Human antibody molecules for il-13

Abstract

Specific binding members, in particular human anti-IL-13 antibody molecules and especially those which neutralize IL-13 activity. Methods for using anti-IL-13 antibody molecules in diagnosis or treatment of IL-13 related disorders, including asthma, atopic dermatitis, allergic rhinitis, fibrosis, inflammatory bowel disease and Hodgkin's lymphoma.

1 - 91 . (canceled) 
     
     
         92 . An isolated nucleic acid molecule comprising a polynucleotide encoding an antibody or antigen-binding fragment thereof that binds human interleukin-13 (IL-13), wherein the antibody or antigen-binding fragment thereof comprises a set of complementarity determining regions (CDRs), HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, selected from the group consisting of:
 (i) the BAK1183H4 set of CDRs, defined wherein the HCDR1 has the amino acid sequence of NYGLS (SEQ ID NO: 97), the HCDR2 has the amino acid sequence of WINYDGGNTQYGQEFQG (SEQ ID NO: 98), the HCDR3 has the amino acid sequence of DSSSSWARWFFDL (SEQ ID NO: 99), the LCDR1 has the amino acid sequence of GGNIIGSKLVH (SEQ ID NO: 100), the LCDR2 has the amino acid sequence of DDGDRPS (SEQ ID NO: 101), and the LCDR3 has the amino acid sequence of QVWDTGSDPVV (SEQ ID NO: 102);   (ii) the BAK1167F02 set of CDRs, defined wherein the HCDR1 has the amino acid sequence QTGVS (SEQ ID NO: 61), the HCDR2 has the amino acid sequence WISANNGDTNYGQEFQG (SEQ ID NO: 62), the HCDR3 has the amino acid sequence DSSSSWARWFFDL (SEQ ID NO: 63), the LCDR1 has the amino acid sequence GGNIIGSKLVH (SEQ ID NO: 64), the LCDR2 has the amino acid sequence DDGDRPS (SEQ ID NO: 65), and the LCDR3 has the amino acid sequence QVWDTGSDPVV (SEQ ID NO: 66);   (iii) the BAK1111D10 set of CDRs, defined wherein the HCDR1 has the amino acid sequence NYGLS (SEQ ID NO: 91), the HCDR2 has the amino acid sequence WIATPDGQTSYGQEFQG (SEQ ID NO: 92), the HCDR3 has the amino acid sequence DSNSSWARWFFDL (SEQ ID NO: 93), the LCDR1 has the amino acid sequence GGNIIGSKLVH (SEQ ID NO: 94), the LCDR2 has the amino acid sequence DDGDRPS (SEQ ID NO: 95), and the LCDR3 has the amino acid sequence of QVWDTGSDPVV (SEQ ID NO: 96);   (iv) the BAK1166G02 set of CDRs, defined wherein the HCDR1 has the amino acid sequence NTGIS (SEQ ID NO: 67), the HCDR2 has the amino acid sequence WISANNGDTNYGQEFQG (SEQ ID NO: 68), the HCDR3 has the amino acid sequence DSSSSWARWFFDL (SEQ ID NO: 69), the LCDR1 has the amino acid sequence GGNIIGSKLVH (SEQ ID NO: 70), the LCDR2 has the amino acid sequence DDGDRPS (SEQ ID NO: 71), and the LCDR3 has the amino acid sequence QVWDTGSDPVV (SEQ ID NO: 72);   (v) the BAK1167F04 set of CDRs, defined wherein the HCDR1 has the amino acid sequence DTGVS (SEQ ID NO: 85), the HCDR2 has the amino acid sequence WISANNGDTNYGQEFQG (SEQ ID NO: 86), the HCDR3 has the amino acid sequence DSSSSWARWFFDL (SEQ ID NO: 87), the LCDR1 has the amino acid sequence GGNIIGSKLVH (SEQ ID NO: 88), the LCDR2 has the amino acid sequence DDGDRPS (SEQ ID NO: 89), and the LCDR3 has the amino acid sequence QVWDTGSDPVV (SEQ ID NO: 90);   (vi) the BAK1184C8 set of CDRs, defined wherein the HCDR1 has the amino acid sequence NYGLS (SEQ ID NO: 73), the HCDR2 has the amino acid sequence WISGSNGYTSYGQEFQG (SEQ ID NO: 74), the HCDR3 has the amino acid sequence DSSSSWARWFFDL (SEQ ID NO: 75), the LCDR1 has the amino acid sequence GGNIIGSKLVH (SEQ ID NO: 76), the LCDR2 has the amino acid sequence DDGDRPS (SEQ ID NO: 77), and the LCDR3 has the amino acid sequence QVWDTGSDPVV (SEQ ID NO: 78);   (vii) the BAK1185E1 set of CDRs, defined wherein the HCDR1 has the amino acid sequence NYGLS (SEQ ID NO: 79), the HCDR2 has the amino acid sequence WINDATGDTQYGQEFQG (SEQ ID NO: 80), the HCDR3 has the amino acid sequence DSSSSWARWFFDL (SEQ ID NO: 81), the LCDR1 has the amino acid sequence GGNIIGSKLVH (SEQ ID NO: 82), the LCDR2 has the amino acid sequence DDGDRPS (SEQ ID NO: 83), and the LCDR3 has the amino acid sequence QVWDTGSDPVV (SEQ ID NO: 84); and   (viii) the BAK1185F8 set of CDRs, defined wherein the HCDR1 has the amino acid sequence DYGLS (SEQ ID NO: 103), the HCDR2 has the amino acid sequence WRINDGYTIYGQEFQG (SEQ ID NO: 104), the HCDR3 has the amino acid sequence DSSSSWARWFFDL (SEQ ID NO: 105), the LCDR1 has the amino acid sequence GGNIIGSKLVH (SEQ ID NO: 106), the LCDR2 has the amino acid sequence DDGDRPS (SEQ ID NO: 107), and the LCDR3 has the amino acid sequence QVWDTGSDPVV (SEQ ID NO: 108).   
     
