Granted Patent B2

US 12,540,161 · App. 17/444,294 · Granted Feb 3, 2026

Inventors: Kevin McDonnell (Lexington, MA); Gemma Mudd (Cambridge, GB); Paul John Beswick (Cambridge, GB)

Assignee: BicycleTx Limited

C07K5/06052A61K38/48A61K47/65

Abstract

Claims (42)

1 . A linker comprising a -P1-P2-P3- moiety, wherein:

P1 represents a basic non-natural amino acid or a derivative thereof;

P2 represents a hydrophobic non-natural amino acid selected from cyclobutyl (cBu), diphenylalanine (Dpa), 1-naphthylalanine (1Nal), and 2-naphthylalanine (2Nal); and

P3 represents an acidic amino acid or an acidic non-natural amino acid.

2 . The linker according to claim 1 , wherein P1 represents a basic non-natural amino acid selected from: 2-amino-4-guanidinobutanoic acid (Agb); 2-amino-4-(3-methylguanidino) butanoic acid (Agb(Me)); 2,4-diaminobutanoic acid (Dab); 2,3-diaminopropanoic acid (Dap); 2-amino-3-guanidinopropanoic acid (Dap(CNNH 2 )); and citrulline (Cit).

3 . The linker according to claim 1 , wherein P2 is 1-naphthylalanine (1Nal).

4 . The linker according to claim 1 , wherein P3 represents an acidic amino acid selected from Asp and Glu.

5 . The linker according to claim 1 , wherein the -P1-P2-P3- moiety is one of the following:

P1

P2

P3

Cit

1Nal

Glu

Dab

cBu

Glu

Dab

Dpa

Glu

Dab

1Nal

Glu

Dab

2Nal

Glu.

6 . A compound comprising a binding agent which binds to a target and a cytotoxic agent, wherein said binding agent is joined to said cytotoxic agent via a linker according to claim 1 .

7 . The compound according to claim 6 , wherein said binding agent is a peptide selected from an antibody or a bicyclic peptide.

8 . The compound according to claim 6 , wherein said cytotoxic agent is DM1 or MMAE.

9 . The compound according to claim 6 which is protease resistant when compared with a conjugate in the absence of said linker.

10 . The compound according to claim 6 which is plasma stable when compared with a conjugate in the absence of said linker.

11 . The compound according to claim 6 which is selected from: BCY10989, BCY10980, BCY10982, BCY10983, BCY10984, BCY10981, BCY10985, BCY10986, BCY10987, and BCY10988.

12 . A pharmaceutical composition comprising the compound according to claim 6 in combination with one or more pharmaceutically acceptable excipients.

13 . A method of treating cancer which comprising administering to a patient in need thereof a compound according to claim 6 .

14 . The compound according to claim 9 , wherein the protease is Cathepsin B.

15 . The compound according to claim 8 , wherein said cytotoxic agent is DM1.

16 . The compound according to claim 8 , wherein said cytotoxic agent is MMAE.

17 . The compound according to claim 7 , wherein said binding agent is an antibody.

18 . The compound according to claim 7 , wherein said binding agent is a bicyclic peptide.

19 . The linker according to claim 2 , wherein P1 is Cit.

20 . The linker according to claim 4 , wherein P3 is Glu.

21 . The linker according to claim 5 , wherein the -P1-P2-P3- moiety is -Cit-1Nal-Glu-.

Assignments (1)

Continuity (2)

References Cited (400)