IP Library › Granted Patent US 12,492,224
Granted Patent B2
US 12,492,224 · App. 17/044,868 · Granted Dec 9, 2025

Bicyclic peptide ligands specific for PD-L1

Inventors: Liuhong Chen (Cambridge, GB); James Cooke (Cambridge, GB); Kevin McDonnell (Lexington, MA); Gemma Mudd (Cambridge, GB); Katerine van Rietschoten (Cambridge, GB); Punit Upadhyaya (Lexington, MA)
Assignee: BicycleTx Limited
C07K7/08A61K47/64A61K49/0056C07K7/64
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Quick Facts
Patent No.
US 12,492,224
App. No.
17/044,868
Granted
Dec 9, 2025
Kind
B2
Abstract

The present invention relates to polypeptides which are covalently bound to non-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 PD-L1. 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 PD-L1.

Claims (628)

1 . A peptide ligand specific for programmed death-ligand 1 (PD-L1) and a non-aromatic molecular scaffold, wherein the polypeptide comprises the amino acid sequence selected from the group consisting of:

(SEQ ID NO: 1)

C i SWSWLTMC ii QKLHLC iii ;

(SEQ ID NO: 2)

C i STSWMNLC ii KQLNLC iii ;

(SEQ ID NO: 3)

C i SPIWTNTC ii IQLGLC iii ;

(SEQ ID NO: 4)

C i TPNWNAMC ii LKLNLC iii ;

(SEQ ID NO: 5)

C i DVFTHC ii ILLAKPC iii ;

(SEQ ID NO: 6)

C i SESWSNMC ii VSLGLC iii ;

(SEQ ID NO: 7)

C i SAEWRNMC ii VQLDLC iii ;

(SEQ ID NO: 8)

C i SASWSNMC ii VELGLC iii ;

(SEQ ID NO: 9)

C i SDNWLNMC ii VELGLC iii ;

(SEQ ID NO: 10)

C i SESWSAMC ii ASLGLC iii ;

(SEQ ID NO: 11)

C i SESWSNMC ii KSLGLC iii ;

(SEQ ID NO: 12)

C i SESWRNMC ii VQLNLC iii ;

(SEQ ID NO: 13)

C i SPEWTNMC ii VQLHLC iii ;

(SEQ ID NO: 14)

C i STQWNNMC ii VQLGLC iii ;

(SEQ ID NO: 18)

C i SSSWTNMC ii VQLGLC iii ;

(SEQ ID NO: 16)

C i SAEWRNMC ii VELNLC iii ;

(SEQ ID NO: 17)

C i SPEWKNMC ii ITLNLC iii ;

(SEQ ID NO: 18)

C i [HArg]DWC ii HWTFSHGHPC iii ;

(SEQ ID NO: 19)

C i SAGWLTMC ii QKLHLC iii ;

(SEQ ID NO: 20)

C i SAGWLTMC ii Q[K(PYA)]LHLC iii ;

(SEQ ID NO: 21)

C i S[Aib]GWLTMC ii QKLHLC iii ;

(SEQ ID NO: 22)

C i S[Abu]GWLTMC ii QKLHLC iii ;

(SEQ ID NO: 23)

C i SA[HSer]NLTMC ii QKLHLC iii ;

(SEQ ID NO: 24)

C i SAGWLT[Nle]C ii QKLHLC iii ;

(SEQ ID NO: 25)

C i S[dA]GWLTMC ii QKLHLC iii ;

(SEQ ID NO: 26)

C i S[HSer]GWLTMC ii QKLHLC iii ;

(SEQ ID NO: 27)

C i S[Nle]GWLTMC ii QKLHLC iii ;

(SEQ ID NO: 28)

C i SAGWLT[HPhe]C ii QKLHLC iii ;

(SEQ ID NO: 29)

C i SAGWLTMC ii VQLGLC iii ;

(SEQ ID NO: 30)

C i SAGWLTMC ii [Chg]KLHLC iii ;

(SEQ ID NO: 31)

C i SAGWLTMC ii LKLHLC iii ;

(SEQ ID NO: 32)

C i SAGWLTMC ii Q[Nle]LHLC iii ;

(SEQ ID NO: 33)

C i SAGWLTMC ii Q[HSer]LHLC iii ;

(SEQ ID NO: 34)

C i SAGWLTMC ii QK[Nle]HLC iii ;