     
         93 . The nucleic acid molecule according to  claim 92 , wherein the nucleic acid molecule is operably linked to a control sequence. 
     
     
         94 . A vector comprising the nucleic acid molecule according to  claim 93 . 
     
     
         95 . A host cell transformed with the vector of  claim 94 . 
     
     
         96 . The host cell of  claim 95 , wherein the host cell is a mammalian host cell. 
     
     
         97 . The mammalian host cell of  claim 96 , wherein the host cell is a Chinese hamster ovary (CHO) cell, a HeLa cell, a baby hamster kidney cell, a NSO mouse melanoma cell, a YB2/0 rat myeloma cell, a human embryonic kidney cell, or a human embryonic retina cell. 
     
     
         98 . A method of making an antibody or antigen-binding fragment thereof that binds human interleukin-13 (IL-13) comprising culturing a host cell according to  claim 95  under suitable conditions for producing the antibody or antigen-binding fragment thereof. 
     
     
         99 . The method of  claim 98 , further comprising isolating the antibody or antigen-binding fragment thereof secreted from the host cell. 
     
     
         100 . An isolated nucleic acid molecule comprising a polynucleotide encoding an antibody or antigen-binding fragment thereof that binds human interleukin-13 (IL-13), wherein the antibody or antigen-binding fragment thereof comprises a set of heavy and light chain variable regions (VH and VL) from the group consisting of: 
       
         
           
                 
                 
               
                   (i) the BAK1183H4 VH sequence 
                     
                 
                   (SEQ ID NO: 37)  
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWINYD 
                     
                 
                   GGNTQYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFF 
                 
                   DLWGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1183H4 VL sequence 
                 
                   (SEQ ID NO: 38) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL, 
                 
                     
                 
                   (ii) the BAK1111D10 VH sequence 
                 
                   (SEQ ID NO: 41) 
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWIATP 
                     
                 
                   DGQTSYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSNSSWARWFF 
                 
                   DLWGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1111D10 VL sequence 
                 
                   (SEQ ID NO: 42) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL, 
                 
                     
                 
                   (iii) the BAK1167F02 VH sequence 
                 
                   (SEQ ID NO: 35) 
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFEQTGVSWVRQAPGQGLEWMGWISAN 
                     
                 
                   NGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFF 
                 
                   DLWGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1167F02 VL sequence 
                 
                   (SEQ ID NO: 36) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL, 
                 
                     
                 
                   (iv) the BAK1166G02 VH sequence 
                 
                   (SEQ ID NO: 53) 
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFANTGISWVRQAPGQGLEWMGWISANN 
                     
                 
                   GDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFD 
                 
                   LWGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1166G02 VL sequence 
                 
                   (SEQ ID NO: 54) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL, 
                 
                     
                 
                   (v) the BAK1167F04 VH sequence 
                 
                   (SEQ ID NO: 43) 
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFIDTGVSWVRQAPGQGLEWMGWISANN 
                     
                 
                   GDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFD 
                 
                   LWGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1167F04 VL sequence 
                 
                   (SEQ ID NO: 44) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL, 
                 
                     
                 
                   (vi) the BAK1184C8 VH sequence 
                 
                   (SEQ ID NO: 45) 
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISGSN 
                     
                 
                   GYTSYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDL 
                 
                   WGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1184C8 VL sequence 
                 
                   (SEQ ID NO: 46) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL, 
                 
                     
                 
                   (vii) the BAK1185E1 VH sequence 
                 
                   (SEQ ID NO: 47) 
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWINDA 
                     
                 
                   TGDTQYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFF 
                 
                   DLWGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1185E1 VL sequence 
                 
                   (SEQ ID NO: 48) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL, 
                 
                   and 
                 
                     
                 
                   (viii) the BAK1185F8 VH sequence 
                 
                   (SEQ ID NO: 49) 
                     
                 
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYGLSWVRQAPGQGLEWMGWIRNID 
                     
                 
                   GYTIYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDL 
                 
                   WGRGTLVTVSS 
                 
                   and 
                 
                     
                 
                   the BAK1185F8 VL sequence 
                 
                   (SEQ ID NO: 50) 
                     
                 
                   SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIP 
                     
                 
                   ERFSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVL. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         101 . The nucleic acid molecule according to  claim 100 , wherein the nucleic acid molecule is operably linked to a control sequence. 
     
     
         102 . A vector comprising the nucleic acid molecule according to  claim 101 . 
     
     
         103 . A host cell transformed with the vector of  claim 102 . 
     
     
         104 . The host cell of  claim 103 , wherein the host cell is a mammalian host cell. 
     
     
         105 . The mammalian host cell of  claim 104 , wherein the host cell is a Chinese hamster ovary (CHO) cell, a HeLa cell, a baby hamster kidney cell, a NSO mouse melanoma cell, a YB2/0 rat myeloma cell, a human embryonic kidney cell, or a human embryonic retina cell. 
     
     
         106 . A method of making an antibody or antigen-binding fragment thereof that binds human interleukin-13 (IL-13) comprising culturing a host cell according to  claim 103  under suitable conditions for producing the antibody or antigen-binding fragment thereof. 
     
     
         107 . The method of  claim 106 , further comprising isolating the antibody or antigen binding fragment thereof secreted from the host cell.