IP Library › Granted Patent US 11,623,012

Granted Patent B2

US 11,623,012 · App. 16/771,142 · Granted Apr 11, 2023

Bicyclic peptide ligands specific for EphA2

Inventors: Liuhong Chen (Cambridge, GB); Silvia Pavan (Cambridge, GB); Catherine Stace (Cambridge, GB); Daniel Teufel (Cambridge, GB); Katerine Van Rietschoten (Cambridge, GB)

Assignee: BicycleRD Limited

A61K47/6415 C07K7/64

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 11,623,012
App. No.: 16/771,142
Granted: Apr 11, 2023
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention relates to polypeptides which are covalently bound to aromatic 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 the Eph receptor tyrosine kinase A2 (EphA2). 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 dmg conjugates in preventing, suppressing or treating a disease or disorder characterised by overexpression of EphA2 in diseased tissue (such as a tumour).

Claims (503)

1. A peptide ligand specific for EphA2 comprising a polypeptide comprising at least three cysteine residues, separated by at least two loop sequences, and an aromatic 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, wherein the molecular scaffold is 1,3,5-tris(bromomethyl)benzene (TBMB), and wherein the polypeptide comprises an amino acid sequence selected from:

ACMNDWLCSLGWTCA (SEQ ID NO: 1);

ACMNDWLCSLGWTC (SEQ ID NO: 2);

ACMNDWLCELGWTCA (SEQ ID NO: 3);

ACTRQGIWCALGFEPCA (SEQ ID NO: 4);

ACMNDWLCTLGWSCA (SEQ ID NO: 5);

ACMNDWLCQLGWTCA (SEQ ID NO: 6);

ACMNDWLCTLGWTCA (SEQ ID NO: 7);

ACMNDWLCDLGWRCA (SEQ ID NO: 8);

ACMNDWLCELGWSCA (SEQ ID NO: 9);

ACRVSPEYCPFGPVWCAGAAA (SEQ ID NO: 10);

ACPWGPAWCPVHGKTCA (SEQ ID NO: 11);

ACPWGPAWCPVNRPGCA (SEQ ID NO: 12);

ACPWGPAWCPVNRPGCAGAAA (SEQ ID NO: 13);

ACPWGPMWCPVNRPGCA (SEQ ID NO: 14);

ACPWGPNWCPVNRPGCA (SEQ ID NO: 15);

AGEMACPWGPFWCPVNRPGCA (SEQ ID NO: 16);

ADVTCPWGPFWCPVNRPGCA (SEQ ID NO: 17);

ADVRTCPWGPFWCPVNRPGCA (SEQ ID NO: 18);

ANDVTCPWGPFWCPVNRPGCA (SEQ ID NO: 19);

ACVPQGIWCALQFEPCA (SEQ ID NO: 20);

ACQKQGLWCALGFEPCA (SEQ ID NO: 21);

ACLVNDDCFYMGLCA (SEQ ID NO: 22);

CANDWLCSLGWTC (SEQ ID NO: 23);

CMNDWLCALGWTC (SEQ ID NO: 24);

CMNDWLCSAGWTC (SEQ ID NO: 25);

ACMNDWLCQLGWKCA (SEQ ID NO: 26);

ACTQNDWLCSLGWTCA (SEQ ID NO: 27);

ACRNIPTMCPFGPVWCA (SEQ ID NO: 28);

ACRVSPEYCPFGPVWCA (SEQ ID NO: 29);

ACRVSPEYCPFGPTWCA (SEQ ID NO: 30);

ACRVSPEYCPFGPSWCA (SEQ ID NO: 31);

ACRVSPEYCPFGPEWCA (SEQ ID NO: 32);

ACRVSPEYCPFGPYWCA (SEQ ID NO: 33);

ACRVSPEYCPFGPLWCA (SEQ ID NO: 34);

ACRVSPEYCPFGPDWCA (SEQ ID NO: 35);

ACPWGPAWCPVRDTNCA (SEQ ID NO: 36);

ACPWGPAWCPVNGARCA (SEQ ID NO: 37);

ACPWGPAWCPVRNPCA (SEQ ID NO: 38);

ACPWGPAWCPVSRVCA (SEQ ID NO: 39);

ACPWGPAWCPVRSCA (SEQ ID NO: 40);

ACPWGPAWCPVKPTCA (SEQ ID NO: 41);

ACPWGPAWCPVNRNGCA (SEQ ID NO: 42);

AVHIPCPWGPSWCPVNRPGCA (SEQ ID NO: 43);

AEGLPCPWGPFWCPVNRPGCA (SEQ ID NO: 44);

ADHACPWGPFWCPVNRPGCA (SEQ ID NO: 45);

ADVHCPWGPFWCPVNRPGCA (SEQ ID NO: 46);

AHDVPCPWGPFWCPVNRPGCA (SEQ ID NO: 47);

ARDDPCPWGPFWCPVNRPGCA (SEQ ID NO: 48);

ACTTGSIWCALQFEPCA (SEQ ID NO: 49);

ACVPQGIWCALRYEPCA (SEQ ID NO: 50);

ACPWGPFWCPVNRPGCA (SEQ ID NO: 51);

ACPWGPFWCPVNRPGC (SEQ ID NO: 52);

AC(HyP)WGPFWCPVNRPGC (SEQ ID NO: 53);

AC(Aib)WGPFWCPVNRPGC (SEQ ID NO: 54);

AC(4FlPro)WGPFWCPVNRPGC (SEQ ID NO: 55);

ACP(1Nal)GPFWCPVNRPGC (SEQ ID NO: 56);

ACP(2Nal)GPFWCPVNRPGC (SEQ ID NO: 57);

ACPWG(Aze)FWCPVNRPGC (SEQ ID NO: 58);

ACPWG(HyP)FWCPVNRPGC (SEQ ID NO: 59);

ACPWG(Aib)FWCPVNRPGC (SEQ ID NO: 60);

ACPWG(4FlPro)FWCPVNRPGC (SEQ ID NO: 61);

ACPWG(Pip)FWCPVNRPGC (SEQ ID NO: 62);

ACPWGPAWCPVNRPGC (SEQ ID NO: 63);

ACPWGP(4Pal)WCPVNRPGC (SEQ ID NO: 64);

