Back to results
US 11,261,214 B2Granted
Bicyclic peptide ligand specific for CD137
AssigneeBicycleTx Limited
InventorsLiuhong Chen, Rachid Lani, Kevin McDonnell, Gemma Mudd, Peter Park
Life of this patent
Estimating the term…
Abstract
The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of CD137. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by CD137.
Claims25
A peptide ligand specific for CD137 comprising a polypeptide comprising at least three cysteine residues, separated by two loop sequences, and a molecular scaffold which forms covalent bonds with the cysteine residues of the polypeptide such that two polypeptide loops are formed on the molecular scaffold, which comprises an amino acid sequence selected from:
- (SEQ ID NO:
- 41)
- Ci-I/L/M/V-E/D/P/S-P/E/A-G-P/Q-Y/F-Cii-Y-A-D-P-
- Y/M-M/L/Y-Ciii;
- (SEQ ID NO:
- 20)
- Ci-I-E-E-G-Q-Y-Cii-X1-X2-D-X3-Y/Q/M-X4-Ciii;
- (SEQ ID NO:
- 21)
- Ci-D-I-G-P-P-Y-Cii-Y-R/A-D-M/P-Y-M-Ciii;
- (SEQ ID NO:
- 22)
- Ci-D-E-W-G-L-F/Y-Cii-I/F-P/A-H-S/P-D-Ciii;
- and
- (SEQ ID NO:
- 19)
- CiIEPGPFCiiYADPYMCiii;
- wherein X1-X4 represent any amino acid residue and Ci, Cii and Ciii represent first, second and third cysteine residues, respectively or a pharmaceutically acceptable salt thereof.
15 more elements
A peptide ligand specific for CD137 comprising a polypeptide comprising at least three cysteine residues, separated by two loop sequences, and a molecular scaffold which forms covalent bonds with the cysteine residues of the polypeptide such that two polypeptide loops are formed on the molecular scaffold, which comprises an amino acid sequence selected from:
- (SEQ ID NO:
- 23)
- CiIEEGQYCiiFADPY(Nle)Ciii;
- (SEQ ID NO:
- 24)
- CiIKEGQYCiiFADPY(Nle)Ciii;
- (SEQ ID NO:
- 25)
- CiIEKGQYCiiFADPY(Nle)Ciii;
- (SEQ ID NO:
- 26)
- CiIEE(D-K)QYCiiFADPY(Nle)Ciii;
- (SEQ ID NO:
- 27)
- CiIEEGKYCiiFADPY(Nle)Ciii;
- (SEQ ID NO:
- 28)
- CiIEEGQYCiiKADPY(Nle)Ciii;
- (SEQ ID NO:
- 29)
- CiIEEGQYCiiFADKY(Nle)Ciii;
