Humanized Anti-CXCR5 Antibodies, Derivatives Thereof and Their Use

Abstract

The present invention relates to humanized antibodies that specifically bind to CXCR5 and can, for example, inhibit CXCR5 function. The invention also includes uses of the antibodies to treat or prevent CXCR5 related diseases or disorders.

1 : An isolated antibody or fragment thereof that specifically binds to the extracellular domain of human CXCR5, wherein the antibody or fragment thereof comprises:
 (a) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 12;   (b) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14, or SEQ ID NO: 15, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 16;   (c) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 19, or SEQ ID NO: 21, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 23;   (d) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 31, or SEQ ID NO: 32, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33 or SEQ ID NO: 34;   (e) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 37;   (f) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 39, SEQ ID NO: 41, or SEQ ID NO: 43, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 45 or SEQ ID NO: 47; or   (g) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 55, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 56 or SEQ ID NO: 57.   
     
     
         2 : The antibody or fragment thereof of  claim 1 , wherein the light chain variable domain comprises the amino acid sequences of RSSKSLLHSSGKTYLY, RMSNLAS, and MQHLEYPYT, and the heavy chain variable domain comprises the amino acid sequences GFSLIDYGVN, VIWGDGTTY, and IVY. 
     
     
         3 : The antibody or fragment thereof of  claim 1 , wherein the light chain variable domain comprises the amino acid sequences of RSSKSLLHSSGKTYLY, RLSNLAS, and MQHLEYPYT, and the heavy chain variable domain comprises the amino acid sequences GFSLIDYGVN, VIWGDGTTY, and IVY. 
     
     
         4 : The antibody or fragment thereof of  claim 1 , wherein the light chain variable domain comprises the amino acid sequences of RSSKSLLHSSGKTYLY, RMSNLA, MQHLEYPYT, and the heavy chain variable domain comprises the amino acid sequences GFSLIDYGVN, VIWGDGTTY, and IVY. 
     
     
         5 : The antibody or fragment thereof of  claim 1 , wherein the light chain variable domain comprises the amino acid sequences of RSSKSLLHSSGKTYLY, RLSSNLAS, and MQHLEYPYT, and the heavy chain variable domain comprises the amino acid sequences GFSLIDYGVN, VIWGDGTTY, and IVY. 
     
     
         6 : The antibody or fragment thereof of  claim 1 , wherein the light chain variable domain comprises the amino acid sequences of RSSKSLLHSSGKTYLY, RLSNLA, MQHLEYPYT, and the heavy chain variable domain comprises the amino acid sequences GFSLIDYGVN, VIWGDGTTY, and IVY. 
     
     
         7 : The antibody or fragment thereof of  claim 1 , wherein the light chain variable domain comprises the amino acid sequences of RSSKSLLHSSGKTYLYW, RMSNLA, MQHLEYPYT, and the heavy chain variable domain comprises the amino acid sequences GFSLIDYGVN, VIWGDGTTY, and IVY. 
     
     
         8 : The antibody or fragment thereof of  claim 1 , wherein the antibody or fragment thereof comprises one or more constant regions. 
     
     
         9 : The antibody or fragment thereof of any one of  claim 1 , wherein the antibody or fragment thereof comprises a C H1 , C H2 , C H3  or combinations thereof. 
     
     
         10 : The antibody or fragment thereof of  claim 8 , wherein the one or more constant regions are from an IgG antibody. 
     
     
         11 : The antibody or fragment thereof of  claim 10 , wherein the IgG antibody is an IgG4 antibody. 
     
     
         12 : An isolated nucleic acid molecule encoding the antibody or fragment thereof of  claim 1 . 
     
     
         13 : A vector comprising the nucleic acid molecule of  claim 12 . 
     
     
         14 : A microbial host cell comprising the vector of  claim 13   
     
     
         15 : An isolated antibody or fragment thereof that specifically binds to the extracellular domain of human CXCR5, wherein the antibody or fragment thereof comprises a variable light chain domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 32, and a variable heavy chain domain comprising the amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33. 
     
     
         16 : The antibody or fragment thereof of  claim 15 , wherein the variable light chain domain comprises the amino acid sequences of RSSKSLLHSSGKTYLY, RLSSLA, and MQHLEYPYT and the variable heavy chain domain comprises the amino acid sequences of GFSLIDYGVN, VIWGDGTTY, and IVY. 
     
     
         17 : The antibody or fragment thereof of  claim 15 , wherein the antibody or fragment thereof comprises one or more constant regions. 
     
     
         18 : The antibody or fragment thereof of any one of  claim 15 , wherein the antibody or fragment thereof comprises a C H1 , C H2 , C H3  or combinations thereof. 
     
     
         19 : The antibody or fragment thereof of  claim 17 , wherein the one or more constant regions are from an IgG antibody. 
     
     
         20 : The antibody or fragment thereof of  claim 19 , wherein the IgG antibody is an IgG4 antibody. 
     
     
         21 : An isolated nucleic acid molecule encoding the antibody or fragment thereof of  claim 1 . 
     
     
         22 : A vector comprising the nucleic acid molecule of  claim 21 . 
     
     
         23 : A microbial host cell comprising the vector of  claim 22 .