US2016264661A1PendingUtilityA1

Anti-il-12/il-23 antibodies

Assignee: TEVA PHARMACEUTICALS AUSTRALIA PTY LTDPriority: Aug 14, 2008Filed: Apr 22, 2016Published: Sep 15, 2016
Est. expiryAug 14, 2028(~2.1 yrs left)· nominal 20-yr term from priority
A61P 37/02A61P 5/14A61P 9/10A61P 41/00A61P 37/08A61P 3/08A61P 9/00A61P 7/00A61P 37/06A61P 25/04A61P 25/00A61P 29/00A61P 25/28A61P 27/00A61P 35/00A61P 27/02A61P 31/00A61P 3/00A61P 31/04A61P 1/16A61P 11/00A61P 1/04A61P 1/02A61P 1/00A61P 19/10A61P 17/14A61P 19/02A61P 17/06A61P 19/08A61P 19/04A61P 13/12A61P 17/00A61K 2039/505A61K 39/395C07K 16/244C07K 2317/622C07K 2317/92C07K 2317/24C07K 2317/565C07K 2317/56C07K 2317/34C07K 14/5434C07K 2317/567C07K 2317/76
47
PatentIndex Score
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Claims

Abstract

Provided herein is an antibody comprising an antigen binding domain which binds to human IL-12 and human IL-23. The antibody binds human IL-12p40 existing as a monomer (human IL-12p40) and as a homodimer (human IL-12p80), and the antibody inhibits the binding of human IL-12 to human IL-12Rβ2 and human IL-23 to human IL-23R but does not inhibit the binding of human IL-12 or human IL-23 or human IL-12p40 or human IL-12p80 to human IL-12Rβ1.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . An antibody which comprises three heavy chain CDR sequences selected from: 
       
         
           
                 
               
                   (SEQ ID NO: 371) 
                 
                 
                 
               
                     
                   HCDR1 DYYX 1 H, 
                 
                     
                   wherein; 
                 
                     
                   X 1  = M or L; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO: 372) 
                 
                 
                 
               
                     
                   HCDR2 WIDPENGDTEX 2 APKFQG, 
                 
                     
                   wherein; 
                 
                     
                   X 2  = Y, H, or S; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO: 373) 
                 
                 
                 
               
                     
                   HCDR3 X 3 KELRYFDV, 
                 
                     
                   wherein; 
                 
                     
                   X 3  = C, A, N, D, E, Q, G, H, I, L, P or V. 
                 
             
                
               
            
             
                
                
                
                
               
            
             
                
               
            
             
                
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
           
         
       
       and three light chain CDR sequences selected from: 
       
         
           
                 
               
                   (SEQ ID NO: 374) 
                 
                 
                 
               
                     
                   LCDR1 RAX 4 X 5 SISINLH, 
                 
                     
                   wherein; 
                 
                     
                   X 4  = S or P; 
                 
                     
                   X 5  = Q or R; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO: 375) 
                 
                 
                 
               
                     
                   LCDR2 FAX 6 QSX 7 S, 
                 
                     
                   wherein; 
                 
                     
                   X 6  = S or R; 
                 
                     
                   X 7  = I or T; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO: 376) 
                 
                 
                 
               
                     
                   LCDR3 QQSNSX 8 PLT, 
                 
                     
                   wherein; 
                 
                     
                   X 8  = W or F. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
             
                
               
            
             
                
                
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
           
         
       
     
     
         2 . An antibody as claimed in  claim 1  in which the antibody further comprises a human heavy chain acceptor framework sequence selected from the group consisting of SEQ ID NO: 202, SEQ ID NO: 205, SEQ ID NO: 208, SEQ ID NO: 203, SEQ ID NO: 206, SEQ ID NO: 209, SEQ ID NO: 204 and SEQ ID NO: 207. 
     
     
         3 . An antibody as claimed in  claim 1  in which the antibody further comprises a human light chain acceptor framework sequence selected from the group consisting of SEQ ID NO: 210, SEQ ID NO: 213, SEQ ID NO: 216, SEQ ID NO: 211, SEQ ID NO: 214, SEQ ID NO: 212 and SEQ ID NO: 215. 
     