(SEQ ID NO: 35)

C i SAGWLTMC ii QKL[dA]LC iii ;

(SEQ ID NO: 36)

C i SAGWLTMC ii QKL[Aib]LC iii ;

(SEQ ID NO: 37)

C i SAGWLTMC ii QKLH[Nle]C iii ;

(SEQ ID NO: 38)

C i SAGWLTMC ii QRLHLC iii ;

(SEQ ID NO: 39)

C i SAGWLTMC ii QKLH[Nva]C iii ;

(SEQ ID NO: 40)

C i SAGWLTMC ii QK[Nva]HLC iii ;

(SEQ ID NO: 41)

C i SAGWLT[Nva]C ii QKLHLC iii ;

(SEQ ID NO: 42)

C i SAGWLTMC ii HKQLNLC iii ;

(SEQ ID NO: 43)

C i S[Aib]GWLT[HPhe]C ii LKL[Aib]LC iii ;

(SEQ ID NO: 44)

C i SAG[7-AzaW]LTMC ii QKLHLC iii ;

(SEQ ID NO: 45)

C i SAGWLTMC ii [Aad]KLHLC iii ;

(SEQ ID NO: 46)

C i SAEWLTMC ii QKLHLC iii ;

(SEQ ID NO: 47)

C i SA[Aad]WLTMC ii QKLHLC iii ;

(SEQ ID NO: 48)

C i SAGWLTMC ii EKLHLC iii ;

(SEQ ID NO: 49)

C i SAGWLTMC ii [Cpap]KLHLC iii ;

(SEQ ID NO: 50)

C i [AlloThr]AGWLTMC ii QKLHLC iii ;

(SEQ ID NO: 51)

C i SAGW[Cpa]TMC ii QKLHLC iii ;

(SEQ ID NO: 52)

C i SAGWLTMC ii QKLH[Cpa]C iii ;

(SEQ ID NO: 53)

C i S[Nle]GWLT[HPhe]C ii LKL[Aib]LC iii ;

(SEQ ID NO: 54)

C i SEGWLTMC ii QKLHLC iii ;

(SEQ ID NO: 55)

C i S[Aad]GWLTMC ii QKLHLC iii ;

(SEQ ID NO: 56)

C i SDQWMQMC ii SKLTC iii ;

(SEQ ID NO: 57)

C i SDGWLTMC ii QKLHLC iii ;

(SEQ ID NO: 58)

C i SDEWLTMC ii QKLHLC iii ;

(SEQ ID NO: 59)

C i SNSWLTMC ii QKLHLC iii ;

(SEQ ID NO: 60)

C i SPAWLTMC ii QKLHLC iii ;

(SEQ ID NO: 61)

C i SPEWLTMC ii QKLHLC iii ;

(SEQ ID NO: 62)

C i SPGWLTMC ii QKLHLC iii ;

(SEQ ID NO: 63)

C i SPQWLTMC ii QKLHLC iii ;

(SEQ ID NO: 64)

C i SPSWLTMC ii QKLHLC iii ;

(SEQ ID NO: 65)

C i SDSWKTMC ii QKLHLC iii ;

(SEQ ID NO: 66)

C i SESWSTMC ii QKLHLC iii ;

(SEQ ID NO: 67)

C i SPSWRTMC ii QKLHLC iii ;

(SEQ ID NO: 68)

C i SPSWRNMC ii QKLHLC iii ;

(SEQ ID NO: 69)

C i SWSWLTMC ii KQLNLC iii ;

(SEQ ID NO: 70)

C i SWSWLTMC ii QKLDLC iii ;

(SEQ ID NO: 71)

C i SSSWLTMC ii QKLHLC iii ;

(SEQ ID NO: 72)

C i SWSWLNMC ii QKLHLC iii ;

(SEQ ID NO: 73)

C i DPLC ii LSIRASLGLC iii ;

(SEQ ID NO: 74)

C i DPLC ii LSIKRSLGLC iii ;

(SEQ ID NO: 75)

C i DPLC ii LSIKRQLGLC iii ;

(SEQ ID NO: 76)

C i DPLC ii LSIKRKLGLC iii ;

(SEQ ID NO: 77)

C i DPLC ii LSIKRGLGLC iii ;

(SEQ ID NO: 78)

C i DMRC ii IRIKQSLGMC iii ;

