US2021269480A1PendingUtilityA1
Bicyclic peptide ligands specific for nectin-4
Est. expiryJun 22, 2038(~11.9 yrs left)· nominal 20-yr term from priority
G01N 33/5759G01N 33/575A61K 31/40A61K 38/00C07K 5/06034C07K 7/08A61P 35/00A61K 38/07A61K 47/64Y02A50/30A61K 38/10A61K 47/65A61K 31/5375A61K 47/55
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Claims
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 Nectin-4.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 Nectin-4.
Claims
exact text as granted — not AI-modified1 . A peptide ligand specific for Nectin-4 comprising a polypeptide comprising at least three cysteine residues, separated by at least two loop sequences, and a molecular scaffold which forms covalent bonds with the cysteine residues of the polypeptide such that at least two polypeptide loops are formed on the molecular scaffold.
2 . The peptide ligand as defined in claim 1 , wherein said loop sequences comprise 3, 6, 7, 8 or 9 amino acids, such as 3, 6, 7 or 9 amino acids, in particular 3 or 9 amino acids.
3 . The peptide ligand as defined in claim 1 or claim 2 , wherein said loop sequences comprise three cysteine residues separated by two loop sequences one of which consists of 3 amino acids and the other of which consists of 9 amino acids.
4 . The peptide ligand as defined in claim 1 or claim 2 , wherein said peptide ligand comprises an amino acid sequence selected from:
(SEQ ID NO: 38)
C i -P/A/Hyp-F/Y-G/A-C ii -X 1 -X2-X 3 -W/1-Nal/2-
Nal-S/A-X 4 -P-I/D/A-W/1-Nal/2-Nal-C iii ;
(SEQ ID NO: 39)
C i -W/A-P-L-D/S-S/D-Y-W-Cn-Xs-R-I-C iii ;
(SEQ ID NO: 40)
C i -V-T-T-S-Y-D-C ii -F/W-L/V-H/R/T-L-
L/G-G/Q/H-C iii ;
(SEQ ID NO: 41)
C i -X 6 -X 7 -X 8 -C ii -X 9 -X 10 -X 11 -X 12 -
X 13 -X 14 -X 15 -X 16 -X 17 -C iii ;
and
(SEQ ID NO: 42)
C i -W/A/Y-P/A-L-D/S/A-S/D/P/A-Y-
W/1-Nal-C ii -X 5 -R/HArg/A-I-C ii ;
wherein:
X 1 -X 5 represent any amino acid residue, including modified and non-natural amino acids;
X 6 represents: Gly; Pro or a non-natural derivative of Pro selected from azetidine (Aze), hydroxyproline (HyP), 4-amino-proline (Pro(4NH)), oxazolidine-4-carboxylic acid (Oxa), octahydroindolecarboxylic acid (Oic) or 4,4-difluoroproline (4,4-DFP); Ala or a non-natural derivative of Ala selected from aminoisobutyric acid (Aib); or Sarcosine (Sar);
X 7 represents: Phe or a non-natural derivative of Phe selected from 3-methyl-phenylalanine (3MePhe), 4-methyl-phenylalanine (4MePhe), homophenylalanine (HPhe), 4,4-biphenylalanine (4,4-BPA) or 3,4-diydroxy-phenylalanine (DOPA); Tyr; or Ala or a non-natural derivative of Ala selected from 1-naphthylalanine (1-Nal), 2-naphthylalanine (2-Nal) or 2-pyridylalanine (2Pal);
X 8 represents: Gly; Ala; Asp; Lys or a non-natural derivative of Lys selected from acetyl-lysine (KAc or Lys(Ac)); Phe; Glu; Gln; Leu; Ser; Arg; or cysteic acid (Cya);
X 9 is either absent or represents: Met or a non-natural derivative of Met selected from methionine sulfone (Met(O2)); Gln or a non-natural derivative of Gln selected from homoglutamine (HGln); Leu or a non-natural derivative of Leu selected from homoleucine (HLeu) or norleucine (Nle); Lys; Ile; t-butyl-alanine (tBuAla); or homoserine-methyl (HSe(Me));
X 10 represents: Pro; Lys or a non-natural derivative of Lys selected from acetyl-lysine (KAc or Lys(Ac)); Arg or a non-natural derivative of Arg selected from 2-amino-4-guanidinobutyric acid (Agb), homoarginine (HArg) or N-methyl-homoarginine; Glu; Ser; Asp; Gln; Ala; hydroxyproline (HyP); or cysteic acid (Cya);
X 11 represents: Asn or a non-natural derivative of Asn selected from N-methyl-asparagine; Thr; Asp; Gly; Ser; His; Ala or a non-natural derivative of Ala selected from thienyl-alanine (Thi), 2-(1,2,4-triazol-1-yl)-alanine (1,2,4-TriAz) or Beta-(4-thiazolyl)-alanine (4ThiAz); Lys; or cysteic acid (Cya);
X 12 represents: Trp or a non-natural derivative of Trp selected from azatryptophan (AzaTrp), 5-fluoro-L-tryptophan (5FTrp) or methyl-tryptophan (TrpMe); or Ala or a non-natural derivative of Ala selected from 1-naphthyl alanine (1-Nal) or 2-naphthyl alanine (2-Nal);
X 13 represents: Ser or a non-natural derivative of Ser selected from homoserine (HSer); Ala; Asp; or Thr;
X 14 represents: Trp or a non-natural derivative of Trp selected from azatryptophan (AzaTrp); Ser; Ala or a non-natural derivative of Ala selected from 2-(1,2,4-triazol-1-y0-alanine (1,2,4-TriAz), 1-naphthyl alanine (1-Nal) or 2-naphthyl alanine (2-Nal); Asp; Phe or a non-natural derivative of Phe selected from 3,4-diydroxy-phenylalanine (DOPA); Tyr; Thr or a non-natural derivative of Thr selected from N-methyl-threonine; tetrahydropyran-4-propanoic acid (TH P(0)); or dioxo-4-tetrahydrothiopyranylacetic acid (THP(SO2));
X 15 represents Pro or a non-natural derivative of Pro selected from azetidine (Aze), pipecolic acid (Pip) or oxazolidine-4-carboxylic acid (Oxa);
X 16 represents: Ile or a non-natural derivative of Ile selected from N-methyl-isoleucine (NMelle); Ala or a non-natural derivative of Ala selected from 3-cyclohexyl-alanine (Cha) or cyclopropyl-alanine (Cpa); Pro or a non-natural derivative of Pro selected from hydroxyproline (HyP); Asp; Lys; cyclopentyl-glycine (C5A); tetrahydropyran-4-propanoic acid (THP(O)); or dioxo-4-tetrahydrothiopyranylacetic acid (THP(SO2));
X 17 represents: Trp or a non-natural derivative of Trp selected from azatryptophan (AzaTrp) or 5-fluoro-L-tryptophan (5FTrp); Phe; Tyr; 1-naphthyl alanine (1-Nal); or 2-naphthyl alanine (2-Nal);
Hyp represents hydroxyproline, 1-Nal represents 1-naphthyl alanine, 2-Nal represents 2-naphthyl alanine, HArg represents homoarginine and C i , C ii and C iii represent first, second and third cysteine residues, respectively or a pharmaceutically acceptable salt thereof.
5 . The peptide ligand as defined in claim 4 , wherein said loop sequences comprise three cysteine residues separated by two loop sequences the first of which consists of 3 amino acids and the second of which consists of 9 amino acids, and said peptide ligand comprises an amino acid sequence selected from:
(SEQ ID NO: 41)
C i -X 6 -X 7 -X 8 -C ii -X 9 -X 10 -X 11 -X 12 -
X 13 -X 14 -X 15 -X 16 -X 17 -C iii ;
wherein X 6 to X 17 are as defined in claim 4 .