- (SEQ ID NO:
- 30)
- CiIEEGQYCiiFADPYKCiii;
- (SEQ ID NO:
- 40;
- 74-22-00)
- CiLPPGQYCiiFPDLLLCiii
- (SEQ ID NO:
- 31;
- BCY3814)
- A-CiIEEGQYCiiFADPY(Nle)Ciii-A;
- (SEQ ID NO:
- 32;
- BCY7732)
- Ac-A-CiIEEGQYCiiFADPY(Nle)Ciii-Dap;
- (SEQ ID NO:
- 33;
- BCY7733)
- Ac-A-CiIKEGQYCiiFADPY(Nle)Ciii-A;
- (SEQ ID NO:
- 34;
- BCY7734)
- Ac-A-CiIEKGQYCiiFADPY(Nle)Ciii-A;
- (SEQ ID NO:
- 35;
- BCY7735)
- Ac-A-CiIEE(D-K)QYCiiFADPY(Nle)Ciii-A;
- (SEQ ID NO:
- 36;
- BCY7736)
- Ac-A-CiIEEGKYCiiFADPY(Nle)Ciii-A;
- (SEQ ID NO:
- 37;
- BCY7737)
- Ac-A-CiIEEGQYCiiKADPY(Nle)Ciii-A;
- (SEQ ID NO:
- 38;
- BCY7738)
- Ac-A-CiIEEGQYCiiFADKY(Nle)Ciii-A;
- and
- (SEQ ID NO:
- 39;
- BCY7739)
- Ac-A-CiIEEGQYCiiFADPYKCiii-A;
- or an amino acid sequence selected from:
- SEQ ID
- Peptide Number
- NO:
- Sequence
- BCY633
- 42
- [B-Ala]-Sar5-ACIEEGQYCYRDMYMCA
- BCY634
- 43
- [Ac]ACIEEGQYCYRDMYIVICA-Sar6-K(Fl)
- BCY636
- 44
- ACIEEGQYCYADPYIVICA-Sar6-K(Fl)
- BCY635
- 45
- [B-Ala]-Sar5-ACIEEGQYCYADPYWICA
- BCY638
- 46
- ACIEEGQYCYADPYYCASar6-K
- BCY637
- 47
- [B-Ala]-Sar5-ACIEEGQYCYADPYYCA
- BCY639
- 48
- ACIEEGQYCYSDPYYCA-Sar6-K
- BCY640
- 49
- ACIEEGQYCFADPYMCA-Sar6-K
- BCY641
- 50
- G-Sar5-ACIEEGQYCFADPYMCA
- BCY7239
- 52
- Ac-CIK(Peg12)EGQYCFADPYMC
- BCY7240
- 53
- Ac-CIEK(Peg12)GQYCFADPYMC
- BCY7242
- 55
- Ac-CIEEGK(Peg12)YCFADPYMC
- BCY7244
- 57
- Ac-CIEEGQYCK(Peg12)ADPYMC
- BCY7245
- 58
- Ac-CIEEGQYCFK(Peg12)DPYMC
- BCY7247
- 60
- Ac-CIEEGQYCFADK(Peg12)YMC
- BCY7248
- 61
- Ac-CIEEGQYCFADPK(Peg12)MC
- BCY7249
- 62
- Ac-CIEEGQYCFADPYK(Peg12)C
- BCY7416
- 63
- [Ac]IEE[dK(PEG12Fl)]QYCFADPY[Nle]C
- BCY7519
- 64
- ACIEEGQYCFADPY[Nle]CA
- BCY7520
- 65
- [Peg12]-ACIEEGQYCFADPY[Nle]CA
- BCY642
- 66
- ACIEEGQYCYADHQLCA-Sar6-K
- BCY643
- 67
- ACIEEGQYCHADPYYCA-Sar6-K
- BCY644
- 68
- ACIEEGQYCHADPYFCA-Sar6-K
- BCY645
- 69
- ACIEEGQYCYADHYMCA-Sar6-K
- BCY646
- 70
- ACIEEGQYCYADPYLCA-Sar6-K
- BCY647
- 71
- ACIEEGQYCYADPYLCSVG-Sar6-K
- BCY648
- 72
- (Fl)G-Sar5-ACIEEGQYCYADPYLCSVG
