ES2620255T3 - Anticuerpos para el receptor del factor de crecimiento epidérmico 3 (HER3) - Google Patents

Anticuerpos para el receptor del factor de crecimiento epidérmico 3 (HER3) Download PDF

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ES2620255T3
ES2620255T3 ES11746252.3T ES11746252T ES2620255T3 ES 2620255 T3 ES2620255 T3 ES 2620255T3 ES 11746252 T ES11746252 T ES 11746252T ES 2620255 T3 ES2620255 T3 ES 2620255T3
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kabat
chothia
her3
mor10703
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Winfried Elis
Seth Ettenberg
Andrew Paul Garner
Nicole Haubst
Christian Carsten Silvester Kunz
Elizabeth Anne Reisinger Sprague
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Novartis AG
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Abstract

Un anticuerpo aislado o un fragmento del mismo que reconoce un epítopo conformacional de un receptor HER3, en donde el epítopo conformacional comprende residuos de aminoácidos 265-377, 315 dentro del dominio 2 y residuos de aminoácidos 571, 582-584, 596-597, 600-602, 609-615 dentro del dominio 4 del receptor HER3 de SEQ ID NO:1, y en donde el anticuerpo o el fragmento del mismo bloquea la transducción de señales tanto dependiente del ligando como independiente del ligando de HER3.

Description

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anticuerpos un dominio VL que tiene una secuencia de aminoácidos de las SEQ ID NOs: 14, 32, 50, 68, 86, 104, 122, 140, 158, 176, 194, 212, 230, 248, 266, 284, 302, 320, 338, 356, y 374. La presente divulgación también proporciona anticuerpos que se enlazan específicamente con la proteína de HER3 (por ejemplo, HER3 humano y/o de cinomolgo), comprendiendo estos anticuerpos una VH CDR que tiene una secuencia de
5 aminoácidos de cualquiera de las VH CDRs enlistadas en la Tabla 1 más adelante. En particular, la divulgación proporciona anticuerpos que se enlazan específicamente a la proteína de HER3 (por ejemplo, HER3 humano y/o de cinomolgo), comprendiendo estos anticuerpos (o de una manera alternativa, consistiendo en) una, dos, tres, cuatro, cinco o más VH CDRs que tienen una secuencia de aminoácidos de cualquiera de las VH CDRs enlistadas en la Tabla 1 más adelante.
10 Otros anticuerpos de la divulgación incluyen aminoácidos que se han mutado, y no obstante tienen cuando menos el 60, 70, 80, 90, 95, o 98 % de identidad en las regiones CDR con las regiones CDR ilustradas en las secuencias descritas en la Tabla 1. En algunas realizaciones, incluye secuencias de aminoácidos mutantes en donde no más de 1, 2, 3, 4 o 5 aminoácidos han sido mutados en las regiones CDR, cuando se comparan con las regiones CDR ilustradas en la secuencia descrita en la Tabla 1, mientras que todavía mantienen su
15 especificidad por el epítopo del anticuerpo original.
Otros anticuerpos de la divulgación incluyen aminoácidos que se han mutado, y no obstante tienen cuando menos el 60, 70, 80, 90, 95, o 98 % de identidad en las regiones de estructura con las regiones de estructura ilustradas en las secuencias descritas en la Tabla 1. En algunas realizaciones, incluye secuencias de aminoácidos mutantes en donde no más de 1, 2, 3, 4, 5, 6, o 7 aminoácidos se han mutado en las regiones de
20 estructura, cuando se comparan con las regiones de estructura ilustradas en la secuencia descrita en la Tabla 1, mientras que todavía mantienen su especificidad por el epítopo del anticuerpo original. La presente divulgación también proporciona secuencias de ácidos nucleicos que codifican VH, VL, la cadena pesada de longitud completa, y la cadena ligera de longitud completa de los anticuerpos que se enlazan específicamente a la proteína de HER3 (por ejemplo, HER3 humano y/o de cinomolgo).
25 Los anticuerpos de HER3 de la divulgación se enlazan al epítopo conformacional de HER3, el cual comprende los residuos de aminoácidos a partir del dominio 2 y del dominio 4 de HER3.
Tabla 1
Ejemplos de anticuerpos HER3 de la presente divulgación
SEQ ID NO:
Región Ab
MOR09823
SEQ ID NO: 2 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 3 (Kabat)
HCDR2 VTGAVGRTYYPDSVKG
SEQ ID NO: 4 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 5 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 6 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 7 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 8 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 9 (Chothia)
HCDR2 GAVGR
SEQIDNO: 10 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO:
Región Ab
SEQIDNO: 11 (Chothia)
LCDR1 SQGISNW
SEQIDNO: 12 (Chothia)
LCDR2 GAS
SEQ ID NO: (Chothia) 13
LCDR3 YSSFPT
SEQ ID NO: 14
VL imagen26
MOR09823
SEQ ID NO: 15
VH imagen27
imagen28
SEQ ID NO: 16
ADN VL imagen29
SEQ ID NO: 17
ADN VH imagen30
SEQ ID NO: 18
Ligera Kappa imagen31
SEQ ID NO: 19
Pesada IgG1 imagen32
MOR09824
SEQIDNO: 20 (Kabat)
HCDR1 SYAMS
SEQIDNO: 21 (Kabat)
HCDR2 VISAWGHVKYYADSVKG
SEQIDNO: 22 (Kabat)
HCDR3 WGDEGFDI
SEQIDNO: 23 (Kabat)
LCDR1 RASQGISNWLA
SEQIDNO: 24 (Kabat)
LCDR2 GASSLQS
SEQ ID NO:
Región Ab
SEQIDNO: 25 (Kabat)
LCDR3 QQYSSFPTT
SEQIDNO: 26 (Chothia)
HCDR1 GFTFSSY
SEQIDNO: 27 (Chothia)
HCDR2 SAWGHV
SEQIDNO: 28 (Chothia)
HCDR3 WGDEGFDI
MOR09824
SEQIDNO: 29 (Chothia)
LCDR1 SQGISNW
SEQIDNO: 30 (Chothia)
LCDR2 GAS
SEQIDNO: 31 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 32
VL imagen33
SEQ ID NO: 33
VH imagen34
SEQ ID NO: 34
ADN VL imagen35
SEQ ID NO: 35
ADN VH imagen36
SEQ ID NO: 36
Ligera Kappa imagen37
SEQ ID NO: 37
Pesada IgG1 imagen38
imagen39
MOR09825
SEQIDNO: 38 (Kabat)
HCDR1 SYAMS
SEQ ID NO:
Región Ab
SEQIDNO: 39 (Kabat)
HCDR2 AINSQGKSTYYADSVKG
SEQIDNO: 40 (Kabat)
HCDR3 WGDEGFDI
SEQIDNO: 41 (Kabat)
LCDR1 RASQGISNWLA
SEQIDNO: 42 (Kabat)
LCDR2 GASSLQS
MOR09825
SEQIDNO: 43 (Kabat)
LCDR3 QQYSSFPTT
SEQIDNO: 44 (Chothia)
HCDR1 GFTFSSY
SEQIDNO: 45 (Chothia)
HCDR2 NSQGKS
SEQIDNO: 46 (Chothia)
HCDR3 WGDEGFDI
SEQIDNO: 47 (Chothia)
LCDR1 SQGISNW
SEQIDNO: 48 (Chothia)
LCDR2 GAS
SEQIDNO: 49 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 50
VL imagen40
SEQ ID NO: 51
VH imagen41
SEQ ID NO: 52
ADN VL imagen42
SEQ ID NO: 53
ADN VH imagen43
SEQ ID NO: 54
Ligera Kappa imagen44
SEQ ID NO:
Región Ab
SEQ ID NO: 55
Pesada IgG1 imagen45
MOR09974
SEQIDNO: 56 (Kabat)
HCDR1 SYAMS
MOR09974
SEQIDNO: 57 (Kabat)
HCDR2 VINPSGNFTNYADSVKG
SEQIDNO: 58 (Kabat)
HCDR3 WGDEGFDI
SEQIDNO: 59 (Kabat)
LCDR1 RASQGISNWLA
SEQIDNO: 60 (Kabat)
LCDR2 GASSLQS
SEQIDNO: 61 (Kabat)
LCDR3 QQYSSFPTT
SEQIDNO: 62 (Chothia)
HCDR1 GFTFSSY
SEQIDNO: 63 (Chothia)
HCDR2 NPSGNF
SEQIDNO: 64 (Chothia)
HCDR3 WGDEGFDI
SEQIDNO: 65 (Chothia)
LCDR1 SQGISNW
SEQIDNO: 66 (Chothia)
LCDR2 GAS
SEQID NO: 67 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 68
VL imagen46
SEQ ID NO: 69
VH imagen47
SEQ ID NO: 70
ADN VL imagen48
SEQ ID NO:
Región Ab
SEQ ID NO: 71
ADN VH imagen49
SEQ ID NO: 72
Ligera Kappa imagen50
MOR09974
SEQ ID NO: 73
Pesada IgG1 imagen51
MOR10452
SEQIDNO: 74 (Kabat)
HCDR1 SYAMS
SEQIDNO: 75 (Kabat)
HCDR2 NTSPIGYTYYAGSVKG
SEQIDNO: 76 (Kabat)
HCDR3 WGDEGFDI
SEQIDNO: 77 (Kabat)
LCDR1 RASQGISNWLA
SEQIDNO: 78 (Kabat)
LCDR2 GASSLQS
SEQIDNO: 79 (Kabat)
LCDR3 QQYSSFPTT
SEQIDNO: 80 (Chothia)
HCDR1 GFTFSSY
SEQIDNO: 81 (Chothia)
HCDR2 SPIGY
SEQIDNO: 82 (Chothia)
HCDR3 WGDEGFDI
SEQIDNO: 83 (Chothia)
LCDR1 SQGISNW
SEQIDNO: 84 (Chothia)
LCDR2 GAS
SEQIDNO: 85 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 86
VL imagen52
SEQ ID NO:
Región Ab
SEQ ID NO: 87
VH imagen53
SEQ ID NO: 88
ADN VL imagen54
MOR10452
SEQ ID NO: 89
ADN VH imagen55
SEQ ID NO: 90
Ligera Kappa imagen56
imagen57
SEQ ID NO: 91
Pesada Chain (only VH and CH1 domains) imagen58
MOR10701
SEQIDNO: 92 (Kabat)
HCDR1 SYAMS
SEQIDNO: 93 (Kabat)
HCDR2 VTGAVGRSTYYPDSVKG
SEQIDNO: 94 (Kabat)
HCDR3 WGDEGFDI
SEQIDNO: 95 (Kabat)
LCDR1 RASQGISNWLA
SEQIDNO: 96 (Kabat)
LCDR2 GASSLQS
SEQIDNO: 97 (Kabat)
LCDR3 QQYSSFPTT
SEQIDNO: 98 (Chothia)
HCDR1 GFTFSSY
SEQIDNO: 99 (Chothia)
HCDR2 GAVGRS
SEQ ID NO: 100 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 101 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 102 (Chothia)
LCDR2 GAS
SEQ ID NO:
Región Ab
SEQ ID NO: 103 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 104
VL imagen59
SEQ ID NO: 105
VH imagen60
