Antibody which binds to myelin oligodendrocyte glycoprotein

Abstract

The invention relates to an antibody which binds to myelin oligodendrocyte glycoprotein (MOG), an antibody fragment thereof, a hybridoma which produces the antibody or the antibody fragment, a nucleic acid containing a nucleotide sequence which encodes the antibody or the antibody fragment, a transformant cell containing a vector containing the nucleic acid, a method for producing the antibody or the antibody fragment, a composition containing the antibody or the antibody fragment and a method for detecting or measuring an antigen that is present in the brain, a method for diagnosing or treating a brain disease, a method for improving the property of an antibody of accumulating in the brain and a method for increasing the amount of an antibody in the brain which use the antibody or the antibody fragment.

1 . An antibody which binds to myelin oligodendrocyte glycoprotein (MOG) or an antibody fragment thereof, wherein the antibody comprises any of the (a) to (q):
 (a) an antibody in which the amino acid sequences of complementarily determining regions (CDRs) 1 to 3 of the heavy chain variable region (VH) of the antibody comprise the amino acid sequences of SEQ ID NOs: 16, 17 and 18, respectively, and in which the amino acid sequences of CDRs 1 to 3 of the light chain variable region (VL) of the antibody comprise the amino acid sequences of SEQ ID NOs: 22, 23 and 24, respectively,   (b) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 28, 29 and 30, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 34, 35 and 36, respectively,   (c) an antibody fragment in which the amino acid sequences of CDRs 1 to 3 of a heavy chain variable region of a heavy chain antibody (VHH) comprise the amino acid sequences of SEQ ID NOs: 40, 41 and 42, respectively,   (d) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 153, 154 and 155, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 158, 159 and 160, respectively,   (e) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 163, 164 and 165, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 168, 169 and 170, respectively,   (f) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 173, 174 and 175, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 178, 179 and 180, respectively,   (g) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 183, 184 and 185, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 188, 189 and 190, respectively,   (h) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 193, 194 and 195, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 198, 199 and 200, respectively,   (i) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 203, 204 and 205, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 208, 209 and 210, respectively,   (j) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 213, 214 and 215, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 218, 219 and 220, respectively,   (k) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 223, 224 and 225, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 228, 229 and 230, respectively,   (l) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 233, 234 and 235, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 238, 239 and 240, respectively,   (m) an antibody in which the amino acid sequences of CDRs 1 to 3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 243, 244 and 245, respectively, and in which the amino acid sequences of CDRs 1 to 3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 248, 249 and 250, respectively,   (n) an antibody which competes in binding to MOG with at least one of the antibodies described in (a) to (m),   (o) an antibody which binds to an epitope comprising an epitope to which any one of the antibodies described in (a) to (m) binds,   (p) an antibody which binds to the same epitope as an epitope to which any one of the antibodies described in (a) to (m) binds, and   (q) an antibody which comprises an amino acid sequence having homology of 85% or higher to the amino acid sequence of any one of the antibodies described in (a) to (m).   
     
     
         2 . The antibody or the antibody fragment according to  claim 1 , wherein the antibody is selected from the group consisting of (a) to (m), (n1) to (n22) and (o):
 (a) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 15 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 21,   (b) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 27 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 33,   (c) an antibody fragment in which the amino acid sequence of VHH comprises the amino acid sequence of SEQ ID NO: 39,   (d) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 152 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 157,   (e) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 162 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 167,   (f) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 172 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 177,   (g) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 182 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 187,   (h) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 192 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 197,   (i) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 202 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 207,   (j) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 212 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 217,   (k) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 222 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 227,   (l) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 232 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 237,   (m) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 242 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 247,   (n1) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 252 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 254,   (n2) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 256 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 258,   (n3) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 260 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 262,   (n4) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 264 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 266,   (n5) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 268 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 270,   (n6) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 272 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 274,   (n7) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 276 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 278,   (n8) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 280 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 282,   (n9) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 284 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 286,   (n10) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 288 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 290,   (n11) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 292 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 294,   (n12) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 296 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 298,   (n13) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 300 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 302,   (n14) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 304 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 306,   (n15) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 308 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 310,   (n16) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 312 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 314,   (n17) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 316 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 318,   (n18) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 320 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 322,   (n19) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 324 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 326,   (n20) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 328 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 330,   (n21) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 332 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 334,   (n22) an antibody in which the amino acid sequence of VH comprises the amino acid sequence of SEQ ID NO: 336 and in which the amino acid sequence of VL comprises the amino acid sequence of SEQ ID NO: 338, and   (o) an antibody which comprises an amino acid sequence having homology of 85% or higher to the amino acid sequence of any one of the antibodies described in (a) to (m) and (n1) to (n22).   
     
     
         3 . The antibody or the antibody fragment according to  claim 1 , wherein the antibody or the antibody fragment is a bispecific antibody. 
     
     
         4 . The antibody or the antibody fragment according to  claim 3 , wherein the bispecific antibody binds to MOG and an antigen that is present in a brain. 
     
     
         5 . The antibody or the antibody fragment according to  claim 3 , wherein the bispecific antibody comprises an antigen binding site which binds to MOG and an antigen binding site which binds to an antigen that is present in a brain. 
     
     
         6 . The antibody fragment according to  claim 1  which is selected from the group consisting of Fab, Fab′, F(ab′) 2 , a single chain antibody (scFv), a dimerized V region (diabody), a disulfide-stabilized V region (dsFv), VHH, and a peptide comprising CDR. 
     
     
         7 . The antibody or the antibody fragment according to  claim 1 , wherein the antibody is a genetically recombinant antibody. 
     
     
         8 . The antibody or the antibody fragment according to  claim 1 , wherein the antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, and a human antibody. 
     
     
         9 . A composition which comprises the antibody or the antibody fragment according to  claim 1 . 
     
     
         10 . The composition according to  claim 9 , wherein the composition further comprises a carrier or a stabilizing agent. 
     
     
         11 . The composition according to  claim 9 , wherein the composition further comprises one or more pharmacologically acceptable carriers.