     
         4 . An antibody as claimed in  claim 1  in which the antibody comprises an immunoglobulin heavy chain variable region selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 62, SEQ ID NO: 114, SEQ ID NO: 142, SEQ ID NO: 28, SEQ ID NO: 87, SEQ ID NO: 115, SEQ ID NO: 143, SEQ ID NO: 29, SEQ ID NO: 88, SEQ ID NO: 116, SEQ ID NO: 144, SEQ ID NO: 30, SEQ ID NO: 90, SEQ ID NO: 117, SEQ ID NO: 145, SEQ ID NO: 31, SEQ ID NO: 91, SEQ ID NO: 118, SEQ ID NO: 146, SEQ ID NO: 33, SEQ ID NO: 92, SEQ ID NO: 119, SEQ ID NO: 147, SEQ ID NO: 34, SEQ ID NO: 93, SEQ ID NO: 120, SEQ ID NO: 148, SEQ ID NO: 35, SEQ ID NO: 94, SEQ ID NO: 122, SEQ ID NO: 149, SEQ ID NO: 36, SEQ ID NO: 95, SEQ ID NO: 124, SEQ ID NO: 150, SEQ ID NO: 38, SEQ ID NO: 96, SEQ ID NO: 125, SEQ ID NO: 151, SEQ ID NO: 39, SEQ ID NO: 97, SEQ ID NO: 126, SEQ ID NO: 152, SEQ ID NO: 40, SEQ ID NO: 99, SEQ ID NO: 127, SEQ ID NO: 153, SEQ ID NO: 41, SEQ ID NO: 100, SEQ ID NO: 128, SEQ ID NO: 154, SEQ ID NO: 42, SEQ ID NO: 101, SEQ ID NO: 129, SEQ ID NO: 155, SEQ ID NO: 43, SEQ ID NO: 102, SEQ ID NO: 130, SEQ ID NO: 156, SEQ ID NO: 44, SEQ ID NO: 103, SEQ ID NO: 131, SEQ ID NO: 157, SEQ ID NO: 45, SEQ ID NO: 104, SEQ ID NO: 132, SEQ ID NO: 158, SEQ ID NO: 53, SEQ ID NO: 105, SEQ ID NO: 133, SEQ ID NO: 159, SEQ ID NO: 54, SEQ ID NO: 106, SEQ ID NO: 134, SEQ ID NO: 160, SEQ ID NO: 55, SEQ ID NO: 107, SEQ ID NO: 135, SEQ ID NO: 161, SEQ ID NO: 56, SEQ ID NO: 108, SEQ ID NO: 136, SEQ ID NO: 162, SEQ ID NO: 57, SEQ ID NO: 109, SEQ ID NO: 137, SEQ ID NO: 163, SEQ ID NO: 58, SEQ ID NO: 110, SEQ ID NO: 138, SEQ ID NO: 164, SEQ ID NO: 59, SEQ ID NO: 111, SEQ ID NO: 139, SEQ ID NO: 165, SEQ ID NO: 60, SEQ ID NO: 112, SEQ ID NO: 140, SEQ ID NO: 166, SEQ ID NO: 61, SEQ ID NO: 113, SEQ ID NO: 141 and SEQ ID NO: 167. 
     
     
         5 . An antibody as claimed in  claim 1  in which the antibody comprises an immunoglobulin light chain variable region selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 169, SEQ ID NO: 181, SEQ ID NO: 193, SEQ ID NO: 32, SEQ ID NO: 170, SEQ ID NO: 182, SEQ ID NO: 194, SEQ ID NO: 37, SEQ ID NO: 171, SEQ ID NO: 183, SEQ ID NO: 195, SEQ ID NO: 42, SEQ ID NO: 172, SEQ ID NO: 184, SEQ ID NO: 196, SEQ ID NO: 46, SEQ ID NO: 173, SEQ ID NO: 185, SEQ ID NO: 197, SEQ ID NO: 47, SEQ ID NO: 174, SEQ ID NO: 186, SEQ ID NO: 198, SEQ ID NO: 48, SEQ ID NO: 175, SEQ ID NO: 187, SEQ ID NO: 199, SEQ ID NO: 49, SEQ ID NO: 176, SEQ ID NO: 188, SEQ ID NO: 200, SEQ ID NO: 50, SEQ ID NO: 177, SEQ ID NO: 189, SEQ ID NO: 201, SEQ ID NO: 51, SEQ ID NO: 178, SEQ ID NO: 190, SEQ ID NO: 52, SEQ ID NO: 179 and SEQ ID NO: 192 
     