MOR10701
SEQ ID NO: 106
ADN VL imagen61
SEQ ID NO: 107
ADN VH imagen62
SEQ ID NO: 108
Ligera Kappa imagen63
SEQ ID NO: 109
Pesada IgG1 imagen64
MOR10702
SEQ ID NO: 110 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 111 (Kabat)
HCDR2 VISAWGHVKYYADSVKG
SEQ ID NO: 112 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 113 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 114 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 115 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 116 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 117 (Chothia)
HCDR2 SAWGHV
SEQ ID NO:
Región Ab
SEQ ID NO: 118 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 119 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 120 (Chothia)
LCDR2 GAS
SEQ ID NO: 121 (Chothia)
LCDR3 YSSFPT
MOR10702
SEQ ID NO: 122
VL imagen65
SEQ ID NO: 123
VH imagen66
SEQ ID NO: 124
ADN VL imagen67
SEQ ID NO: 125
ADN VH imagen68
SEQ ID NO: 126
Ligera Kappa imagen69
SEQ ID NO: 127
Pesada IgG1 imagen70
MOR10703
SEQ ID NO: 128 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 129 (Kabat)
HCDR2 AINSQGKSTYYADSVKG
SEQ ID NO: 130 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 131 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO:
Región Ab
SEQ ID NO: 132 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 133 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 134 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 135 (Chothia)
HCDR2 NSQGKS
SEQ ID NO: 136 (Chothia)
HCDR3 WGDEGFDI
MOR10703
SEQ ID NO: 137 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 138 (Chothia)
LCDR2 GAS
SEQ ID NO: 139 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 140
VL imagen65
SEQ ID NO: 141
VH imagen71
SEQ ID NO: 142
ADN VL imagen67
SEQ ID NO: 143
ADN VH imagen72
SEQ ID NO: 144
Ligera Kappa imagen73
imagen74
SEQ ID NO: 145
Pesada IgG1 imagen75
MOR10703 N52S
SEQ ID NO:
Región Ab
SEQ ID NO: 146 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 147 (Kabat)
HCDR2 AISSQGKSTYYADSVKG
SEQ ID NO: 148 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 149 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 150 (Kabat)
LCDR2 GASSLQS
MOR10703 N52S
SEQ ID NO: 151 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 152 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 153 (Chothia)
HCDR2 SSQGKS
SEQ ID NO: 154 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 155 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 156 (Chothia)
LCDR2 GAS
SEQ ID NO: 157 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 158
VL imagen76
SEQ ID NO: 159
VH imagen77
SEQ ID NO: 160
DNA VL imagen78
SEQ ID NO: 161
DNA VH imagen79
SEQ ID NO: 162
Light Kappa imagen80
SEQ ID NO:
Región Ab
SEQ ID NO: 163
Heavy IgG1 imagen81
MOR10703 N52G
SEQ ID NO: 164 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 165 (Kabat)
HCDR2 AIGSQGKSTYYADSVKG
MOR10703 N52G
SEQ ID NO: 166 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 167 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 168 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 169 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 170 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 171 (Chothia)
HCDR2 GSQGKS
SEQ ID NO: 172 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 173 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 174 (Chothia)
LCDR2 GAS
SEQ ID NO: 175 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 176
VL imagen76
SEQ ID NO: 177
VH imagen82
SEQ ID NO: 178
DNA VL imagen61
SEQ ID NO:
Región Ab
SEQ ID NO: 179
DNA VH imagen83
SEQ ID NO: 180
Light Kappa imagen84
SEQ ID NO: 181
Heavy IgG1 imagen85
MOR10703 N52S_S52aN
SEQ ID NO: 182 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 183 (Kabat)
HCDR2 AISNQGKSTYYADSVKG
SEQ ID NO: 184 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 185 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 186 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 187 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 188 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 189 (Chothia)
HCDR2 SNQGKS
SEQ ID NO: 190 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 191 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 192 (Chothia)
LCDR2 GAS
SEQ ID NO: 193 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 194
VL imagen86
SEQ ID NO:
Región Ab
SEQ ID NO: 195
VH imagen87
SEQ ID NO: 196
DNA VL imagen88
SEQ ID NO: 197
DNA VH imagen89
SEQ ID NO: 198
Light Kappa imagen90
MOR10703 N52S_S52aN
SEQ ID NO: 199
Heavy IgG1 imagen91
MOR10703 A50V_N52S
SEQ ID NO: 200 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 201 (Kabat)
HCDR2 VISSQGKSTYYADSVKG
SEQ ID NO: 202 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 203 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 204 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 205 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 206 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 207 (Chothia)
HCDR2 SSQGKS
SEQ ID NO: 208 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO:
Región Ab
SEQ ID NO: 209 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 210 (Chothia)
LCDR2 GAS
SEQ ID NO: 211 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 212
VL imagen28
imagen28
SEQ ID NO: 213
VH imagen92
SEQ ID NO: 214
DNA VL imagen88
MOR10703 A50V_N52S
SEQ ID NO: 215
DNA VH imagen93
SEQ ID NO: 216
Light Kappa imagen94
SEQ ID NO: 217
Heavy IgG1 imagen95
MOR10703 A50V_N52G
SEQ ID NO: 218 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 219 (Kabat)
HCDR2 VIGSQGKSTYYADSVKG
SEQ ID NO: 220 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 221 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 222 (Kabat)
LCDR2 GASSLQS
SEQ ID NO:
Región Ab
SEQ ID NO: 223 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 224 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 225 (Chothia)
HCDR2 GSQGKS
SEQ ID NO: 226 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 227 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 228 (Chothia)
LCDR2 GAS
SEQ ID NO: 229 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 230
VL imagen96
MOR10703 A50V_N52G
SEQ ID NO: 231
VH imagen97
SEQ ID NO: 232
DNA VL imagen98
imagen99
SEQ ID NO: 233
DNA VH imagen100
SEQ ID NO: 234
Light Kappa imagen101
SEQ ID NO: 235
Heavy IgG1 imagen102
MOR10703 S52aA
SEQ ID NO: 236 (Kabat)
HCDR1 SYAMS
SEQ ID NO:
Región Ab
SEQ ID NO: 237 (Kabat)
HCDR2 AINAQGKSTYYADSVKG
SEQ ID NO: 238 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 239 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 240 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 241 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 242 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 243 (Chothia)
HCDR2 NAQGKS
SEQ ID NO: 244 (Chothia)
HCDR3 WGDEGFDI
MOR10703 S52aA
SEQ ID NO: 245 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 246 (Chothia)
LCDR2 GAS
SEQ ID NO: 247 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 248
VL imagen76
SEQ ID NO: 249
VH imagen103
SEQ ID NO: 250
DNA VL imagen67
SEQ ID NO: 251
DNA VH imagen104
SEQ ID NO: 252
Light Kappa imagen105
SEQ ID NO:
Región Ab
SEQ ID NO: 253
Heavy IgG1 imagen106
MOR10703 S52aT
SEQ ID NO: 254 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 255 (Kabat)
HCDR2 AINTQGKSTYYADSVKG
SEQ ID NO: 256 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 257 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 258 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 259 (Kabat)
LCDR3 QQYSSFPTT
MOR10703 S52aT
SEQ ID NO: 260 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 261 (Chothia)
HCDR2 NTQGKS
SEQ ID NO: 262 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 263 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 264 (Chothia)
LCDR2 GAS
SEQ ID NO: 265 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 266
VL imagen76
SEQ ID NO: 267
VH imagen107
SEQ ID NO: 268
DNA VL imagen61
SEQ ID NO:
Región Ab
SEQ ID NO: 269
DNA VH imagen108
SEQ ID NO: 270
Light Kappa imagen109
SEQ ID NO: 271
Heavy IgG1 imagen110
imagen111
MOR10701 R55S
SEQID NO: 272 (Kabat)
HCDR1 SYAMS
SEQID NO: 273 (Kabat)
HCDR2 VTGAVGSSTYYPDSVKG
MOR10701 R55S