6 . The peptide ligand as defined in claim 4 or claim 5 , wherein:
X 6 represents: Pro or a non-natural derivative of Pro selected from azetidine (Aze), hydroxyproline (HyP), 4-amino-proline (Pro(4NH)), oxazolidine-4-carboxylic acid (Oxa), octahydroindolecarboxylic acid (Oic) or 4,4-difluoroproline (4,4-DFP)m such as Pro; and/or
X 7 represents: Phe or a non-natural derivative of Phe selected from 3-methyl-phenylalanine (3MePhe), 4-methyl-phenylalanine (4MePhe), homophenylalanine (HPhe), 4,4-biphenylalanine (4,4-BPA) or 3,4-diydroxy-phenylalanine (DOPA); Ala or a non-natural derivative of Ala selected from 1-naphthylalanine (1-Nal), 2-naphthylalanine (2-Nal) or 2-pyridylalanine (2Pal), such as Phe or 1-naphthylalanine (1-Nal), in particular 1-naphthylalanine (1-Nal); and/or
X 8 represents Asp, Arg, Lys or cysteic acid (Cya), such as D-Asp, D-Arg, D-Lys or D-Cya, in particular D-Asp; and/or
X 9 represents: Met or a non-natural derivative of Met selected from methionine sulfone (Met(O2)); or Leu or a non-natural derivative of Leu selected from homoleucine (HLeu) or norleucine (Nle), such as Met or Leu, in particular Met; and/or
X 10 represents Arg or a non-natural derivative of Arg selected from 2-amino-4-guanidinobutyric acid (Agb), homoarginine (HArg) or N-methyl-homoarginine; or cysteic acid (Cya), such as homoarginine (HArg) or cysteic acid (Cya) (such as D-Cya), in particular homoarginine (HArg); and/or
X 11 represents: Asn or a non-natural derivative of Asn selected from N-methyl-asparagine; Asp; or His; or cysteic acid (Cya), such as Asn, Asp, His or cysteic acid (Cya) (such as D-Cya), in particular Asp; and/or
X 12 represents: Trp or a non-natural derivative of Trp selected from azatryptophan (AzaTrp), 5-fluoro-L-tryptophan (5FTrp) or methyl-tryptophan (TrpMe), such as Trp; and/or
X 13 represents Ser or a non-natural derivative of Ser selected from homoserine (HSer), such as Ser; and/or
X 14 represents Thr or a non-natural derivative of Thr selected from N-methyl-thyronine, such as Thr; and/or
X 15 represents Pro; and/or
X 16 represents: Ile or a non-natural derivative of Ile selected from N-methyl-isoleucine (NMelle); or Pro or a non-natural derivative of Pro selected from hydroxyproline (HyP), such as Ile; or Pro or a non-natural derivative of Pro selected from hydroxyproline (HyP), in particular Ile, Pro or hydroxyproline (HyP), more particularly hydroxyproline (HyP); and/or
X 17 represents Trp or a non-natural derivative of Trp selected from azatryptophan (AzaTrp) or 5-fluoro-L-tryptophan (5FTrp), such as Trp.
7 . The peptide ligand as defined in any one of claims 4 to 6 , wherein said loop sequences comprise three cysteine residues separated by two loop sequences the first of which consists of 3 amino acids and the second of which consists of 9 amino acids, and said peptide ligand comprises an amino acid sequence selected from:
(SEQ ID NO: 204)
C i -P-X 7 -X 8 -C ii -X 9 -HArg-X 11 -W-S-T-P-X 16 -W-C ii ;
wherein X 7, X 8, X 9, X 11 and X 16 are as defined in claim 4 or claim 6 .
8 . The peptide ligand as defined in any one of claims 4 to 7 , wherein said loop sequences comprise three cysteine residues separated by two loop sequences the first of which consists of 3 amino acids and the second of which consists of 9 amino acids, and said peptide ligand comprises an amino acid sequence selected from:
(SEQ ID NO: 205)
C i -P-F/1-Nal-dD/dR-C ii -M/L-HArg-
N/H/D-W-S-T-P-I/P/HyP-W-C iii .
9 . The peptide ligand as defined in claim 4 , wherein the peptide ligand of C i -X 6 -X 7 -X 8 -C ii -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17 -C iii (SEQ ID NO: 41) comprises an amino acid sequence selected from:
(SEQ ID NO: 45)
CPFGCMETWSWPIWC
(SEQ ID NO: 46)
CPFGCMRGWSWPIWC
(SEQ ID NO: 47)
CPFGCMSGWSWPIWC
(SEQ ID NO: 48)
CPFGCMEGWSWPIWC
(SEQ ID NO: 49)
CPFGCMEDWSWPIWC
(SEQ ID NO: 50)
CPFGCMPGWSWPIWC
(SEQ ID NO: 51)
CPFGCMKSWSWPIWC
(SEQ ID NO: 52)
CPFGCMKTWSWPIWC
(SEQ ID NO: 53)
CPFGCMKGWSWPIWC
(SEQ ID NO: 54)
CPFGCQEHWSWPIWC
(SEQ ID NO: 55)
CPFGCIKSWSWPIWC
(SEQ ID NO: 56)
CPFGCQEDWSWPIWC
(SEQ ID NO: 57)
CPFGCMSDWSWPIWC
(SEQ ID NO: 59)
CPFGCM[HArg]NWSWPIWC
(SEQ ID NO: 60)
CPFGCM[K(Ac)]NWSWPIWC
(SEQ ID NO: 61)
CPFGCM[K(Ac)]SWSWPIWC
(SEQ ID NO: 62)
CPFGC[Nle]KSWSWPIWC
(SEQ ID NO: 63)
CPFGCM[HArg]SWSWPIWC
(SEQ ID NO: 64)
CPFGCM[dK]SWSWPIWC
(SEQ ID NO: 66)
CP[dA]GCMKNWSWPIWC
(SEQ ID NO: 67)
CPF[dA]CMKNWSWPIWC
(SEQ ID NO: 68)
CPFGCM[dA]NWSWPIWC
(SEQ ID NO: 69)
CPFGCMK[dA]WSWPIWC
(SEQ ID NO: 70)
CPFGCMKN[dA]SWPIWC
(SEQ ID NO: 71)
CPFGCMKNWSWP[dA]WC
(SEQ ID NO: 72)
C[dA]FGCMKNWSWPIWC
(SEQ ID NO: 73)
CPFGC[tBuAla]KNWSWPIWC
(SEQ ID NO: 74)
CPFGC[HLeu]KNWSWPIWC
(SEQ ID NO: 75)
CPFGCMKNWSWPI[1Nal]C
(SEQ ID NO: 76)
CPF[dD]CM[HArg]NWSWPIWC
(SEQ ID NO: 77)
CPF[dA]CM[HArg]NWSWPIWC
(SEQ ID NO: 78)
CP[3MePhe]GCMKNWSWPIWC
(SEQ ID NO: 79)
CP[4MePhe]GCMKNWSWPIWC
(SEQ ID NO: 80)
CP[HPhe]GCMKNWSWPIWC
(SEQ ID NO: 81)
CPF[dD]CMKNWSWPIWC
(SEQ ID NO: 82)
CPFGC[Hse(Me)]KNWSWPIWC
(SEQ ID NO: 83)
CPFGCMKN[AzaTrp]SWPIWC
(SEQ ID NO: 84)
CPFGCMKNWSFPIWC
(SEQ ID NO: 85)
CPFGCMKNWSYPIWC
(SEQ ID NO: 86)
CPFGCMKNWS[1Nal]PIWC
(SEQ ID NO: 87)
CPFGCMKNWS[2Nal]PIWC
(SEQ ID NO: 88)
CPFGCMKNWS[AzaTrp]PIWC
(SEQ ID NO: 89)
CPFGCMKNWSW[Aze]IWC
(SEQ ID NO: 90)
CPFGCMKNWSW[Pip]IWC
(SEQ ID NO: 91)
CPFGCMKNWSWPIFC
(SEQ ID NO: 92)
CPFGCMKNWSWPIYC
(SEQ ID NO: 93)
CPFGCMKNWSWPI[AzaTrp]C
(SEQ ID NO: 94)
CGFGCMKNWSWPIWC
(SEQ ID NO: 95)
C[Aze]FGCMKNWSWPIWC
(SEQ ID NO: 96)
CPF[K(Ac)]CMKNWSWPIWC
(SEQ ID NO: 97)
CPFGCLKNWSWPIWC
(SEQ ID NO: 98)
CPFGC[MetO2]KNWSWPIWC
(SEQ ID NO: 99)
CPFGCMPNWSWPIWC
(SEQ ID NO: 100)
CPFGCMQNWSWPIWC
(SEQ ID NO: 101)
CPFGCMKNWSWPPWC
(SEQ ID NO: 102)
CP[2Pal]GCMKNWSWPIWC
(SEQ ID NO: 111)
CPFGCMKN[1Nal]SWPIWC
(SEQ ID NO: 112)
CPFGCMKN[2Nal]SWPIWC
(SEQ ID NO: 113)