ACPWGP(4BrPhe)WCPVNRPGC (SEQ ID NO: 65);

ACPWGP(4MeOPhe)WCPVNRPGC (SEQ ID NO: 66);

ACPWGP(HPhe)WCPVNRPGC (SEQ ID NO: 67);

ACPWGP(4,4-BPA)WCPVNRPGC (SEQ ID NO: 68);

ACPWGP(NO2Phe5)WCPVNRPGC (SEQ ID NO: 69);

ACPWGP(3,4-DCPhe)WCPVNRPGC (SEQ ID NO: 70);

ACPWGPYWCPVNRPGC (SEQ ID NO: 71);

ACPWGP(3Pal)WCPVNRPGC (SEQ ID NO: 72);

ACPWGP(Phg)WCPVNRPGC (SEQ ID NO: 73);

ACPWGP(1Nal)WCPVNRPGC (SEQ ID NO: 74);

ACPWGP(2Nal)WCPVNRPGC (SEQ ID NO: 75);

ACPWGPF(1Nal)CPVNRPGC (SEQ ID NO: 76);

ACPWGPFWC(Aze)VNRPGC (SEQ ID NO: 77);

ACPWGPFWC(HyP)VNRPGC (SEQ ID NO: 78);

ACPWGPFWC(4F1Pro)VNRPGC (SEQ ID NO: 79);

ACPWGPFWCP(tBuGly)NRPGC (SEQ ID NO: 80);

ACPWGPFWCPVARPGC (SEQ ID NO: 81);

ACPWGPFWCPV(D-Ala)RPGC (SEQ ID NO: 82);

ACPWGPFWCPVN(HArg)PGC (SEQ ID NO: 83);

ACPWGPFWCPVNRAGC (SEQ ID NO: 84);

ACPWGPFWCPVNR(D-Ala)GC (SEQ ID NO: 85);

ACPWGPFWCPVNR(Aze)GC (SEQ ID NO: 86);

ACPWGPFWCPVNR(HyP)GC (SEQ ID NO: 87);

ACPWGPFWCPVNR(Pip)GC (SEQ ID NO: 88);

ACPWGPFWCPVNR(4FlPro)GC (SEQ ID NO: 89);

ACPWGPFWCPVNR(Aib)GC (SEQ ID NO: 90);

ACPWGPFWCPVNRPAC (SEQ ID NO: 91);

ACPWGPFWCPVNRP(D-Ala)C (SEQ ID NO: 92);

AC(Aib)(1Nal2)GPFWCPVNRPGC (SEQ ID NO: 93);

AC(Aib)WGPF(1Nal)CPVNRPGC (SEQ ID NO: 94);

ACP(1Nal)GPFWCPV(D-Ala)RPGC (SEQ ID NO: 95);

ACP(1Nal)GPFWCPVNRP(D-Ala)C (SEQ ID NO: 96);

ACPWGPF(1Nal)CPV(D-Ala)RPGC (SEQ ID NO: 97);

ACPWGPF(1Nal)CPVNRP(D-Ala)C (SEQ ID NO: 98);

ACP(1Nal)G(Aib)FWCPVNRPGC (SEQ ID NO: 99);

ACP(1Nal)GPF(1Nal)CPVNRPGC (SEQ ID NO: 100);

ACP(1Nal)GPFWCP(tBuGly)NRPGC (SEQ ID NO: 101);

ACP(1Nal)GPFWCPVN(HArg)PGC (SEQ ID NO: 102);

ACPWG(Aib)F(1Nal)CPVNRPGC (SEQ ID NO: 103);

AC(Aib)(1Nal)GPFWCPV(D-Ala)RPGC (SEQ ID NO: 104);

AC(Aib)(1Nal)GPFWCPVNRP(D-Ala)C (SEQ ID NO: 105);

ACP(1Nal)G(Aib)FWCP(tBuGly)NRPGC (SEQ ID NO: 106);

ACP(1Nal)G(Aib)FWCPV(D-Ala)RPGC (SEQ ID NO: 107);

ACP(1Nal)G(Aib)FWCPVNRP(D-Ala)C (SEQ ID NO: 108);

ACP(1Nal)GPFWCP(tBuGly)(D-Ala)RPGC (SEQ ID NO: 109);

ACP(1Nal)GPFWCP(tBuGly)N(HArg)PGC (SEQ ID NO: 110);

ACP(1Nal)GPFWCP(tBuGly)NR(Aib)GC (SEQ ID NO: 111);

ACP(1Nal)GPFWCP(tBuGly)NRP(D-Ala)C (SEQ ID NO: 112);

ACP(1Nal)GPFWCPV(D-Ala)(HArg)PGC (SEQ ID NO: 113);

ACP(1Nal)GPFWCPVN(HArg)P(D-Ala)C (SEQ ID NO: 114);

AC(Aib)(1Nal)G(Aib)FWCPVNR(Aib)GC (SEQ ID NO: 115);

ACP(1Nal)G(Aib)FWCP(tBuGly)N(HArg)PGC (SEQ ID NO: 116);

ACP(1Nal)G(Aib)FWCP(tBuGly)NR(Aib)GC (SEQ ID NO: 117);

ACP(1Nal)GPFWCP(tBuGly)N(HArg)(Aib)GC (SEQ ID NO: 118);

H(D-Asp)VPCPWGPFWCPVNRPGCA (SEQ ID NO: 119);

H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 120);

H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C (SEQ ID NO: 121);

H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 122);

H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 123);

H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C (SEQ ID NO: 124);

H(D-Asp)(C5g)P-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C (SEQ ID NO: 125);

H(D-Asp)(C5g)P-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 126);

ADVH-CPWGPFWCPVNRPGC (SEQ ID NO: 127);

ADVH-CP(3,3-DPA)GPFWCPVNRPGCA (SEQ ID NO: 128);

ADVH-CP(1Nal)GPFWCPVNRPGCA (SEQ ID NO: 129);

ADVH-CPWAPFWCPVNRPGCA (SEQ ID NO: 130);

ADVH-CPWGAFWCPVNRPGCA (SEQ ID NO: 131);

ADVH-CPWG(Aib)FWCPVNRPGCA (SEQ ID NO: 132);

ADVH-CPWGPFWCAPVNRPGCA (SEQ ID NO: 133);