- BCY649
- 73
- ACIEEGQYCYSDPYLCA-Sar6-K
- BCY650
- 74
- ACIEEGQYCFADPYLCA-Sar6-K
- BCY652
- 75
- ACIEEGQYCHADPYIVICA-Sar6-K
- BCY653
- 76
- ACIEEGQYCHADPQMCA-Sar6-K
- BCY655
- 77
- ACDIGPPYCYRDMYIVICA-Sar6-K
- BCY656
- 78
- ADIGPPYCYADPYIVICA-Sar6-K
- BCY7251
- 79
- ACLDPGPFCFADPYIVICA-Sar6-K
- BCY7253
- 80
- ACLDEGPYCFADPYFCA-Sar6-K
- BCY7255
- 81
- ACINEGPYCFADPYIVICA-Sar6-K
- BCY7257
- 82
- ACIEQGPFCFADPYIVICA-Sar6-K
- BCY7259
- 83
- ACVEEGPFCFADPYYCA-Sar6-K
- BCY7261
- 84
- ACLDEGPFCFSDPYIVICA-Sar6-K
- BCY657
- 85
- [B-Ala]-Sar5-ACDEWGLFCIPHSDCA
- BCY659
- 86
- ACDEWGLYCFAHPDCA-Sar6-K
- BCY7119
- 87
- ACLDPGPYCYADPYIVICTFH-Sar6-K
- BCY660
- 88
- ACIEPGPFCYADPYMCNRV-Sar6-K
- BCY661
- 89
- G-Sar5-ACIEPGPFCYADPYMCNRV
- BCY7120
- 90
- ACLEPGPYCYADPYIVICTHL-Sar6-K
- BCY7122
- 91
- ACLPPGPYCFPDPYFCA-Sar6-K
- BCY7151
- 92
- [PEG3]-ACIEEGQYCFADPY[Nle]CA
- BCY7152
- 115
- [PEG3]-ACLEEGQYCFADPY[Nle]CA
- BCY7153
- 116
- [PEG3]-AC[Nle]EEGQYCFADPY[Nle]CA
- BCY7154
- 117
- [PEG3]-AC-Chg-EEGQYCFADPY[Nle]CA
- BCY7155
- 118
- [PEG3]-AC-Cha-EEGQYCFADPY[Nle]CA
- BCY7156
- 119
- [PEG3]-ACIPEGQYCFADPY[Nle]CA
- BCY7157
- 120
- [PEG3]-ACIDEGQYCFADPY[Nle]CA
- BCY7158
- 121
- [PEG3]-ACI-Aad-EGQYCFADPY[Nle]CA
- BCY7159
- 122
- [PEG3]-ACI-Api-EGQYCFADPY[Nle]CA
- BCY7160
- 123
- [PEG3]-ACIEPGQYCFADPY[Nle]CA
- BCY7161
- 124
- [PEG3]-ACIEDGQYCFADPY[Nle]CA
- BCY7162
- 125
- [PEG3]-ACIE-Aad-GQYCFADPY[Nle]CA
- BCY7163
- 126
- [PEG3]-ACIE-Api-GQYCFADPY[Nle]CA
- BCY7164
- 127
- [PEG3]-ACIEE-Sar-QYCFADPY[Nle]CA
- BCY7165
- 128
- [PEG3]-ACIEE-DLys-QYCFADPY[Nle]CA
- BCY7166
- 129
- [PEG3]-ACIEE-DPhe-QYCFADPY[Nle]CA
- BCY7167
- 130
- [PEG3]-ACIEE-DGlu-QYCFADPY[Nle]CA
- BCY7168
- 131
- [PEG3]-ACIEE-DGln-QYCFADPY[Nle]CA
- BCY7169
- 132
- [PEG3]-ACIEE-DLeu-QYCFADPY[Nle]CA
- BCY7170
- 133
- [PEG3]-ACIEE-DSer-QYCFADPY[Nle]CA
- BCY7172
- 134
- [PEG3]-ACIEE-MeDala-QYCFADPY[Nle]CA
- BCY7173
- 135
- [PEG3]-ACIEE-Aib-QYCFADPY[Nle]CA
- BCY7174
- 136
- [PEG3]-ACIEEGPYCFADPY[Nle]CA
