US2008118505A1PendingUtilityA1

Reagents and treatment methods for autoimmune diseases

Assignee: UNIV DUKEPriority: Feb 21, 2002Filed: Aug 6, 2007Published: May 22, 2008
Est. expiryFeb 21, 2022(expired)· nominal 20-yr term from priority
A61P 35/00A61P 9/00A61P 5/16A61P 37/02A61P 9/08A61P 7/02A61P 3/10A61P 37/04A61P 7/04A61P 9/10A61P 7/00A61P 5/14A61P 7/06A61P 37/08A61P 35/02A61P 37/06A61P 37/00A61P 5/00A61P 27/02A61P 25/00A61P 29/00C07K 2317/73A61P 19/02A61K 39/39533C07K 2317/56A61P 1/04A61P 19/00A61P 13/12A61P 21/00A61P 17/06C07K 16/2803A61P 1/00A61P 13/02C07K 2317/76A61P 21/04A61P 19/04A61K 2039/505A61P 17/02A61P 17/00A61K 39/395C07K 16/28C12N 15/11
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Claims

Abstract

The invention concerns treatment methods using anti-CD22 monoclonal antibodies with unique physiologic properties. In particular, the invention concerns methods for the treatment of B-cell malignancies and autoimmune diseases by administering an effective amount of a blocking anti-CD22 monoclonal antibody specifically binding to the first two Ig-like domains, or to an epitope within the first two Ig-like domains of native human CD22 (hCD22).

Claims

exact text as granted — not AI-modified
1 - 38 . (canceled) 
     
     
         39 . A humanized monoclonal antibody that specifically binds to human CD22 comprising a heavy chain with variable heavy (VH) complementarity determining regions (CDRs) and a light chain with variable light (VL) CDRs, wherein said antibody specifically binds to the first two Ig-like domains or to an epitope associated with the first two Ig-like domains of native human CD22. 
     
     
         40 . A humanized monoclonal antibody that specifically binds to human CD22 comprising a heavy chain with VH CDRs and a light chain with VL CDRs, wherein said antibody binds essentially the same epitope as an antibody selected from the group consisting of HB22-7, HB22-23, or HB22-33. 
     
     
         41 . The humanized monoclonal antibody of  claim 39  or  40 , wherein the heavy chain of said antibody further comprises the amino acid sequence of the VH CDR1, VH CDR2, and VH CDR3 of HB22-7. 
     
     
         42 . The humanized monoclonal antibody of  claim 39  or  40 , wherein the light chain of said antibody further comprises the amino acid sequence of the VL CDR1, VL CDR2, and VL CDR3 of HB22-7. 
     
     
         43 . The humanized monoclonal antibody of  claim 39  or  40 , wherein said antibody further comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO:34 (DYGVN), a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 40 (IIWGDGRTDYNSALKS), and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:46 (APGNRA). 
     
     
         44 . The humanized monoclonal antibody of  claim 39  or  40 , wherein said antibody further comprises a VL CDR1 comprising the amino acid sequence KASQSVTNDVA (SEQ ID NO: 51), a VL CDR2 comprising the amino acid sequence YASNRYT (SEQ ID NO: 57), and a VL CDR3 comprising the amino acid sequence QQDYRSPWT (SEQ ID NO: 63). 
     
     
         45 . The humanized monoclonal antibody of  claim 44 , wherein said antibody further comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO:34 (DYGVN), a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 40 (IIWGDG RTDYNSALKS), and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:46 (APGNRA). 
     