(SEQ ID NO: 79)

C i RDWC ii HWTFDNGHPC iii ;

(SEQ ID NO: 80)

C i RDWC ii HWTFSHGTPC iii ;

(SEQ ID NO: 81)

C i RDWC ii HWTFSHGHPC iii ;

(SEQ ID NO: 82)

C i RDWC ii HWTFTHGHPC iii ;

(SEQ ID NO: 83)

C i RDWC ii HWTFTHSHPC iii ;

(SEQ ID NO: 84)

C i S[Aad]GWLTMC ii QKLHLC iii ;

(SEQ ID NO: 85)

C i S[Aad]GWLTMC ii LKLHLC iii ;

(SEQ ID NO: 86)

C i S[Aad]GWL[3HyV]MC ii LKLHLC iii ;

(SEQ ID NO: 87)

C i SKGWLTMC ii Q[K(Ac)]LHC iii ;

(SEQ ID NO: 88)

C i SAGWLTKC ii Q[K(Ac)]LHLC iii ;

(SEQ ID NO: 89)

C i SAGWLTMC ii K[K(Ac)]LHLC iii ;

(SEQ ID NO: 90)

C i SAGWLTMC ii Q[K(Ac)]LKLC iii ;

(SEQ ID NO: 91)

C i SAGWLTMC ii Q[HArg]LHLC iii ;

(SEQ ID NO: 92)

C i SAGWLTMC ii [HArg]QLNLC iii ;

(SEQ ID NO: 93)

C i S[Aad]GWLTMC ii KQLNLC iii ;

(SEQ ID NO: 94)

C i S[Aad]G[1Nal]LTMC ii KQLNLC iii ;

(SEQ ID NO: 95)

[Pen] i S[Aad]GWLTMC ii KQLNLC iii ;

(SEQ ID NO: 96)

C i S[Aad]GWLTM[Pen] ii KQLNLC iii ;

and

(SEQ ID NO: 97)

C i S[Aad]GWLTMC ii KQLNL[Pen] iii ;

wherein C i , [Pen] i , C ii [Pen] ii , C iii and [Pen] iii represent first, second and third reactive groups, respectively, dA represents D-alanine, AlloThr represents allothreonine, K(Ac) represents Lys (K) with an acetyl group attached to the side chain, HArg represents homoarginine, HSer represents homoserine, HPhe represents homophenylalanine, Aib represents 2-aminoisobutyric acid, Abu represents 2-aminobutyric acid, 1Nal represents 1-naphthylalanine, Chg represents cyclohexylglycine, Nva represents norvaline, 7-AzaW represents 7-azatryptophan, Aad represents 2-aminoadipic acid, Cpa represents β-cyclopropylalanine, Dab represents 2,4-diaminobutyric acid, 3HyV represents 2-amino-3-hydroxy-3-methyl-butyric acid, Nle represents norleucine, Pen represents penicillamine, PYA represents 4-pentynoic acid, and K(PYA) represents Lys (K) with PYA attached to the side chain; and wherein the non-aromatic molecular scaffold forms covalent bonds with the three reactive groups of the polypeptide such that at least two polypeptide loops are formed on the non-aromatic molecular scaffold, or a pharmaceutically acceptable salt thereof.

2 . The peptide ligand as defined in claim 1 , wherein the peptide ligand comprises the amino acid sequence selected from the group consisting of:

(B-Ala)-[Sar] 5 -A-(SEQ ID NO: 1)-A;

A-(SEQ ID NO: 1)-A;

A-(SEQ ID NO: 2)-A;

A-(SEQ ID NO: 3)-A;

A-(SEQ ID NO: 4)-A;

A-(SEQ ID NO: 5)-A;

A-(SEQ ID NO: 6)-A;

A-(SEQ ID NO: 7)-A;

A-(SEQ ID NO: 8)-A;

A-(SEQ ID NO: 9)-A;

A-(SEQ ID NO: 10)-A;

A-(SEQ ID NO: 11)-A;

A-(SEQ ID NO: 12)-A;

A-(SEQ ID NO: 13)-A;

A-(SEQ ID NO: 14)-A;

A-(SEQ ID NO: 15)-A;

A-(SEQ ID NO: 16)-A;

A-(SEQ ID NO: 17)-A;

[PYA]-[B-Ala]-[Sar] 10 -(SEQ ID NO: 18);