- BCY7175
- 137
- [PEG3]-ACIEEGQFCFADPY[Nle]CA
- BCY7176
- 138
- [PEG3]-ACIEEGQ-2MeF-CFADPY[Nle]CA
- BCY7177
- 139
- [PEG3]-ACIEEGQ-3MeF-CFADPY[Nle]CA
- BCY7178
- 140
- [PEG3]-ACIEEGQ-4MeF-CFADPY[Nle]CA
- BCY7179
- 141
- [PEG3]-ACIEEGQ-4FF-CFADPY[Nle]CA
- BCY7180
- 142
- [PEG3]-ACIEEGQ-3FF-CFADPY[Nle]CA
- BCY7181
- 143
- [PEG3]-ACIEEGQYC-2MeF-ADPY[Nle]CA
- BCY7182
- 144
- [PEG3]-ACIEEGQYC-3MeF-ADPY[Nle]CA
- BCY7183
- 145
- [PEG3]-ACIEEGQYC-4MeF-ADPY[Nle]CA
- BCY7184
- 146
- [PEG3]-ACIEEGQYC-PheG-ADPY[Nle]CA
- BCY7185
- 147
- [PEG3]-ACIEEGQYC-4FF-ADPY[Nle]CA
- BCY7186
- 148
- [PEG3]-ACIEEGQYCFGDPY[Nle]CA
- BCY7187
- 149
- [PEG3]-ACIEEGQYCFSDPY[Nle]CA
- BCY7188
- 150
- [PEG3]-ACIEEGQYCFPDPY[Nle]CA
- BCY7189
- 151
- [PEG3]-ACIEEGQYCFANPY[Nle]CA
- BCY7190
- 152
- [PEG3]-ACIEEGQYCFAD-Pip-Y[Nle]CA
- BCY7191
- 153
- [PEG3]-ACIEEGQYCFAD-MeAla-Y[Nle]CA
- BCY7192
- 154
- [PEG3]-ACIEEGQYCFAD-Sar-Y[Nle]CA
- BCY7193
- 155
- [PEG3]-ACIEEGQYCFAD-Aib-Y[Nle]CA
- BCY7195
- 156
- [PEG3]AC[tBuAla]EEGQYCFADPY[Nle]CA
- BCY7196
- 157
- [PEG3]AC[HLeu]EEGQYCFADPY[Nle]CA
- BCY7197
- 158
- [PEG3]ACIEEGQ[2FPhe]CFADPY[Nle]CA
- BCY7198
- 159
- [PEG3]ACIEEGQYC[2FPhe]ADPY[Nle]CA
- BCY7199
- 160
- [PEG3]ACIEEGQYCF[CF3G]DPY[Nle]CA
- BCY7200
- 161
- [PEG3]ACIEEGQYCFADP[pCoPhe][Nle]CA
- BCY7201
- 162
- [PEG3]ACIEEGQYCFADP[pCaPhe][Nle]CA
- BCY7202
- 163
- [PEG3]ACIEEGQYCFADPQ[Nle]CA
- BCY7205
- 164
- [PEG3]ACIEEGQYCFADP[2MePhe][Nle]CA
- BCY7206
- 165
- [PEG3]ACIEEGQYCFADP[3MePhe][Nle]CA
- BCY7207
- 166
- [PEG3]ACIEEGQYCFADP[4MePhe][Nle]CA
- BCY7208
- 167
- [PEG3]ACIEEGQYCFADP[Cit][Nle]CA
- BCY7209
- 168
- [PEG3]ACIEEGQYCFADP[4FPhe][Nle]CA
- BCY7210
- 169
- [PEG3]ACIEEGQYCFADPY[tBuAla]CA
- BCY7211
- 170
- [PEG3]ACIEEGQYCFADPY[HLeu]CA
- BCY7212
- 171
- [PEG3]ACIEEGQYCFADPYICA
- BCY7213
- 172
- [PEG3]ACIEEGQYCFADPY[Cha]CA
- BCY7214
- 173
- [PEG3]ACIEEGQYCFADPYFCA
- BCY7215
- 174
- [PEG3]ACIEEGQYCFADPY[2MePhe]CA
- BCY7216
- 175
- [PEG3]ACIEEGQYCFADPY[3MePhe]CA
- BCY7217
- 176
