Il-13 binding agents

Abstract

Agents (e.g., antibodies and fragments thereof) that bind specifically to IL 13 and modulate the ability of IL-13 to interact with IL-13 receptors and signaling mediators are disclosed.

1 - 35 . (canceled) 
     
     
         36 . A method of treating an immune disorder in patient comprising administering to the patient an effective amount of an IL-13 antibody comprising a heavy chain immunoglobulin variable domain sequence and a light chain immunoglobulin variable domain that binds to IL-13 with a K D  of less than 10 −7  M, wherein the heavy chain variable domain comprises the amino acid sequence of: 
       
         
           
                 
               
                   (SEQ ID NO: 48) 
                 
                 
                 
               
                   (i) 
                   G-(YF)-(NT)-I-K-D-T-Y-(MI)-H 
                 
                     
                   in CDR1, 
                 
                     
                 
                 
               
                   (SEQ ID NO: 49) 
                 
                 
                 
               
                   (ii) 
                   (WR)-I-D-P-(GA)-N-D-N-I-K-Y-(SD)-(PQ)-K-F-Q-G 
                 
                     
                   in CDR2, 
                 
                   and 
                     
                 
                     
                 
                 
               
                   (SEQ ID NO: 17) 
                 
                 
                 
               
                   (iii) 
                   SEENWYDFFDY 
                 
                     
                   in CDR3; 
                 
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
                
               
            
             
                
               
            
             
                
                
               
            
           
         
         and wherein the light chain variable domain comprises the amino acid sequence of: 
       
       
         
           
                 
               
                   (SEQ ID NO: 25) 
                 
                 
                 
               
                   (i) 
                   (RK)-S-S-Q-S-(LI)-(KV)-H-S-(ND)-G-N-(TN)-Y- 
                 
                     
                   L-(EDNQYAS) 
                 
                     
                   in CDR1, 
                 
                     
                 
                 
               
                   (SEQ ID NO: 27) 
                 
                 
                 
               
                   (ii) 
                   K-(LVI)-S-(NY)-(RW)-(FD)-S 
                 
                     
                   in CDR2, 
                 
                   and 
                     
                 
                     
                 
                 
               
                   (SEQ ID NO: 28) 
                 
                 
                 
               
                   (iii) 
                   Q-(GSA)-(ST)-(HEQ)-I-P 
                 
                     
                   in CDR3. 
                 
             
                
               
            
             
                
                
                
                
               
            
             
                
               
            
             
                
                
                
                
               
            
             
                
               
            
             
                
                
               
            
           
         
       
     
     
         37 . The method of  claim 36 , wherein the heavy chain variable domain comprises: GFNIKDTYIH (SEQ ID NO:15), in CDR1, RIDPANDNIKYDPKFQG (SEQ ID NO:16), in CDR2, and SEENWYDFFDY (SEQ ID NO:17), in CDR3; and wherein the light chain variable domain sequence comprises: RSSQSIVHSNGNTYLE (SEQ ID NO:18), in CDR1, KVSNRFS (SEQ ID NO:19), in CDR2, and FQGSHIPYT (SEQ ID NO:20), in CDR3. 
     
     
         38 . The method of  claim 36 , wherein the antibody is a recombinant IgG that includes an Fc domain. 
     
     
         39 . The method of  claim 36 , wherein the antibody comprises an Fc domain that is mutated to reduce on or more of Fc receptor binding, antibody glycosylation, number of cysteine residues, effector cell function or complement function. 
     
     
         40 . The method of  claim 36 , wherein the antibody is a Fab or scFv. 
     
     
         41 . The method of  claim 36 , wherein the antibody comprises human framework regions, a human Fc region, or both. 
     
     
         42 . The method of  claim 36 , wherein the frameworks of the heavy chain domain sequence comprise: (i) at a position corresponding to 49, Gly; (ii) at a position corresponding to 72, Ala; (iii) at a position corresponding to 48, Ile, and to 49, Gly; (iv) at a position corresponding to 48, Ile, to 49, Gly, and to 72, Ala; (v) at a position corresponding to 67, Lys, to 68, Ala, and to 72, Ala; and/or (vi) at a position corresponding to 48, Ile, to 49, Gly, to 72, Ala, to 79, Ala. 
     
     
         43 . The method of  claim 36 , wherein the heavy chain variable domain sequence comprises the amino acid sequence of one or more of: GFNIKDTYIH (SEQ ID NO:15), in CDR1, R1DPANDNIKYDPKFQG (SEQ ID NO:16), in CDR2, or SEENWYDFFDY (SEQ ID NO:17), in CDR3. 
     
     
         44 . The method of  claim 36 , wherein the light chain variable domain sequence comprises the amino acid sequence of one more more of: RSSQSIVHSNGNTYLE (SEQ ID NO:18), in CDR1, KVSNRFS (SEQ ID NO:19), in CDR2, or FQGSHIPYT (SEQ ID NO:20), in CDR3. 
     
     
         45 . The method of  claim 36 , wherein the antibody molecule is an isolated, recombinant IgG antibody that comprises two polypeptide chains: a light chain that comprises the light chain variable domain of V2.11 (SEQ ID NO:36) and a heavy chain that comprises the heavy chain variable domain of V2.1 (SEQ ID NO:71), V2.3 (SEQ ID NO:73), V2.4 (SEQ ID NO:74), V2.5 (SEQ ID NO:75), V2.6 (SEQ ID NO:76), V2.7 (SEQ ID NO:77), or V2.11 (SEQ ID NO:80). 
     
     
         46 . The method of  claim 36 , wherein the immune disorder is an IL-13 related disorder. 
     
     
         47 . The method of  claim 36 , wherein the immune disorder is selected from the group consisting of: asthmatic disorders, atopic disorders, chronic obstructive pulmonary disease, conditions involving airway inflammation, eosinophilia, fibrosis and excess mucus production, inflammatory conditions, autoimmune conditions, tumors or cancers, viral infection, inflammatory bowel disease, Crohn's disease, and ulcerative colitis. 
     
     
         48 . The method of  claim 47 , wherein the immune disorder is ulcerative colitis.