CPFGCMKNWSWPI[2Nal]C
(SEQ ID NO: 114)
C[HyP]FGCMKNWSWPIWC
(SEQ ID NO: 115)
CPF[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 116)
CPF[dD]CM[HArg][dK]WSTPIWC
(SEQ ID NO: 117)
CPF[dD]CM[HArg]NWSTPKWC
(SEQ ID NO: 118)
C[Pro(4NH)]F[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 119)
CPF[dD]CMKNWSTPIWC
(SEQ ID NO: 120)
CPF[dK]CM[HArg]NWSTPIWC
(SEQ ID NO: 121)
CPF[dD]CK[HArg]NWSTPIWC
(SEQ ID NO: 122)
CPF[dD]CM[HArg]KWSTPIWC
(SEQ ID NO: 123)
C[Oxa]F[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 124)
CPF[dD]CM[HArg][Thi]WSTPIWC
(SEQ ID NO: 125)
CPF[dD]CM[HArg][4ThiAz]WSTPIWC
(SEQ ID NO: 126)
CPF[dD]CM[HArg][124TriAz]WSTPIWC
(SEQ ID NO: 127)
CPF[dD]CM[HArg]NWS[124TriAz]PIWC
(SEQ ID NO: 128)
CPF[dD]CM[HArg]NWST[Oxa]IWC
(SEQ ID NO: 129)
CP[DOPA][dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 130)
CPF[dD]CM[HArg]NWS[DOPA]PIWC
(SEQ ID NO: 131)
CPF[dD]CM[HArg]NWS[THP(SO2)]PIWC
(SEQ ID NO: 132)
CPF[dD]CM[HArg]NWSTP[THP(SO2)]WC
(SEQ ID NO: 133)
CPF[dD]CM[HArg]N[5FTrp]STPIWC
(SEQ ID NO: 134)
CPF[dD]CM[HArg]NWSTPI[5FTrp]C
(SEQ ID NO: 135)
CPF[dD]CM[HArg]NWS[THP(O)]PIWC
(SEQ ID NO: 136)
CPF[dD]CM[HArg]NWSTP[THP(O)]WC
(SEQ ID NO: 137)
C[44DFP]F[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 138)
C[Oic]F[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 139)
CPF[dF]CM[HArg]NWSTPIWC
(SEQ ID NO: 140)
CPF[dE]CM[HArg]NWSTPIWC
(SEQ ID NO: 141)
CPF[dQ]CM[HArg]NWSTPIWC
(SEQ ID NO: 142)
CPF[dL]CM[HArg]NWSTPIWC
(SEQ ID NO: 143)
CPF[dS]CM[HArg]NWSTPIWC
(SEQ ID NO: 144)
CPF[dD]CM[HArg]NW[HSer]TPIWC
(SEQ ID NO: 145)
CPF[dD]CM[HArg]NWSTP[C5A]WC
(SEQ ID NO: 146)
CPF[dD]CM[HArg]NWSTP[Cpa]WC
(SEQ ID NO: 147)
CPF[dD]CM[HArg]NWSTP[Cha]WC
(SEQ ID NO: 148)
CPF[dD]C[HGln][HArg]NWSTPIWC
(SEQ ID NO: 149)
CPF[dD]C[C5A][HArg]NWSTPIWC
(SEQ ID NO: 150)
CPF[dD]CM[HArg]N[Trp(Me)]STPIWC
(SEQ ID NO: 151)
CPF[dD][NMeCys]M[HArg]NWSTPIWC
(SEQ ID NO: 152)
CPF[dD]C[HArg]NWS[NMeThr]PIWC
(SEQ ID NO: 155)
CP[1Nal][dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 156)
CP[2Nal][dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 157)
CP[44BPA][dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 158)
CPF[dD]CM[HArg]NWSTPPWC
(SEQ ID NO: 159)
CPF[dD]CM[HArg]NWSTP[HyP]WC
(SEQ ID NO: 160)
CPF[dD]CL[HArg]NWSTPPWC
(SEQ ID NO: 161)
CPF[dD]CL[HArg]NWSTPIWC
(SEQ ID NO: 162)
CPY[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 163)
C[Aib]F[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 164)
C[Sar]F[dD]CM[HArg]NWSTPIWC
(SEQ ID NO: 165)
CPF[dR]CM[HArg]NWSTPIWC
(SEQ ID NO: 166)
CPF[dD]CM[HArg]NWSTPKWC
(SEQ ID NO: 167)
CP[1Nal][dD]CM[HArg]NWSTP[HyP]WC
(SEQ ID NO: 168)
CP[1Nal][dD]CM[HArg]HWSTP[HyP]WC
(SEQ ID NO: 169)
CP[1Nal][dD]CM[HArg]DWSTP[HyP]WC
(SEQ ID NO: 170)
CP[1Nal][dD]CM[HArg]DWSTPIWC
(SEQ ID NO: 171)
CP[1Nal][dR]CM[HArg]NWSTP[HyP]WC
(SEQ ID NO: 172)
CP[1Nal][dR]CM[HArg]HWSTP[HyP]WC
(SEQ ID NO: 173)
CPF[dD]CM[NMeHArg]NWSTPIWC
(SEQ ID NO: 174)
CPF[dD]CM[HArg][NMeAsn]WSTPIWC
(SEQ ID NO: 175)
CPF[dD]CM[HArg]NWS[NMeThr]PIWC
(SEQ ID NO: 176)
CPF[dD]CM[HArg]NWSTP[NMelle]WC
(SEQ ID NO: 177)
CP[1Nal][dD]CM[HArg][Cya]WSTP[HyP]WC
(SEQ ID NO: 178)
CP[1Nal][dD]CM[Cya]DWSTP[HyP]WC
(SEQ ID NO: 179)
CP[1Nal][DCya]CM[HArg]DWSTP[HyP]WC
(SEQ ID NO: 180)
CP[1Nal][dD]CM[HArg]DWDTP[HyP]WC
(SEQ ID NO: 181)
CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC
(SEQ ID NO: 182)
CP[1Nal][dD]CM[HArg]DWTTP[HyP]WC
(SEQ ID NO: 183)
CP[1Nal][dD]CM[HArg]DW[HSer]TP[HyP]WC
(SEQ ID NO: 184)
CP[1Nal][dD]CM[HArg]DW[dS]TP[HyP]WC
(SEQ ID NO: 185)
CP[1Nal][dD]CM[HArg]DWSSP[HyP]WC
(SEQ ID NO: 186)
CP[1Nal][dD]CM[Agb]DWSTP[HyP]WC
(SEQ ID NO: 187)
CP[1Nal][dD]CMPDWSTP[HyP]WC
(SEQ ID NO: 188)
CP[1Nal][dD]CM[HyP]DWSTP[HyP]WC
(SEQ ID NO: 189)
CP[1Nal][dR]CM[HArg]DWSTP[HyP]WC
(SEQ ID NO: 190)
CP[1Nal][dR]CM[HArg]DWDTP[HyP]WC
(SEQ ID NO: 191)
CP[2Nal][dR]CM[HArg]DWSTP[HyP]WC
(SEQ ID NO: 192)
CP[1Nal][dR]CM[HArg]DWTTP[HyP]WC
(SEQ ID NO: 193)
CP[1Nal][dR]CM[HArg]DW[HSer]TP[HyP]WC
(SEQ ID NO: 194)
CP[1Nal][dR]CM[HArg]DW[dS]TP[HyP]WC
(SEQ ID NO: 195)
CP[1Nal][dR]CM[HArg]DWSSP[HyP]WC
(SEQ ID NO: 196)
CP[1Nal][dR]CM[Agb]DWSTP[HyP]WC
(SEQ ID NO: 197)
CP[1Nal][dR]CMPDWSTP[HyP]WC
(SEQ ID NO: 198)
CP[1Nal][dR]CM[HyP]DWSTP[HyP]WC
(SEQ ID NO: 199)
CP[1Nal][dD]CL[HArg]DWSTPIWC
(SEQ ID NO: 200)
CP[1Nal][dD]CL[HArg]DWSTP[HyP]WC
(SEQ ID NO: 201)
CP[1Nal][dR]CL[HArg]DWSTP[HyP]WC
(SEQ ID NO: 202)
CP[1Nal][dR]CL[HArg]HWSTP[HyP]WC
(SEQ ID NO: 203)
CP[1Nal][dR]CM[HArg]DWSTPIWC
(SEQ ID NO: 208)
CP[1Nal][DCya]CM[Cya]DWSTP[HyP]WC
(SEQ ID NO: 209)
CP[1Nal][DCya]CM[HArg][Cya]WSTP[HyP]WC
(SEQ ID NO: 210)
CP[1Nal][dD]CM[Cya][Cya]WSTP[HyP]WC
(SEQ ID NO: 211)
CP[1Nal][dK]CM[HArg]DWSTP[HyP]WC
(SEQ ID NO: 212)
CP[1Nal][dD]CMKDWSTP[HyP]WC
(SEQ ID NO: 215)
CP[1Nal][dD]CM[HArg]D[dW]STP[HyP][dW]C
and
(SEQ ID NO: 216)
CPFGCM[HArg]DWSTP[HyP]WC
such as:
(SEQ ID NO: 169)
CP[1Nal][dD]CM[HArg]DWSTP[HyP]WC;
in particular:
DDA-(SEQ ID NO: 45)-A (hereinafter referred to as BCY3386);
DTA-(SEQ ID NO: 46)-A (hereinafter referred to as BCY3388);
DSE-(SEQ ID NO: 47)-A (hereinafter referred to as BCY3389);
HDA-(SEQ ID NO: 48)-A (hereinafter referred to as BCY3390);
MDT-(SEQ ID NO: 49)-A (hereinafter referred to as BCY3391);
DPG-(SEQ ID NO: 50)-A (hereinafter referred to as BCY3392);
HDS-(SEQ ID NO: 51)-A (hereinafter referred to as BCY3393);
(D-H)DS-(SEQ ID NO: 51)-A (hereinafter referred to as BCY7272);
A-(SEQ ID NO: 52)-TDK (hereinafter referred to as BCY3394);
A-(SEQ ID NO: 53)-LKD (hereinafter referred to as BCY3395);
A-(SEQ ID NO: 54)-TTA (hereinafter referred to as BCY3396);
A-(SEQ ID NO: 55)-QME (hereinafter referred to as BCY3397);
A-(SEQ ID NO: 56)-LSE (hereinafter referred to as BCY3398);
A-(SEQ ID NO: 57)-STD (hereinafter referred to as BCY3399);
A-(SEQ ID NO: 59)-TNK (hereinafter referred to as BCY7265);