SEQ ID NO: 274 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 275 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 276 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 277 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 278 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 279 (Chothia)
HCDR2 GAVGSS
SEQ ID NO: 280 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 281 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 282 (Chothia)
LCDR2 GAS
SEQ ID NO: 283 (Chothia)
LCDR3 YSSFPT
SEQ ID NO:
Región Ab
SEQ ID NO: 284
VL imagen112
SEQ ID NO: 285
VH imagen113
SEQ ID NO: 286
DNA VL imagen114
SEQ ID NO: 287
DNA VH imagen115
SEQ ID NO: 288
Light Kappa imagen116
SEQ ID NO: 289
Heavy IgG1 imagen117
MOR10701 R55G
SEQ ID NO: 290 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 291 (Kabat)
HCDR2 VTGAVGGSTYYPDSVKG
SEQ ID NO: 292 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 293 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 294 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 295 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 296 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 297 (Chothia)
HCDR2 GAVGGS
SEQ ID NO: 298 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO:
Región Ab
SEQ ID NO: 299 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 300 (Chothia)
LCDR2 GAS
SEQ ID NO: 301 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 302
VL imagen76
SEQ ID NO: 303
VH imagen118
SEQ ID NO: 304
DNA VL imagen119
SEQ ID NO: 305
DNA VH imagen120
SEQ ID NO: 306
Light Kappa imagen84
MOR10701 R55G
SEQ ID NO: 307
Heavy IgG1 imagen121
MOR10701 R55K
SEQ ID NO: 308 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 309 (Kabat)
HCDR2 VTGAVGKSTYYPDSVKG
SEQ ID NO: 310 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 311 (Kabat)
LCDR1 RASQGISNWLA
SEQID NO: 312 (Kabat)
LCDR2 GASSLQS
SEQ ID NO:
Región Ab
SEQ ID NO: 313 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 314 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 315 (Chothia)
HCDR2 GAVGKS
SEQ ID NO: 316 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 317 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 318 (Chothia)
LCDR2 GAS
SEQ ID NO: 319 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 320
VL imagen122
SEQ ID NO: 321
VH imagen123
SEQ ID NO: 322
DNA VL imagen61
MOR10701 R55K
SEQ ID NO: 323
DNA VH imagen124
SEQ ID NO: 324
Light Kappa imagen90
SEQ ID NO: 325
Heavy IgG1 imagen125
MOR10701 deletion S56
SEQID NO: 326 (Kabat)
HCDR1 SYAMS
SEQ ID NO:
Región Ab
SEQ ID NO: 327 (Kabat)
HCDR2 VTGAVGRTYYPDSVKG
SEQ ID NO: 328 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 329 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 330 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 331 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 332 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 333 (Chothia)
HCDR2 GAVGRT
SEQ ID NO: 334 (Chothia)
HCDR3 WGDEGFDI
SEQID NO: 335 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 336 (Chothia)
LCDR2 GAS
SEQ ID NO: 337 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 338
VL imagen86
MOR10701 deletion S56
SEQ ID NO: 339
VH imagen126
SEQ ID NO: 340
DNA VL imagen127
SEQ ID NO: 341
DNA VH imagen128
SEQ ID NO: 342
Light Kappa imagen129
SEQ ID NO:
Región Ab
SEQ ID NO: 343
Heavy IgG1 imagen130
MOR12609
SEQ ID NO: 344 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 345 (Kabat)
HCDR2 VINGLGYTTFYADSVKG
SEQ ID NO: 346 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 347 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 348 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 349 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 350 (Chothia)
HCDR1 GFTFSSY
SEQ ID NO: 351 (Chothia)
HCDR2 NGLGYT
SEQ ID NO: 352 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 353 (Chothia)
LCDR1 SQGISNW
MOR12609
SEQ ID NO: 354 (Chothia)
LCDR2 GAS
SEQ ID NO: 355 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 356
VL imagen28
imagen28
SEQ ID NO: 357
VH imagen131
SEQ ID NO: 358
DNA VL imagen132
SEQ ID NO:
Región Ab
SEQ ID NO: 359
DNA VH imagen133
SEQ ID NO: 360
Light Kappa imagen134
SEQ ID NO: 361
Heavy IgG1 imagen135
MOR12610
SEQ ID NO: 362 (Kabat)
HCDR1 SYAMS
SEQ ID NO: 363 (Kabat)
HCDR2 GTGPYGGTYYPDSVKG
SEQ ID NO: 364 (Kabat)
HCDR3 WGDEGFDI
SEQ ID NO: 365 (Kabat)
LCDR1 RASQGISNWLA
SEQ ID NO: 366 (Kabat)
LCDR2 GASSLQS
SEQ ID NO: 367 (Kabat)
LCDR3 QQYSSFPTT
SEQ ID NO: 368 (Chothia)
HCDR1 GFTFSSY
MOR12610
SEQ ID NO: 369 (Chothia)
HCDR2 GPYGG
SEQ ID NO: 370 (Chothia)
HCDR3 WGDEGFDI
SEQ ID NO: 371 (Chothia)
LCDR1 SQGISNW
SEQ ID NO: 372 (Chothia)
LCDR2 GAS
SEQ ID NO: 373 (Chothia)
LCDR3 YSSFPT
SEQ ID NO: 374
VL imagen136
SEQ ID NO:
Región Ab
SEQ ID NO: 375
VH imagen137
SEQ ID NO: 376
DNA VL imagen138
imagen139
SEQ ID NO: 377
DNA VH imagen140
SEQ ID NO: 378
Light Kappa imagen141
SEQ ID NO: 379
Heavy IgG1 imagen142
Otros anticuerpos de la divulgación incluyen aquéllos en donde los aminoácidos o ácidos nucleicos que codifican los aminoácidos se han mutado, tienen cuando menos el 60, 70, 80, 90, 95, 96, 97, 98, y 99 % de identidad con las secuencias descritas en la Tabla 1. En algunas realizaciones, incluyen secuencias de
5 aminoácidos mutantes, en donde se han mutado no más de 1, 2, 3, 4 o 5 aminoácidos en las regiones variables cuando se comparan con las regiones variables ilustradas en la secuencia descrita en la Tabla 1, mientras que conservan sustancialmente la misma actividad terapéutica.
Debido a que cada uno de estos anticuerpos o fragmentos de los mismos puede enlazarse a HER3, las secuencias VH, VL, de cadena ligera de longitud completa, y de cadena pesada de longitud completa (las 10 secuencias de aminoácidos y las secuencias de nucleótidos que codifican las secuencias de aminoácidos) se pueden "mezclar y emparejar" para crear otros anticuerpos de enlace con HER3 de la divulgación. Estos anticuerpos de enlace con HER3 "mezclados y emparejados" se pueden probar utilizando los ensayos de enlace conocidos en la materia (por ejemplo, ELISAs, y otros ensayos descritos en la sección de Ejemplos). Cuando estas cadenas se mezclan y se emparejan, una secuencia VH a partir de un emparejamiento de VH/VL particular 15 debe ser reemplazada con una secuencia VH estructuralmente similar. De la misma manera, una secuencia de cadena pesada de longitud completa a partir de un emparejamiento particular de cadena pesada de longitud completa / cadena ligera de longitud completa, debe ser reemplazada con una secuencia de cadena pesada de longitud completa estructuralmente similar. De la misma manera, una secuencia VL a partir de un emparejamiento de VH/VL particular debe ser reemplazada con una secuencia VL estructuralmente similar. De 20 la misma manera, una secuencia de cadena ligera de longitud completa a partir de un emparejamiento particular de cadena pesada de longitud completa / cadena ligera de longitud completa debe ser reemplazada con una secuencia de cadena ligera de longitud completa estructuralmente similar. De conformidad con lo anterior, en un aspecto, la divulgación proporciona un anticuerpo monoclonal aislado o un fragmento del mismo, que tiene: una región variable de cadena pesada que comprende una secuencia de aminoácidos seleccionada a partir del 25 grupo que consiste en las SEQ ID NO: 15, 33, 51, 69, 87, 105, 123, 141, 159, 177, 195, 213, 231, 249, 267, 285, 303, 321, 339, 357, y 375; y una región variable de cadena ligera, la cual comprende una secuencia de aminoácidos seleccionada a partir del grupo que consiste en las SEQ ID NOs: 14, 32, 50, 68, 86, 104, 122, 140, 158, 176, 194, 212, 230, 248, 266, 284, 302, 320, 338, 356, y 374; en donde el anticuerpo se enlaza
imagen143
imagen144
imagen145
utilizando la numeración de Kabat. Las posiciones de CDR se resaltan en negrillas. La anotación utilizada en las Tablas con las secuencias de la línea germinal es como sigue: MOR10701-VH_3-07 significa ciclos de MOR10701 CDR en las regiones de estructura de la secuencia de la línea germinal VH 3-07 (la nomenclatura es de acuerdo con Vbase), MOR10703-VK_L1 significa CDR a partir de MOR10703 en las regiones de la línea germinal de estructura a partir de VK_L1, en donde VK es la cadena ligera kappa.