SDK-(SEQ ID NO: 19)-A;

[PYA]-[B-Ala]-[Sar] 10 -SDK-(SEQ ID NO: 19);

NH 2 -SDK-(SEQ ID NO: 19)-[Sar] 10 -[K(PYA)];

[Ac][dS]DK-(SEQ ID NO: 19)-A;

SD[HArg]-(SEQ ID NO: 19)-A;

SD[HSer]-(SEQ ID NO: 19)-A;

[Ac]SDK-(SEQ ID NO: 19)-A;

[Ac]SDR-(SEQ ID NO: 19);

[Ac]SDK-(SEQ ID NO: 19)-PSH;

[Ac]SEK-(SEQ ID NO: 19);

[Ac]-SDK-(SEQ ID NO: 19);

[Ac]-A-(SEQ ID NO: 19)-PSH;

SDK-(SEQ ID NO: 19)-A[Sar] 6 ;

[Ac]D [HArg]-(SEQ ID NO: 19);

NH 2 -SDK-(SEQ ID NO: 20);

[Ac]-SDK-(SEQ ID NO: 20)-PSH;

[Ac]-SDK-(SEQ ID NO: 20);

SDK-(SEQ ID NO: 21)-A;

SDK-(SEQ ID NO: 22)-A;

SDK-(SEQ ID NO: 23)-A;

SDK-(SEQ ID NO: 24)-A;

SDK-(SEQ ID NO: 25)-A;

SDK-(SEQ ID NO: 26)-A;

SDK-(SEQ ID NO: 27)-A;

SDK-(SEQ ID NO: 28)-A;

SDK-(SEQ ID NO: 29)-A;

SDK-(SEQ ID NO: 30)-A;

SDK-(SEQ ID NO: 31)-A;

[Ac]-SDK-(SEQ ID NO: 31)-PSH;

SDK-(SEQ ID NO: 32)-A;

SDK-(SEQ ID NO: 33)-A;

SDK-(SEQ ID NO: 34)-A;

SDK-(SEQ ID NO: 35)-A;

SDK-(SEQ ID NO: 36)-A;

SDK-(SEQ ID NO: 37)-A;

[Ac]SDK-(SEQ ID NO: 38);

SDK-(SEQ ID NO: 39)-A;

SDK-(SEQ ID NO: 40)-A;

SDK-(SEQ ID NO: 41)-A;

[Ac]SDK-(SEQ ID NO: 42)-PSH;

[Ac]SDK-(SEQ ID NO: 42)-PS;

[Ac]SDK-(SEQ ID NO: 42)-P;

[Ac]SDK-(SEQ ID NO: 42)-PS—COOH;

[Ac]SDK-(SEQ ID NO: 42)-P—COOH;

[Ac]SDK-(SEQ ID NO: 42)-COOH;

[Ac]SDK-(SEQ ID NO: 42)-PSH—COOH;

[Ac]DK-(SEQ ID NO: 42)-PSH;

[Ac]K-(SEQ ID NO: 42)-PSH;

[Ac]-(SEQ ID NO: 42)-PSH;

[Ac]SD[HArg]-(SEQ ID NO: 43)-PSH;

[Ac]SDK-(SEQ ID NO: 44);

[Ac]SDK-(SEQ ID NO: 45);

[Ac]SDK-(SEQ ID NO: 46);

[Ac]SDK-(SEQ ID NO: 47);

[Ac]SDK-(SEQ ID NO: 48);

[Ac]SDK-(SEQ ID NO: 49);

[Ac]SDK-(SEQ ID NO: 50);

[Ac]SDK-(SEQ ID NO: 51);

[Ac]SDK-(SEQ ID NO: 52);

[Ac]SD[HArg]-(SEQ ID NO: 53)-PSH;

[Ac]SDK-(SEQ ID NO: 54);

[Ac]SDK-(SEQ ID NO: 55);

[B-Ala][Sar]sA-(SEQ ID NO: 56)-A;

VER-(SEQ ID NO: 57)-A [Sar] 6 ;

REN-(SEQ ID NO: 58)-A [Sar] 6 ;

QQE-(SEQ ID NO: 59)-A [Sar] 6 ;

SGK-(SEQ ID NO: 59)-A [Sar] 6 ;

AGS-(SEQ ID NO: 60)-A [Sar] 6 ;

AQT-(SEQ ID NO: 61)-A [Sar] 6 ;