Ac-(SEQ ID NO: 59) (hereinafter referred to as BCY7660);
A-(SEQ ID NO: 60)-TNK (hereinafter referred to as BCY7266);
Ac-(SEQ ID NO: 60) (hereinafter referred to as BCY7616);
HDS-(SEQ ID NO: 61)-A (hereinafter referred to as BCY7273);
HDS-(SEQ ID NO: 62)-A (hereinafter referred to as BCY7274);
HDS-(SEQ ID NO: 63)-A (hereinafter referred to as BCY7275);
HDS-(SEQ ID NO: 64)-A (hereinafter referred to as BCY7276);
A-(SEQ ID NO: 66)-TNK (hereinafter referred to as BCY7349);
A-(SEQ ID NO: 67)-TNK (hereinafter referred to as BCY7350);
Ac-(SEQ ID NO: 67) (hereinafter referred to as BCY7538);
A-(SEQ ID NO: 68)-TNK (hereinafter referred to as BCY7359);
A-(SEQ ID NO: 69)-TNK (hereinafter referred to as BCY7360);
A-(SEQ ID NO: 70)-TNK (hereinafter referred to as BCY7361);
A-(SEQ ID NO: 71)-TNK (hereinafter referred to as BCY7365);
A-(SEQ ID NO: 72)-TNK (hereinafter referred to as BCY7370);
Ac-(SEQ ID NO: 73) (hereinafter referred to as BCY7535);
Ac-(SEQ ID NO: 74) (hereinafter referred to as BCY7536);
Ac-(SEQ ID NO: 75) (hereinafter referred to as BCY7541);
[B-Ala][Sar 5 ]-(SEQ ID NO: 76) (hereinafter referred to as BCY7556);
Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 76) (hereinafter referred to as BCY7558); [B-Ala][Sar 5 ]-(SEQ ID NO: 77) (hereinafter referred to as BCY7557);
Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 77) (hereinafter referred to as BCY7559);
Ac-(SEQ ID NO: 78) (hereinafter referred to as BCY7580);
Ac-(SEQ ID NO: 79) (hereinafter referred to as BCY7581);
Ac-(SEQ ID NO: 80) (hereinafter referred to as BCY7582);
Ac-(SEQ ID NO: 81) (hereinafter referred to as BCY7584);
Ac-(SEQ ID NO: 82) (hereinafter referred to as BCY7585);
Ac-(SEQ ID NO: 83) (hereinafter referred to as BCY7588);
Ac-(SEQ ID NO: 84) (hereinafter referred to as BCY7589);
Ac-(SEQ ID NO: 85) (hereinafter referred to as BCY7590);
Ac-(SEQ ID NO: 86) (hereinafter referred to as BCY7591);
Ac-(SEQ ID NO: 87) (hereinafter referred to as BCY7592);
Ac-(SEQ ID NO: 88) (hereinafter referred to as BCY7593);
Ac-(SEQ ID NO: 89) (hereinafter referred to as BCY7594);
Ac-(SEQ ID NO: 90) (hereinafter referred to as BCY7595);
Ac-(SEQ ID NO: 91) (hereinafter referred to as BCY7596);
Ac-(SEQ ID NO: 92) (hereinafter referred to as BCY7597);
Ac-(SEQ ID NO: 93) (hereinafter referred to as BCY7598);
Ac-(SEQ ID NO: 94) (hereinafter referred to as BCY7607);
Ac-(SEQ ID NO: 95) (hereinafter referred to as BCY7608);
Ac-(SEQ ID NO: 96) (hereinafter referred to as BCY7611);
Ac-(SEQ ID NO: 97) (hereinafter referred to as BCY7612);
Ac-(SEQ ID NO: 98) (hereinafter referred to as BCY7613);
Ac-(SEQ ID NO: 99) (hereinafter referred to as BCY7614);
Ac-(SEQ ID NO: 100) (hereinafter referred to as BCY7615);
Ac-(SEQ ID NO: 101) (hereinafter referred to as BCY7618);
Ac-(SEQ ID NO: 102) (hereinafter referred to as BCY7620);
Ac-(SEQ ID NO: 111) (hereinafter referred to as BCY7663);
Ac-(SEQ ID NO: 112) (hereinafter referred to as BCY7664);
Ac-(SEQ ID NO: 113) (hereinafter referred to as BCY7667);
Ac-(SEQ ID NO: 114) (hereinafter referred to as BCY7668);
Ac-(SEQ ID NO: 115) (hereinafter referred to as BCY7765);
(SEQ ID NO: 115) (hereinafter referred to as BCY7793);
(MeO-dPEG12)(SEQ ID NO: 115) (hereinafter referred to as BCY8087);
(Carboxyfluorescein)(SEQ ID NO: 115) (hereinafter referred to as BCY8208);
(PEG3)(PEG3)(SEQ ID NO: 115) (hereinafter referred to as BCY7815);
(MeO-dPEG12)(PEG3)(PEG3)(SEQ ID NO: 115) (hereinafter referred to as BCY8094);
Ac-DDD-(SEQ ID NO: 115) (hereinafter referred to as BCY8028);
Ac-[dD][dD][dD]-(SEQ ID NO: 115) (hereinafter referred to as BCY8029);
[B-Ala][Sar10]-(SEQ ID NO: 115) (hereinafter referred to as BCY7814);
Ac-(SEQ ID NO: 116) (hereinafter referred to as BCY7816);
Ac-(SEQ ID NO: 116) (MeO-dPEG12) linked to D-Lys6 (hereinafter referred to as BCY8084);
Ac-(SEQ ID NO: 117) (hereinafter referred to as BCY7817);
Ac-(SEQ ID NO: 118) (hereinafter referred to as BCY7818;
Ac-(SEQ ID NO: 118) (MeO-dPEG12) linked to Pro(4NH)1 (hereinafter referred to as BCY8086);
Ac-(SEQ ID NO: 119) (hereinafter referred to as BCY7819;
Ac-(SEQ ID NO: 119) (MeO-dPEG12) linked to Lys5 (hereinafter referred to as BCY8088);
Ac-(SEQ ID NO: 120) (hereinafter referred to as BCY7820;
Ac-(SEQ ID NO: 120) (MeO-dPEG12) linked to D-Lys3 (hereinafter referred to as BCY8089);
Ac-(SEQ ID NO: 121) (hereinafter referred to as BCY7821);
Ac-(SEQ ID NO: 121) (MeO-dPEG12) linked to Lys4 (hereinafter referred to as BCY8090);
Ac-(SEQ ID NO: 122) (hereinafter referred to as BCY7822);
Ac-(SEQ ID NO: 122) (MeO-dPEG12) linked to Lys6 (hereinafter referred to as BCY8091);
Ac-(SEQ ID NO: 123) (hereinafter referred to as BCY7876);
Ac-(SEQ ID NO: 124) (hereinafter referred to as BCY7877);
Ac-(SEQ ID NO: 125) (hereinafter referred to as BCY7879);
Ac-(SEQ ID NO: 126) (hereinafter referred to as BCY7881);
Ac-(SEQ ID NO: 127) (hereinafter referred to as BCY7883);
Ac-(SEQ ID NO: 128) (hereinafter referred to as BCY7884);
Ac-(SEQ ID NO: 129) (hereinafter referred to as BCY7886);
Ac-(SEQ ID NO: 130) (hereinafter referred to as BCY7887);
Ac-(SEQ ID NO: 131) (hereinafter referred to as BCY7889);
Ac-(SEQ ID NO: 132) (hereinafter referred to as BCY7890);
Ac-(SEQ ID NO: 133) (hereinafter referred to as BCY7891);
Ac-(SEQ ID NO: 134) (hereinafter referred to as BCY7892);
Ac-(SEQ ID NO: 135) (hereinafter referred to as BCY7894);
Ac-(SEQ ID NO: 136) (hereinafter referred to as BCY7895);
Ac-(SEQ ID NO: 137) (hereinafter referred to as BCY7896);
Ac-(SEQ ID NO: 138) (hereinafter referred to as BCY7897);
Ac-(SEQ ID NO: 139) (hereinafter referred to as BCY7902);
Ac-(SEQ ID NO: 140) (hereinafter referred to as BCY7903);
Ac-(SEQ ID NO: 141) (hereinafter referred to as BCY7904);
Ac-(SEQ ID NO: 142) (hereinafter referred to as BCY7906);