Tabla 2
Versiones de la línea germinal diferentes de un número seleccionado de anticuerpos representativos
SEQ ID NO:
Nombre de secuencia Secuencia de Aminoácidos
Dominio MOR10701 VH
SEQ ID NO: 380
MOR10701-VH_3-07 imagen146
SEQ ID NO: 381
MOR10701-VH_3-09 imagen147
SEQ ID NO: 382
MOR10701-VH_3-11 imagen148
SEQ ID NO: 383
MOR10701-VH_3-13 imagen149
SEQ ID NO: 384
MOR10701-VH_3-15 imagen150
SEQ ID NO: 385
MOR10701-VH_3-20 imagen151
SEQ ID NO: 386
MOR10701-VH_3-21 imagen152
SEQ ID NO: 387
MOR10701-VH_3-23 imagen153
SEQ ID NO: 388
MOR10701-VH_3-30 imagen154
SEQ ID NO: 389
MOR10701-VH_3-30.3 imagen155
SEQ ID NO: 390
MOR10701-VH_3-30.5 imagen154
Dominio MOR10701 VH
SEQ ID NO: 391
MOR10701-VH_3-33 imagen156
SEQ ID NO: 392
MOR10701-VH_3-43 imagen157
SEQ ID NO: 393
MOR10701-VH_3-48 imagen158
SEQ ID NO: 394
MOR10701-VH_3-49 imagen159
SEQ ID NO: 395
MOR10701-VH_3-53 imagen160
SEQ ID NO: 396
MOR10701-VH_3-64 imagen161
SEQ ID NO:
Nombre de secuencia Secuencia de Aminoácidos
SEQ ID NO: 397
MOR10701-VH_3-66 imagen162
SEQ ID NO: 398
MOR10701-VH_3-72 imagen163
SEQ ID NO: 399
MOR10701-VH_3-73 imagen164
SEQ ID NO: 400
MOR10701-VH_3-74 imagen165
SEQ ID NO: 401
MOR10701-VH_3-d imagen166
Dominio MOR10703 VH
SEQ ID NO: 402
MOR10703-VH_3-07 imagen167
SEQ ID NO: 403
MOR10703-VH_3-09 imagen168
SEQID NO: 404
MOR10703-VH_3-11 imagen169
SEQ ID NO: 405
MOR10703-VH_3-13 imagen170
SEQ ID NO: 406
MOR10703-VH_3-15 imagen171
SEQ ID NO: 407
MOR10703-VH_3-20 imagen172
SEQ ID NO: 408
MOR10703-VH_3-21 imagen173
SEQ ID NO: 409
MOR10703-VH_3-23 imagen174
SEQ ID NO: 410
MOR10703-VH_3-30 imagen175
Dominio MOR10703 VH
SEQ ID NO: 411
MOR10703-VH_3-30.3 imagen176
SEQ ID NO: 412
MOR10703-VH_3-30.5 imagen177
SEQ ID NO: 413
MOR10703-VH_3-33 imagen176
SEQ ID NO: 414
MOR10703-VH_3-43 imagen178
SEQ ID NO: 415
MOR10703-VH_3-48 imagen179
SEQ ID NO: 416
MOR10703-VH_3-49 imagen180
SEQ ID NO: 417
MOR10703-VH_3-53 imagen181
SEQ ID NO:
Nombre de secuencia Secuencia de Aminoácidos
SEQ ID NO: 418
MOR10703-VH_3-64 imagen182
SEQ ID NO: 419
MOR10703-VH_3-66 imagen183
SEQ ID NO: 420
MOR10703-VH_3-72 imagen184
SEQID NO: 421
MOR10703-VH_3-73 imagen185
SEQ ID NO: 422
MOR10703-VH_3-74 imagen186
SEQ ID NO: 423
MOR10703-VH_3-d imagen187
Dominio MOR10701 VK
SEQ ID NO: 424
MOR10701-VKI_012 (same as MOR10701 wt) imagen188
SEQ ID NO: 425
MOR10701-VKI_O2 imagen189
SEQ ID NO: 426
MOR10701-VKI_O18 imagen190
SEQ ID NO: 427
MOR10701-VKI_O8 imagen191
SEQ ID NO: 428
MOR10701-VKI_A20 imagen192
SEQ ID NO: 429
MOR10701-VKI_A30 imagen193
SEQ ID NO: 430
MOR10701-VKI_L14 imagen194
SEQ ID NO: 431
MOR10701-VKI_L1 imagen195
Dominio MOR10703 VH
SEQ ID NO: 432
MOR10701-VKI_L15 imagen196
SEQ ID NO: 433
MOR10701-VKI_L4 imagen197
SEQ ID NO: 434
MOR10701-VKI_L18 imagen198
SEQ ID NO: 435
MOR10701-VKI_L5 imagen199
SEQ ID NO: 436
MOR10701-VKI_L19 imagen199
SEQ ID NO: 437
MOR10701-VKI_L8 imagen200
SEQ ID NO: 438
MOR10701-VKI_L23 imagen201
SEQ ID NO:
Nombre de secuencia Secuencia de Aminoácidos
SEQ ID NO: 439
MOR10701-VKI_L9 imagen202
SEQ ID NO: 440
MOR10701-VKI_L24 imagen203
SEQ ID NO: 441
MOR10701-VKI_L11 imagen204
SEQ ID NO: 442
MOR10701-VKI_L12 imagen205
Dominio MOR10701 VK
SEQ ID NO: 443
MOR10703-VKI_O12 (same as MOR10703 wt) imagen206
SEQ ID NO: 444
MOR10703-VKI_O2 imagen189
SEQ ID NO: 445
MOR10703-VKI_O18 imagen190
SEQ ID NO: 446
MOR10703-VKI_O8 imagen191
SEQ ID NO: 447
MOR10703-VKI_A20 imagen207
SEQ ID NO: 448
MOR10703-VKI_A30 imagen208
SEQ ID NO: 449
MOR10703-VKI_L14 imagen209
SEQ ID NO: 450
MOR10703-VKI_L1 imagen195
SEQ ID NO: 451
MOR10703-VKI_L15 imagen210
SEQ ID NO: 452
MOR10703-VKI_L4 imagen197
Dominio MOR10701 VK
SEQ ID NO: 453
MOR10703-VKI_L18 imagen198
SEQ ID NO: 454
MOR10703-VKI_L5 imagen211
SEQ ID NO: 455
MOR10703-VKI_L19 imagen212
SEQ ID NO: 456
MOR10703-VKI_L8 imagen213
SEQ ID NO: 457
MOR10703-VKI_L23 imagen201
SEQ ID NO: 458
MOR10703-VKI_L9 imagen214
SEQ ID NO: 459
MOR10703-VKI_L24 imagen215
imagen216
SEQ 477
ID NO: MOR10701-VKI_02_JK1 imagen28
SEQ 478
ID NO: MOR10701-VKI_02_JK4 imagen28
SEQ 479
ID NO: MOR10703-VKI_A20_JK4 imagen28
SEQ 480
ID NO: MOR10703-VKI_A20_JK1 imagen28
Una vez que la VH se ha combinado con JH y la VK con JK, entonces se puede utilizar cualquier combinación de VH o JH con VK o JK. En una realización, cualquiera de las regiones de la línea germinal VH se puede combinar con cualquiera de las regiones de la línea germinal VK (VL) para cada anticuerpo. Un número representativo de los ejemplos de combinaciones se muestra en la Tabla 7.
Tabla 7: Ejemplos representativos de las combinaciones de las secuencias de la línea germinal
Combination 1
SEQ 481
ID NO: MOR10701-VH 3-15_JH3 imagen217
SEQ 482
ID NO: MOR10701-VKI_A30_JK4 imagen218
Combination 2
SEQ 483
ID NO: MOR10701-VH_3-30_JH1 imagen219
SEQ 484
ID NO: MOR10701-VKI_L1_JK2 imagen220
Combination 3
SEQ 485
ID NO: MOR10701-VH_3-30_JH2 imagen221
SEQ 486
ID NO: MOR10701-VKI_L1_JK2 imagen222
Combination 4
SEQ 487
ID NO: MOR10703-VH_3-20_JH5 imagen223
SEQ 488
ID NO: MOR10703-VKI_L15_JK3 imagen224
Combination 5
SEQ 489
ID NO: MOR10703-VH_3-33_JH2 imagen225
SEQ 490
ID NO: MOR10703-VKI_A20_JK1 imagen226
Combination 6
SEQ 491
ID NO: MOR10703-VH_3-33_JH3 imagen227
SEQ 492
ID NO: MOR10703-VKI_A20_JK2 imagen228
En una realización, la divulgación pertenece a una región variable de cadena pesada, la cual comprende una
61
imagen229
imagen230
imagen231
imagen232
imagen233
imagen234
imagen235
imagen236
imagen237
imagen238
imagen239
imagen240
imagen241
imagen242
imagen243
imagen244
imagen245
imagen246
imagen247
imagen248
imagen249
imagen250
imagen251
imagen252
imagen253
imagen254
imagen255
imagen256
imagen257
imagen258
imagen259
imagen260
Tabla 8
Generación de vectores de expresión de HER3. La numeración de aminoácidos de HER3 se basa en NP_001973 (humana), NP_034283 (ratón), y NP_058914 (rata).
Nombre
Descripción
Hu HER3
CD33-[HER3 humano, residuos 20-640]-TAG
Mu HER3
CD33-[HER3 de murino, residuos 20-643]-TAG
Rata HER3
CD33-[HER3 de rata, residuos 20-643]-TAG
Cino HER3
CD33-[HER3 de cinomolgo, residuos 20-643]-TAG
HER3 D1-2
CD33-[HER3 humano, residuos 20-329]-TAG
HER3 D2
CD33-[HER3 humano, residuos 185-329]-TAG
HER3 D3-4
CD33-[HER3 humano, residuos 330-643]-TAG
HER3 D4
CD33-[HER3 humano, residuos 496-643]-TAG
Hu HER3-Fc
[HER3 humano, residuos 1-643]-Fc
Mu HER3-Fc
[HER3 de murino, residuos 1-643]-Fc
Cino HER3 Fc
[HER3 de cinomolgo, residuos 1-643]-Fc
Rata HER3-Fc
[HER3 de rata, residuos 1-643]-Fc
HER3 D2-Fc
[HER3 humano, residuos 207-329]-Fc
imagen261
imagen262
imagen263
imagen264
imagen265
imagen266
imagen267
imagen268
imagen269
imagen270
imagen271
TABLA 9
Valores de KD de IgGs anti-HER3 según se determina mediante titulación en equilibrio en solución (SET). Hu ( humano), Cy ( Cinomolgo), Mu ( múrido) y ra (rata)
MOR#
SET KD (pM)
hu HER3-Marca
cy HER3-Marca mu HER3-Marca ra HER3-Marca
09823
9 4 2 11
09824
3 3 2 7
09825
25 56 24 96
09974
350 200 120 n.d.
10701
4 4 6 10
10702
3 3 5 6
10703
26 23 20 40
12609
10 n.d n.d n.d
12610
37 n.d n.d n.d
10703 N52S
57 n.d n.d n.d
10703 N52G
60 n.d n.d n.d
10703_A50V_N52S
16 n.d n.d n.d
10703_A50V_N52G
22 n.d n.d n.d
10701 R55G
18 n.d n.d n.d
10701 R55K
11 n.d n.d n.d
5 (ii) Determinación de CE50 en célula SK-Br-3
La capacidad de los anticuerpos identificados para unirse a células que expresan HER3 se determina calculando los valores de CE50 para su unión a la línea de célula amplificada con HER2, SK-Br-3 (véase Figura 2 y Tabla 10).
TABLA 10
10 Valores de CE50 de FACS de IgG anti-HER3 en células SK-Br-3. n.d. (no determinado)
MOR#
SK-Br-3 FACS CE50 (pM)
09823
630
09824
324
09825
839
09974
n.d.
10701
n.d.
imagen272
imagen273
Pro
276 2
Tyr
32 VH Pro 276 2
His
277 2
Ala
33 VH Asn 266 2
Leu
268 2
Ser
35 VH Leu 268 2
Val
50 VH Leu 268 2
Thr
269 2
Gly
52 VH Glu 273 2
Thr
269 2
Ala
53 VH Glu 273 2
Pro
274 2
Val
54 VH Glu 273 2
Tyr
58 VH Pro 583 4
Asp
571 4
His
584 4
Thr
269 2
Gln
271 2
Asn
73 VH Asn 315 2
Ser
74 VH Asn 315 2
Trp
98 VH Leu 268 2
Lys
267 2
Asn
266 2
Asp
100 VH Ala 596 4
Lys
597 4
Pro
276 2
His
277 2
Glu
101 VH Lys 267 2
Lys
597 4
Phe
103 VH Leu 268 2

TABLA 12: Interacciones entre la cadena ligera de Fab de MOR09823 y HER3 de humano. Los residuos de VL de Fab se numeran tomando como base su secuencia de aminoácido lineal (SEQ ID NO: 14). Los residuos de HER3 se numeran tomando como base NP_001973. Los residuos de HER3 mostrados tienen por lo menos un átomo dentro de 5Å de un átomo en el Fab de MOR09823.