ADVH-CPWGPFWCPV(D-Ala)RPGCA (SEQ ID NO: 134);

ADVH-CPWGPFWCPVN(D-Ala)PGCA (SEQ ID NO: 135);

ADVT-CPWGPFWCPVNRPGC (SEQ ID NO: 136);

A(D-Asp)VT-CPWGPFWCPVNRPGC (SEQ ID NO: 137);

A(D-Asp)(D-Asp)T-CPWGPFWCPVNRPGC (SEQ ID NO: 138);

A(D-Asp)(Cba)T-CPWGPFWCPVNRPGC (SEQ ID NO: 139);

A(D-Asp)(Cpa)T-CPWGPFWCPVNRPGC (SEQ ID NO: 140);

A(D-Asp)(Cpg)T-CPWGPFWCPVNRPGC (SEQ ID NO: 141);

A(D-Asp)(C5g)VT-CPWGPFWCPVNRPGC (SEQ ID NO: 142);

AD(tBuGly)T-CPWGPFWCPVNRPGC (SEQ ID NO: 143);

A(D-Asp)VT-C(AC3C)WGPFWCPVNRPGC (SEQ ID NO: 144);

A(D-Asp)VT-C(AC4C)WGPFWCPVNRPGC (SEQ ID NO: 145);

A(D-Asp)VT-C(AC5C)WGPFWCPVNRPGC (SEQ ID NO: 146);

A(D-Asp)VT-C(4BenzyPro)WGPFWCPVNRPGC (SEQ ID NO: 147);

A(D-Asp)VT-C(4PhenyPro)WGPFWCPVNRPGC (SEQ ID NO: 148);

A(D-Asp)VT-CP(1Nal)GPFWCPVNRPGC (SEQ ID NO: 149);

A(D-Asp)VT-CPWGP(HArg)WCPVNRPGC (SEQ ID NO: 150);

A(D-Asp)VT-CPWGPNWCPVNRPGC (SEQ ID NO: 151);

A(D-Asp)VT-CPWGPAWCPVNRPGC (SEQ ID NO: 152);

A(D-Asp)VT-CPWGPFWCPLNRPGC (SEQ ID NO: 153);

A(D-Asp)VT-CPWGPFWCPVNRP(D-Asp)C (SEQ ID NO: 154);

A(D-Asp)VT-CPWGPFWCPVN(HArg)P(D-Asp)C (SEQ ID NO: 155);

A(D-Asp)VT-CPWGPFWCPVNR(Aib)(D-Asp)C (SEQ ID NO: 156);

A(D-Asp)VT-CP(1Nal)G(Aib)FWCPVNR(Aib)GC (SEQ ID NO: 157);

A(D-Asp)VT-CPWG(Aib)F(1Nal)CPVNR(Aib)GC (SEQ ID NO: 158);

A(D-Asp)VT-CPWG(Aib)FWCP(tBuGly)NR(Aib)GC (SEQ ID NO: 159);

A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CPVNR(Aib)GC (SEQ ID NO: 160);

A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC (SEQ ID NO: 161);

A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 162);

A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 163);

(D-Asp)VT-CPWGPFWCPVNRPGC (SEQ ID NO: 164);

(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 165);

AHDVP-CP(1Nal)GPFWCPVNRPGCA (SEQ ID NO: 166);

AHDVP-CP(1Nal)GPFWCPVNRPGC (SEQ ID NO: 167);

AHDVP-CPWGPF(1Nal)CPVNRPGC (SEQ ID NO: 168);

AHDVP-CP(1Nal)GPFWCP(tBuGly)NRPGC (SEQ ID NO: 169);

AHDVP-CP(1Nal)G(Aib)FWCP(tBuGly)N(HArg)PGC (SEQ ID NO: 170);

AHDVP-CP(1Nal)G(Aib)FWCP(tBuGly)NR(Aib)GC (SEQ ID NO: 171);

AHDVP-CPWGPFWCPVNRPGC (SEQ ID NO: 172);

(D-Ala)HDVP-CPWGPFWCPVNRPGC (SEQ ID NO: 173);

AADVP-CPWGPFWCPVNRPGC (SEQ ID NO: 174);

A(D-His)DVP-CPWGPFWCPVNRPGC (SEQ ID NO: 175);

A(D-His)DVCPWGPFWCPVNRPGC (SEQ ID NO: 176);

A(D-Ala)DVP-CPWGPFWCPVNRPGC (SEQ ID NO: 177);

A(D-Asp)DVP-CPWGPFWCPVNRPGC (SEQ ID NO: 178);

A(Thi)DVP-CPWGPFWCPVNRPGC (SEQ ID NO: 179);

A(ThiAz)DVP-CPWGPFWCPVNRPGC (SEQ ID NO: 180);

A(2FuAla)DVP-CPWGPFWCPVNRPGC (SEQ ID NO: 181);

A(D-His)D(tBuGly)P-CPWGPFWCPVNRPGC (SEQ ID NO: 182);

AHAVP-CPWGPFWCPVNRPGC (SEQ ID NO: 183);

AH(D-Ala)VP-CPWGPFWCPVNRPGC (SEQ ID NO: 184);

AHEVP-CPWGPFWCPVNRPGC (SEQ ID NO: 185);

AH(D-Glu)VP-CPWGPFWCPVNRPGC (SEQ ID NO: 186);

AH(D-Asp)VP-CPWGPFWCPVNRPGC (SEQ ID NO: 187);

AH(D-Asp)(tBuGly)P-CPWGPFWCPVNRPGC (SEQ ID NO: 188);

AH(D-Asp)V(Sar)-CPWGPFWCPVNRPGC (SEQ ID NO: 189);

AH(D-Asp)V(Aib)-CPWGPFWCPVNRPGC (SEQ ID NO: 190);

AHDAP-CPWGPFWCPVNRPGC (SEQ ID NO: 191);

AHD(D-Ala)P-CPWGPFWCPVNRPGC (SEQ ID NO: 192);

AHD(Aib)P-CPWGPFWCPVNRPGC (SEQ ID NO: 193);

AHD(tBuGly)P-CPWGPFWCPVNRPGC (SEQ ID NO: 194);

AHDVA-CPWGPFWCPVNRPGC (SEQ ID NO: 195);

