Granted Patent B2

US 12,459,974 · App. 18/906,616 · Granted Nov 4, 2025

Inventors: Paul Beswick (Cambridge, GB); Liuhong Chen (Cambridge, GB); Gemma Elizabeth Mudd (Cambridge, GB); Peter Park (Lexington, MA); Katerine Van Rietschoten (Cambridge, GB); Michael Rigby (Saffron Walden, GB); Stephen Blakemore (Littleton, MA); Tara Gelb (Cambridge, MA); Nicholas Keen (Carlisle, MA)

Assignee: BicycleTx Limited

C07K7/08A61K38/10A61K47/55A61K47/64A61K47/65A61P35/00A61K31/40A61K31/5375A61K38/00

Abstract

Claims (49)

1 . A peptide ligand comprising a polypeptide comprising the amino acid sequence

(SEQ ID NO: 218)

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 ;

or pharmaceutically acceptable salt thereof,

and a molecular scaffold covalently bound to the polypeptide at amino acids C i , C ii , and C iii ;

wherein each of C i , C ii and C iii is independently cysteine or an amino acid isosteric and isoelectronic with cysteine;

X 6 represents Pro;

X 7 represents 1-naphthylalanine (1-Nal);

X 8 represents D-Asp;

X 9 represents Met;

X 10 represents homoarginine (HArg);

X 11 represents Asp;

X 12 represents Trp;

X 13 represents Ser;

X 14 represents Thr;

X 15 represents Pro;

X 16 represents hydroxyproline (HyP); and

X 17 represents Trp.

2 . The peptide ligand of claim 1 , comprising a N-terminal spacer group.

3 . The peptide ligand of claim 1 , comprising a C-terminal amide group.

4 . The peptide ligand of claim 1 , wherein the polypeptide is cyclised with the molecular scaffold such that at least two polypeptide loops are formed on the molecular scaffold, and wherein the molecular scaffold is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA).

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

6 . A drug conjugate comprising the peptide ligand of claim 1 , conjugated to one or more cytotoxic agents.

7 . The drug conjugate of claim 6 , wherein said one or more cytotoxic agents are independently selected from MMAE and DM1.

8 . The drug conjugate of claim 7 , comprising a linker between said one or more cytotoxic agent and said peptide ligand.

9 . The drug conjugate of claim 8 , wherein the linker comprises-PABC-Cit-Val-Glutaryl- or -PABC-cyclobutyl-Ala-Cit-βAla-.

10 . The drug conjugate of claim 9 , wherein said one or more cytotoxic agent is MMAE and the linker comprises-PABC-Cit-Val-Glutaryl-.

11 . A drug conjugate comprising

a peptide ligand comprising a polypeptide cyclised with a molecular scaffold such that at least two polypeptide loops are formed on the molecular scaffold, wherein the molecular scaffold is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA);

wherein the polypeptide comprises the amino acid sequence

(SEQ ID NO: 218)

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 ;

the molecular scaffold being covalently bound to the polypeptide at amino acids C i , C ii , and C iii ;

each of C i , C ii and C iii being independently cysteine or an amino acid isosteric and isoelectronic with cysteine;

X 6 represents Pro;

X 7 represents 1-naphthylalanine (1-Nal);

X 8 represents D-Asp;

X 9 represents Met;

X 10 represents homoarginine (HArg);

X 11 represents Asp;

X 12 represents Trp;

X 13 represents Ser;

X 14 represents Thr;

X 15 represents Pro;

X 16 represents hydroxyproline (HyP);

X 17 represents Trp;

the peptide ligand comprising a N-terminal spacer group; and

the peptide ligand being conjugated via a linker to a cytotoxic agent; wherein the cytotoxic agent is MMAE and the linker is -PABC-Cit-Val-Glutaryl-;

or a pharmaceutically acceptable salt thereof.

Assignments (3)

Priority Claims (4)

Continuity (2)

References Cited (400)