MOR09823 Fab
HER3 de humano
Residuo
Número Cadena Residuo Número Dominio
Gln
27 VL Arg 611 4
Glu
609 4
Gly
28 VL Arg 611 4
Pro
612 4
Ile
29 VL Pro 612 4
Ser
30 VL Pro 612 4
Cys
613 4
His
614 4
Glu
615 4
Asn
31 VL Glu 615 4
Cys
613 4
Trp
32 VL Lys 267 2
Tyr
265 2
Pro
612 4
Cys
613 4
Ile
600 4
Lys
602 4
Tyr
49 VL Lys 597 4
Gly
66 VL Glu 615 4
Ser
67 VL His 614 4
Glu
615 4
Gln
89 VL Leu 268 2
Tyr
91 VL Lys 267 2
Leu
268 2
Phe
270 2
Ser
92 VL Phe 270 2
Lys
602 4
Pro
612 4
Ser
93 VL Phe 270 2
Glu
609 4
Phe
94 VL Phe 270 2
Leu
268 2
Gly
582 4
Pro
583 4
Thr
96 VL Leu 268 2

TABLA 13: Interacciones entre la cadena pesada de Fab de MOR09825 y HER3 de humano. Los residuos de VH de Fab se numeran tomando como base su secuencia de aminoácido lineal (SEQ ID NO: 51). Los residuos de HER3 se numeran tomando como base NP_001973. Los residuos de HER3 mostrados tienen por lo menos un átomo dentro de 5Å de un átomo en el Fab de MOR09825.
MOR09825 Fab
HER3 de humano
Residuo
Número Cadena Residuo Número Dominio
Ser
30 VH Asn 315 2
Ser
31 VH Pro 274 2
Pro
276 2
Tyr
32 VH Pro 276 2
His
277 2
Ala
33 VH Asn 266 2
Thr
269 2
Ser
35 VH Leu 268 2
Trp
47 VH Leu 268 2
Ala
50 VH Leu 268 2
Asn
52 VH Glu 273 2
Gln
271 2
Thr
269 2
Ser
53 VH Glu 273 2
Pro
274 2
Gln
54 VH Glu 273 2
Pro
274 2
Ser
57 VH Gln 271 2
Tyr
59 VH Pro 583 4
Asp
571 4
His
584 4
Thr
269 2
Gln
271 2
Asn
74 VH Asn 315 2
Trp
99 VH Leu 268 2
Lys
267 2
Asn
266 2
Asp
101 VH Ala 596 4
Lys
597 4
Pro
276 2
His
277 2
Glu
102 VH Lys 267 2
Lys
597 4
Phe
104 VH Leu 268 2
TABLA 14: Interacciones entre la cadena ligera de Fab de MOR09825 y HER3 de humano. Los residuos de VL de Fab se numeran tomando como base su secuencia de aminoácido lineal (SEQ ID NO: 50). Los residuos de HER3 se numeran tomando como base NP_001973. Los residuos de HER3 mostrados tienen por lo menos un átomo dentro de 5Å de un átomo en el Fab de MOR09825.
MOR09825 Fab
HER3 de humano
Residuo
Número Cadena Residuo Número Dominio
Gln
27 VL Arg 611 4
Gly
28 VL Arg 611 4
Pro
612 4
Ile
29 VL Pro 612 4
Ser
30 VL Pro 612 4
Cys
613 4
His
614 4
Glu
615 4
Asn
31 VL Glu 615 4
His
614 4
Cys
613 4
Trp
32 VL Lys 267 2
Tyr
265 2
Pro
612 4
Cys
613 4
Ile
600 4
Lys
602 4
Tyr
49 VL Lys 597 4
Gly
66 VL Glu 615 4
Ser
67 VL His 614 4
Glu
615 4
Gln
89 VL Leu 268 2
Tyr
91 VL Lys 267 2
Leu
268 2
Phe
270 2
Ser
92 VL Phe 270 2
Lys
602 4
Pro
612 4
Arg
611 4
Ser
93 VL Phe 270 2
Glu
609 4
Phe
94 VL Phe 270 2
Gly
582 4
Pro
583 4
Thr
96 VL Leu 268 2
La inspección visual de las estructuras de cristal de MOR09823/MOR09825 resalta que los residuos Lys267 y Leu268 de HER3 forman interacciones múltiples con varias CDRs del anticuerpo lo que sugiere que éstos pueden ser importantes para la unión del anticuerpo. Por consiguiente, Lys267 y/o Leu268 se mutan a alanina,
5 expresan y las proteínas recombinantes resultantes se purifican con el fin de evaluar su impacto sobre la unión del anticuerpo. Las pruebas de unión ELISA indican que la mutación de cualquiera de Lys267 o Leu268 elimina la unión de MOR10703 a HER3 (Figura 5F) lo que sugiere que ambos residuos son una parte integral del epítopo de HER3 y por lo tanto apoyan las interacciones propuestas entre MOR09823/MOR09825 y HER3.
(viii) Inhibición de la señalización celular
10 Para determinar el efecto de los anticuerpos anti-HER3 sobre la actividad de HER3 dependiente del ligando se incuban células MCF7 con IgG antes de la estimulación con neuregulina. Las curvas de inhibición de ejemplo se ilustran en la Figura 6A y se presentan en forma resumida en la Tabla 15. También se estudia el efecto de los anticuerpos anti-HER3 sobre la activación de HER3 mediada por HER2 utilizando la línea celular SK-Br-3 amplificada con HER2 (Figura 6B y Tabla 15).
TABLA 15
CI50 de pHER3 y valores del grado de inhibición de IgG anti-HER3 en células MCF7, y SK-Br-3
MOR#
MCF7 pHER3 SK-Br-3 pHER3
CI50 (pM)
% de inhibición CI50 (pM) % de inhibición
09823
181 89 56 59
09824
103 91 110 64
09825
399 80 169 66
09974
3066 69 1928 67
10701
n.d. n.d. 370 74
10702
n.d. n.d. n.d. n.d.
10703
333 80 167 69
12609
5 86 241 71
12610
126 84 192 75
Para determinar si la inhibición de la actividad de HER3 impacta Akt de señalización celular corriente abajo, también se mide la fosforilación en células amplificadas con HER2 después del tratamiento con anticuerpos 10 anti-HER3 (véase Figura 7 y Tabla 16).
TABLA 16
CI50 de pAkt (S473) y valores del grado de inhibición de IgG anti-HER3 en células SK-Br-3 BT-474 y MCF7
MOR#
SK-Br-3 pAkt BT-474 pAkt MCF7 pAkt
CI50 (pM)
% de inhibición % de inhibición CI50 (pM) % de inhibición
09823
55 92 57 n.d. n.d.
09824
62 93 46 n.d. n.d.
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Families Citing this family (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PH12012501157A1 (en) 2009-12-22 2012-10-29 Roche Glycart Ag Anti-her3 antibodies and uses thereof
ME02637B (me) * 2010-08-20 2017-06-20 Novartis Ag Antitela za receptor 3 faktora rasta epiderma (her3)
WO2012059857A2 (en) 2010-11-01 2012-05-10 Symphogen A/S Pan-her antibody composition
ITRM20100577A1 (it) * 2010-11-02 2012-05-03 Takis Srl Immunoterapia contro il recettore erbb-3
MX336197B (es) * 2011-04-19 2016-01-11 Merrimack Pharmaceuticals Inc Anicuerpos anti-igf-1r y anti-erbb3 monoespecificos y biespecificos.