Ac-(SEQ ID NO: 143) (hereinafter referred to as BCY7907);
Ac-(SEQ ID NO: 144) (hereinafter referred to as BCY7908);
Ac-(SEQ ID NO: 145) (hereinafter referred to as BCY7911);
Ac-(SEQ ID NO: 146) (hereinafter referred to as BCY7912);
Ac-(SEQ ID NO: 147) (hereinafter referred to as BCY7913);
Ac-(SEQ ID NO: 148) (hereinafter referred to as BCY7914);
Ac-(SEQ ID NO: 149) (hereinafter referred to as BCY7915);
Ac-(SEQ ID NO: 150) (hereinafter referred to as BCY7916);
Ac-(SEQ ID NO: 151) (hereinafter referred to as BCY7973);
Ac-(SEQ ID NO: 152) (hereinafter referred to as BCY7979);
Ac-(SEQ ID NO: 155) (hereinafter referred to as BCY8030);
Ac-(SEQ ID NO: 156) (hereinafter referred to as BCY8031);
Ac-(SEQ ID NO: 157) (hereinafter referred to as BCY8032);
Ac-(SEQ ID NO: 158) (hereinafter referred to as BCY8036);
Ac-(SEQ ID NO: 159) (hereinafter referred to as BCY8037);
Ac-(SEQ ID NO: 160) (hereinafter referred to as BCY8038);
Ac-(SEQ ID NO: 161) (hereinafter referred to as BCY8039);
Ac-(SEQ ID NO: 162) (hereinafter referred to as BCY8040);
Ac-(SEQ ID NO: 163) (hereinafter referred to as BCY8041);
Ac-(SEQ ID NO: 164) (hereinafter referred to as BCY8042);
Ac-(SEQ ID NO: 165) (hereinafter referred to as BCY8042);
Ac-(SEQ ID NO: 166) (hereinafter referred to as BCY8085);
Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 167) (hereinafter referred to as BCY8120);
Ac-(SEQ ID NO: 167) (hereinafter referred to as BCY8124);
Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 168) (hereinafter referred to as BCY8121);
Ac-(SEQ ID NO: 168) (hereinafter referred to as BCY8125);
Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 169) (hereinafter referred to as BCY8122);
Ac-(SEQ ID NO: 169) (hereinafter referred to as BCY8126);
(SEQ ID NO: 169) (hereinafter referred to as BCY8116);
Fluorescein-(SEQ ID NO: 169) (hereinafter referred to as BCY8205);
[B-Ala][Sar10]-(SEQ ID NO: 169) (hereinafter referred to as BCY8234);
[PYA][B-Ala][Sar10]-(SEQ ID NO: 169) (hereinafter referred to as BCY8846);
Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 170) (hereinafter referred to as BCY8123);
Ac-(SEQ ID NO: 170) (hereinafter referred to as BCY8127);
(SEQ ID NO: 170) (hereinafter referred to as BCY8206);
Ac-(SEQ ID NO: 171) (hereinafter referred to as BCY8128);
(SEQ ID NO: 171) (hereinafter referred to as BCY8207);
[B-Ala][Sar10]-(SEQ ID NO: 171) (hereinafter referred to as BCY8232);
Ac-(SEQ ID NO: 172) (hereinafter referred to as BCY8129);
Ac-(SEQ ID NO: 173) (hereinafter referred to as BCY8153);
Ac-(SEQ ID NO: 174) (hereinafter referred to as BCY8154);
Ac-(SEQ ID NO: 175) (hereinafter referred to as BCY8157);
Ac-(SEQ ID NO: 176) (hereinafter referred to as BCY8158);
Ac-(SEQ ID NO: 177) (hereinafter referred to as BCY8161);
Ac[B-Ala][Sar10]-(SEQ ID NO: 177) (hereinafter referred to as BCY8278);
Ac-(SEQ ID NO: 178) (hereinafter referred to as BCY8162);
Ac[B-Ala][Sar10]-(SEQ ID NO: 178) (hereinafter referred to as BCY8277);
Ac-(SEQ ID NO: 179) (hereinafter referred to as BCY8163);
Ac[B-Ala][Sar10]-(SEQ ID NO: 179) (hereinafter referred to as BCY8276);
[B-Ala][Sar10]-(SEQ ID NO: 179) (hereinafter referred to as BCY8269);
Ac-(SEQ ID NO: 180) (hereinafter referred to as BCY8174);
Ac-(SEQ ID NO: 181) (hereinafter referred to as BCY8175);
Ac-(SEQ ID NO: 182) (hereinafter referred to as BCY8176);
Ac-(SEQ ID NO: 183) (hereinafter referred to as BCY8177);
Ac-(SEQ ID NO: 184) (hereinafter referred to as BCY8178);
Ac-(SEQ ID NO: 185) (hereinafter referred to as BCY8180);
Ac-(SEQ ID NO: 186) (hereinafter referred to as BCY8181);
Ac-(SEQ ID NO: 187) (hereinafter referred to as BCY8182);
Ac-(SEQ ID NO: 188) (hereinafter referred to as BCY8183);
Ac-(SEQ ID NO: 189) (hereinafter referred to as BCY8184);
[B-Ala][Sar10]-(SEQ ID NO: 189) (hereinafter referred to as BCY8235);
Ac-(SEQ ID NO: 190) (hereinafter referred to as BCY8185);
Ac-(SEQ ID NO: 191) (hereinafter referred to as BCY8186);
Ac-(SEQ ID NO: 192) (hereinafter referred to as BCY8187);
Ac-(SEQ ID NO: 193) (hereinafter referred to as BCY8188);
Ac-(SEQ ID NO: 194) (hereinafter referred to as BCY8189);
Ac-(SEQ ID NO: 195) (hereinafter referred to as BCY8191);
Ac-(SEQ ID NO: 196) (hereinafter referred to as BCY8192);
Ac-(SEQ ID NO: 197) (hereinafter referred to as BCY8193);
Ac-(SEQ ID NO: 198) (hereinafter referred to as BCY8194);
Ac-(SEQ ID NO: 199) (hereinafter referred to as BCY8211);
Ac-(SEQ ID NO: 200) (hereinafter referred to as BCY8212);
Ac-(SEQ ID NO: 201) (hereinafter referred to as BCY8213);
Ac-(SEQ ID NO: 202) (hereinafter referred to as BCY8214);
[B-Ala][Sar10]-(SEQ ID NO: 202) (hereinafter referred to as BCY8231);
Ac-(SEQ ID NO: 203) (hereinafter referred to as BCY8215);
Ac[B-Ala][Sar10]-(SEQ ID NO: 208) (hereinafter referred to as BCY8279);
Ac[B-Ala][Sar10]-(SEQ ID NO: 209) (hereinafter referred to as BCY8280);
[B-Ala][Sar10]-(SEQ ID NO: 209) (hereinafter referred to as BCY8273);
Ac[B-Ala][Sar10]-(SEQ ID NO: 210) (hereinafter referred to as BCY8281);
Ac-(SEQ ID NO: 211) (hereinafter referred to as BCY8831);
[B-Ala][Sar10]-(SEQ ID NO: 212) (hereinafter referred to as BCY8238);
(SEQ ID NO: 215) (hereinafter referred to as BCY11415);
[PYA][B-Ala][Sar10]-(SEQ ID NO: 215) (hereinafter referred to as BCY11942); and
(SEQ ID NO: 216) (hereinafter referred to as BCY11414);
more particularly:
Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 169) (hereinafter referred to as BCY8122);
Ac-(SEQ ID NO: 169) (hereinafter referred to as BCY8126);
(SEQ ID NO: 169) (hereinafter referred to as BCY8116);
Fluorescein-(SEQ ID NO: 169) (hereinafter referred to as BCY8205); and
[B-Ala][Sar10]-(SEQ ID NO: 169) (hereinafter referred to as BCY8234);
especially:
[B-Ala][Sar10]-(SEQ ID NO: 169) (hereinafter referred to as BCY8234).