APV-(SEQ ID NO: 62)-A [Sar] 6 ;

ADV-(SEQ ID NO: 63)-A [Sar] 6 ;

GNK-(SEQ ID NO: 64)-A [Sar] 6 ;

KPK-(SEQ ID NO: 64)-A [Sar] 6 ;

ERV-(SEQ ID NO: 65)-A [Sar] 6 ;

AER-(SEQ ID NO: 66)-A [Sar] 6 ;

KEL-(SEQ ID NO: 67)-A [Sar] 6 ;

G[Sar] 5 KEL-(SEQ ID NO: 67)-A;

KEL-(SEQ ID NO: 68)-A [Sar] 6 ;

A-(SEQ ID NO: 69)-PSH [Sar] 6 ;

A-(SEQ ID NO: 70)-DHEN [Sar] 6 ;

REE-(SEQ ID NO: 71)-A [Sar] 6 ;

QAEK-(SEQ ID NO: 72)-A [Sar] 6 ;

A-(SEQ ID NO: 73)-A [Sar] 6 ;

A-(SEQ ID NO: 74)-A [Sar] 6 ;

A-(SEQ ID NO: 75)-A [Sar] 6 ;

A-(SEQ ID NO: 76)-A [Sar] 6 ;

A-(SEQ ID NO: 77)-A [Sar] 6 ;

A-(SEQ ID NO: 78)-A [Sar] 6 ;

A-(SEQ ID NO: 79)-A [Sar] 6 ;

A-(SEQ ID NO: 80)-A [Sar] 6 ;

A-(SEQ ID NO: 81)-A [Sar] 6 ;

A-(SEQ ID NO: 82)-A [Sar] 6 ;

A-(SEQ ID NO: 83)-A [Sar] 6 ;

[Ac]-DK-(SEQ ID NO: 84);

[Ac]-K-(SEQ ID NO: 84);

[Ac]-SEK-(SEQ ID NO: 84);

[Ac]-EK-(SEQ ID NO: 84);

[Ac]-DK-(SEQ ID NO: 84)-PSH—COOH;

[Ac]-SDK-(SEQ ID NO: 85);

[Ac]-DK-(SEQ ID NO: 85);

[Ac]-K-(SEQ ID NO: 85);

[Ac]-SEK-(SEQ ID NO: 85);

[Ac]-EK-(SEQ ID NO: 85);

[Ac]-[HArg]-(SEQ ID NO: 85);

[Ac]-SDK-(SEQ ID NO: 85)-A;

[Ac]-SEK-(SEQ ID NO: 85)-PSH;

[Ac]-SDK-(SEQ ID NO: 86);

[Ac]-D [HArg]-(SEQ ID NO: 87)-PSH;

[Ac]-D [HArg]-(SEQ ID NO: 88)-PSH;

[Ac]-D [HArg]-(SEQ ID NO: 89)-PSH;

[Ac]-D [HArg]-(SEQ ID NO: 90)-PSH;

[Ac]-SD[HArg]-(SEQ ID NO: 91)-PSHK;

[Ac]-SD[HArg]-(SEQ ID NO: 92)-PSHK;

[Ac]-[HArg]-(SEQ ID NO: 93)-PSH;

[Ac]-[HArg]-(SEQ ID NO: 94)-PSH;

[Ac]-[HArg]-(SEQ ID NO: 95)-PSH;

[Ac]-[HArg]-(SEQ ID NO: 96)-PSH; and

[Ac]-[HArg]-(SEQ ID NO: 97)-PSH;

wherein Ac represents an acetyl group, dS represents D-Serine, B-Ala represents beta-alanine, and Sar represents sarcosine, or a pharmaceutically acceptable salt thereof.