WO2012176779A1 (ja) * 2011-06-20 2012-12-27 協和発酵キリン株式会社 抗ｅｒｂＢ３抗体
US9273143B2 (en) 2011-09-30 2016-03-01 Regeneron Pharmaceuticals, Inc. Methods and compositions comprising a combination of an anti-ErbB3 antibody and an anti-EGFR antibody
WO2013048883A2 (en) 2011-09-30 2013-04-04 Regeneron Pharmaceuticals, Inc. Anti-erbb3 antibodies and uses thereof
GB2504139B (en) * 2012-07-20 2014-12-31 Argen X Bv Antibodies to highly conserved targets produced by the immunisation of Camelidae species
WO2013071058A1 (en) * 2011-11-09 2013-05-16 The Uab Research Foundation Her3 antibodies and uses thereof
CN108424456B (zh) 2011-11-23 2022-04-26 医学免疫有限责任公司 特异于her3的结合分子及其用途
EP2788382A2 (en) * 2011-12-05 2014-10-15 Novartis AG Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3
CN108341873B (zh) * 2011-12-05 2022-03-25 诺华股份有限公司 表皮生长因子受体3(her3)的抗体
US20150037336A1 (en) * 2012-02-22 2015-02-05 U3 Pharma Gmbh Combination of hb-egf binding protein and egfr inhibitor
WO2014018747A2 (en) 2012-07-26 2014-01-30 Momenta Pharmaceuticals, Inc. Glycoproteins with anti-inflammatory properties
ES2870004T3 (es) * 2012-08-21 2021-10-26 Janssen Pharmaceutica Nv Anticuerpos contra la risperidona y uso de los mismos
JP2015534997A (ja) * 2012-10-25 2015-12-07 ソレント・セラピューティクス・インコーポレイテッドＳｏｒｒｅｎｔｏ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． ＥｒｂＢ３と結合する抗原結合タンパク質
CN104755500B (zh) 2012-11-08 2020-10-02 霍夫曼-拉罗奇有限公司 结合HER3 β-发夹的HER3抗原结合蛋白
CN104755499B (zh) * 2012-11-08 2020-10-02 霍夫曼-拉罗奇有限公司 结合HER3 β-发夹和HER4 β-发夹的抗HER3/HER4抗原结合蛋白
CN102993305B (zh) * 2012-11-16 2015-05-13 上海赛伦生物技术有限公司 人源抗人表皮生长因子受体抗体及其编码基因与应用
AR094403A1 (es) 2013-01-11 2015-07-29 Hoffmann La Roche Terapia de combinación de anticuerpos anti-her3
US20160228589A1 (en) * 2013-09-18 2016-08-11 Sloan-Kettering Institute For Cancer Research Methods and compositions for imaging disorders using polyspecific agents
US11305012B2 (en) 2013-09-24 2022-04-19 Medimmune, Llc Binding molecules specific for HER3 and uses thereof
EP3049442A4 (en) 2013-09-26 2017-06-28 Costim Pharmaceuticals Inc. Methods for treating hematologic cancers
WO2015066543A1 (en) * 2013-11-01 2015-05-07 Board Of Regents, The University Of Texas System Targeting her2 and her3 with bispecific antibodies in cancerous cells
UA122479C2 (uk) 2014-01-24 2020-11-25 Дана-Фарбер Кенсер Інстітьют, Інк. Виділена молекула антитіла, яка зв’язується з людським білком програмованої смерті-1 (pd-1)
PL3099717T3 (pl) 2014-01-31 2019-10-31 Novartis Ag Cząsteczki przeciwciała dla TIM-3 i ich zastosowanie
DK3805268T3 (da) 2014-02-28 2025-01-20 Merus Nv Antistof, der binder erbb-2 og erbb-3
CA2941030C (en) 2014-02-28 2025-05-13 Merus N.V. ANTIBODIES THAT BIND TO EGFR AND ERBB3
EA201691765A1 (ru) 2014-03-14 2016-12-30 Новартис Аг Молекулы антител против lag-3 и их применения
US10745490B2 (en) 2014-04-11 2020-08-18 Celldex Therapeutics, Inc. Anti-ErbB antibodies and methods of use thereof
FR3020063A1 (fr) 2014-04-16 2015-10-23 Gamamabs Pharma Anticorps humain anti-her4
JP6695812B2 (ja) * 2014-05-14 2020-05-20 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト Ｈｅｒ３のベータヘアピン及びｈｅｒ２のドメインｉｉに結合するｈｅｒ３／ｈｅｒ２二重特異性抗体
KR20160144465A (ko) * 2014-05-14 2016-12-16 에프. 호프만-라 로슈 아게 Her3의 베타-헤어핀에 결합하는 항-her3 항체
US20170291956A1 (en) 2014-07-16 2017-10-12 David Livingston HER3 Inhibition in Low-grade Serous Ovarian Cancers
CN105367657B (zh) * 2014-08-14 2019-09-13 上海生物制品研究所有限责任公司 抗her3抗体、其制法及其应用
EP3191126B1 (en) 2014-09-13 2020-05-13 Novartis AG Combination therapies of alk inhibitors
KR20170066546A (ko) 2014-10-03 2017-06-14 노파르티스 아게 조합 요법
MA41044A (fr) 2014-10-08 2017-08-15 Novartis Ag Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer
SG11201702401RA (en) 2014-10-14 2017-04-27 Novartis Ag Antibody molecules to pd-l1 and uses thereof
EP3229803B1 (en) * 2014-12-12 2020-01-29 Massachusetts General Hospital Treatment of breast cancer brain metastases
TWI706958B (zh) 2015-03-10 2020-10-11 美商艾杜諾生物科技公司 活化「干擾素基因刺激因子」依賴性訊息傳導之組合物及方法
JP2018524373A (ja) * 2015-07-15 2018-08-30 ザイムワークス，インコーポレイテッド 薬物がコンジュゲートされた二重特異性抗原結合コンストラクト
TW201716439A (zh) 2015-07-20 2017-05-16 美國禮來大藥廠 Ｈｅｒ３抗體
US20180207273A1 (en) 2015-07-29 2018-07-26 Novartis Ag Combination therapies comprising antibody molecules to tim-3
EP3328418A1 (en) 2015-07-29 2018-06-06 Novartis AG Combination therapies comprising antibody molecules to pd-1
US20180340025A1 (en) 2015-07-29 2018-11-29 Novartis Ag Combination therapies comprising antibody molecules to lag-3
EP3334762A1 (en) 2015-08-14 2018-06-20 Allergan, Inc. Heavy chain only antibodies to pdgf
JP7296728B2 (ja) 2015-10-23 2023-06-23 メルス ナムローゼ フェンノートシャップ 癌の成長を抑制する結合分子
PT3370768T (pt) 2015-11-03 2022-04-21 Janssen Biotech Inc Anticorpos que se ligam especificamente ao pd-1 e seus usos
JP6629581B2 (ja) * 2015-11-30 2020-01-15 サントリーホールディングス株式会社 ヒドロキシチロソール含有茶飲料
US10689458B2 (en) 2015-11-30 2020-06-23 Pfizer Inc. Site specific HER2 antibody drug conjugates
KR101746152B1 (ko) * 2015-12-07 2017-06-13 주식회사 이수앱지스 ＥｒｂＢ3에 특이적으로 결합하는 항체 및 그의 용도
MA43416A (fr) 2015-12-11 2018-10-17 Regeneron Pharma Méthodes pour ralentir ou empêcher la croissance de tumeurs résistantes au blocage de l'egfr et/ou d'erbb3
CN108495651A (zh) 2015-12-17 2018-09-04 诺华股份有限公司 抗pd-1的抗体分子及其用途
WO2017160990A1 (en) 2016-03-15 2017-09-21 Merrimack Pharmaceuticals, Inc. Methods for treating er+, her2-, hrg+ breast cancer using combination therapies comprising an anti-erbb3 antibody
EP3507367A4 (en) 2016-07-05 2020-03-25 Aduro BioTech, Inc. CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF
US12667557B2 (en) 2017-02-28 2026-06-30 Daiichi Sankyo Company, Limited Method for treating EGFR-TKI-resistant non-small cell lung cancer by administration of anti-HER3 antibody-drug conjugate
JP7737220B2 (ja) 2017-03-31 2025-09-10 メルス ナムローゼ フェンノートシャップ ＮＲＧ１融合遺伝子を有する細胞の処置における使用のためのＥｒｂＢ－２及びＥｒｂＢ３結合二重特異性抗体
MX2019011658A (es) 2017-03-31 2019-11-18 Merus Nv Agente que se dirige al receptor 2 del factor de crecimiento epidermico humano (erbb-2) y anticuerpo biespecifico con sitios de union a antigeno que se unen a un epitopo sobre una parte extracelular de erbb-2 y el receptor 3 del factor de crecimiento epidermico humano (erbb-3), para el tratamiento de un individuo con un tumor positivo para erbb-2, erbb-2/erbb-3.
UY37695A (es) 2017-04-28 2018-11-30 Novartis Ag Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo
EP3625264B9 (en) 2017-05-17 2023-10-25 Merus N.V. Combination of an erbb-2/erbb-3 bispecific antibody with endocrine therapy for breast cancer
US20200172628A1 (en) 2017-06-22 2020-06-04 Novartis Ag Antibody molecules to cd73 and uses thereof
RS66708B9 (sr) 2017-08-09 2025-08-29 Merus Nv Antitela koja se vezuju za egfr i cmet
TWI808092B (zh) 2017-08-30 2023-07-11 中國大陸商北京軒義醫藥科技有限公司 作為干擾素基因調節劑之刺激劑的環狀二核苷酸
MX2020004531A (es) 2017-11-03 2020-08-03 Aurigene Discovery Tech Ltd Inhibidores dobles de tim-3 y las vias de pd-1.
EP3706798A1 (en) 2017-11-06 2020-09-16 Aurigene Discovery Technologies Limited Conjoint therapies for immunomodulation
US12398209B2 (en) 2018-01-22 2025-08-26 Janssen Biotech, Inc. Methods of treating cancers with antagonistic anti-PD-1 antibodies
EP3768259A4 (en) 2018-03-14 2022-04-06 Aurigene Discovery Technologies Limited METHODS OF MODULATION OF TIGIT AND PD-1 SIGNALING PATHWAYS USING 1,2,4-OXADIAZOLE COMPOUNDS
WO2019185164A1 (en) * 2018-03-29 2019-10-03 Hummingbird Bioscience Holdings Pte. Ltd. Her3 antigen-binding molecules
UY38247A (es) 2018-05-30 2019-12-31 Novartis Ag Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación
CA3112043A1 (en) 2018-09-10 2020-03-19 Mirati Therapeutics, Inc. Combination therapies
WO2020059772A1 (ja) 2018-09-20 2020-03-26 第一三共株式会社 抗ｈｅｒ３抗体－薬物コンジュゲート投与によるｈｅｒ３変異がんの治療
CN110760003A (zh) * 2019-09-10 2020-02-07 广东药科大学 一种抗her3单链抗体的制备方法
JP2022548881A (ja) 2019-09-18 2022-11-22 ノバルティス アーゲー Ｅｎｔｐｄ２抗体、組合せ療法並びに抗体及び組合せ療法を使用する方法
KR20230012560A (ko) * 2020-05-19 2023-01-26 모멘타 파머슈티컬스 인코포레이티드 과시알화된 IgG의 제조 및 정제
EP4355787A4 (en) * 2021-06-15 2025-04-30 Beijing Sinotau Bio-Pharmaceuticals Technology Co., Ltd. Anti-her3 antibody, antibody drug conjugate containing the same, and use thereof
CN113788895B (zh) * 2021-10-14 2023-09-15 陕西健吉跃生物科技有限公司 一种兔多克隆抗体及其制备方法和应用
JPWO2024248123A1 (es) 2023-06-02 2024-12-05

Family Cites Families (185)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
EP0092918B1 (en) 1982-04-22 1988-10-19 Imperial Chemical Industries Plc Continuous release formulations
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
CA1247080A (en) 1983-03-08 1988-12-20 Commonwealth Serum Laboratories Commission Antigenically active amino acid sequences
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
DE3572982D1 (en) 1984-03-06 1989-10-19 Takeda Chemical Industries Ltd Chemically modified lymphokine and production thereof
US5128326A (en) 1984-12-06 1992-07-07 Biomatrix, Inc. Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same
US5374548A (en) 1986-05-02 1994-12-20 Genentech, Inc. Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor
MX9203291A (es) 1985-06-26 1992-08-01 Liposome Co Inc Metodo para acoplamiento de liposomas.