- [PEG3]ACIEEGQYCFADPY[4MePhe]CA
- BCY7218
- 177
- [PEG3]A[Pen]IEEGQYCFADPY[Nle]CA
- BCY7219
- 178
- [PEG3]ACIEEGQY[Pen]FADPY[Nle]CA
- BCY7220
- 179
- [PEG3]ACIEEGQYCFADPY[Nle][Pen]A
- BCY7221
- 180
- [PEG3]A[HCys]IEEGQYCFADPY[Nle]CA
- BCY7222
- 181
- [PEG3]ACIEEGQY[HCys]FADPY[Nle]CA
- BCY7223
- 182
- [PEG3]ACIEEGQYCFADPY[Nle][HCys]A
- BCY7224
- 183
- [PEG3]ACIEEGQYC[3FPhe]ADPY[Nle]CA
- BCY7306
- 184
- [PEG3]-ACI[TetraZ]EGQYCFADPY[Nle]CA
- BCY7308
- 185
- [PEG3]-ACIEEGQYCFA[TetraZ]PY[Nle]CA
- BCY7309
- 186
- [PEG3]-ACIEEGQYCFADP[HGln][Nle]CA
- BCY7310
- 187
- [PEG3]-AC[Ahp]EEGQYCFADPY[Nle]CA
- BCY7311
- 188
- [PEG3]-ACIEEGQYCFADPY[Ahp]CA
- BCY592
- 189
- ACIEEGQYCFADPYIVICA
- BCY589
- 190
- HEHCIEEGQYCYADPYIVICA
- BCY599
- 191
- ACIEEGQYCFADPYLCA
- BCY631
- 192
- ACLPPGPYCFPDPYFCA
- BCY592
- 189
- ACIEEGQYCFADPYIVICA
- BCY593
- 193
- [Ac]CIEEGQYCFADPYMC
- BCY3814
- 31
- ACIEEGQYCFADPY(Nle)CA
- BCY7527
- 194
- [Ac]CIEEGQYCFADPY[Nle]C[Dap]
- BCY7768
- 195
- [PEG3]ACIPE[dF]QYCFADPY[Nle]CA
- BCY7770
- 196
- [PEG3]ACIPE[dF]PYCFADPY[Nle]CA
- BCY7772
- 197
- [PEG3]ACIEE[dF]PYCFADPY[Nle]CA
- BCY7773
- 198
- PEG3]ACIPEGPYCFADPY[Nle]CA
- BCY7774
- 199
- [PEG3]AC[tBuAla]PE[dF]P[4MePhe]C[4FPhe]ADPY[Nle]CA
- BCY7775
- 200
- [PEG3]AC[tBuAla]PE[dF]Q[4MePhe]C[4FPhe]ADPY[Nle]CA
- BCY7776
- 201
- [PEG3]AC[tBuAla]EE[dF]P[4MePhe]C[4FPhe]ADPY[Nle]CA
- BCY7777
- 202
- [PEG3]AC[tBuAla]EE[dF]Q[4MePhe]C[4FPhe]ADPY[Nle]CA
- BCY7796
- 203
- [PEG3]ACI[HyP]EGQYCFADPY[Nle]CA
- BCY7798
- 204
- [PEG3]ACIEE[dW]QYCFADPY[Nle]CA
- BCY7799
- 205
- [PEG3]ACIEEG[Aze]YCFADPY[Nle]CA
- BCY7800
- 206
- [PEG3]ACIEEG[Pip]YCFADPY[Nle]CA
- BCY7801
- 207
- [PEG3]ACIEEGQ[2Nal]CFADPY[Nle]CA
- BCY7802
- 208
- [PEG3]ACIEEGQ[4MeoPhe]CFADPY[Nle]CA
- BCY7803
- 209
- [PEG3]ACIEEGQYCYADPY[Nle]CA
- BCY7804
- 210
- [PEG3]ACIEEGQYCFAD[Aze]Y[Nle]CA
- BCY7806
- 211
- [PEG3]ACIEEGQYCFADPY[Hse(Me)]CA
- BCY7923
- 212
- [Ac]AC[NMeIle]EEGQYCFADPY[Nle]CA
- BCY7924
- 213
- [Ac]ACI[Aze]EGQYCFADPY[Nle]CA