10 . The peptide ligand as defined in claim 4 , which comprises an amino acid sequence selected from:
A-(SEQ ID NO: 1)-A (herein referred to as 80-09-02-N002 or BCY428); FI-A-(SQ ID NO: 1)-A (herein referred to as 80-09-02-N006); Ac-(SEQ ID NO: 1) (herein referred to as 80-09-02-N008 or BCY7390); Ac-[dD]-(SEQ ID NO: 1) (herein referred to as BCY7606); A-(SEQ ID NO: 2)-A (herein referred to as 80-09-02-N003 or BCY429); (1-Nal)A-(SEQ ID NO: 1)-A (herein referred to as 80-09-02-N009 or BCY7420); (2-Nal)A-(SEQ ID NO: 1)-A (herein referred to as 80-09-02-N010 or BCY7421); (33DPA)A-(SEQ ID NO: 1)-A (herein referred to as 80-09-02-N011 or BCY7422); (44BPA)A-(SEQ ID NO: 1)-A (herein referred to as 80-09-02-N012 or BCY7521); Ac-(SEQ ID NO: 3) (herein referred to as 80-09-02-N017); Ac-(SEQ ID NO: 4) (herein referred to as 80-09-02-N018); Ac-(SQ ID NO: 5) (herein referred to as 80-09-02-N019 or BCY7537); Ac-(SEQ ID NO: 6) (herein referred to as 80-09-02-N020); Ac-(SEQ ID NO: 7) (herein referred to as 80-09-02-N021 or BCY7539); Ac-(SEQ ID NO: 8) (herein referred to as 80-09-02-N022 or BCY7540); Ac-(SEQ ID NO: 9) (herein referred to as 80-09-02-N023); Ac-(pCoF)-(SEQ ID NO: 1) (herein referred to as 80-09-02-N044); Ac-(SEQ ID NO: 10) (herein referred to as 80-09-02-N045); Ac-(SEQ ID NO: 11) (herein referred to as 80-09-02-N046 or BCY7657); Ac-(SEQ ID NO: 12) (herein referred to as 80-09-02-N047 or BCY7658); Ac-(SEQ ID NO: 13) (herein referred to as 80-09-02-N048 or BCY7659); Ac-(SEQ ID NO: 14) (herein referred to as 80-09-02-N049); Ac-(SEQ ID NO: 15) (herein referred to as 80-09-02-N050 or BCY7661); SDN-(SEQ ID NO: 15)-A (herein referred to as BCY3387); Ac-(SEQ ID NO: 16) (herein referred to as 80-09-02-N051 or BCY7662); Ac-(SEQ ID NO: 17) (herein referred to as 80-09-02-N052); Ac-(SEQ ID NO: 18) (herein referred to as 80-09-02-N053); Ac-(SEQ ID NO: 19) (herein referred to as 80-09-02-N054 or BCY7665); Ac-(SEQ ID NO: 20) (herein referred to as 80-09-02-N055 or BCY7666); Ac-(SEQ ID NO: 21) (herein referred to as 80-09-02-N056); A-(SEQ ID NO: 1)-TNK (herein referred to as 80-09-02-T01-N001 or BCY3385); A-(SEQ ID NO: 1)-TN(HArg) (herein referred to as 80-09-02-T01-N003 or BCY7281); A-(SEQ ID NO: 1)-TN(D-K) (herein referred to as 80-09-02-T01-N004 or BCY7282); A-(SEQ ID NO: 22)-TNK (herein referred to as 80-09-02-T01-N005); A-(SEQ ID NO: 23)-TNK (herein referred to as 80-09-02-T01-N006); Ac-(SEQ ID NO: 1)-TNK (herein referred to as 80-09-02-T01-N011 or BCY7391); A-(SEQ ID NO: 24)-TNK (herein referred to as 80-09-02-T01-N012 or BCY7342); A-(SEQ ID NO: 25)-TNK (herein referred to as 80-09-02-T01-N014 or BCY7344); A-(SEQ ID NO: 1)-ANK (herein referred to as 80-09-02-T01-N016 or BCY7346); A-(SEQ ID NO: 1)-[dA]NK (herein referred to as BCY7367); A-(SEQ ID NO: 1)-TAK (herein referred to as 80-09-02-T01-N017 or BCY7347); A-(SEQ ID NO: 1)-T[dA]K (herein referred to as BCY7368); A-(SEQ ID NO: 1)-TNA (herein referred to as 80-09-02-T01-N018 or BCY7348); A-(SEQ ID NO: 1)-TN[dA] (herein referred to as BCY7369); Ac-[pCoPhe]-(SEQ ID NO: 1) (herein referred to as BCY7656); A-(SEQ ID NO: 6)-TNK (herein referred to as 80-09-02-T01-N020 or BCY7354); A-(SEQ ID NO: 26)-TNK (herein referred to as 80-09-02-T01-N022 or BCY7352); A-(SEQ ID NO: 27)-TNK (herein referred to as 80-09-02-T01-N026 or BCY7356); A-(SEQ ID NO: 28)-TNK (herein referred to as 80-09-02-T01-N027 or BCY7357); A-(SEQ ID NO: 29)-TNK (herein referred to as 80-09-02-T01-N041 or BCY7372); A-(SEQ ID NO: 30)-TNK (herein referred to as 80-09-02-T01-N042 or BCY7424); A-(SEQ ID NO: 31)-A (herein referred to as 80-10-00 or BCY488); A-(SEQ ID NO: 32)-A (herein referred to as BCY432); DDW-(SEQ ID NO: 32)-A (herein referred to as 80-10-11-T01 or BCY433); VDW-(SEQ ID NO: 33)-A (herein referred to as 80-10-12-T01 or BCY462); QKW-(SEQ ID NO: 34)-A (herein referred to as 80-10-13-T01 or BCY3400); Q[HArg]W-(SEQ ID NO: 34)-A (herein referred to as BCY7278); Q[K(Ac)]W-(SEQ ID NO: 34)-A (herein referred to as BCY7280); [Ac]QKW-(SEQ ID NO: 34) (herein referred to as BCY7392); Q[dK]W-(SEQ ID NO: 34)-A (herein referred to as BCY7426); Ac-AKW-(SEQ ID NO: 34) (herein referred to as BCY7622); Ac-QAW-(SEQ ID NO: 34) (herein referred to as BCY7623); Ac-QKA-(SEQ ID NO: 34) (herein referred to as BCY7624); Ac-[dA]KW-(SEQ ID NO: 34) (herein referred to as BCY7634); Ac-Q[dA]W-(SEQ ID NO: 34) (herein referred to as BCY7635); Ac-QK[dA]-(SEQ ID NO: 34) (herein referred to as BCY7636); Ac-Q[dD]W-(SEQ ID NO: 34) (herein referred to as BCY7993); Ac-QK[1Nal]-(SEQ ID NO: 34) (herein referred to as BCY7996); Ac-QK[2Nal]-(SEQ ID NO: 34) (herein referred to as BCY7997); Ac-(SEQ ID NO: 34) (herein referred to as BCY8044); A-(SEQ ID NO: 43)-A (hereinafter referred to as BCY430); A-(SEQ ID NO: 44)-A (hereinafter referred to as BCY431); A-(SEQ ID NO: 58)-PQA (hereinafter referred to as BCY3401); QKW-(SEQ ID NO: 65)-A (hereinafter referred to as BCY7279); Ac-QKW-(SEQ ID NO: 103) (hereinafter referred to as BCY7625); Ac-QKW-(SEQ ID NO: 104) (hereinafter referred to as BCY7627); Ac-QKW-(SEQ ID NO: 105) (hereinafter referred to as BCY7628); Ac-QKW-(SEQ ID NO: 106) (hereinafter referred to as BCY7631); Ac-QKW-(SEQ ID NO: 107) (hereinafter referred to as BCY7632); Ac-QKW-(SEQ ID NO: 108) (hereinafter referred to as BCY7639); Ac-QKW-(SEQ ID NO: 109) (hereinafter referred to as BCY7640); Ac-QKW-(SEQ ID NO: 110) (hereinafter referred to as BCY7643); Ac-QKW-(SEQ ID NO: 153) (hereinafter referred to as BCY7998); Ac-QKW-(SEQ ID NO: 154) (hereinafter referred to as BCY8000); A-(SEQ ID NO: 35)-A (herein referred to as 80-11-00 or BCY471); A-(SEQ ID NO: 36)-A (herein referred to as 80-11-01 or BCY472); A-(SEQ ID NO: 37)-SRF (herein referred to as 80-11-08-T01 or BCY3406); Ac-(SEQ ID NO: 37)-SRF (herein referred to as BCY7393); DDA-(SEQ ID NO: 45)-A (hereinafter referred to as BCY3386); DTA-(SEQ ID NO: 46)-A (hereinafter referred to as BCY3388); DSE-(SEQ ID NO: 47)-A (hereinafter referred to as BCY3389); HDA-(SEQ ID NO: 48)-A (hereinafter referred to as BCY3390); MDT-(SEQ ID NO: 49)-A (hereinafter referred to as BCY3391); DPG-(SEQ ID NO: 50)-A (hereinafter referred to as BCY3392); HDS-(SEQ ID NO: 51)-A (hereinafter referred to as BCY3393); (D-H)DS-(SEQ ID NO: 51)-A (hereinafter referred to as BCY7272); A-(SEQ ID NO: 52)-TDK (hereinafter referred to as BCY3394); A-(SEQ ID NO: 53)-LKD (hereinafter referred to as BCY3395); A-(SEQ ID NO: 54)-TTA (hereinafter referred to as BCY3396); A-(SEQ ID NO: 55)-QME (hereinafter referred to as BCY3397); A-(SEQ ID NO: 56)-LSE (hereinafter referred to as BCY3398); A-(SEQ ID NO: 57)-STD (hereinafter referred to as BCY3399); A-(SEQ ID NO: 59)-TNK (hereinafter referred to as BCY7265); Ac-(SEQ ID NO: 59) (hereinafter referred to