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US5260203A (en) 1986-09-02 1993-11-09 Enzon, Inc. Single polypeptide chain binding molecules
US4881175A (en) 1986-09-02 1989-11-14 Genex Corporation Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
JP3101690B2 (ja) 1987-03-18 2000-10-23 エス・ビィ・２・インコーポレイテッド 変性抗体の、または変性抗体に関する改良
US5013653A (en) 1987-03-20 1991-05-07 Creative Biomolecules, Inc. Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage
JPH02500329A (ja) 1987-05-21 1990-02-08 クリエイテイブ・バイオマリキユールズ・インコーポレーテツド ターゲット化多機能蛋白質
US5091513A (en) 1987-05-21 1992-02-25 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
US5258498A (en) 1987-05-21 1993-11-02 Creative Biomolecules, Inc. Polypeptide linkers for production of biosynthetic proteins
US5132405A (en) 1987-05-21 1992-07-21 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
US4880078A (en) 1987-06-29 1989-11-14 Honda Giken Kogyo Kabushiki Kaisha Exhaust muffler
US5677425A (en) 1987-09-04 1997-10-14 Celltech Therapeutics Limited Recombinant antibody
US5336603A (en) 1987-10-02 1994-08-09 Genentech, Inc. CD4 adheson variants
US5476996A (en) 1988-06-14 1995-12-19 Lidak Pharmaceuticals Human immune system in non-human animal
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
KR900005995A (ko) 1988-10-31 1990-05-07 우메모또 요시마사 변형 인터류킨-2 및 그의 제조방법
FI903489A7 (fi) 1988-11-11 1990-07-10 Medical Res Council Yhden osan sisältävät ligandit, näitä ligandeja sisältävät reseptorit, menetelmiä niiden valmistamiseksi sekä ligandien ja reseptorien käytt ö
EP0401384B1 (en) 1988-12-22 1996-03-13 Kirin-Amgen, Inc. Chemically modified granulocyte colony stimulating factor
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
ATE92107T1 (de) 1989-04-29 1993-08-15 Delta Biotechnology Ltd N-terminale fragmente von menschliches serumalbumin enthaltenden fusionsproteinen.
US6291158B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertoire
US5112946A (en) 1989-07-06 1992-05-12 Repligen Corporation Modified pf4 compositions and methods of use
FR2650598B1 (fr) 1989-08-03 1994-06-03 Rhone Poulenc Sante Derives de l'albumine a fonction therapeutique
AU6430190A (en) 1989-10-10 1991-05-16 Pitman-Moore, Inc. Sustained release composition for macromolecular proteins
WO1991006570A1 (en) 1989-10-25 1991-05-16 The University Of Melbourne HYBRID Fc RECEPTOR MOLECULES
CA2071867A1 (en) 1989-11-06 1991-05-07 Edith Mathiowitz Method for producing protein microspheres
US5183884A (en) 1989-12-01 1993-02-02 United States Of America Dna segment encoding a gene for a receptor related to the epidermal growth factor receptor
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP1690935A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
US5349053A (en) 1990-06-01 1994-09-20 Protein Design Labs, Inc. Chimeric ligand/immunoglobulin molecules and their uses
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
ES2246502T3 (es) 1990-08-29 2006-02-16 Genpharm International, Inc. Animales no humanos transgenicos capaces de producir anticuerpos heterologos.
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ATE145428T1 (de) 1990-12-14 1996-12-15 Cell Genesys Inc Chimärische ketten zur transduktion von rezeptorverbundenen signalwegen
JPH06507404A (ja) 1991-05-01 1994-08-25 ヘンリー　エム．ジャクソン　ファウンデイション　フォー　ザ　アドバンスメント　オブ　ミリタリー　メディスン 感染性の呼吸性疾患の治療方法
PT1024191E (pt) 1991-12-02 2008-12-22 Medical Res Council Produção de auto-anticorpos a partir de reportórios de segmentos de anticorpo e exibidos em fagos
DE69233408T2 (de) 1991-12-02 2005-09-22 Cambridge Antibody Technology Ltd., Melbourn Herstellung von Antikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken.
JPH07503132A (ja) 1991-12-17 1995-04-06 ジェンファーム　インターナショナル，インコーポレイティド 異種抗体を産生することができるトランスジェニック非ヒト動物
US5622929A (en) 1992-01-23 1997-04-22 Bristol-Myers Squibb Company Thioether conjugates
FR2686901A1 (fr) 1992-01-31 1993-08-06 Rhone Poulenc Rorer Sa Nouveaux polypeptides antithrombotiques, leur preparation et compositions pharmaceutiques les contenant.
FR2686899B1 (fr) 1992-01-31 1995-09-01 Rhone Poulenc Rorer Sa Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant.
US5714350A (en) 1992-03-09 1998-02-03 Protein Design Labs, Inc. Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region
US5912015A (en) 1992-03-12 1999-06-15 Alkermes Controlled Therapeutics, Inc. Modulated release from biocompatible polymers
US5447851B1 (en) 1992-04-02 1999-07-06 Univ Texas System Board Of Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells
AU4116793A (en) 1992-04-24 1993-11-29 Board Of Regents, The University Of Texas System Recombinant production of immunoglobulin-like domains in prokaryotic cells
DE69334275D1 (de) 1992-08-21 2009-05-20 Univ Bruxelles Immunoglobuline ohne Leichtkette
US6765087B1 (en) 1992-08-21 2004-07-20 Vrije Universiteit Brussel Immunoglobulins devoid of light chains
US5958708A (en) 1992-09-25 1999-09-28 Novartis Corporation Reshaped monoclonal antibodies against an immunoglobulin isotype
CA2103323A1 (en) 1992-11-24 1994-05-25 Gregory D. Plowman Her4 human receptor tyrosine kinase
US5934272A (en) 1993-01-29 1999-08-10 Aradigm Corporation Device and method of creating aerosolized mist of respiratory drug
AU6819494A (en) 1993-04-26 1994-11-21 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1994025591A1 (en) 1993-04-29 1994-11-10 Unilever N.V. PRODUCTION OF ANTIBODIES OR (FUNCTIONALIZED) FRAGMENTS THEREOF DERIVED FROM HEAVY CHAIN IMMUNOGLOBULINS OF $i(CAMELIDAE)
AU691811B2 (en) 1993-06-16 1998-05-28 Celltech Therapeutics Limited Antibodies
SE9400088D0 (sv) 1994-01-14 1994-01-14 Kabi Pharmacia Ab Bacterial receptor structures
US5837458A (en) 1994-02-17 1998-11-17 Maxygen, Inc. Methods and compositions for cellular and metabolic engineering
US5834252A (en) 1995-04-18 1998-11-10 Glaxo Group Limited End-complementary polymerase reaction
US5605793A (en) 1994-02-17 1997-02-25 Affymax Technologies N.V. Methods for in vitro recombination
CZ25697A3 (en) 1994-07-29 1997-09-17 Smithkline Beecham Plc Novel compounds
US6132764A (en) 1994-08-05 2000-10-17 Targesome, Inc. Targeted polymerized liposome diagnostic and treatment agents
ATE252894T1 (de) 1995-01-05 2003-11-15 Univ Michigan Oberflächen-modifizierte nanopartikel und verfahren für ihre herstellung und verwendung
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US6019968A (en) 1995-04-14 2000-02-01 Inhale Therapeutic Systems, Inc. Dispersible antibody compositions and methods for their preparation and use
US6121022A (en) 1995-04-14 2000-09-19 Genentech, Inc. Altered polypeptides with increased half-life
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
AU710347B2 (en) 1995-08-31 1999-09-16 Alkermes Controlled Therapeutics, Inc. Composition for sustained release of an agent
US5985320A (en) 1996-03-04 1999-11-16 The Penn State Research Foundation Materials and methods for enhancing cellular internalization
CA2249195A1 (en) 1996-03-18 1997-09-25 Board Of Regents, The University Of Texas System Immunoglobin-like domains with increased half lives
US5874064A (en) 1996-05-24 1999-02-23 Massachusetts Institute Of Technology Aerodynamically light particles for pulmonary drug delivery
US5855913A (en) 1997-01-16 1999-01-05 Massachusetts Instite Of Technology Particles incorporating surfactants for pulmonary drug delivery
US5985309A (en) 1996-05-24 1999-11-16 Massachusetts Institute Of Technology Preparation of particles for inhalation
US6056973A (en) 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
WO1998023289A1 (en) 1996-11-27 1998-06-04 The General Hospital Corporation MODULATION OF IgG BINDING TO FcRn
DE69732306T2 (de) 1997-01-16 2006-01-12 Massachusetts Institute Of Technology, Cambridge Zubereitung von partikelhaltigen arzneimitteln zur inhalation
US6136558A (en) 1997-02-10 2000-10-24 Genentech, Inc. Heregulin variants
US6277375B1 (en) 1997-03-03 2001-08-21 Board Of Regents, The University Of Texas System Immunoglobulin-like domains with increased half-lives
EP0983303B1 (en) 1997-05-21 2006-03-08 Biovation Limited Method for the production of non-immunogenic proteins
AU736707B2 (en) 1997-06-11 2001-08-02 Anaphore, Inc. Trimerising module
JP3614866B2 (ja) 1997-06-12 2005-01-26 リサーチ コーポレイション テクノロジーズ，インコーポレイティド 人工抗体ポリペプチド
US5989463A (en) 1997-09-24 1999-11-23 Alkermes Controlled Therapeutics, Inc. Methods for fabricating polymer-based controlled release devices
DE19742706B4 (de) 1997-09-26 2013-07-25 Pieris Proteolab Ag Lipocalinmuteine
AU9805398A (en) 1997-10-15 1999-05-03 Children's Medical Center Corporation Novel human egf receptors and use thereof
GB9722131D0 (en) 1997-10-20 1997-12-17 Medical Res Council Method
SE512663C2 (sv) 1997-10-23 2000-04-17 Biogram Ab Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
JP4334141B2 (ja) 1998-04-20 2009-09-30 グリカート バイオテクノロジー アクチェンゲゼルシャフト 抗体依存性細胞傷害性を改善するための抗体のグリコシル化操作
ES2198922T3 (es) 1998-06-24 2004-02-01 Advanced Inhalation Research, Inc. Particulas porosas grandes emitadas por un inhalador.