- BCY7925
- 214
- [Ac]ACI[Pip]EGQYCFADPY[Nle]CA
- BCY7926
- 215
- [Ac]ACI[NMeGlu]EGQYCFADPY[Nle]CA
- BCY7927
- 216
- [Ac]ACIE[NMeGlu]GQYCFADPY[Nle]CA
- BCY7928
- 217
- [Ac]ACIEE[dD]QYCFADPY[Nle]CA
- BCY7929
- 218
- [Ac]ACIEEG[NMeAla]YCFADPY[Nle]CA
- BCY7930
- 219
- [Ac]ACIEEGQ[NMeTyr]CFADPY[Nle]CA
- BCY7931
- 220
- [Ac]ACIEEGQ[HPhe]CFADPY[Nle]CA
- BCY7933
- 221
- [Ac]ACIEEGQ[2Pal]CFADPY[Nle]CA
- BCY7934
- 222
- [Ac]ACIEEGQ[3Pal]CFADPY[Nle]CA
- BCY7936
- 223
- [Ac]ACIEEGQ[44BPA]CFADPY[Nle]CA
- BCY7937
- 224
- [Ac]ACIEEGQYC[HPhe]ADPY[Nle]CA
- BCY7939
- 225
- [Ac]ACIEEGQYC[2Pal]ADPY[Nle]CA
- BCY7940
- 226
- [Ac]ACIEEGQYC[3Pal]ADPY[Nle]CA
- BCY7941
- 227
- [Ac]ACIEEGQYC[4Pal]ADPY[Nle]CA
- BCY7942
- 228
- [Ac]ACIEEGQYC[44BPA]ADPY[Nle]CA
- BCY7943
- 229
- [Ac]ACIEEGQYC[1Nal]ADPY[Nle]CA
- BCY7944
- 230
- [Ac]ACIEEGQYC[4tBuPhe]ADPY[Nle]CA
- BCY7945
- 231
- [Ac]ACIEEGQYCF[NMeAla]DPY[Nle]CA
- BCY7950
- 232
- [Ac]ACIEEG[55DMp]YCFADPY[Nle]CA
- BCY7953
- 233
- [Ac]ACIEEGQYCFAD[HyP]Y[Nle]CA
- BCY7954
- 234
- [Ac]ACIEEG[Oic]YCFADPY[Nle]CA
- BCY7955
- 235
- [Ac]ACIEEGQYCFAD[Oic]Y[Nle]CA
- BCY7956
- 236
- [Ac]ACI[Oic]EGQYCFADPY[Nle]CA
- BCY7957
- 237
- [Ac]ACIEEGQYCFAD[Oxa]Y[Nle]CA
- BCY7958
- 238
- [Ac]ACI[Oxa]EGQYCFADPY[Nle]CA
- BCY7959
- 239
- [Ac]ACIEEG[Oxa]YCFADPY[Nle]CA
- BCY7960
- 240
- [Ac]ACIPEGPYCFADPY[Nle]CA
- BCY7952
- 241
- [Ac]ACIEEG[HyP]YCFADPY[Nle]CA
- BCY7961
- 242
- [Ac]ACIPE[dA]PYCFADPY[Nle]CA
- BCY7965
- 243
- [Ac]AC[tBuAla]PE[dA]PYCFADPY[Nle]CA
- BCY8217
- 244
- ACIEEGQYCF[dA]DPY[Nle]CA
- BCY8656
- 245
- [Ac]AC[tBuAla]EEGQYCFADPY[Nle]CA
- BCY8657
- 246
- [Ac]AC[Chg]EEGQYCFADPY[Nle]CA
- BCY8658
- 247
- [Ac]AC[AC5C]EEGQYCFADPY[Nle]CA
- BCY8659
- 248
- [Ac]ACIPEGQYCFADPY[Nle]CA
- BCY8660
- 249
- [Ac]ACIQEGQYCFADPY[Nle]CA
- BCY8661
- 250
- [Ac]ACIEPGQYCFADPY[Nle]CA
- BCY8662
- 251
- [Ac]ACIEQGQYCFADPY[Nle]CA
- BCY8663
- 252
- [Ac]ACIEE[df]QYCFADPY[Nle]CA
- BCY8664
- 253
- [Ac]ACIEE[dA]QYCFADPY[Nle]CA
- BCY8665
- 254
- [Ac]ACIEE[AC5C]QYCFADPY[Nle]CA