AHDV(D-Ala)-CPWGPFWCPVNRPGC (SEQ ID NO: 196);

AHDV(Aib)-CPWGPFWCPVNRPGC (SEQ ID NO: 197);

AHDV(Aze)-CPWGPFWCPVNRPGC (SEQ ID NO: 198);

AHDV(Pip)-CPWGPFWCPVNRPGC [(SEQ ID NO: 199);

HDVP-CPWGPFWCPVNRPGC (SEQ ID NO: 200);

(D-His)DVP-CPWGPFWCPVNRPGC (SEQ ID NO: 201);

H(D-Asp)VP-CPWGPFWCPVNRPGC (SEQ ID NO: 202);

AH(D-Asp)VP-CP(1Nal)GPFWCP(tBuGly)N(HArg)PGC (SEQ ID NO: 203);

A(D-His)DVP-CPWGP(ΨAla)WCPVNRPGC (SEQ ID NO: 204);

A(D-His)DVP-CPWGPFWCP(HArg)NRPGC (SEQ ID NO: 205);

A(D-His)DVP-CP(1Nal)GPFWCP(tBuGly)N(HArg)PGC (SEQ ID NO: 206);

A(D-His)DVP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC (SEQ ID NO: 207);

A(D-His)DVP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 208);

A(D-His)DVP-CPWG(Aib)FWCP(tBuGly)NR(Aib)GC (SEQ ID NO: 209);

H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NRPGC (SEQ ID NO: 210);

H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC (SEQ ID NO: 211);

H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)(Aib)(D-Asp)C (SEQ ID NO: 212);

H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 213);

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)FWCP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 214))

H(D-Asp)VP-C(Aib)(1Nal)GP(HArg)(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 215);

H(D-Asp)VP-C(Aib)(1Nal)GP(HArg)(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 216);

H(D-Asp)VP-C(Aib)WGP(HArg)(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 217);

H(D-Asp)VP-C(Aib)WGP(HArg)WCP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 218);

H(D-Asp)VP-C(D-Ala)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 219);

H(D-Asp)VP-CP(1Nal)G(Aib)(HArg)(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 220);

H(D-Asp)VP-CP(1Nal)G(Aib)(HArg)(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C (SEQ ID NO: 221);

H(D-Asp)VP-CP(1Nal)G(Aib)(HArg)(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 222);

H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NRPGC (SEQ ID NO: 223);

H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC (SEQ ID NO: 224);

H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)(Aib)(D-Asp)C (SEQ ID NO: 225);

H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CPVNR(Aib)GC (SEQ ID NO: 226);

H(D-Asp)VP-CP(1Nal)G(Aib)FWCP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 227);

H(D-Asp)VP-CP(1Nal)G(Aib)FWCPVNR(Aib)GC (SEQ ID NO: 228);

H(D-Asp)VP-CPW(Aza-Gly)PFWCPVNRPGC (SEQ ID NO: 229);

H(D-Asp)VP-CPWG(Aib)F(1Nal)CPVNR(Aib)GC (SEQ ID NO: 230);

H(D-Asp)VP-CPWG(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 231);

H(D-Asp)VP-CPWG(Aib)FWCP(tBuGly)NR(Aib)GC (SEQ ID NO: 232);

H(D-Asp)VP-CPWG(Aib)FWCP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 233);

H(D-Asp)VP-CPWGP(HArg)WCP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 234);

H(D-Asp)(C5g)P-C(Aib)WG(Aib)FWCP(tBuGly)NR(Aib)(D-Asp)C (SEQ ID NO: 235);

H(D-Asp)(C5g)P-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 236);

H(D-Asp)(C5g)T-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 237);

H(D-Asp)(C5g)T-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (SEQ ID NO: 238);

A(D-Asp)DVT-CPWGPFWCPVNRPGC (SEQ ID NO: 239);

A(D-Asp)DVT-CP(1Nal)GPFWCPVNRPGC (SEQ ID NO: 240);

A(D-Asp)DVT-CP(1Nal)GPF(1Nal)CPVNRPGC (SEQ ID NO: 241);

A(D-Asp)DVT-CP(1Nal)G(Aib)FWCP(tBuGly)N(HArg)PGC (SEQ ID NO: 242);

H(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (SEQ ID NO: 243);

ACAWGPFWCPVNRPGC (SEQ ID NO: 244);

ACPAGPFWCPVNRPGC (SEQ ID NO: 245);

ACPWAPFWCPVNRPGC (SEQ ID NO: 246);

ACPWGAFWCPVNRPGC (SEQ ID NO: 247);

ACPWGPFACPVNRPGC (SEQ ID NO: 248);

ACPWGPFWCAVNRPGC (SEQ ID NO: 249);

ACPWGPFWCPANRPGC (SEQ ID NO: 250);

ACPWGPFWCPVNAPGC (SEQ ID NO: 251);

AC(D-Ala)WGPFWCPVNRPGC (SEQ ID NO: 252);

ACP(D-Ala)GPFWCPVNRPGC (SEQ ID NO: 253);

ACPW(D-Ala)PFWCPVNRPGC (SEQ ID NO: 254);

ACPWG(D-Ala)FWCPVNRPGC (SEQ ID NO: 255);

ACPWGP(D-Ala)WCPVNRPGC (SEQ ID NO: 256);

ACPWGPF(D-Ala)CPVNRPGC (SEQ ID NO: 257);

ACPWGPFWC(D-Ala)VNRPGC (SEQ ID NO: 258);

ACPWGPFWCP(D-Ala)NRPGC (SEQ ID NO: 259);

ACPWGPFWCPVN(D-Ala)PGC (SEQ ID NO: 260);

ACPWAPFWCAVNRPGC (SEQ ID NO: 261); and

H(D-Asp)VPCP(1Nal)A(Aib)F(1Nal)CA(tBuGly)NR(Aib)(D-Asp)C (SEQ ID NO: 262);

or a pharmaceutically acceptable salt thereof.

2. The peptide ligand as defined in claim 1 , wherein the peptide ligand is the free acid or a pharmaceutically acceptable salt selected from a sodium salt, a potassium salt, a calcium salt, and an ammonium salt.

3. The peptide ligand as defined in claim 1 , wherein the EphA2 is human EphA2.

4. A pharmaceutical composition which comprises the peptide ligand as defined in claim 1 , or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable excipients.