     
         6 . An antibody as claimed in  claim 5  in which the antibody binds human IL-12p40 existing as a monomer (human IL-12p40) and as a homodimer (human IL-12p80) and wherein the antibody inhibits the binding of human IL-12 to human IL-12Rβ2 and human IL-23 to human IL-23R but does not inhibit the binding of human IL-12 or human IL-23 or human IL-12p40 or human IL-12p80 to human IL-12Rβ1. 
     
     
         7 . An antibody as claimed in  claim 1  in which the antibody comprises two immunoglobulin variable regions, wherein the said two immunoglobulin variable regions are selected from a group consisting of: 
       
         
           
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO: 6 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 6 & SEQ ID NO: 169 
                 
                     
                   SEQ ID NO: 28 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 29 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 30 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 31 & SEQ ID NO: 32 
                 
                     
                   SEQ ID NO: 33 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 34 & SEQ ID NO: 51 
                 
                     
                   SEQ ID NO: 34 & SEQ ID NO: 47 
                 
                     
                   SEQ ID NO: 35 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 36 & SEQ ID NO: 37 
                 
                     
                   SEQ ID NO: 38 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 38 & SEQ ID NO: 51 
                 
                     
                   SEQ ID NO: 38 & SEQ ID NO: 32 
                 
                     
                   SEQ ID NO: 38 & SEQ ID NO: 47 
                 
                     
                   SEQ ID NO: 38 & SEQ ID NO: 52 
                 
                     
                   SEQ ID NO: 39 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 40 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 41 & SEQ ID NO: 42 
                 
                     
                   SEQ ID NO: 43 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 44 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 44 & SEQ ID NO: 51 
                 
                     
                   SEQ ID NO: 44 & SEQ ID NO: 32 
                 
                     
                   SEQ ID NO: 44 & SEQ ID NO: 47 
                 
                     
                   SEQ ID NO: 44 & SEQ ID NO: 52 
                 
                     
                   SEQ ID NO: 45 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 45 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 53 & SEQ ID NO: 41 
                 
                     
                   SEQ ID NO: 54 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 55 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 56 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 57 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 58 & SEQ ID NO: 42 
                 
                     
                   SEQ ID NO: 59 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 60 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 61 & SEQ ID NO: 42 
                 
                     
                   SEQ ID NO: 62 & SEQ ID NO: 42 
                 
                     
                   SEQ ID NO: 87 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 88 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 90 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 91 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 92 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 93 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 94 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 95 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 96 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 97 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 99 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 100 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 101 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 102 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 103 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 104 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 105 & SEQ ID NO: 7 
                 
                     
                   SEQ ID NO: 106 & SEQ ID NO: 171 
                 
                     
                   SEQ ID NO: 106 & SEQ ID NO: 172 
                 
                     
                   SEQ ID NO: 107 & SEQ ID NO: 171 
                 
                     
                   SEQ ID NO: 107 & SEQ ID NO: 172 
                 
                     
                   SEQ ID NO: 108 & SEQ ID NO: 171 
                 
                     
                   SEQ ID NO: 108 & SEQ ID NO: 172 
                 
                     
                   SEQ ID NO: 109 & SEQ ID NO: 170 
                 
                     
                   SEQ ID NO: 110 & SEQ ID NO: 171 
                 
                     
                   SEQ ID NO: 111 & SEQ ID NO: 172 
                 
                     
                   SEQ ID NO: 112 & SEQ ID NO: 169 
                 
                     
                   SEQ ID NO: 113 & SEQ ID NO: 173 
                 
                     
                   SEQ ID NO: 113 & SEQ ID NO: 174 
                 
                     
                   SEQ ID NO: 113 & SEQ ID NO: 175 
                 
                     
                   SEQ ID NO: 113 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 113 & SEQ ID NO: 177 
                 
                     
                   SEQ ID NO: 113 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 114 & SEQ ID NO: 173 
                 