3 . The peptide ligand as defined in claim 1 , wherein the peptide ligand is selected from the group consisting of:

Molecular

Sequence

Scaffold

Fl-(B-Ala)-[Sar] 5 -A-(SEQ ID NO: 1)-A

TATA

A-(SEQ ID NO: 1)-A

TATA

A-(SEQ ID NO: 2)-A

TATA

A-(SEQ ID NO: 3)-A

TATA

A-(SEQ ID NO: 4)-A

TATA

A-(SEQ ID NO: 5)-A

TATA

A-(SEQ ID NO: 6)-A

TATA

A-(SEQ ID NO: 7)-A

TATA

A-(SEQ ID NO: 8)-A

TATA

A-(SEQ ID NO: 9)-A

TATA

A-(SEQ ID NO: 10)-A

TATA

A-(SEQ ID NO: 11)-A

TATA

A-(SEQ ID NO: 12)-A

TATA

A-(SEQ ID NO: 13)-A

TATA

A-(SEQ ID NO: 14)-A

TATA

A-(SEQ ID NO: 15)-A

TATA

A-(SEQ ID NO: 16)-A

TATA

A-(SEQ ID NO: 17)-A

TATA

[Fl][B-Ala][Sar] 5 -A-(SEQ ID NO: 1)-A

TATA

[Fl][B-Ala][Sar] 5 -A-(SEQ ID NO: 2)-A

TATA

[Fl][B-Ala][Sar] 5 -A-(SEQ ID NO: 4)-A

TATA

[Fl][B-Ala][Sar] 5 -A-(SEQ ID NO: 6)-A

TATA

[Fl][B-Ala][Sar] 5 -A-(SEQ ID NO: 16)-A

TATA

[Fl][B-Ala][Sar] 5 - A-(SEQ ID NO: 17)-A

TATA

[Fl][B-Ala][Sar]5A-(SEQ ID NO: 56)-A

TATA

SDK-(SEQ ID NO: 19)-A[Sar] 6 [KFl]

TATA

VER-(SEQ ID NO: 57)-A[Sar] 6 [KFl]

TATA

REN-(SEQ ID NO: 58)-A[Sar] 6 [KFl

TATA

QQE-(SEQ ID NO: 59)-A[Sar] 6 [KFl]

TATA

AGS-(SEQ ID NO: 60)-A[Sar] 6 [KFl]

TATA

AQT-(SEQ ID NO: 61)-A[Sar] 6 [KFl]

TATA

APV-(SEQ ID NO: 62)-A[Sar] 6 [KFl]

TATA

ADV-(SEQ ID NO: 63)-A[Sar] 6 [KFl]

TATA

GNK-(SEQ ID NO: 64)-A[Sar] 6 [KFl]

TATA

ERV-(SEQ ID NO: 65)-A[Sar] 6 [KFl]

TATA

AER-(SEQ ID NO: 66)-A[Sar] 6 [KFl]

TATA

SGK-(SEQ ID NO: 59)-A[Sar] 6 [KFl]

TATA

KEL-(SEQ ID NO: 67)-A[Sar] 6 [KFl]

TATA

KEL-(SEQ ID NO: 68)-A[Sar] 6 [KFl

TATA

KPK-(SEQ ID NO: 64)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 69)-PSH[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 70)-DHEN[Sar] 6 [KFl]

TATA

[Fl][B-Ala][Sar] 5 -A-(SEQ ID NO: 12)-A

TATA

[Fl]G[Sar] 5 -A-(SEQ ID NO: 15)-A

TATA

A-(SEQ ID NO: 15)-A-[Sar] 6 [KFl]

TATA

[Fl]G[Sar] 5 KEL-(SEQ ID NO: 67)-A

TATA

(REE-(SEQ ID NO: 71)-A[Sar] 6 [KFl]

TATA

(QAEK-(SEQ ID NO: 72)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 73)-A[ Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 74)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 75)-A[Sar] 6 |KFl]

TATA

A-(SEQ ID NO: 76)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 77)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 78)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 79)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 80)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 81)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 82)-A[Sar] 6 [KFl]

TATA

A-(SEQ ID NO: 83)-A[Sar] 6 [KFl]

TATA

(SDK-(SEQ ID NO: 19)-A

TATA

[Ac][dS]DK-(SEQ ID NO: 19)-A

TATA

(SD[HArg]-(SEQ ID NO: 19)-A

TATA

(SD[HSer]-(SEQ ID NO: 19)-A

TATA

(SDK-(SEQ ID NO: 21)-A

TATA

(SDK-(SEQ ID NO: 22)-A

TATA

(SDK-(SEQ ID NO: 23)-A)