5. A peptide ligand specific for EphA2 comprising a polypeptide comprising at least three cysteine residues, separated by at least two loop sequences, and an aromatic 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, wherein the molecular scaffold is 1,3,5-tris(bromomethyl)benzene (TBMB), and wherein the polypeptide comprises an amino acid sequence selected from:

Ac-CANDWLCSLGWTC (Ac-(SEQ ID NO: 23));

Ac-CMNDWLCALGWTC (Ac-(SEQ ID NO: 24));

Ac-CMNDWLCSAGWTC (Ac-(SEQ ID NO: 25));

Sar 2 -ACPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 52));

Ac-Sar 2 -ACPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 52));

(β-Ala)-Sar 10 -ACPWGPFWCPVNRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 52));

Sar 2 -AC(HyP)WGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 53));

Sar 2 -AC(Aib)WGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 54));

Sar 2 -AC(4FlPro)WGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 55));

Sar 2 -ACP(1Nal)GPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 56));

Sar 2 -ACP(2Nal)GPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 57));

Sar 2 -ACPWG(Aze)FWCPVNRPGC (Sar 2 -(SEQ ID NO: 58));

Sar 2 -ACPWG(HyP)FWCPVNRPGC (Sar 2 -(SEQ ID NO: 59));

Sar 2 -ACPWG(Aib)FWCPVNRPGC (Sar 2 -(SEQ ID NO: 60));

Sar 2 -ACPWG(4FlPro)FWCPVNRPGC (Sar 2 -(SEQ ID NO: 61));

Sar 2 -ACPWG(Pip)FWCPVNRPGC (Sar 2 -(SEQ ID NO: 62));

Sar 2 -ACPWGPAWCPVNRPGC (Sar 2 -(SEQ ID NO: 63));

Sar 2 -ACPWGP(4Pal)WCPVNRPGC (Sar 2 -(SEQ ID NO: 64));

Sar 2 -ACPWGP(4BrPhe)WCPVNRPGC (Sar 2 -(SEQ ID NO: 65));

Sar 2 -ACPWGP(4MeOPhe)WCPVNRPGC (Sar 2 -(SEQ ID NO: 66));

Sar 2 -ACPWGP(HPhe)WCPVNRPGC (Sar 2 -(SEQ ID NO: 67));

Sar 2 -ACPWGP(4,4-BPA)WCPVNRPGC (Sar 2 -(SEQ ID NO: 68));

Sar 2 -ACPWGP(NO2Phe5)WCPVNRPGC (Sar 2 -(SEQ ID NO: 69));

Sar 2 -ACPWGP(3,4-DCPhe)WCPVNRPGC (Sar 2 -(SEQ ID NO: 70));

Sar 2 -ACPWGPYWCPVNRPGC (Sar 2 -(SEQ ID NO: 71));

Sar 2 -ACPWGP(3Pal)WCPVNRPGC (Sar 2 -(SEQ ID NO: 72));

Sar 2 -ACPWGP(Phg)WCPVNRPGC (Sar 2 -(SEQ ID NO: 73));

Sar 2 -ACPWGP(1Nal)WCPVNRPGC (Sar 2 -(SEQ ID NO: 74));

Sar 2 -ACPWGP(2Nal)WCPVNRPGC (Sar 2 -(SEQ ID NO: 75));

Sar 2 -ACPWGPF(1Nal)CPVNRPGC (Sar 2 -(SEQ ID NO: 76));

Sar 2 -ACPWGPFWC(Aze)VNRPGC (Sar 2 -(SEQ ID NO: 77));

Sar 2 -ACPWGPFWC(HyP)VNRPGC (Sar 2 -(SEQ ID NO: 78));

Sar 2 -ACPWGPFWC(4FlPro)VNRPGC (Sar 2 -(SEQ ID NO: 79));

Sar 2 -ACPWGPFWCP(tBuGly)NRPGC (Sar 2 -(SEQ ID NO: 80));

Sar 2 -ACPWGPFWCPVARPGC (Sar 2 -(SEQ ID NO: 81));

Sar 2 -ACPWGPFWCPV(D-Ala)RPGC (Sar 2 -(SEQ ID NO: 82));

Sar 2 -ACPWGPFWCPVN(HArg)PGC (Sar 2 -(SEQ ID NO: 83));

Sar 2 -ACPWGPFWCPVNRAGC (Sar 2 -(SEQ ID NO: 84));

Sar 2 -ACPWGPFWCPVNR(D-Ala)GC (Sar 2 -(SEQ ID NO: 85));

Sar 2 -ACPWGPFWCPVNR(Aze)GC (Sar 2 -(SEQ ID NO: 86));

Sar 2 -ACPWGPFWCPVNR(HyP)GC (Sar 2 -(SEQ ID NO: 87));

Sar 2 -ACPWGPFWCPVNR(Pip)GC (Sar 2 -(SEQ ID NO: 88));

Sar 2 -ACPWGPFWCPVNR(4FlPro)GC (Sar 2 -(SEQ ID NO: 89));

Sar 2 -ACPWGPFWCPVNR(Aib)GC (Sar 2 -(SEQ ID NO: 90));

Sar 2 -ACPWGPFWCPVNRPAC (Sar 2 -(SEQ ID NO: 91));

Sar 2 -ACPWGPFWCPVNRP(D-Ala)C (Sar 2 -(SEQ ID NO: 92));

Sar 2 -AC(Aib)(1Nal2)GPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 93));

Sar 2 -AC(Aib)WGPF(1Nal)CPVNRPGC (Sar 2 -(SEQ ID NO: 94));

Sar 2 -ACP(1Nal)GPFWCPV(D-Ala)RPGC (Sar 2 -(SEQ ID NO: 95));

Sar 2 -ACP(1Nal)GPFWCPVNRP(D-Ala)C (Sar 2 -(SEQ ID NO: 96));

Sar 2 -ACPWGPF(1Nal)CPV(D-Ala)RPGC (Sar 2 -(SEQ ID NO: 97));

Sar 2 -ACPWGPF(1Nal)CPVNRP(D-Ala)C (Sar 2 -(SEQ ID NO: 98));

Sar 2 -ACP(1Nal)G(Aib)FWCPVNRPGC (Sar 2 -(SEQ ID NO: 99));

