Human monoclonal antibodies against interleukin 8 (il-8)

Abstract

Isolated human monoclonal antibodies which bind to IL-8 (e.g., human IL-8) are disclosed. The human antibodies can be produced in a hybridoma, transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals, hybridomas, and transfectomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

1 - 5 . (canceled) 
     
     
         6 . An in vitro or in vivo method for detecting the presence of IL-8 antigen, or a cell expressing IL-8, in a sample comprising:
 contacting the sample, and a control sample, with an antibody comprising:
 (a) a light chain variable region CDR1 domain having the amino acid sequence set forth in SEQ ID NO: 16, a light chain variable region CDR2 domain having the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region CDR3 domain having the amino acid sequence: 
   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 46) 
                 
                     
                   Gln-Gln-Tyr-X1-X2-Ser-X3-Thr 
                 
             
                
                
               
            
           
         
       
       wherein X1, X2 and X3 each represents a natural amino acid residue, and X1 is different from Gly, or X2 is different from Ser, or X3 is different from Pro; or
   (b) a heavy chain variable region CDR1 domain having the amino acid sequence set forth in SEQ ID NO: 22, a heavy chain variable region CDR2 domain having the amino acid sequence set forth in SEQ ID NO: 23, and a heavy chain variable region CDR3 domain having the amino acid sequence:   
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 47) 
                 
                     
                   Asp-X4-Val-Gly-X5-Phe-Asp-Tyr, 
                 
             
                
                
               
            
           
         
       
       wherein X4 is Lys, Arg, or His, and X5 is Gly, Ala, Val, Leu, or Ile,
 under conditions that allow formation of a complex between the antibody and IL-8, and detecting the formation of the complex, 
 wherein a difference in complex formation between the sample compared to the control sample is indicative of the presence of IL-8 in the sample. 
 
     
     
         7 . The method of  claim 6 , wherein X1 is different from Gly, X2 is different from Ser, and X3 is different from Pro. 
     
     
         8 . The method of  claim 7 , wherein X1 is Ala, and X2 and X3 independently are Gly, Ala, Val, Leu, or Ile. 
     
     
         9 . The method of  claim 6 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12 or encoded by the nucleotide sequence set forth in SEQ ID NO: 10, and/or a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 8 or encoded by the nucleotide sequence set forth in SEQ ID NO: 6. 
     
     
         10 . The method of  claim 6 , wherein the sample is from an individual suspected of having an IL-8-related disease. 
     
     
         11 . The method of  claim 10 , wherein the IL-8 related disease is selected from the group consisting of inflammatory disorder, hyperproliferative disorder, immune disease, autoimmune disease, and infectious disease. 
     
     
         12 . The method of  claim 11 , wherein the hyperproliferative disorder is cancer. 
     
     
         13 . The method of  claim 11 , wherein the inflammatory disorder is an inflammatory skin disorder. 
     
     
         14 . The method of  claim 13 , wherein the disorder is selected from the group consisting of pustulosis palmoplantaris, psoriasis, plaque psoriasis, guttate type psoriasis, bullous skin disease, contact dermatitis, eczema, erythematosus, and atopic dermatitis. 
     
     
         15 . A kit comprising:
 (a) an antibody which binds to human IL-8, wherein the antibody comprises:
 (i) a light chain variable region CDR1 domain having the amino acid sequence set forth in SEQ ID NO: 16, a light chain variable region CDR2 domain having the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region CDR3 domain having the amino acid sequence: 
   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 46) 
                 
                     
                   Gln-Gln-Tyr-X1-X2-Ser-X3-Thr 
                 
             
                
                
               
            
           
         
       
       wherein X1, X2 and X3 each represents a natural amino acid residue, and X1 is different from Gly, or X2 is different from Ser, or X3 is different from Pro; or
   (ii) a heavy chain variable region CDR1 domain having the amino acid sequence set forth in SEQ ID NO: 22, a heavy chain variable region CDR2 domain having the amino acid sequence set forth in SEQ ID NO: 23, and a heavy chain variable region CDR3 domain having the amino acid sequence:   
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 47) 
                 
                     
                   Asp-X4-Val-Gly-X5-Phe-Asp-Tyr, 
                 
             
                
                
               
            
           
         
       
       wherein X4 is Lys, Arg, or His, and X5 is Gly, Ala, Val, Leu, or Ile; and
 (b) instructions for use. 
 
     
     
         16 . The kit of  claim 15 , wherein X1 is different from Gly, X2 is different from Ser, and X3 is different from Pro. 
     
     
         17 . The kit of  claim 16 , wherein X1 is Ala, and X2 and X3 independently are Gly, Ala, Val, Leu, or Ile. 
     
     
         18 . The kit of  claim 15 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12 or encoded by the nucleotide sequence set forth in SEQ ID NO: 10, and/or a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 8 or encoded by the nucleotide sequence set forth in SEQ ID NO: 6. 
     
     
         19 . The kit of  claim 15 , further comprising one or more additional agents. 
     
     
         20 . The kit of  claim 19 , wherein the kit further comprises an immunosuppressive agent. 
     
     
         21 . The kit of  claim 19 , wherein the kit further comprises an antibody which binds to an epitope on IL-8 that differs from the epitope bound by an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12 or encoded by the nucleotide sequence set forth in SEQ ID NO: 10, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 8 or encoded by the nucleotide sequence set forth in SEQ ID NO: 6. 
     
     
         22 . An anti-idiotypic antibody capable of binding to an antibody comprising:
 (i) a light chain variable region CDR1 domain having the amino acid sequence set forth in SEQ ID NO: 16, a light chain variable region CDR2 domain having the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region CDR3 domain having the amino acid sequence:   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 46) 
                 
                     
                   Gln-Gln-Tyr-X1-X2-Ser-X3-Thr 
                 
             
                
                
               
            
           
         
       
       wherein X1, X2 and X3 each represents a natural amino acid residue, and X1 is different from Gly, or X2 is different from Ser, or X3 is different from Pro; or
 (ii) a heavy chain variable region CDR1 domain having the amino acid sequence set forth in SEQ ID NO: 22, a heavy chain variable region CDR2 domain having the amino acid sequence set forth in SEQ ID NO: 23, and a heavy chain variable region CDR3 domain having the amino acid sequence: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 47) 
                 
                     
                   Asp-X4-Val-Gly-X5-Phe-Asp-Tyr, 
                 
             
                
                
               
            
           
         
       
       wherein X4 is Lys, Arg, or His, and X5 is Gly, Ala, Val, Leu, or Ile. 
     
     
         23 . The anti-idiotypic antibody of  claim 22 , wherein X1 is different from Gly, X2 is different from Ser, and X3 is different from Pro. 
     
     
         24 . The anti-idiotypic antibody of  claim 23 , wherein X1 is Ala, and X2 and X3 independently are Gly, Ala, Val, Leu, or Ile. 
     
     
         25 . The anti-idiotypic antibody of  claim 21 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12 or encoded by the nucleotide sequence set forth in SEQ ID NO: 10, and/or a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 8 or encoded by the nucleotide sequence set forth in SEQ ID NO: 6.