US6818418B1 (en) 1998-12-10 2004-11-16 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
HUP0104865A3 (en) 1999-01-15 2004-07-28 Genentech Inc Polypeptide variants with altered effector function
EP2275540B1 (en) 1999-04-09 2016-03-23 Kyowa Hakko Kirin Co., Ltd. Method for controlling the activity of immunologically functional molecule
DE19932688B4 (de) 1999-07-13 2009-10-08 Scil Proteins Gmbh Design von Beta-Faltblatt-Proteinen des gamma-II-kristallins antikörperähnlichen
CA2347973C (en) 1999-07-20 2010-06-22 Morphosys Ag Novel methods for displaying (poly)peptides/proteins on bacteriophage particles via disulfide bonds
NZ517202A (en) 1999-08-24 2004-05-28 Medarex Inc Human CTLA-4 antibodies and their uses
US6926898B2 (en) 2000-04-12 2005-08-09 Human Genome Sciences, Inc. Albumin fusion proteins
CA2441903C (en) 2000-05-26 2012-07-31 National Research Council Of Canada Single-domain brain-targeting antibody fragments derived from llama antibodies
DE60131456T2 (de) 2000-11-30 2008-07-10 Medarex, Inc., Milpitas Transchromosomale transgen-nagetiere zur herstellung von humanen antikörpern
CN1551767A (zh) 2001-02-19 2004-12-01 ��˹��ŵ�� 癌症的治疗
US20040175756A1 (en) 2001-04-26 2004-09-09 Avidia Research Institute Methods for using combinatorial libraries of monomer domains
US20050053973A1 (en) 2001-04-26 2005-03-10 Avidia Research Institute Novel proteins with targeted binding
US20050048512A1 (en) 2001-04-26 2005-03-03 Avidia Research Institute Combinatorial libraries of monomer domains
JP2004532038A (ja) 2001-05-17 2004-10-21 ディヴァーサ コーポレイション 新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法
JP4303105B2 (ja) 2001-06-28 2009-07-29 ドマンティス リミテッド 二重特異性リガンドとその利用
ITMI20011483A1 (it) 2001-07-11 2003-01-11 Res & Innovation Soc Coop A R Uso di composti come antagonisti funzionali ai recettori centrali deicannabinoidi
WO2003011897A1 (en) 2001-07-27 2003-02-13 The Regents Of The University Of California Modulation of heregulin and her3 interaction
EP1283053A1 (en) 2001-08-09 2003-02-12 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Inhibitors of HER3 activity
PL213948B1 (pl) 2001-10-25 2013-05-31 Genentech Inc Kompozycje zawierajace glikoproteine, czasteczka kwasu nukleinowego kodujaca te glikoproteine, komórka gospodarza, sposób wytwarzania glikoproteiny, kompozycja do zastosowania do leczenia, zastosowanie kompozycji i zestaw zawierajacy kompozycje
US7771951B2 (en) 2001-12-03 2010-08-10 Amgen Fremont Inc. Antibody categorization based on binding characteristics
EP1478648B1 (en) 2002-02-01 2014-04-30 ARIAD Pharmaceuticals, Inc. Phosphorus-containing compounds and uses thereof
US20030157579A1 (en) 2002-02-14 2003-08-21 Kalobios, Inc. Molecular sensors activated by disinhibition
US7335478B2 (en) 2002-04-18 2008-02-26 Kalobios Pharmaceuticals, Inc. Reactivation-based molecular interaction sensors
AU2003217912A1 (en) 2002-03-01 2003-09-16 Xencor Antibody optimization
CN1678634A (zh) 2002-06-28 2005-10-05 多曼蒂斯有限公司 免疫球蛋白单个变体抗原结合区及其特异性构建体
NZ540194A (en) 2002-11-08 2008-07-31 Ablynx Nv Single domain antibodies directed against tumour necrosis factor-alpha and uses therefor
CA2511910A1 (en) 2002-12-27 2004-07-15 Domantis Limited Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand
WO2004072266A2 (en) 2003-02-13 2004-08-26 Kalobios Inc. Antibody affinity engineering by serial epitope-guided complementarity replacement
JP4889493B2 (ja) 2003-05-14 2012-03-07 ドマンティス リミテッド ポリペプチドレパートリーから可逆的にアンフォールドするポリペプチドを回収するための方法
DE10324447A1 (de) 2003-05-28 2004-12-30 Scil Proteins Gmbh Generierung künstlicher Bindungsproteine auf der Grundlage von Ubiquitin
JP5087274B2 (ja) 2003-06-30 2012-12-05 ドマンティス リミテッド ポリペプチド
US7399865B2 (en) 2003-09-15 2008-07-15 Wyeth Protein tyrosine kinase enzyme inhibitors
US7981843B2 (en) 2004-01-20 2011-07-19 Kalobios Pharmaceuticals, Inc. Antibody specificity transfer using minimal essential binding determinants
US20060008844A1 (en) 2004-06-17 2006-01-12 Avidia Research Institute c-Met kinase binding proteins
JP2008528010A (ja) 2005-01-31 2008-07-31 アブリンクス ナームローゼ フェンノートシャップ 重鎖抗体の可変ドメイン配列を作出する方法
GB0503546D0 (en) * 2005-02-21 2005-03-30 Hellenic Pasteur Inst Antibody
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
KR20080080482A (ko) 2005-09-07 2008-09-04 메디뮨 엘엘씨 독소가 컨쥬게이트된 ｅｐｈ 수용체 항체
CA2618489A1 (en) 2005-09-07 2007-03-15 Laboratoires Serono S.A. Pi3k inhibitors for the treatment of endometriosis
KR101866623B1 (ko) 2005-11-28 2018-07-04 젠맵 에이/에스 재조합 １가 항체 및 그의 제조 방법
AR056857A1 (es) 2005-12-30 2007-10-24 U3 Pharma Ag Anticuerpos dirigidos hacia her-3 (receptor del factor de crecimiento epidérmico humano-3) y sus usos
AU2007257683A1 (en) 2006-06-12 2007-12-21 Symphogen A/S Pan-cell surface receptor- specific therapeutics
KR20090058512A (ko) * 2006-08-04 2009-06-09 아스트라제네카 아베 Ｅｒｂｂ2에 대한 인간 항체
AU2007287794B2 (en) * 2006-08-21 2013-03-28 F. Hoffmann-La Roche Ag Tumor therapy with an anti-VEGF antibody
US7825127B2 (en) 2006-12-28 2010-11-02 Takeda Pharmaceutical Company, Limited Method for treating cancer
NZ579644A (en) 2007-02-16 2012-05-25 Merrimack Pharmaceuticals Inc Antibodies against erbb3 and uses thereof
MX2009008981A (es) 2007-03-02 2009-09-02 Genentech Inc Prediccion de respuesta a un inhibidor her.
US20080245375A1 (en) 2007-04-05 2008-10-09 Medtronic Vascular, Inc. Benign Prostatic Hyperplasia Treatments
BRPI0816769A2 (pt) 2007-09-12 2016-11-29 Hoffmann La Roche combinações de compostos inibidores de fosfoinositida 3-cinase e agentes quimioterapêuticos, e métodos de uso
RU2010119556A (ru) 2007-10-16 2011-11-27 Симфоген А/С (Dk) Композиции, содержащие оптимизированные мультимеры her1 и her3, и способы их применения
WO2009055730A1 (en) 2007-10-25 2009-04-30 Genentech, Inc. Process for making thienopyrimidine compounds
UY31800A (es) 2008-05-05 2009-11-10 Smithkline Beckman Corp Metodo de tratamiento de cancer usando un inhibidor de cmet y axl y un inhibidor de erbb
JP2012525432A (ja) 2009-04-29 2012-10-22 トレリス バイオサイエンス リミテッド ライアビリティー カンパニー ヘレグリン共役型ｈｅｒ３と免疫反応性の改善された抗体
AU2010284018C1 (en) 2009-08-21 2015-10-15 Merrimack Pharmaceuticals, Inc. Antibodies against the ectodomain of ErbB3 and uses thereof
US8654108B2 (en) 2009-09-25 2014-02-18 Sharp Kabushiki Kaisha Liquid crystal display device
JP2013507926A (ja) 2009-10-14 2013-03-07 メリマック ファーマシューティカルズ インコーポレーティッド ＩＧＦ−１Ｒ及びＥｒｂＢ３シグナル伝達を標的とする二重特異的結合剤及びその使用
KR101806323B1 (ko) 2009-11-13 2017-12-07 다이이치 산쿄 유럽 게엠베하 Ｈｅｒ-３ 관련 질병을 치료하거나 예방하기 위한 물질 및 방법
PH12012501157A1 (en) 2009-12-22 2012-10-29 Roche Glycart Ag Anti-her3 antibodies and uses thereof
ES2519348T3 (es) 2010-02-18 2014-11-06 Genentech, Inc. Antagonistas de neurregulina y uso de los mismos en el tratamiento del cáncer
US8895001B2 (en) 2010-03-11 2014-11-25 Merrimack Pharmaceuticals, Inc. Use of ErbB3 inhibitors in the treatment of triple negative and basal-like breast cancers
KR101764453B1 (ko) 2010-04-09 2017-08-02 아베오 파마슈티컬즈, 인크. 항-erbb3 항체
CA2799217A1 (en) 2010-05-13 2011-11-17 Fox Chase Cancer Center Recombinantly produced antibodies targeting erbb signaling molecules and methods of use thereof for the diagnosis and treatment of disease
US9932403B2 (en) 2010-05-20 2018-04-03 Ablynx Nv Biological materials related to HER3
UY33492A (es) 2010-07-09 2012-01-31 Abbott Lab Inmunoglobulinas con dominio variable dual y usos de las mismas
WO2012019024A2 (en) 2010-08-04 2012-02-09 Immunogen, Inc. Her3-binding molecules and immunoconjugates thereof
AU2011286407A1 (en) 2010-08-06 2013-02-21 Amgen Use of HER3 binding agents in prostate treatment
ME02637B (me) 2010-08-20 2017-06-20 Novartis Ag Antitela za receptor 3 faktora rasta epiderma (her3)
TW201302793A (zh) 2010-09-03 2013-01-16 Glaxo Group Ltd 新穎之抗原結合蛋白
US9155802B2 (en) 2010-11-01 2015-10-13 Symphogen A/S Pan-HER antibody composition
ITRM20100577A1 (it) 2010-11-02 2012-05-03 Takis Srl Immunoterapia contro il recettore erbb-3
UY33707A (es) 2010-11-04 2012-05-31 Abbott Lab Inmunoglobulinas con dominio variable dual y usos de las mismas
NO2707391T3 (es) 2011-05-13 2018-04-07
CA2842860A1 (en) 2011-07-28 2013-01-31 Sea Lane Biotechnologies, Llc Sur-binding proteins
EP2788382A2 (en) 2011-12-05 2014-10-15 Novartis AG Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3
CN108341873B (zh) * 2011-12-05 2022-03-25 诺华股份有限公司 表皮生长因子受体3(her3)的抗体

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