Sar 2 -ACP(1Nal)GPF(1Nal)CPVNRPGC (Sar 2 -(SEQ ID NO: 100));

Sar 2 -ACP(1Nal)GPFWCP(tBuGly)NRPGC (Sar 2 -(SEQ ID NO: 101));

Sar 2 -ACP(1Nal)GPFWCPVN(HArg)PGC (Sar 2 -(SEQ ID NO: 102));

Sar 2 -ACPWG(Aib)F(1Nal)CPVNRPGC (Sar 2 -(SEQ ID NO: 103));

Sar 2 -AC(Aib)(1Nal)GPFWCPV(D-Ala)RPGC (Sar 2 -(SEQ ID NO: 104));

Sar 2 -AC(Aib)(1Nal)GPFWCPVNRP(D-Ala)C (Sar 2 -(SEQ ID NO: 105));

Sar 2 -ACP(1Nal)G(Aib)FWCP(tBuGly)NRPGC (Sar 2 -(SEQ ID NO: 106));

Sar 2 -ACP(1Nal)G(Aib)FWCPV(D-Ala)RPGC (Sar 2 -(SEQ ID NO: 107));

Sar 2 -ACP(1Nal)G(Aib)FWCPVNRP(D-Ala)C (Sar 2 -(SEQ ID NO: 108));

Sar 2 -ACP(1Nal)GPFWCP(tBuGly)(D-Ala)RPGC (Sar 2 -(SEQ ID NO: 109));

Sar 2 -ACP(1Nal)GPFWCP(tBuGly)N(HArg)PGC (Sar 2 -(SEQ ID NO: 110));

Sar 2 -ACP(1Nal)GPFWCP(tBuGly)NR(Aib)GC (Sar 2 -(SEQ ID NO: 111));

Sar 2 -ACP(1Nal)GPFWCP(tBuGly)NRP(D-Ala)C (Sar 2 -(SEQ ID NO: 112));

Sar 2 -ACP(1Nal)GPFWCPV(D-Ala)(HArg)PGC (Sar 2 -(SEQ ID NO: 113));

Sar 2 -ACP(1Nal)GPFWCPVN(HArg)P(D-Ala)C (Sar 2 -(SEQ ID NO: 114));

Sar 2 -AC(Aib)(1Nal)G(Aib)FWCPVNR(Aib)GC (Sar 2 -(SEQ ID NO: 115));

Sar 2 -ACP(1Nal)G(Aib)FWCP(tBuGly)N(HArg)PGC (Sar 2 -(SEQ ID NO: 116));

Sar 2 -ACP(1Nal)G(Aib)FWCP(tBuGly)NR(Aib)GC (Sar 2 -(SEQ ID NO: 117));

Sar 2 -ACP(1Nal)GPFWCP(tBuGly)N(HArg)(Aib)GC (Sar 2 -(SEQ ID NO: 118));

Ac-Sar 2 -ADVH-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 127));

Ac-Sar 2 -ADVT-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 136));

Ac-Sar 2 -A(D-Asp)VT-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 137));

Ac-Sar 2 -A(D-Asp)(D-Asp)T-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 138));

Ac-Sar 2 -A(D-Asp)(Cba)T-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 139));

Ac-Sar 2 -A(D-Asp)(Cpa)T-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 140));

Ac-Sar 2 -A(D-Asp)(Cpg)T-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 141));

Ac-Sar 2 -A(D-Asp)(C5g)VT-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 142));

Ac-Sar 2 -AD(tBuGly)T-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 143));

Ac-Sar 2 -A(D-Asp)VT-C(AC3C)WGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 144));

Ac-Sar 2 -A(D-Asp)VT-C(AC4C)WGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 145));

Ac-Sar 2 -A(D-Asp)VT-C(AC5C)WGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 146));

Ac-Sar 2 -A(D-Asp)VT-C(4BenzyPro)WGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 147));

Ac-Sar 2 -A(D-Asp)VT-C(4PhenyPro)WGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 148));

Ac-Sar 2 -A(D-Asp)VT-CP(1Nal)GPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 149));

Ac-Sar 2 -A(D-Asp)VT-CPWGP(HArg)WCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 150));

Ac-Sar 2 -A(D-Asp)VT-CPWGPNWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 151));

Ac-Sar 2 -A(D-Asp)VT-CPWGPAWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 152));

Ac-Sar 2 -A(D-Asp)VT-CPWGPFWCPLNRPGC (Ac-Sar 2 -(SEQ ID NO: 153));

Ac-Sar 2 -A(D-Asp)VT-CPWGPFWCPVNRP(D-Asp)C (Ac-Sar 2 -(SEQ ID NO: 154));

Ac-Sar 2 -A(D-Asp)VT-CPWGPFWCPVN(HArg)P(D-Asp)C (Ac-Sar 2 -(SEQ ID NO: 155));

Ac-Sar 2 -A(D-Asp)VT-CPWGPFWCPVNR(Aib)(D-Asp)C (Ac-Sar 2 -(SEQ ID NO: 156));

Ac-Sar 2 -A(D-Asp)VT-CP(1Nal)G(Aib)FWCPVNR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 157));

Ac-Sar 2 -A(D-Asp)VT-CPWG(Aib)F(1Nal)CPVNR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 158));

Ac-Sar 2 -A(D-Asp)VT-CPWG(Aib)FWCP(tBuGly)NR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 159));

Ac-Sar 2 -A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CPVNR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 160));

Ac-Sar 2 -A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC (Ac-Sar 2 -(SEQ ID NO: 161));

Ac-Sar 2 -A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 162));

Ac-Sar 2 -A(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (Ac-Sar 2 -(SEQ ID NO: 163));

Ac-Sar 2 -AHDVP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 172);

Ac-Sar 2 -(D-Ala)HDVP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 173);

Ac-Sar 2 -AADVP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 174);

Ac-Sar 2 -A(D-His)DVP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 175);

Sar 2 -A(D-His)DVP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 175);

Ac-Sar 2 -A(D-His)DVCPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 176);

Sar 2 -A(D-Ala)DVP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 177);

Ac-Sar 2 -A(D-Asp)DVP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 178);

Sar 2 -A(Thi)DVP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 179);

Sar 2 -A(ThiAz)DVP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 180);

