Antibody specific for cd22 and methods of use thereof

Abstract

The present disclosure provides antibodies specific for an epitope present on CD22. The antibodies are useful in various treatment, diagnostic, and monitoring applications, which are also provided.

1 . An antibody that specifically binds an epitope in CD22, wherein the antibody comprises:
 a) an immunoglobulin heavy chain comprising a VH region having the amino acid sequence   EVQLVESGGGLVKPGGSLX 1 LSCAASGFAFSIYDMSWVRQAPGKGLEWVAYISSGGGTT YYPDTVKGRFTISRDNAKNX 2 LYLQMX 3 SLRAEDTAMYYCARHSGYGSSYGVLFAYWG QGTLVTVSS (SEQ ID NO:1), where X 1  is K or R; X 2  is S or T; and X 3  is N or S; and   b) an immunoglobulin light chain.   
     
     
         2 . The antibody of  claim 1 , wherein the immunoglobulin light chain comprises the amino acid sequence 
       
         
           
                 
               
                   (SEQ ID NO: 7; VK1) 
                 
                   DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAVKLLIYY 
                 
                     
                 
                   TSILHSGVPSRFSGSGSGTDYTLTISSLQQEDFATYFCQQGNTLPWTFGG 
                 
                     
                 
                   GTKVEIK; 
                 
                     
                 
                   (SEQ ID NO: 8; VK2 
                 
                   
                     DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAVKLLIYY 
                   
                 
                     
                 
                   
                     TSILHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYFCQQGNTLPWTFGG 
                   
                 
                     
                 
                   GTKVEIK; 
                 
                   or 
                 
                     
                 
                   (SEQ ID NO: 9; VK4) 
                 
                   
                     DIQMTQSPSSVSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYY 
                   
                 
                     
                 
                   
                     TSILHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYFCQQGNTLPWTFGG 
                   
                 
                     
                 
                     GTKVEIK . 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 .- 4 . (canceled) 
     
     
         5 . An antibody that specifically binds an epitope in CD22, wherein the antibody comprises:
 a) an immunoglobulin light chain comprising the amino acid sequence   
       
         
           
                 
               
                   (SEQ ID NO: 2) 
                 
                   DIQMTQSPSSX 1 SASVGDRVTITCRASQDISNYLNWYQQKPGKAX 2 KLLI 
                 
                     
                 
                   YYTSILHSGVPSRFSGSGSGTDYTLTISSLQX 3 EDFATYFCQQGNTLPWT 
                 
                     
                 
                   EGGGTKVEIK, 
                 
             
                
                
                
                
                
                
               
            
           
         
       
       where X 1  is L (Leu) or V (Val); X 2  is V or P; and X 3  is Q or P; and
 b) an immunoglobulin heavy chain. 
 
     
     
         6 . The antibody of  claim 5 , wherein the immunoglobulin heavy chain comprises an amino acid sequence selected from: 
       
         
           
                 
               
                   (SEQ ID NO: 3; VH3) 
                 
                   EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEWVAY 
                 
                     
                 
                   ISSGGGTTYYPDTVKGRFTISRDNAKNTLYLQMSSLRAEDTAMYYCARHS 
                 
                     
                 
                   GYGSSYGVLFAYWGQGTLVTVSS; 
                 
                     
                 
                   (SEQ ID NO: 4; VH4) 
                 
                   EVQLVESGGGLVKPGGSLRLSCAASGFAFSIYDMSWVRQAPGKGLEWVAY 
                 
                     
                 
                   ISSGGGTTYYPDTVKGRFTISRDNAKNSLYLQMSSLRAEDTAMYYCARHS 
                 
                     
                 
                   GYGSSYGVLFAYWGQGTLVTVSS; 
                 
                     
                 
                   (SEQ ID NO: 5; VH5) 
                 
                   EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEWVAY 
                 
                     
                 
                   ISSGGGTTYYPDTVKGRFTISRDNAKNSLYLQMNSLRAEDTAMYYCARHS 
                 
                     
                 
                   GYGSSYGVLFAYWGQGTLVTVSS; 
                 
                   and 
                 
                     
                 
                   (SEQ ID NO: 6; VH6) 
                 
                   EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEWVAY 
                 
                     
                 
                   ISSGGGTTYYPDTVKGRFTISRDNAKNSLYLQMSSLRAEDTAMYYCARHS 
                 
                     
                 
                   GYGSSYGVLFAYWGQGTLVTVSS. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         7 . The antibody of  claim 1 , wherein (i) the light chain region and the heavy chain region are present in separate polypeptides or (ii) the light chain region and the heavy chain region are present in a single polypeptide. 
     
     
         8 . (canceled) 
     
     
         9 . The antibody of  claim 1 , wherein the antibody binds the epitope with an affinity of from about 10 7  M −1  to about 10 12  M −1 . 
     
     
         10 . The antibody of  claim 1 , wherein the heavy chain region is of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         11 . The antibody of  claim 1 , wherein the antibody is detectably labeled. 
     
     
         12 . The antibody of  claim 1 , wherein the antibody is a Fv, scFv, Fab, F(ab′)2, or Fab′. 
     
     
         13 . The antibody of  claim 1 , wherein
 i. the antibody comprises a covalently linked non-peptide synthetic polymer, optionally a poly(ethylene glycol) polymer;   ii. the antibody comprises a covalently linked lipid or fatty acid moiety   iii. the antibody comprises a covalently linked polysaccharide or carbohydrate moiety;   iv. the antibody comprises a contrast agent;   v. the antibody comprises an affinity domain; and/or   vi. the antibody comprises a covalently linked cytotoxin.   
     
     
         14 .- 18 . (canceled) 
     
     
         19 . The antibody of  claim 1 , wherein the antibody is immobilized on a solid support. 
     
     
         20 . The antibody of  claim 1 , wherein the antibody is a single chain Fv (scFv) antibody. 
     
     
         21 . The antibody of  claim 20 , wherein the scFv is multimerized. 
     
     
         22 . (canceled) 
     
     
         23 . The antibody of  claim 1 , wherein the antibody comprises a constant region amino acid sequence comprising an amino acid sequence of a sulfatase motif; wherein, optionally, the sulfatase motif is modified to comprise a 2-formylglycine (FGly) moiety. 
     
     
         24 . (canceled) 
     
     
         25 . The antibody of  claim 23 , wherein the sulfatase motif is modified to comprise the 2-formylglycine (FGly) moiety and the antibody comprises a heterologous moiety covalently linked to the antibody via the FGly moiety. 
     
     
         26 . The antibody of  claim 25 , wherein the heterologous moiety is selected from a drug, a toxin, a detectable label, a water-soluble polymer, and a synthetic peptide. 
     
     
         27 . A recombinant expression vector comprising a nucleotide sequence encoding the antibody of  claim 1 , wherein the nucleotide sequence is operably linked to a transcriptional control element that is active in a eukaryotic cell. 
     
     
         28 . A pharmaceutical composition comprising:
 a) the antibody of  claim 1 ; and   b) a pharmaceutically acceptable carrier.   
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein the antibody is encapsulated in a liposome. 
     
     
         30 . A method of treating B cell malignancy in a subject, the method comprising:
 administering to a subject having cancer an effective amount of the pharmaceutical composition of  claim 28 .