                     
                   SEQ ID NO: 114 & SEQ ID NO: 174 
                 
                     
                   SEQ ID NO: 114 & SEQ ID NO: 175 
                 
                     
                   SEQ ID NO: 114 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 114 & SEQ ID NO: 177 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 173 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 174 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 175 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 177 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 181 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 182 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 183 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 184 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 185 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 186 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 187 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 188 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 190 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 192 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 193 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 194 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 195 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 196 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 197 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 198 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 199 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 200 
                 
                     
                   SEQ ID NO: 115 & SEQ ID NO: 201 
                 
                     
                   SEQ ID NO: 116 & SEQ ID NO: 173 
                 
                     
                   SEQ ID NO: 116 & SEQ ID NO: 174 
                 
                     
                   SEQ ID NO: 116 & SEQ ID NO: 175 
                 
                     
                   SEQ ID NO: 116 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 116 & SEQ ID NO: 177 
                 
                     
                   SEQ ID NO: 117 & SEQ ID NO: 173 
                 
                     
                   SEQ ID NO: 117 & SEQ ID NO: 174 
                 
                     
                   SEQ ID NO: 117 & SEQ ID NO: 175 
                 
                     
                   SEQ ID NO: 117 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 117 & SEQ ID NO: 177 
                 
                     
                   SEQ ID NO: 118 & SEQ ID NO: 178 
                 
                     
                   SEQ ID NO: 118 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 178 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 51 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 46 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 47 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 48 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 49 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 50 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 51 
                 
                     
                   SEQ ID NO: 119 & SEQ ID NO: 52 
                 
                     
                   SEQ ID NO: 120 & SEQ ID NO: 178 
                 
                     
                   SEQ ID NO: 120 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 122 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 124 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 125 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 126 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 127 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 128 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 129 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 130 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 131 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 132 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 133 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 134 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 135 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 136 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 137 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 138 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 139 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 140 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 141 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 142 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 143 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 144 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 145 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 146 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 147 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 148 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 149 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 150 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 151 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 152 & SEQ ID NO: 176 
                 
                     
                   SEQ ID NO: 153 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 154 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 155 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 156 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 157 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 158 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 159 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 160 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 161 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 161 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 162 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 162 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 163 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 163 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 164 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 164 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 165 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 165 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 166 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 166 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 167 & SEQ ID NO: 189 
                 
                     
                   SEQ ID NO: 167 & SEQ ID NO: 179 
                 
                     
                   SEQ ID NO: 168 & SEQ ID NO: 189 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         8 . An antibody as claimed in  claim 1  in which the antibody comprises a human or non-human primate heavy chain immunoglobulin constant region selected from a group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA 
     
     
         9 . An antibody as claimed in  claim 1  in which the antibody comprises a human or non-human primate light chain immunoglobulin constant region selected from a group consisting of kappa or lambda. 
     
     
         10 . An antibody as claimed in  claim 1  in which the antibody is modified by the covalent attachment of an organic moiety. 
     
     
         11 . An antibody as claimed in  claim 10  in which the organic moiety is a linear or branched hydrophilic polymeric group, fatty acid group, or fatty acid ester group. 
     
     
         12 . An antibody as claimed in  claim 1  in which the antibody is modified to modulate a functional characteristic selected from the group consisting of antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, serum half-life, biodistribution and binding to Fc receptors. 
     
     
         13 . An antibody as claimed in  claim 12  in which the modification is by protein engineering, glycoengineering or chemical methods. 
     
     
         14 . A nucleic acid molecule in which the nucleic acid encodes a VH domain as claimed in  claim 1 . 
     
     
         15 . A nucleic acid molecule as claimed in  claim 14  in which the nucleic acid has a sequence selected from: 
       
         
           