Sar 2 -A(2FuAla)DVP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 181);

Ac-Sar 2 -A(D-His)D(tBuGly)P-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 182);

Sar 2 -AHAVP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 183);

Sar 2 -AH(D-Ala)VP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 184);

Sar 2 -AHEVP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 185);

Sar 2 -AH(D-Glu)VP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 186);

Sar 2 -AH(D-Asp)VP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 187);

Ac-Sar 2 -AH(D-Asp)VP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 187);

Ac-Sar 2 -AH(D-Asp)(tBuGly)P-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 188);

Ac-Sar 2 -AH(D-Asp)V(Sar)-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 189);

Ac-Sar 2 -AH(D-Asp)V(Aib)-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 190);

Sar 2 -AHDAP-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 191);

Sar 2 -AHD(D-Ala)P-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 192);

Sar 2 -AHD(Aib)P-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 193);

Sar 2 -AHD(tBuGly)P-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 194);

Sar 2 -AHDVA-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 195);

Sar 2 -AHDV(D-Ala)-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 196);

Sar 2 -AHDV(Aib)-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 197);

Sar 2 -AHDV(Aze)-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 198);

Sar 2 -AHDV(Pip)-CPWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 199);

(β-Ala)-Sar 10 -HDVP-CPWGPFWCPVNRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 200));

Ac-Sar 2 -(D-His)DVP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 201));

Ac-Sar 2 -H(D-Asp)VP-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 202));

(β-Ala)-Sar 10 -H(D-Asp)VP-CPWGPFWCPVNRPGC (β-Ala)-Sar 10 -(SEQ ID NO: 202));

Ac-Sar 2 -AH(D-Asp)VP-CP(1Nal)GPFWCP(tBuGly)N(HArg)PGC (Ac-Sar 2 -(SEQ ID NO: 203));

Ac-Sar 2 -A(D-His)DVP-CPWGP(ΨAla)WCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 204));

Ac-Sar 2 -A(D-His)DVP-CPWGPFWCP(HArg)NRPGC (Ac-Sar 2 -(SEQ ID NO: 205));

Ac-Sar 2 -A(D-His)DVP-CP(1Nal)GPFWCP(tBuGly)N(HArg)PGC (Ac-Sar 2 -(SEQ ID NO: 206));

Ac-Sar 2 -A(D-His)DVP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC (Ac-Sar 2 -(SEQ ID NO: 207));

Ac-Sar 2 -A(D-His)DVP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 208));

Ac-Sar 2 -A(D-His)DVP-CPWG(Aib)FWCP(tBuGly)NR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 209));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 210));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC ((β-Ala)-Sar 10 -(SEQ ID NO: 211));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 120));

Ac-(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (Ac-(β-Ala)-Sar 10 -(SEQ ID NO: 120));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)(Aib)(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 212));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC ((β-Ala)-Sar 10 -(SEQ ID NO: 213));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 121));

Ac-(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C (Ac-(β-Ala)-Sar 10 -(SEQ ID NO: 121));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)G(Aib)FWCP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 214));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)GP(HArg)(1Nal)CP(tBuGly)NR(Aib)GC ((β-Ala)-Sar 10 -(SEQ ID NO: 215));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)(1Nal)GP(HArg)(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 216));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)WGP(HArg)(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 217));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(Aib)WGP(HArg)WCP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 218));

(β-Ala)-Sar 10 -H(D-Asp)VP-C(D-Ala)(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 219));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)(HArg)(1Nal)CP(tBuGly)NR(Aib)GC ((β-Ala)-Sar 10 -(SEQ ID NO: 220));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)(HArg)(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 221));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)(HArg)(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 222));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 223));

Ac-Sar 2 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC (Ac-Sar 2 -(SEQ ID NO: 224));

Ac-Sar 2 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (Ac-Sar 2 -(SEQ ID NO: 122));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 122));

Ac-(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (Ac-(β-Ala)-Sar 10 -(SEQ ID NO: 122));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)PGC ((β-Ala)-Sar 10 -(SEQ ID NO: 224));

Ac-(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (Ac-(β-Ala)-Sar 10 -(SEQ ID NO: 123));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)(Aib)(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 225));

Ac-(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C (Ac-(β-Ala)-Sar 10 -(SEQ ID NO: 124));

Ac-Sar 2 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CPVNR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 226));

Ac-Sar 2 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 123));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC ((β-Ala)-Sar 10 -(SEQ ID NO: 123));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 124));

(β-Ala)-Sar 10 -H(D-Asp)VP-CP(1Nal)G(Aib)FWCP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 227));

Ac-Sar 2 -H(D-Asp)VP-CP(1Nal)G(Aib)FWCPVNR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 228));

Ac-Sar 2 -H(D-Asp)VP-CPW(Aza-Gly)PFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 229));

Ac-Sar 2 -H(D-Asp)VP-CPWG(Aib)F(1Nal)CPVNR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 230));

(β-Ala)-Sar 10 -H(D-Asp)VP-CPWG(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 231));

Ac-Sar 2 -H(D-Asp)VP-CPWG(Aib)FWCP(tBuGly)NR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 232));

(β-Ala)-Sar 10 -H(D-Asp)VP-CPWG(Aib)FWCP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 233));

(β-Ala)-Sar 10 -H(D-Asp)VP-CPWGP(HArg)WCP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 234));

(β-Ala)-Sar 10 -H(D-Asp)(C5g)P-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 125));

Ac-(β-Ala)-Sar 10 -H(D-Asp)(C5g)P-C(Aib)(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)(D-Asp)C (Ac-(β-Ala)-Sar 10 -(SEQ ID NO: 125));

(β-Ala)-Sar 10 -H(D-Asp)(C5g)P-C(Aib)WG(Aib)FWCP(tBuGly)NR(Aib)(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 235));

(β-Ala)-Sar 10 -H(D-Asp)(C5g)P-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 126));

Ac-(β-Ala)-Sar 10 -H(D-Asp)(C5g)P-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C (Ac-(β-Ala)-Sar 10 -(SEQ ID NO: 126));

(β-Ala)-Sar 10 -H(D-Asp)(C5g)P-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC ((β-Ala)-Sar 10 -(SEQ ID NO: 236));

