NO: 15); and the VL region amino acid sequence comprises LCDR1 of RASQEISTYLS (SEQ ID NO: 261), LCDR2 of AASTLQS (SEQ ID NO:26) and LCDR3 of LQYDSSPLT (SEQ ID NO: 262); or   (b) the VH region amino acid sequence comprises HCDR1 of GFTFSDYSMS (SEQ ID NO: 24), HCDR2 of VSTISDSGTYTYYPDSVKG (SEQ ID NO: 25) and HCDR3 of EWGDYDGFDF (SEQ ID NO: 15); and the VL region amino acid sequence comprises LCDR1 of RASQEISSYLS (SEQ ID NO: 21), LCDR2 of AASSLDT (SEQ ID NO: 263) and LCDR3 of amino acids 89-97 of SEQ ID NO: 224.   
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein
 (a) the VH region amino acid sequence comprises SEQ ID NO:236 and the VL region amino acid sequence comprises SEQ ID NO:225; or   (b) the VH region amino acid sequence comprises SEQ ID NO:235 and the VL region amino acid sequence comprises SEQ ID NO:224.   
     
     
         3 . The nucleic acid molecule of  claim 1 , wherein the antibody or antigen-binding portion is humanized or chimeric. 
     
     
         4 . The nucleic acid molecule of  claim 1 , wherein the VH region, the VL region, or both the VH and the VL region comprise one or more human framework region amino acid sequences. 
     
     
         5 . The nucleic acid molecule of  claim 1 , wherein the VH region, the VL region, or both the VH and the VL region comprise a human variable region framework scaffold amino acid sequence into which the CDRs have been inserted. 
     
     
         6 . The nucleic acid molecule of  claim 1 , wherein the VH region comprises an IGHV3-11 human germline scaffold amino acid sequence into which the HCDR1, HCDR2 and HCDR3 amino acid sequences have been inserted. 
     
     
         7 . The nucleic acid molecule of  claim 1 , wherein the VL region comprises an IGKV1-39 human germline scaffold amino acid sequence into which the LCDR1, LCDR2 and LCDR3 amino acid sequences have been inserted. 
     
     
         8 . The nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule further encodes an immunoglobulin constant region. 
     
     
         9 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region is IgG, IgE, IgM, IgD or IgA. 
     
     
         10 . The nucleic acid molecule of  claim 9 , wherein the immunoglobulin constant region is IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2. 
     
     
         11 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region is immunologically inert. 
     
     
         12 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region is a wild-type human IgG4 constant region, a human IgG4 constant region comprising the amino acid substitution S228P, a wild-type human IgG1 constant region, a human IgG1 constant region comprising the amino acid substitutions L234A, L235A and G237A or a wild-type human IgG2 constant region, wherein numbering is according to the EU index as in Kabat. 
     
     
         13 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region comprises any one of SEQ ID NOs: 239-245. 
     
     
         14 . The nucleic acid molecule of  claim 1 , wherein the antibody or antigen-binding portion is an Fab, an Fab′, an F(ab′)2, an Fv, an scFv, a diabody, a triabody, a tetrabody or a bis-scFv. 
     
     
         15 . An expression vector comprising the nucleic acid molecule of  claim 1 . 
     
     
         16 . A recombinant host cell comprising the nucleic acid molecule of  claim 1 . 
     
     
         17 . A recombinant host cell comprising the expression vector of  claim 15 .