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO: 217 
                 
                     
                   SEQ ID NO: 218 
                 
                     
                   SEQ ID NO: 219 
                 
                     
                   SEQ ID NO: 220 
                 
                     
                   SEQ ID NO: 222 
                 
                     
                   SEQ ID NO: 223 
                 
                     
                   SEQ ID NO: 224 
                 
                     
                   SEQ ID NO: 225 
                 
                     
                   SEQ ID NO: 227 
                 
                     
                   SEQ ID NO: 228 
                 
                     
                   SEQ ID NO: 229 
                 
                     
                   SEQ ID NO: 230 
                 
                     
                   SEQ ID NO: 232 
                 
                     
                   SEQ ID NO: 233 
                 
                     
                   SEQ ID NO: 234 
                 
                     
                   SEQ ID NO: 242 
                 
                     
                   SEQ ID NO: 243 
                 
                     
                   SEQ ID NO: 244 
                 
                     
                   SEQ ID NO: 245 
                 
                     
                   SEQ ID NO: 246 
                 
                     
                   SEQ ID NO: 247 
                 
                     
                   SEQ ID NO: 248 
                 
                     
                   SEQ ID NO: 249 
                 
                     
                   SEQ ID NO: 250 
                 
                     
                   SEQ ID NO: 251 
                 
                     
                   SEQ ID NO: 252 
                 
                     
                   SEQ ID NO: 254 
                 
                     
                   SEQ ID NO: 255 
                 
                     
                   SEQ ID NO: 257 
                 
                     
                   SEQ ID NO: 258 
                 
                     
                   SEQ ID NO: 259 
                 
                     
                   SEQ ID NO: 260 
                 
                     
                   SEQ ID NO: 261 
                 
                     
                   SEQ ID NO: 262 
                 
                     
                   SEQ ID NO: 263 
                 
                     
                   SEQ ID NO: 264 
                 
                     
                   SEQ ID NO: 266 
                 
                     
                   SEQ ID NO: 267 
                 
                     
                   SEQ ID NO: 268 
                 
                     
                   SEQ ID NO: 269 
                 
                     
                   SEQ ID NO: 270 
                 
                     
                   SEQ ID NO: 271 
                 
                     
                   SEQ ID NO: 272 
                 
                     
                   SEQ ID NO: 273 
                 
                     
                   SEQ ID NO: 274 
                 
                     
                   SEQ ID NO: 275 
                 
                     
                   SEQ ID NO: 276 
                 
                     
                   SEQ ID NO: 277 
                 
                     
                   SEQ ID NO: 278 
                 
                     
                   SEQ ID NO: 279 
                 
                     
                   SEQ ID NO: 280 
                 
                     
                   SEQ ID NO: 281 
                 
                     
                   SEQ ID NO: 282 
                 
                     
                   SEQ ID NO: 283 
                 
                     
                   SEQ ID NO: 284 
                 
                     
                   SEQ ID NO: 285 
                 
                     
                   SEQ ID NO: 286 
                 
                     
                   SEQ ID NO: 287 
                 
                     
                   SEQ ID NO: 289 
                 
                     
                   SEQ ID NO: 291 
                 
                     
                   SEQ ID NO: 292 
                 
                     
                   SEQ ID NO: 293 
                 
                     
                   SEQ ID NO: 294 
                 
                     
                   SEQ ID NO: 295 
                 
                     
                   SEQ ID NO: 296 
                 
                     
                   SEQ ID NO: 297 
                 
                     
                   SEQ ID NO: 298 
                 
                     
                   SEQ ID NO: 299 
                 
                     
                   SEQ ID NO: 300 
                 
                     
                   SEQ ID NO: 301 
                 
                     
                   SEQ ID NO: 302 
                 
                     
                   SEQ ID NO: 303 
                 
                     
                   SEQ ID NO: 304 
                 
                     
                   SEQ ID NO: 305 
                 
                     
                   SEQ ID NO: 306 
                 
                     
                   SEQ ID NO: 307 
                 
                     
                   SEQ ID NO: 308 
                 
                     
                   SEQ ID NO: 309 
                 
                     
                   SEQ ID NO: 310 
                 
                     
                   SEQ ID NO: 311 
                 
                     
                   SEQ ID NO: 312 
                 
                     
                   SEQ ID NO: 313 
                 
                     
                   SEQ ID NO: 314 
                 
                     
