Granted Patent B2

US 12,551,567 · App. 17/416,562 · Granted Feb 17, 2026

Inventors: Liuhong Chen (Cambridge, GB); James Cooke (Cambridge, GB); Kevin McDonnell (Cambridge, GB); Gemma Mudd (Cambridge, GB); Katerine Van Rietschoten (Cambridge, GB); Punit Upadhyaya (Cambridge, GB)

Assignee: BicycleRD Limited

A61K47/64A61K49/0056C07K7/64

Abstract

Claims (72)

1 . A peptide ligand, or pharmaceutically acceptable salt thereof, specific for programmed cell death 1 ligand 1 (PD-L1) 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 said polypeptide comprises an amino acid sequence of:

(SEQ ID NO: 7)

C i -P-F-P-V/E-E-W-C ii -S/P-R-C iii ;

wherein C i , C ii and C iii represent first, second and third cysteine residues, respectively.

2 . The peptide ligand as defined in claim 1 , wherein the amino acid sequence C i -P-F-P-V/E-E-W-C ii -S/P-R-C iii (SEQ ID NO: 7) is selected from SEQ ID NOS: 1-3:

(SEQ ID NO: 1)

C i PFPVEWC ii SRC iii ;

(SEQ ID NO: 2)

C i PFPEEWCHPRC iii ;

and

(SEQ ID NO: 3)

C i PFPVEWCHPRC iii ;

wherein C i , C ii and C iii represent first, second and third cysteine residues, respectively.

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

Peptide 

Molecular

Number

Sequence

Scaffold

BCY507

ACPFPVEWCSRCA (SEQ ID NO: 10)

TBMB

BCY508

ACPFPEEWCPRCA (SEQ ID NO: 13)

TBMB

BCY509

ACPFPVEWCPRCA (SEQ ID NO: 14)

TBMB

BCY543

ACPFPVEWCSRCA[Sar] 6 [KFI] (SEQ ID NO: 25)

TBMB

BCY544

[F]][B-Ala][Sar] 5 ACPFPEEWCPRCA (SEQ ID NO: 26)

TBMB

BCY545

[F]][B-Ala][Sar] 5 ACPFPVEWCPRCA (SEQ ID NO: 27)

TBMB

BCY546

ACPFPVEWCPRCA[Sar] 6 [KF1] (SEQ ID NO: 28)

TBMB.

4 . The peptide ligand as defined in claim 1 , wherein the molecular scaffold is 1,3,5-tris(bromomethyl)benzene (TBMB).

5 . The peptide ligand as defined in claim 1 , wherein the peptide ligand is the free acid or a sodium, potassium, calcium, or ammonium salt.

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

7 . The peptide ligand as defined in claim 2 , wherein the polypeptide has an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 10)

ACPFPVEWCSRCA;

(SEQ ID NO: 11)

ACPFPVEWCSRCA[Sar] 6 ;

(SEQ ID NO: 12)

ACPFPEEWCPRCA;

(SEQ ID NO: 13)

[B-Ala][Sar] 5 ACPFPEEWCPRCA;

(SEQ ID NO: 14)

ACPFPVEWCPRCA;

(SEQ ID NO: 15)

[B-Ala][Sar] 5 ACPFPVEWCPRCA; and

(SEQ ID NO: 16)

ACPFPVEWCPRCA[Sar] 6 .

8 . The peptide ligand as defined in claim 2 , wherein the polypeptide comprises the amino acid sequence:

(SEQ ID NO: 14)

ACPFPVEWCPRCA.

9 . The peptide ligand as defined in claim 8 , wherein the molecular scaffold is 1,3,5-tris(bromomethyl)benzene (TBMB).

10 . A pharmaceutical composition which comprises the peptide ligand of claim 1 , in combination with one or more pharmaceutically acceptable excipients.

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

12 . The drug conjugate as defined in claim 11 , wherein the one or more effector and/or functional groups are cytotoxic agents.

13 . The drug conjugate as defined in claim 11 , wherein the one of more effector and/or functional group is a metal chelator.

14 . The drug conjugate as defined in claim 13 , wherein the metal chelator is complexed to a metal radioisotope.

15 . The drug conjugate as defined in claim 14 , wherein the metal radioisotope is selected from the group consisting of 64 Cu, 67 Ga, 68 Ga, 177 Lu, 90 Y, and 213 Bi.

16 . The drug conjugate as defined in claim 15 , wherein the metal radioisotope is 68 Ga.

17 . The drug conjugate as defined in claim 14 , further incorporating a radioactive isotope, wherein the radioactive isotope is selected from the group consisting of 11 C, 18 F, 15 O and 13 N.

18 . The drug conjugate as defined in claim 17 , wherein the radioactive isotope is 18 F.

19 . A pharmaceutical composition which comprises the drug conjugate as defined in claim 11 , in combination with one or more pharmaceutically acceptable excipients.

Assignments (1)

Priority Claims (2)

Continuity (1)

References Cited (400)