TATA

(SDK-(SEQ ID NO: 24)-A

TATA

(SDK-(SEQ ID NO: 25)-A

TATA

(SDK-(SEQ ID NO: 26)-A

TATA

(SDK-(SEQ ID NO: 27)-A

TATA

(SDK-(SEQ ID NO: 28)-A

TATA

(SDK-(SEQ ID NO: 29)-A

TATA

(SDK-(SEQ ID NO: 30)-A

TATA

(SDK-(SEQ ID NO: 31)-A

TATA

(SDK-(SEQ ID NO: 32)-A

TATA

(SDK-(SEQ ID NO: 33)-A

TATA

(SDK-(SEQ ID NO: 34)-A

TATA

(SDK-(SEQ ID NO: 35)-A

TATA

(SDK-(SEQ ID NO: 36)-A

TATA

(SDK-(SEQ ID NO: 37)-A

TATA

[Ac]SDK-(SEQ ID NO: 19)-A

TATA

[Ac]SDR-(SEQ ID NO: 19)

TATA

[Ac]SDK-(SEQ ID NO: 38)

TATA

(SDK-(SEQ ID NO: 39)-A

TATA

(SDK-(SEQ ID NO: 40)-A

TATA

(SDK-(SEQ ID NO: 41)-A

TATA

[Ac]SDK-(SEQ ID NO: 42)-PSH

TATA

[Ac]SDK-(SEQ ID NO: 42)-PS

TATA

[Ac]SDK-(SEQ ID NO: 42)-P

TATA

[Ac]SDK-(SEQ ID NO: 42)-PS-COOH

TATA

[Ac]SDK-(SEQ ID NO: 42)-P-COOH

TATA

[Ac]SDK-(SEQ ID NO: 42)-COOH

TATA

[Ac]SDK-(SEQ ID NO: 42)-PSH-COOH

TATA

[Ac]DK-(SEQ ID NO: 42)-PSH)

TATA

[Ac]K-(SEQ ID NO: 42)-PSH

TATA

[Ac]-(SEQ ID NO: 42)-PSH

TATA

[Ac]SDK-(SEQ ID NO: 19)-PSH

TATA

[Ac]SD[HArg]-(SEQ ID NO: 43)-PSH

TATA

[Ac]SDK-(SEQ ID NO: 44)

TATA

[Ac]SDK-(SEQ ID NO: 45)

TATA

[Ac]SDK-(SEQ ID NO: 46)

TATA

[Ac]SDK-(SEQ ID NO: 47)

TATA

[Ac]SDK-(SEQ ID NO: 48)

TATA

[Ac]SDK-(SEQ ID NO: 49)

TATA

[Ac]SEK-(SEQ ID NO: 19)

TATA

[Ac]SDK-(SEQ ID NO: 50)

TATA

[Ac]SDK-(SEQ ID NO: 51)

TATA

[Ac]SDK-(SEQ ID NO: 52)

TATA

[Ac]SD[HArg]-(SEQ ID NO: 53)-PSH

TATA

[Ac]SDK-(SEQ ID NO: 54)

TATA

[Ac]SDK-(SEQ ID NO: 55)

TATA

[Ac]-SDK-(SEQ ID NO: 31)-PSH

TATA

[Ac]-SEK-(SEQ ID NO: 85)-PSH

TATA

[Ac]-A-(SEQ ID NO: 19)-PSH

TATA

[Ac]-DK-(SEQ ID NO: 84)-PSH-COOH

TATA

[Ac]-DK-(SEQ ID NO: 84)

TATA

[Ac]-K-(SEQ ID NO: 84)

TATA

[Ac]-SEK-(SEQ ID NO: 84)

TATA

[Ac]-EK-(SEQ ID NO: 84)

TATA

[Ac]-SDK-(SEQ ID NO: 85)

TATA

[Ac]-DK-(SEQ ID NO: 85)

TATA

[Ac]-K-(SEQ ID NO: 85)

TATA

[Ac]-SEK-(SEQ ID NO: 85)

TATA

[Ac]-EK-(SEQ ID NO: 85)

TATA

[Ac]-[HArg]-(SEQ ID NO: 85)

TATA

[Ac]-SDK-(SEQ ID NO: 85)-A

TATA

[Ac]-SDK-(SEQ ID NO: 86)

TATA

[Ac]-SDK-(SEQ ID NO: 19)

TATA

[PYA]-[B-Ala]-[ Sar]10-(SEQ ID NO: 18)

TATA

and wherein Fl represents fluorescein, KFl represents Lys (K) with fluorescein attached to the side chain, and TATA is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA).

4 . The peptide ligand as defined in claim 1 , wherein the non-aromatic molecular scaffold is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA).