as BCY7660); A-(SEQ ID NO: 60)-TNK (hereinafter referred to as BCY7266); Ac-(SEQ ID NO: 60) (hereinafter referred to as BCY7616); HDS-(SEQ ID NO: 61)-A (hereinafter referred to as BCY7273); HDS-(SEQ ID NO: 62)-A (hereinafter referred to as BCY7274); HDS-(SEQ ID NO: 63)-A (hereinafter referred to as BCY7275); HDS-(SEQ ID NO: 64)-A (hereinafter referred to as BCY7276); A-(SEQ ID NO: 66)-TNK (hereinafter referred to as BCY7349); A-(SEQ ID NO: 67)-TNK (hereinafter referred to as BCY7350); Ac-(SEQ ID NO: 67) (hereinafter referred to as BCY7538); A-(SEQ ID NO: 68)-TNK (hereinafter referred to as BCY7359); A-(SEQ ID NO: 69)-TNK (hereinafter referred to as BCY7360); A-(SEQ ID NO: 70)-TNK (hereinafter referred to as BCY7361); A-(SEQ ID NO: 71)-TNK (hereinafter referred to as BCY7365); A-(SEQ ID NO: 72)-TNK (hereinafter referred to as BCY7370); Ac-(SEQ ID NO: 73) (hereinafter referred to as BCY7535); Ac-(SEQ ID NO: 74) (hereinafter referred to as BCY7536); Ac-(SEQ ID NO: 75) (hereinafter referred to as BCY7541); [B-Ala][Sar 5 ]-(SEQ ID NO: 76) (hereinafter referred to as BCY7556); Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 76) (hereinafter referred to as BCY7558); [B-Ala][Sar 5 ]-(SEQ ID NO: 77) (hereinafter referred to as BCY7557); Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 77) (hereinafter referred to as BCY7559); Ac-(SEQ ID NO: 78) (hereinafter referred to as BCY7580); Ac-(SEQ ID NO: 79) (hereinafter referred to as BCY7581); Ac-(SEQ ID NO: 80) (hereinafter referred to as BCY7582); Ac-(SEQ ID NO: 81) (hereinafter referred to as BCY7584); Ac-(SEQ ID NO: 82) (hereinafter referred to as BCY7585); Ac-(SEQ ID NO: 83) (hereinafter referred to as BCY7588); Ac-(SEQ ID NO: 84) (hereinafter referred to as BCY7589); Ac-(SEQ ID NO: 85) (hereinafter referred to as BCY7590); Ac-(SEQ ID NO: 86) (hereinafter referred to as BCY7591); Ac-(SEQ ID NO: 87) (hereinafter referred to as BCY7592); Ac-(SEQ ID NO: 88) (hereinafter referred to as BCY7593); Ac-(SEQ ID NO: 89) (hereinafter referred to as BCY7594); Ac-(SEQ ID NO: 90) (hereinafter referred to as BCY7595); Ac-(SEQ ID NO: 91) (hereinafter referred to as BCY7596); Ac-(SEQ ID NO: 92) (hereinafter referred to as BCY7597); Ac-(SEQ ID NO: 93) (hereinafter referred to as BCY7598); Ac-(SEQ ID NO: 94) (hereinafter referred to as BCY7607); Ac-(SEQ ID NO: 95) (hereinafter referred to as BCY7608); Ac-(SEQ ID NO: 96) (hereinafter referred to as BCY7611); Ac-(SEQ ID NO: 97) (hereinafter referred to as BCY7612); Ac-(SEQ ID NO: 98) (hereinafter referred to as BCY7613); Ac-(SEQ ID NO: 99) (hereinafter referred to as BCY7614); Ac-(SEQ ID NO: 100) (hereinafter referred to as BCY7615); Ac-(SEQ ID NO: 101) (hereinafter referred to as BCY7618); Ac-(SEQ ID NO: 102) (hereinafter referred to as BCY7620); Ac-(SEQ ID NO: 111) (hereinafter referred to as BCY7663); Ac-(SEQ ID NO: 112) (hereinafter referred to as BCY7664); Ac-(SEQ ID NO: 113) (hereinafter referred to as BCY7667); Ac-(SEQ ID NO: 114) (hereinafter referred to as BCY7668); Ac-(SEQ ID NO: 115) (hereinafter referred to as BCY7765); (SEQ ID NO: 115) (hereinafter referred to as BCY7793); (MeO-dPEG12)(SEQ ID NO: 115) (hereinafter referred to as BCY8087); (Carboxyfluorescein)(SEQ ID NO: 115) (hereinafter referred to as BCY8208); (PEG 3 )(PEG 3 )(SEQ ID NO: 115) (hereinafter referred to as BCY7815); (MeO-dPEG12)(PEG3)(PEG3)(SEQ ID NO: 115) (hereinafter referred to as BCY8094); Ac-DDD-(SEQ ID NO: 115) (hereinafter referred to as BCY8028); Ac-[dD][dD][dD]-(SEQ ID NO: 115) (hereinafter referred to as BCY8029); [B-Ala][Sar10]-(SEQ ID NO: 115) (hereinafter referred to as BCY7814); Ac-(SEQ ID NO: 116) (hereinafter referred to as BCY7816); Ac-(SEQ ID NO: 116) (MeO-dPEG12) linked to D-Lys6 (hereinafter referred to as BCY8084); Ac-(SEQ ID NO: 117) (hereinafter referred to as BCY7817); Ac-(SEQ ID NO: 118) (hereinafter referred to as BCY7818; Ac-(SEQ ID NO: 118) (MeO-dPEG12) linked to Pro(4NH)1 (hereinafter referred to as BCY8086); Ac-(SEQ ID NO: 119) (hereinafter referred to as BCY7819; Ac-(SEQ ID NO: 119) (MeO-dPEG12) linked to Lys5 (hereinafter referred to as BCY8088); Ac-(SEQ ID NO: 120) (hereinafter referred to as BCY7820; Ac-(SEQ ID NO: 120) (MeO-dPEG12) linked to D-Lys3 (hereinafter referred to as BCY8089); Ac-(SEQ ID NO: 121) (hereinafter referred to as BCY7821); Ac-(SEQ ID NO: 121) (MeO-dPEG12) linked to Lys4 (hereinafter referred to as BCY8090); Ac-(SEQ ID NO: 122) (hereinafter referred to as BCY7822); Ac-(SEQ ID NO: 122) (MeO-dPEG12) linked to Lys6 (hereinafter referred to as BCY8091); Ac-(SEQ ID NO: 123) (hereinafter referred to as BCY7876); Ac-(SEQ ID NO: 124) (hereinafter referred to as BCY7877); Ac-(SEQ ID NO: 125) (hereinafter referred to as BCY7879); Ac-(SEQ ID NO: 126) (hereinafter referred to as BCY7881); Ac-(SEQ ID NO: 127) (hereinafter referred to as BCY7883); Ac-(SEQ ID NO: 128) (hereinafter referred to as BCY7884); Ac-(SEQ ID NO: 129) (hereinafter referred to as BCY7886); Ac-(SEQ ID NO: 130) (hereinafter referred to as BCY7887); Ac-(SEQ ID NO: 131) (hereinafter referred to as BCY7889); Ac-(SEQ ID NO: 132) (hereinafter referred to as BCY7890); Ac-(SEQ ID NO: 133) (hereinafter referred to as BCY7891); Ac-(SEQ ID NO: 134) (hereinafter referred to as BCY7892); Ac-(SEQ ID NO: 135) (hereinafter referred to as BCY7894); Ac-(SEQ ID NO: 136) (hereinafter referred to as BCY7895); Ac-(SEQ ID NO: 137) (hereinafter referred to as BCY7896); Ac-(SEQ ID NO: 138) (hereinafter referred to as BCY7897); Ac-(SEQ ID NO: 139) (hereinafter referred to as BCY7902); Ac-(SEQ ID NO: 140) (hereinafter referred to as BCY7903); Ac-(SEQ ID NO: 141) (hereinafter referred to as BCY7904); Ac-(SEQ ID NO: 142) (hereinafter referred to as BCY7906); Ac-(SEQ ID NO: 143) (hereinafter referred to as BCY7907); Ac-(SEQ ID NO: 144) (hereinafter referred to as BCY7908); Ac-(SEQ ID NO: 145) (hereinafter referred to as BCY7911); Ac-(SEQ ID NO: 146) (hereinafter referred to as BCY7912); Ac-(SEQ ID NO: 147) (hereinafter referred to as BCY7913); Ac-(SEQ ID NO: 148) (hereinafter referred to as BCY7914); Ac-(SEQ ID NO: 149) (hereinafter referred to as BCY7915); Ac-(SEQ ID NO: 150) (hereinafter referred to as BCY7916); Ac-(SEQ ID NO: 151) (hereinafter referred to as BCY7973); Ac-(SEQ ID NO: 152) (hereinafter referred to as BCY7979); Ac-(SEQ ID NO: 155) (hereinafter referred to as BCY8030); Ac-(SEQ ID NO: 156) (hereinafter referred to as BCY8031); Ac-(SEQ ID NO: 157) (hereinafter referred to as BCY8032); Ac-(SEQ ID NO: 158) (hereinafter referred to as BCY8036); Ac-(SEQ ID NO: 159) (hereinafter referred to as BCY8037); Ac-(SEQ ID NO: 160) (hereinafter referred to as BCY8038); Ac-(SEQ ID NO: 161) (hereinafter referred to as BCY8039); Ac-(SEQ ID NO: 162) (hereinafter referred to as BCY8040); Ac-(SEQ ID NO: 163) (hereinafter referred to as BCY8041); Ac-(SEQ ID NO: 164) (hereinafter referred to as BCY8042); Ac-(SEQ ID NO: 165) (hereinafter referred to as BCY8042); Ac-(SEQ ID NO: 166) (hereinafter referred to as BCY8085); Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 167) (hereinafter referred to as BCY8120); Ac-(SEQ ID NO: 167) (hereinafter referred to as BCY8124); Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 168) (hereinafter referred to as BCY8121); Ac-(SEQ ID NO: 168) (hereinafter referred to as BCY8125); Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 169) (hereinafter referred to as BCY8122); Ac-(SEQ ID NO: 169) (hereinafter referred to as BCY8126); (SEQ ID NO: 169) (hereinafter referred to as BCY8116); Fluorescein-(SEQ ID NO: 169) (hereinafter referred to as BCY8205); [B-Ala][Sar10]-(SEQ ID NO: 169) (hereinafter referred to as BCY8234); [PYA][B-Ala][Sar10]-(SEQ ID NO: 169) (hereinafter referred to as BCY8846); Ac[B-Ala][Sar 5 ]-(SEQ ID NO: 170) (hereinafter referred to as BCY8123); Ac-(SEQ ID NO: 170) (hereinafter referred to as BCY8127); (SEQ ID NO: 170) (hereinafter referred to as BCY8206); Ac-(SEQ ID NO: 171) (hereinafter referred to as BCY8128); (SEQ ID NO: 171) (hereinafter referred to as BCY8207); [B-Ala][Sar10]-(SEQ ID NO: 171) (hereinafter referred to as BCY8232); Ac-(SEQ ID NO: 172) (hereinafter referred to as BCY8129); Ac-(SEQ ID NO: 173) (hereinafter referred to as BCY8153); Ac-(SEQ ID NO: 174) (hereinafter referred to as BCY8154); Ac-(SEQ ID NO: 175) (hereinafter referred to as BCY8157); Ac-(SEQ ID NO: 176) (hereinafter referred to as BCY8158); Ac-(SEQ ID NO: 177) (hereinafter referred to as BCY8161); Ac[B-Ala][Sar10]-(SEQ ID NO: 177) (hereinafter referred to as BCY8278); Ac-(SEQ ID NO: 178) (hereinafter referred to as BCY8162); Ac[B-Ala][Sar10]-(SEQ ID NO: 178) (hereinafter referred to as BCY8277); Ac-(SEQ ID NO: 179) (hereinafter referred to as BCY8163); Ac-[B-Ala][Sar10]-(SEQ ID NO: 179) (hereinafter referred to as BCY8276); [B-Ala][Sar10]-(SEQ ID NO: 179) (hereinafter referred to as BCY8269); Ac-(SEQ ID NO: 180) (hereinafter referred to as BCY8174); Ac-(SEQ ID NO: 181) (hereinafter referred to as BCY8175); Ac-(SEQ ID NO: 182) (hereinafter referred to as BCY8176); Ac-(SEQ ID NO: 183) (hereinafter referred to as BCY8177); Ac-(SEQ ID NO: 184) (hereinafter referred to as BCY8178); Ac-(SEQ ID NO: 185) (hereinafter referred to as BCY8180); Ac-(SEQ ID NO: 186) (hereinafter referred to as BCY8181); Ac-(SEQ ID NO: 187) (hereinafter referred to as BCY8182); Ac-(SEQ ID NO: 188) (hereinafter referred to as BCY8183); Ac-(SEQ ID NO: 189) (hereinafter referred to as BCY8184); [B-Ala][Sar10]-(SEQ ID NO: 189) (hereinafter referred to as BCY8235); Ac-(SEQ ID NO: 190) (hereinafter referred to as BCY8185); Ac-(SEQ ID NO: 191) (hereinafter referred to as BCY8186); Ac-(SEQ ID NO: 192) (hereinafter referred to as BCY8187); Ac-(SEQ ID NO: 193) (hereinafter referred to as BCY8188); Ac-(SEQ ID NO: 194) (hereinafter referred to as BCY8189); Ac-(SEQ ID NO: 195) (hereinafter referred to as BCY8191); Ac-(SEQ ID NO: 196) (hereinafter referred to as BCY8192); Ac-(SEQ ID NO: 197) (hereinafter referred to as BCY8193); Ac-(SEQ ID NO: 198) (hereinafter referred to as BCY8194); Ac-(SEQ ID NO: 199) (hereinafter referred to as BCY8211); Ac-(SEQ ID NO: 200) (hereinafter referred to as BCY8212); Ac-(SEQ ID NO: 201) (hereinafter referred to as BCY8213); Ac-(SEQ ID NO: 202) (hereinafter referred to as BCY8214); [B-Ala][Sar10]-(SEQ ID NO: 202) (hereinafter referred to as BCY8231); Ac-(SEQ ID NO: 203) (hereinafter referred to as BCY8215); Ac[B-Ala][Sar10]-(SEQ ID NO: 208) (hereinafter referred to as BCY8279); Ac[B-Ala][Sar10]-(SEQ ID NO: 209) (hereinafter referred to as BCY8280); [B-Ala][Sar10]-(SEQ ID NO: 209) (hereinafter referred to as BCY8273); Ac[B-Ala][Sar10]-(SEQ ID NO: 210) (hereinafter referred to as BCY8281); Ac-(SEQ ID NO: 211) (hereinafter referred to as BCY8831); [B-Ala][Sar10]-(SEQ ID NO: 212) (hereinafter referred to as BCY8238); (SEQ ID NO: 215) (hereinafter referred to as BCY11415); [PYA][B-Ala][Sar10]-(SEQ ID NO: 215) (hereinafter referred to as BCY11942); and (SEQ ID NO: 216) (hereinafter referred to as BCY11414).
11 . The peptide ligand as defined in any one of claims 1 to 10 , wherein the molecular scaffold is selected from 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA).
12 . The peptide ligand as defined in any one of claims 1 to 11 , wherein the pharmaceutically acceptable salt is selected from the free acid or the sodium, potassium, calcium, ammonium salt.
13 . The peptide ligand as defined in any one of claims 1 to 12 , wherein the Nectin-4 is human Nectin-4.
14 . A drug conjugate comprising a peptide ligand as defined in any one of claims 1 to 13 , conjugated to one or more effector and/or functional groups.
15 . The drug conjugate as defined in claim 14 , conjugated to one or more cytotoxic agents.
16 . The drug conjugate as defined in claim 15 , wherein said cytotoxic agent is selected from MMAE or DM1, in particular MMAE.
17 . The drug conjugate as defined in claim 16 , wherein the cytotoxic agent is MMAE and said conjugate additionally comprises a linker selected from: -PABC-Cit-Val-Glutaryl- or -PABC-cyclobutyl-Ala-Cit-pAla-, such as -PABC-Cit-Val-Glutaryl-, wherein PABC represents p-aminobenzylcarbamate.
18 . The drug conjugate as defined in claim 16 , wherein the cytotoxic agent is DM1 and said conjugate additionally comprises a linker which is -SPDB-(SO 3 H)—, wherein SPDB represents N-succinimidyl 3-(2-pyridyldithio)propionate.
19 . The drug conjugate as defined in any one of claims 14 to 18 , which is selected from any one of: BCY7683, BCY7825, BCY7826, BCY8245, BCY8253, BCY8254, BCY8255, BCY8549, BCY8550, BCY8783 and BCY8784, such as: BCY7683, BCY7825, BCY7826, BCY8245, BCY8253, BCY8254, BCY8255, BCY8783 and BCY8784, in particular BCY8245.
20 . A pharmaceutical composition which comprises the peptide ligand of any one of claims 1 to 13 or the drug conjugate of any one of claims 14 to 19 , in combination with one or more pharmaceutically acceptable excipients.
21 . The pharmaceutical composition as defined in claim 20 , which additionally comprises one or more therapeutic agents.
22 . The drug conjugate as defined in any one of claims 14 to 19 , for use in preventing, suppressing or treating a disease or disorder mediated by Nectin-4.
23 . A method of preventing, suppressing or treating cancer, which comprises administering to a patient in need thereof the drug conjugate as defined in any one of claims 14 to 19 , wherein said patient is identified as having an increased copy number variation (CNV) of Nectin-4.Cited by (0)
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