(β-Ala)-Sar 10 -H(D-Asp)(C5g)T-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC ((β-Ala)-Sar 10 -(SEQ ID NO: 237));

(β-Ala)-Sar 10 -H(D-Asp)(C5g)T-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)N(HArg)P(D-Asp)C ((β-Ala)-Sar 10 -(SEQ ID NO: 238));

Ac-Sar 2 -A(D-Asp)DVT-CPWGPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 239));

Ac-Sar 2 -A(D-Asp)DVT-CP(1Nal)GPFWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 240));

Ac-Sar 2 -A(D-Asp)DVT-CP(1Nal)GPF(1Nal)CPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 241));

Ac-Sar 2 -A(D-Asp)DVT-CP(1Nal)G(Aib)FWCP(tBuGly)N(HArg)PGC (Ac-Sar 2 -(SEQ ID NO: 242));

Ac-Sar 2 -H(D-Asp)VT-CP(1Nal)G(Aib)F(1Nal)CP(tBuGly)NR(Aib)GC (Ac-Sar 2 -(SEQ ID NO: 243));

Ac-CANDWLCSLGWTC (Ac-(SEQ ID NO: 23));

Ac-CMNDWLCALGWTC (Ac-(SEQ ID NO: 24));

Ac-CMNDWLCSAGWTC (Ac-(SEQ ID NO: 25));

Sar 2 -ACAWGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 244));

Sar 2 -ACPAGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 245));

Sar 2 -ACPWAPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 246));

Sar 2 -ACPWGAFWCPVNRPGC (Sar 2 -(SEQ ID NO: 247));

Sar 2 -ACPWGPAWCPVNRPGC (Sar 2 -(SEQ ID NO: 63));

Sar 2 -ACPWGPFACPVNRPGC (Sar 2 -(SEQ ID NO: 248));

Sar 2 -ACPWGPFWCAVNRPGC (Sar 2 -(SEQ ID NO: 249));

Sar 2 -ACPWGPFWCPANRPGC (Sar 2 -(SEQ ID NO: 250));

Sar 2 -ACPWGPFWCPVARPGC (Sar 2 -(SEQ ID NO: 81));

Sar 2 -ACPWGPFWCPVNAPGC (Sar 2 -(SEQ ID NO: 251));

Sar 2 -ACPWGPFWCPVNRAGC (Sar 2 -(SEQ ID NO: 84));

Sar 2 -ACPWGPFWCPVNRPAC (Sar 2 -(SEQ ID NO: 91));

Sar 2 -AC(D-A1)WGPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 252));

Sar 2 -ACP(D-Ala)GPFWCPVNRPGC (Sar 2 -(SEQ ID NO: 253));

Sar 2 -ACPW(D-Ala)PFWCPVNRPGC (Sar 2 -(SEQ ID NO: 254));

Sar 2 -ACPWG(D-Ala)FWCPVNRPGC (Sar 2 -(SEQ ID NO: 255));

Sar 2 -ACPWGP(D-Ala)WCPVNRPGC (Sar 2 -(SEQ ID NO: 256));

Sar 2 -ACPWGPF(D-Ala)CPVNRPGC (Sar 2 -(SEQ ID NO: 257));

Sar 2 -ACPWGPFWC(D-Ala)VNRPGC (Sar 2 -(SEQ ID NO: 258));

Sar 2 -ACPWGPFWCP(D-Ala)NRPGC (Sar 2 -(SEQ ID NO: 259));

Sar 2 -ACPWGPFWCPV(D-Ala)RPGC (Sar 2 -(SEQ ID NO: 82));

Sar 2 -ACPWGPFWCPVN(D-Ala)PGC (Sar 2 -(SEQ ID NO: 260));

Sar 2 -ACPWGPFWCPVNR(D-Ala)GC (Sar 2 -(SEQ ID NO: 85));

Sar 2 -ACPWGPFWCPVNRP(D-Ala)C (Sar 2 -(SEQ ID NO: 92));

(β-Ala)-Sar 10 -ACPWAPFWCAVNRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 261));

Ac-Sar 2 -A(D-Asp)VTCPWGPAWCPVNRPGC (Ac-Sar 2 -(SEQ ID NO: 152)); and

(β-Ala)-Sar 10 -H(D-Asp)VPCP(1Nal)A(Aib)F(1Nal)CA(tBuGly)NR(Aib)(D-Asp)C (β-Ala)-Sar 10 -(SEQ ID NO: 262));

or a pharmaceutically acceptable salt thereof.

6. The peptide ligand as defined in claim 5 , wherein the peptide ligand comprises an amino acid sequence selected from:

(β-Ala)-Sar 10 -ACPWGPFWCPVNRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 52));

(β-Ala)-Sar 10 -H(D-Asp)VP-CPWGPFWCPVNRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 202));

Ac-Sar 2 -AH(D-Asp)VP-CP(1Nal)GPFWCP(tBuGly)N(HArg)PGC (Ac-Sar 2 -(SEQ ID NO: 203)); and

(β-Ala)-Sar 10 -ACPWAPFWCAVNRPGC ((β-Ala)-Sar 10 -(SEQ ID NO: 261));

or a pharmaceutically acceptable salt thereof.

7. The peptide ligand as defined in claim 5 , wherein the peptide ligand is the free acid or a pharmaceutically acceptable salt selected from a sodium salt, a potassium salt, a calcium salt, and an ammonium salt.

8. The peptide ligand as defined in claim 5 , wherein the EphA2 is human EphA2.

9. A pharmaceutical composition which comprises the peptide ligand as defined in claim 5 , or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable excipients.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2020

From: CHEN, LIUHONG; PAVAN, SILVIA; STACE, CATHERINE; TEUFEL, DANIEL; VAN RIETSCHOTEN, KATERINE

To: BICYCLERD LIMITED

Reel/Frame 053642/0474 →

Priority Claims (1)

GB 1721265 · Dec 19, 2017 · national

Continuity (1)

Related Publication 20200338203A1 · Oct 29, 2020

Cited By (15)

US 12,318,454 US 12,350,343 US 12,377,155 US 12,378,288 US 12,435,107 US 12,459,974 US 12,491,253 US 12,492,224 US 12,516,084 US 12,540,161 US 12,551,567 US 12,552,837 US 12,570,695 US 12,606,594 US 12,630,588