     
         46 . A humanized monoclonal antibody that specifically binds to human CD22 comprising a heavy chain with VH CDRs and a light chain with VL CDRs, wherein said antibody further comprises:
 (a) a VH CDR1 comprising an amino acid sequence selected from the following:   
       
         
           
                 
                 
                 
                 
               
                     
                   DYTMN, 
                   (SEQ ID NO: 32) 
                     
                 
                     
                     
                 
                     
                   GYYMH, 
                   (SEQ ID NO: 33) 
                 
                     
                     
                 
                     
                   DYGVN, 
                   (SEQ ID NO: 34) 
                 
                     
                     
                 
                     
                   GYYWN, 
                   (SEQ ID NO: 35) 
                 
                     
                     
                 
                     
                   DYYMN, 
                   (SEQ ID NO: 36) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   YYWMN; 
                   (SEQ ID NO: 37) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (b) a VH CDR2 comprising an amino acid sequence selected from the following: 
       
       
         
           
                 
                 
                 
                 
               
                     
                   LLHPFNGGTSYNQKFKG, 
                   (SEQ ID NO: 38) 
                     
                 
                     
                     
                 
                     
                   AVNPNTAGLTYNQRFKD, 
                   (SEQ ID NO: 39) 
                 
                     
                     
                 
                     
                   IIWGDGRTDYNSALKS, 
                   (SEQ ID NO: 40) 
                 
                     
                     
                 
                     
                   YIRYDGSNNYNPSLKN, 
                   (SEQ ID NO: 41) 
                 
                     
                     
                 
                     
                   FIKNKFNGYTTEYNTSVKG, 
                   (SEQ ID NO: 42) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   AEIRLKSNNYATHYAESVKG; 
                   (SEQ ID NO: 43) 
                 
                     
                   and 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (c) a VH CDR3 comprising an amino acid sequence selected from the following: 
       
       
         
           
                 
                 
                 
                 
               
                     
                   GTGRNYA, 
                   (SEQ ID NO: 44) 
                     
                 
                     
                     
                 
                     
                   VDYDDYGYWF, 
                   (SEQ ID NO: 45) 
                 
                     
                     
                 
                     
                   APGNRA, 
                   (SEQ ID NO: 46) 
                 
                     
                     
                 
                     
                   GGITVA, 
                   (SEQ ID NO: 47) 
                 
                     
                     
                 
                     
                   GLGRSYA, 
                   (SEQ ID NO: 48) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   YDGSSR. 
                   (SEQ ID NO: 49) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         47 . A humanized monoclonal antibody that specifically binds to human CD22 comprising a heavy chain with VH CDRs and a light chain with VL CDRs, wherein said antibody further comprises:
 (a) a VL CDR1 comprising an amino acid sequence selected from the following:   
       
         
           
                 
                 
                 
                 
               
                     
                   KASQTVTNDLA, 
                   (SEQ ID NO: 50) 
                     
                 
                     
                     
                 
                     
                   KASQSVTNDVA, 
                   (SEQ ID NO: 51) 
                 
                     
                     
                 
                     
                   KASQSVTNDVT, 
                   (SEQ ID NO: 52) 
                 
                     
                     
                 
                     
                   KASQSVSNDVA, 
                   (SEQ ID NO: 53) 
                 
                     
                     
                 
                     
                   RSSQSLVHSNGNTYLH, 
                   (SEQ ID NO: 54) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   KASENVVTYVS; 
                   (SEQ ID NO: 55) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (b) a VL CDR2 comprising an amino acid sequence selected from the following: 
       
       
         
           
                 
                 
                 
                 
               
                     
                   YASNRYT, 
                   (SEQ ID NO: 56) 
                     
                 
                     
                     
                 
                     
                   YASNRYT, 
                   (SEQ ID NO: 57) 
                 
                     
                     
                 
                     
                   FASNRYT, 
                   (SEQ ID NO: 58) 
                 
                     
                     
                 
                     
                   YASKRYT, 
                   (SEQ ID NO: 59) 
                 
                     
                     
                 
                     
                   KVSNRFS, 
                   (SEQ ID NO: 60) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   GASNRYT; 
                   (SEQ ID NO: 61) 
                 
                     
                   and 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (c) a VL CDR3 comprising an amino acid sequence selected from the following: 
       
       
         
           
                 
                 
                 
                 
               
                     
                   QQDYSSPLT, 
                   (SEQ ID NO: 62) 
                     
                 
                     
                     
                 
                     
                   QQDYRSPWT, 
                   (SEQ ID NO: 63) 
                 
                     
                     
                 
                     
                   QQDYSSPLT, 
                   (SEQ ID NO: 64) 
                 
                     
                     
                 
                     
                   QQDHSYPWT, 
                   (SEQ ID NO: 65) 
                 
                     
                     
                 
                     
                   SQSTHVPYT, 
                   (SEQ ID NO: 66) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   GQGYSYPYT. 
                   (SEQ ID NO: 67) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         48 . The humanized monoclonal antibody of  claim 47 , wherein said antibody further comprises:
 (a) a VH CDR1 comprising an amino acid sequence selected from the following:   
       
         
           
                 
                 
                 
                 
               
                     
                   DYTMN, 
                   (SEQ ID NO: 32) 
                     
                 
                     
                     
                 
                     
                   GYYMH, 
                   (SEQ ID NO: 33) 
                 
                     
                     
                 
                     
                   DYGVN, 
                   (SEQ ID NO: 34) 
                 
                     
                     
                 
                     
                   GYYWN, 
                   (SEQ ID NO: 35) 
                 
                     
                     
                 
                     
                   DYYMN, 
                   (SEQ ID NO: 36) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   YYWMN; 
                   (SEQ ID NO: 37) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (b) a VH CDR2 comprising an amino acid sequence selected from the following: 
       
       
         
           
                 
                 
                 
                 
               
                     
                   LLHPFNGGTSYNQKFKG, 
                   (SEQ ID NO: 38) 
                     
                 
                     
                     
                 
                     
                   AVNPNTAGLTYNQRFKD, 
                   (SEQ ID NO: 39) 
                 
                     
                     
                 
                     
                   IIWGDGRTDYNSALKS, 
                   (SEQ ID NO: 40) 
                 
                     
                     
                 
                     
                   YIRYDGSNNYNPSLKN, 
                   (SEQ ID NO: 41) 
                 
                     
                     
                 
                     
                   FIKNKFNGYTTEYNTSVKG, 
                   (SEQ ID NO: 42) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   AEIRLKSNNYATHYAESVKG; 
                   (SEQ ID NO: 43) 
                 
                     
                   and 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (c) a VH CDR3 comprising an amino acid sequence selected from the following: 
       
       
         
           
                 
                 
                 
                 
               
                     
                   GTGRNYA, 
                   (SEQ ID NO: 44) 
                     
                 
                     
                     
                 
                     
                   VDYDDYGYWF, 
                   (SEQ ID NO: 45) 
                 
                     
                     
                 
                     
                   APGNRA, 
                   (SEQ ID NO: 46) 
                 
                     
                     
                 
                     
                   GGITVA, 
                   (SEQ ID NO: 47) 
                 
                     
                     
                 
                     
                   GLGRSYA, 
                   (SEQ ID NO: 48) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   YDGSSR. 
                   (SEQ ID NO: 49) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         49 . A pharmaceutical composition comprising a humanized anti-CD22 monoclonal antibody of  claim 39  or  40 , in a pharmaceutically-acceptable carrier. 
     
     
         50 . A method of treating a human diagnosed with an autoimmune disease or disorder, comprising administering to said human an effective amount of the humanized monoclonal antibody of  claim 39  or  40 . 
     
     
         51 . The method of  claim 50 , wherein said treatment is unaccompanied by any other treatment for the autoimmune disease. 
     
     
         52 . The method of  claim 50 , wherein said antibody is a fragment of a complete antibody. 
     
     
         53 . The method of  claim 50 , wherein said antibody is a bispecific antibody. 
     
     
         54 . The method of  claim 50 , wherein said antibody is administered intravenously.

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