                   SEQ ID NO: 315 
                 
                     
                   SEQ ID NO: 316 
                 
                     
                   SEQ ID NO: 317 
                 
                     
                   SEQ ID NO: 318 
                 
                     
                   SEQ ID NO: 319 
                 
                     
                   SEQ ID NO: 320 
                 
                     
                   SEQ ID NO: 321 
                 
                     
                   SEQ ID NO: 322 
                 
                     
                   SEQ ID NO: 323 
                 
                     
                   SEQ ID NO: 324 
                 
                     
                   SEQ ID NO: 325 
                 
                     
                   SEQ ID NO: 326 
                 
                     
                   SEQ ID NO: 327 
                 
                     
                   SEQ ID NO: 328 
                 
                     
                   SEQ ID NO: 329 
                 
                     
                   SEQ ID NO: 330 
                 
                     
                   SEQ ID NO: 331 
                 
                     
                   SEQ ID NO: 332 
                 
                     
                   SEQ ID NO: 333 
                 
                     
                   SEQ ID NO: 334 
                 
                     
                   SEQ ID NO: 335 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         16 . A nucleic acid molecule in which the nucleic acid encodes a VL domain as claimed in  claim 1 . 
     
     
         17 . A nucleic acid molecule as claimed in  claim 16  in which the nucleic acid has a sequence selected from: 
       
         
           
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO: 221 
                 
                     
                   SEQ ID NO: 226 
                 
                     
                   SEQ ID NO: 231 
                 
                     
                   SEQ ID NO: 235 
                 
                     
                   SEQ ID NO: 236 
                 
                     
                   SEQ ID NO: 237 
                 
                     
                   SEQ ID NO: 238 
                 
                     
                   SEQ ID NO: 239 
                 
                     
                   SEQ ID NO: 240 
                 
                     
                   SEQ ID NO: 241 
                 
                     
                   SEQ ID NO: 336 
                 
                     
                   SEQ ID NO: 338 
                 
                     
                   SEQ ID NO: 339 
                 
                     
                   SEQ ID NO: 340 
                 
                     
                   SEQ ID NO: 341 
                 
                     
                   SEQ ID NO: 342 
                 
                     
                   SEQ ID NO: 343 
                 
                     
                   SEQ ID NO: 344 
                 
                     
                   SEQ ID NO: 345 
                 
                     
                   SEQ ID NO: 346 
                 
                     
                   SEQ ID NO: 347 
                 
                     
                   SEQ ID NO: 348 
                 
                     
                   SEQ ID NO: 350 
                 
                     
                   SEQ ID NO: 351 
                 
                     
                   SEQ ID NO: 352 
                 
                     
                   SEQ ID NO: 353 
                 
                     
                   SEQ ID NO: 354 
                 
                     
                   SEQ ID NO: 355 
                 
                     
                   SEQ ID NO: 356 
                 
                     
                   SEQ ID NO: 357 
                 
                     
                   SEQ ID NO: 358 
                 
                     
                   SEQ ID NO: 359 
                 
                     
                   SEQ ID NO: 361 
                 
                     
                   SEQ ID NO: 362 
                 
                     
                   SEQ ID NO: 363 
                 
                     
                   SEQ ID NO: 364 
                 
                     
                   SEQ ID NO: 365 
                 
                     
                   SEQ ID NO: 366 
                 
                     
                   SEQ ID NO: 367 
                 
                     
                   SEQ ID NO: 368 
                 
                     
                   SEQ ID NO: 369 
                 
                     
                   SEQ ID NO: 370 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         18 . A method of treating a disease in a subject comprising administering to the subject an antibody as claimed in  claim 1  wherein the disease is selected from the group consisting of rheumatoid arthritis, osteoarthritis, reactive arthritis, psoriatic arthritis, bone loss, airways hypersensitivity, chronic obstructive pulmonary disease, a demyelinating disorder, psoriasis, multiple sclerosis, dermal hypersensitivity, acute and chronic transplant rejection, allograft rejection, graft-versus host disease, systemic sclerosis, systemic lupus erythematosus, an autoimmune inflammatory bowel disease, a urological inflammatory disorder, a cardiovascular disease, a vasculitis, a periodic fever, a glucose metabolism disorder, a pulmonary disease, a cancer, peridontitis, hepatic stromal keratitis, an allergy, inflammatory pain, a spondyloarthropathy, septicaemia, septic or endotoxic shock, meningitis, surgical trauma, an autoimmune haematological disorder, Alzheimer's disease, sarcoidosis, cirrhosis, hepatitis (including autoimmune hepatitis), primary biliary cirrhosis, uveitis, thyroiditis, atherosclerosis, alopecia, Wilson's disease, glomerulonephritis and dislipidemia.

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