Antibodies targeting the b-cell receptor of chronic lymphocytic leukemia and uses thereof

Abstract

The present invention provides antibodies for the treatment of chronic lymphocytic leukemia (CLL). These antibodies target the B-cell receptor (BCR) of CLL cells characterised by R110-mutated immunoglobulin lambda variable 3-21 (IGLV3-21 R110 ). The invention also provides nucleic acid sequences encoding the forgoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

1 . A method of treatment of CLL in IGLV3-21 R110  positive patients comprising administering antibodies, wherein said antibodies have
 a heavy chain amino acid sequence of SEQ ID NO: 1 and a light chain amino acid sequence of SEQ ID NO: 2; or   a heavy chain amino acid sequence of SEQ ID NO: 11 and a light chain amino acid sequence of SEQ ID NO: 12; or   
       comprise a
 variable heavy chain having a sequence selected from the list consisting of SEQ ID NO: 15 and SEQ ID NO: 20 in any combination with a 
 variable light chain having a sequence selected from the list of SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19. 
 
     
     
         2 . The method according to  claim 1 , wherein said antibodies are characterized by a heavy chain corresponding to SEQ ID NO: 1 and a light chain corresponding to SEQ ID NO: 2. 
     
     
         3 . The method according to  claim 1 , wherein said antibodies are characterized by a heavy chain amino acid sequence of SEQ ID NO: 11 and a light chain amino acid sequence of SEQ ID NO: 12. 
     
     
         4 . The method according to  claim 1 , wherein said antibodies are characterized by a heavy chain corresponding to SEQ ID NO: 13 and a light chain corresponding to SEQ ID NO: 14. 
     
     
         5 . The method according to  claim 1 , wherein said antibodies are characterized by a heavy chain corresponding to SEQ ID NO: 21 and a light chain corresponding to SEQ ID NO: 14. 
     
     
         6 . The method according to  claim 1 , wherein said antibodies are chimeric. 
     
     
         7 . The method according to  claim 4 , wherein said antibodies are humanized. 
     
     
         8 . The method according to  claim 1 , wherein the antibodies are administered at a dose of from 0.25 to 25 mg/kg bodyweight . 
     
     
         9 . The method according to  claim 8 , wherein the antibodies are administered at a dose of from 1 to 20 mg/kg bodyweight . 
     
     
         10 . The method according to  claim 8 , wherein the antibodies are administered at a dose of from 7 to 15 mg/kg bodyweight . 
     
     
         11 . The method according to  claim 8 , wherein the antibodies are administered at a dose of from 8 to 12 mg/kg bodyweight . 
     
     
         12 . The method according to  claim 1  wherein said antibodies are administered as a pharmaceutical composition further comprising a pharmaceutically acceptable carrier or excipient. 
     
     
         13 . The method according to  claim 12  wherein said pharmaceutical composition is comprised within a kit. 
     
     
         14 . The method according to  claim 3 , wherein said antibodies are chimeric. 
     
     
         15 . The method according to  claim 5 , wherein said antibodies are humanized. 
     
     
         16 . The method according to  claim 7 , wherein the antibodies are administered at a dose of from 0.25 to 25 mg/kg bodyweight . 
     
     
         17 . The method according to  claim 7 , wherein the antibodies are administered at a dose of from 8 to 12 mg/kg bodyweight . 
     
     
         18 . The method according to  claim 15 , wherein the antibodies are administered at a dose of from 0.25 to 25 mg/kg bodyweight . 
     
     
         19 . The method according to  claim 15 , wherein the antibodies are administered at a dose of from 1 to 20 mg/kg bodyweight . 
     
     
         20 . The method according to  claim 15 , wherein the antibodies are administered at a dose of from 8 to 12 mg/kg bodyweight .