Anti-cd52 antibodies

Abstract

Anti-human CD52 antibodies and antigen-binding fragments thereof are provided. Also provided are isolated nucleic acids, recombinant vectors and host cells for making the antibodies and fragments. The antibodies and fragments can be used in therapeutic applications to treat, for example, autoimmune diseases, cancer, and graft rejection.

1 . An anti-human CD52 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region comprises:
 (a) the heavy chain CDR1 of SEQ ID NO: 7;   (b) the heavy chain CDR2 of SEQ ID NO: 8; and   (c) the heavy chain CDR3 of SEQ ID NO: 9,   wherein said light chain variable region comprises   (a) the light chain CDR1 of SEQ ID NO: 86, wherein residue 11 is   
       
         
           
                 
               
                   (SEQ ID NO: 136) 
                 
                 
               
                   K, R, Q, H, S, Y, A, D, E, F, I, L, M, N, T, or V; 
                 
             
                
               
            
             
                
               
            
           
         
         (b) the light chain CDR2 of SEQ ID NO: 34; and 
         (c) the light chain CDR3 of SEQ ID NO: 35. 
       
     
     
         2 . The antibody or fragment according to  claim 1 , wherein said antibody or fragment demonstrates increased stability relative to an antibody comprising the heavy chain amino acid sequence of SEQ ID NO: 3 without the signal sequence and the light chain amino acid sequence of SEQ ID NO: 4 without the signal sequence. 
     
     
         3 . The antibody or fragment according to  claim 1 , wherein residue 11 in SEQ ID NO: 86 is:
 (a) K (SEQ ID NO: 24);   (b) R (SEQ ID NO: 29); or   (c) Q (SEQ ID NO: 28).   
     
     
         4 - 6 . (canceled) 
     
     
         7 . The antibody or fragment according to  claim 1 , wherein:
 (a) said heavy chain variable region comprises SEQ ID NO: 59;   (b) said light chain variable region comprises a sequence selected from the group consisting of SEQ ID NOs: 68-83; or   (c) said heavy chain variable region comprises SEQ ID NO: 59 and said light chain variable region comprises a sequence selected from the group consisting of SEQ ID NOs: 68-83.   
     
     
         8 - 9 . (canceled) 
     
     
         10 . The antibody according to  claim 1 , comprising:
 (a) a heavy chain of SEQ ID NO: 3 without the signal sequence;   (b) a light chain selected from the group consisting of SEQ ID NOs: 43-58; or   (c) a heavy chain of SEQ ID NO: 3 without the signal sequence and a light chain selected from the group consisting of SEQ ID NOs: 43-58.   
     
     
         11 . (canceled) 
     
     
         12 . An antibody comprising:
 (a) a heavy chain amino acid sequence of SEQ ID NO: 3 without the signal sequence and a light chain amino acid sequence of SEQ ID NO: 49;   (b) a heavy chain amino acid sequence of SEQ ID NO: 3 without the signal sequence and a light chain amino acid sequence of SEQ ID NO: 53; or   (c) a heavy chain amino acid sequence of SEQ ID NO: 3 without the signal sequence and a light chain amino acid sequence of SEQ ID NO: 54.   
     
     
         13 . The antibody according to  claim 1  that is an immunoglobulin G (IgG). 
     
     
         14 . The fragment according to  claim 1 , wherein said fragment is selected from the group consisting of an scFv fragment, an Fab fragment, an Fv fragment, an F(ab′) 2  fragment, a minibody, a diabody, a triabody, and a tetrabody. 
     
     
         15 . (canceled) 
     
     
         16 . The antibody or fragment according to  claim 1 , wherein said antibody comprises a human IgG1, IgG2, IgG3, or IgG4 Fc region. 
     
     
         17 - 22 . (canceled) 
     
     
         23 . The antibody or fragment according to  claim 1 , wherein the heavy chain C-terminal lysine is cleaved. 
     
     
         24 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes the heavy chain or an antigen-binding fragment thereof, or the light chain or an antigen-binding fragment thereof, or both, of the antibody or fragment according to  claim 1 . 
     
     
         25 . (canceled) 
     
     
         26 . A recombinant expression vector comprising the nucleic acid molecule of  claim 24 . 
     
     
         27 . (canceled) 
     
     
         28 . An isolated host cell comprising the vector according to  claim 26 . 
     
     
         29 . An isolated cell line that produces the antibody or fragment according to  claim 1  or the heavy or light chain of the antibody or fragment. 
     
     
         30 . A method of making an anti-human CD52 antibody or an antigen-binding fragment thereof, comprising (1) maintaining a cell comprising a nucleotide sequence encoding the heavy chain or an antigen-binding fragment thereof, and a nucleotide sequence encoding the light chain or an antigen-binding fragment thereof, of the antibody or fragment according to  claim 1  under conditions appropriate for expression of the antibody or fragment; and (2) recovering the antibody or fragment. 
     
     
         31 . A composition comprising the antibody or antigen-binding fragment according to  claim 1  and a pharmaceutically acceptable vehicle or carrier. 
     
     
         32 . A method for treating a human patient in need thereof, comprising administering to the patient an effective amount of the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         33 - 42 . (canceled) 
     
     
         43 . The method of  claim 32 , wherein said method is for:
 (a) treating an autoimmune disease in the patient;   (b) treating cancer in the patient; or   (c) inhibiting angiogenesis in the patient.   
     
     
         44 . The method according to  claim 43 , wherein said method is for treating multiple sclerosis. 
     
     
         45 . The method according to  claim 43 , wherein said method is for treating chronic lymphocytic leukemia.