5 . The peptide ligand as defined in claim 1 , wherein the pharmaceutically acceptable salt is selected from sodium, potassium, calcium, or ammonium salt.

6 . The peptide ligand as defined in claim 1 , wherein the PD-L1 is human or mouse PD-L1.

7 . The peptide ligand as defined in claim 1 , wherein the polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 42 and 53, or a pharmaceutically acceptable salt thereof.

8 . The peptide ligand as defined in claim 1 , wherein the polypeptide comprises the amino acid sequence of (SEQ ID NO: 42), or a pharmaceutically acceptable salt thereof.

9 . The peptide ligand as defined in claim 1 , wherein the polypeptide comprises the amino acid sequence of (SEQ ID NO: 53), or a pharmaceutically acceptable salt thereof.

10 . The peptide ligand as defined in claim 1 , wherein the polypeptide comprises the amino acid sequence selected from the group consisting of:

[Ac]SDK-(SEQ ID NO: 42)-PSH—COOH; and

[Ac]SD[HArg]-(SEQ ID NO: 53)-PSH;

wherein Ac represents an acetyl group, or a pharmaceutically acceptable salt thereof.

11 . The peptide ligand as defined in claim 1 , wherein the polypeptide comprises the amino acid sequence [Ac]SDK-(SEQ ID NO: 42)-PSH—COOH,

wherein Ac represents an acetyl group, or a pharmaceutically acceptable salt thereof.

12 . The peptide ligand as defined in claim 1 , wherein the polypeptide comprises the amino acid sequence [Ac]SD[HArg]-(SEQ ID NO: 53)-PSH,

wherein Ac represents an acetyl group, or a pharmaceutically acceptable salt thereof.

13 . A pharmaceutical composition comprising the peptide ligand of claim 1 , and one or more pharmaceutically acceptable excipients.

14 . A drug conjugate comprising the peptide ligand as defined in claim 1 , conjugated to one or more effector and/or functional group.

15 . The drug conjugate as defined in claim 14 , wherein the one or more effector and/or functional group is an antibody or a fragment thereof.

16 . The drug conjugate as defined in claim 14 , wherein the one or more effector and/or functional group is a metal chelator.

17 . The drug conjugate as defined in claim 16 , wherein the metal chelator is complexed to a metal radioisotope.

18 . The drug conjugate as defined in claim 17 , wherein the metal radioisotope is selected from the group consisting of 64 Cu, 67 Ga, 68 Ga, 177 Lu, 90 Y, and 213 Bi.

19 . The drug conjugate as defined in claim 18 , wherein the metal radioisotope is 68 Ga.

20 . The drug conjugate as defined in claim 14 , wherein the one or more effector and/or functional groups is a radioactive isotope, selected from the group consisting of 11 C, 18 F, 150 and 13 N.

21 . The drug conjugate as defined in claim 20 , wherein the radioactive isotope is 18 F.

22 . A pharmaceutical composition comprising the drug conjugate of claim 18 , and one or more pharmaceutically acceptable excipients.

23 . A drug conjugate comprising the peptide ligand as defined in claim 1 , conjugated to one or more cytotoxic agent.

24 . The drug conjugate as defined in claim 23 , wherein the one or more cytotoxic agent is a maytansinoid or a monomethyl auristatin.

25 . The drug conjugate as defined in claim 24 , wherein the maytansinoid is DM1.

26 . The drug conjugate as defined in claim 24 , wherein the monomethyl auristatin is monomethyl auristatin E (MMAE).

27 . A pharmaceutical composition comprising the drug conjugate of claim 20 , and one or more pharmaceutically acceptable excipients.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 19, 2020
From: CHEN, LIUHONG; COOKE, JAMES; MCDONNELL, KEVIN; MUDD, GEMMA; VAN RIETSCHOTEN, KATERINE; UPADHYAYA, PUNIT
To: BICYCLETX LIMITED
Reel/Frame 054096/0793 →
Priority Claims (3)
GB 1820956 · Dec 21, 2018 · national
GB 1904621 · Apr 2, 2019 · national
GB 1905631 · Apr 23, 2019 · national
Continuity (3)
Provisional Application 62910113 · Oct 3, 2019
Related Publication 20210101932A1 · Apr 8, 2021
Related Publication 20220306689A9 · Sep 29, 2022
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