Anti cd37 antibodies

Abstract

Chimeric and humanized anti-CD37 antibodies and pharmaceutical compositions containing them are useful for the treatment of B cell malignancies and autoimmune and inflammatory diseases that involve B cells in their pathology.

What is claimed is: 
     
         1 . A nucleic acid molecule encoding an antibody that binds to human CD37, said antibody comprising
 (a) two identical heavy chains, each comprising (i) SEQ ID NO: 2, fused to (ii) SEQ ID NO: 24 or a mutated form of SEQ ID NO: 24, wherein the mutated form has no more than 1, 2 or 3 mutations relative to SEQ ID NO: 24 selected from the group consisting of:
 a substitution at position 332, numbered according to the Kabat EU numbering index, wherein the substitution at position 332 is I332E; 
 a substitution a position 236, numbered according to the Kabat EU numbering index, wherein the substitution at position 236 is G236A; and 
 a substitution at position 239, numbered according to the Kabat EU numbering index, wherein the substitution at position 239 is S239D; and 
   (b) two identical light chains, each comprising SEQ ID NO: 4 fused to a human kappa light chain constant region.   
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein each encoded heavy chain comprises a sequence selected from the group consisting of:
 SEQ ID NO: 2 fused to SEQ ID NO: 24;   SEQ ID NO: 2 fused to a first mutated form of SEQ ID NO: 24, wherein SEQ ID NO: 24 is modified to have a single substitution at position 332, numbered according to the Kabat EU numbering index, wherein the single substitution is I332E;   SEQ ID NO: 28;   SEQ ID NO: 2 fused to a second mutated form of SEQ ID NO: 24, wherein SEQ ID NO: 24 is modified to have two substitutions, at positions 332 and 236, numbered according to the Kabat EU numbering index, wherein the two substitutions are I332E and G236A, respectively; and   SEQ ID NO: 32.   
     
     
         3 . The nucleic acid molecule of  claim 1 , wherein the antibody comprises:
 (a) two heavy chains, each comprising SEQ ID NO: 2 fused to SEQ ID NO: 24; and two light chains, each comprising SEQ ID NO: 4 fused to SEQ ID NO: 26; or   (b) two heavy chains, each comprising SEQ ID NO: 2 fused to a first mutated form of SEQ ID NO: 24, wherein SEQ ID NO: 24 is modified to have a single substitution at position 332, numbered according to the Kabat EU numbering index, wherein the single substitution is I332E; and two light chains, each comprising SEQ ID NO: 4 fused to SEQ ID NO: 26; or   (c) two heavy chains, each comprising SEQ ID NO: 28; and two light chains, each comprising SEQ ID NO: 30; or   (d) two heavy chains, each comprising SEQ ID NO: 2 fused to a second mutated form of SEQ ID NO: 24, wherein SEQ ID NO: 24 is modified to have two substitutions, at positions 332 and 236, numbered according to the Kabat EU numbering index, wherein the two substitutions are I332E and G236A, respectively; and two light chains, each comprising SEQ ID NO: 4 fused to SEQ ID NO: 26; or   (e) two heavy chains, each comprising SEQ ID NO: 32; and two light chains, each comprising SEQ ID NO: 34.   
     
     
         4 . A nucleic acid molecule encoding a chimeric antibody that binds to human CD37, wherein the chimeric antibody comprises:
 (a) two identical heavy chains, in which the sequence of each heavy chain is SEQ ID NO: 28; and   (b) two identical light chains, in which the sequence of each light chain is SEQ ID NO: 30.