- BCY8667
- 255
- [Ac]ACIEEGAYCFADPY[Nle]CA
- BCY8668
- 256
- [Ac]ACIEEG[Aib]YCFADPY[Nle]CA
- BCY8669
- 257
- [Ac]ACIEEG[AC5C]YCFADPY[Nle]CA
- BCY8670
- 258
- [Ac]ACIEEGQ[4MePhe]CFADPY[Nle]CA
- BCY8671
- 259
- [Ac]ACIEEGQ[1Nal]CFADPY[Nle]CA
- BCY8673
- 260
- [Ac]ACIEEGQYC[2Nal]ADPY[Nle]CA
- BCY8674
- 261
- [Ac]ACIEEGQYC[NO2Phe]ADPY[Nle]CA
- BCY8675
- 262
- [Ac]ACIEEGQYC[4BrPhe]ADPY[Nle]CA
- BCY8676
- 263
- [Ac]ACIEEGQYCF[Abu]DPY[Nle]CA
- BCY8677
- 264
- [Ac]ACIEEGQYCFADPY[Ahp]CA
- BCY9273
- 265
- [Ac]ACIEEGQYCFADPYMCA
- wherein Ci, Cii and Ciii represent first, second and third cysteine residues, respectively, Ac represents an N-terminal acetyl group and Dap represents diaminopropionic acid or a pharmaceutically acceptable salt thereof.
668 more elements
A peptide ligand specific for CD137 comprising a polypeptide comprising at least three cysteine residues, separated by two loop sequences, and a molecular scaffold which forms covalent bonds with the cysteine residues of the polypeptide such that two polypeptide loops are formed on the molecular scaffold, wherein the peptide ligand comprises an amino acid sequence which is:
- (SEQ ID NO:
- 266)
- Ci-X5-X6-X7-X8-X9-X10-Cii-X11-X12-D-X13-X14-X15-Ciii;
- wherein Ci, Cii and Ciii represent first, second and third cysteine residues, respectively;
- X5 represents lie, tBuAla or Chg;
- X6 represents Glu, Pro, Asp, Lys, Aad, HyP or Oxa;
- X7 represents Glu, Lys or Aad;
- X8 represents Gly, D-Lys, D-Ala, L-Ala, D-Phe, D-Glu, D-Gln, D-Leu, D-Ser or D-Trp;
- X9 represents Gin, Lys, Ala, Pro, 5,5-dmP, Oic, Oxa, HyP, Aib or Ac5c;
- X10 represents Tyr, Phe, 3MePhe, 4MePhe, 4FPhe, 2Nal, 4MeOPhe or 4,4-BPA;
- X11 represents Phe, Lys, 4MePhe, 2FPhe, 4FPhe, 4Pal, 4,4-BPA, 4tBuPhe, NO2Phe or 4BrPhe;
- X12 represents Ala or Lys;
- X13 represents Pro or Lys;
- X14 represents Tyr or Lys;
- and
- X15 represents Met, Lys, Nle, HLeu or Ahp.
13 more elements
Dependencies are inferred from the claim text.