Bicyclic peptide ligands specific for CD137
AssigneeBicycleTx Limited
InventorsLiuhong Chen, Rachid Lani, Kevin McDonnell, Gemma Elizabeth Mudd, Peter Park
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Abstract
The present invention relates to polypeptides which are covalently bound to 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 CD137. 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 CD137.
Claims17
A peptide ligand specific for CD137, or a pharmaceutically acceptable salt thereof, comprising a polypeptide, or a pharmaceutically acceptable salt thereof, wherein said polypeptide comprises at least three reactive groups, separated by at least two loop sequences, and a molecular scaffold which forms covalent bonds with the reactive groups of the polypeptide such that at least two polypeptide loops are formed on the molecular scaffold;
- wherein the peptide ligand comprises an amino acid sequence comprising SEQ ID NO:
- 266, or a modified derivative thereof:
- (SEQ ID NO:
- 266)
- Ci-X5-X6-X7-X8-X9-X10-Cii-X11-
- X12-D-X13-X14-X15-Ciii;
- wherein Ci, Cii and Ciii represent first, second and third cysteine residues, respectively;
- X5 represents Ile, tBuAla or Chg;
- X6 represents Glu, Pro, Asp, Lys, Aad, HyP or Oxa;
- X7 represents Glu, Lys or Aad;
- X8 represents Gly, D-Lys, D-Ala, L-Ala, D-Phe, D-Glu, D-Gln, D-Leu, D-Ser or D-Trp;
- X9 represents Gln, Lys, Ala, Pro, 5,5-dmP, Oic, Oxa, HyP, Aib or Ac5c;
- X10 represents Tyr, Phe, 3MePhe, 4MePhe, 4FPhe, 2Nal, 4MeOPhe or 4,4-BPA;
- X11 represents Phe, Lys, 4MePhe, 2FPhe, 4FPhe, 4Pal, 4,4 BPA, 4tBuPhe, NO2Phe or 4BrPhe;
- X12 represents Ala or Lys;
- X13 represents Pro or Lys;
- X14 represents Tyr or Lys;
- and
- X15 represents Met, Lys, Nle, HLeu or Ahp,
- wherein Chg represents L-cyclohexyl glycine;
- Aad represents 2-aminoadipic acid;
- HyP represents hydroxyproline;
- Oxa represents oxazolidine-4-carboxylic acid;
- 5,5-dmP represents 5,5-Dimethyl-L-proline;
- Oic represents octahydroindolecarboxylic acid;
- Aib represents aminoisobutyric acid;
- Ac5c represents aminocyclopentanecarboxylic acid;
- MePhe represents methyl phenylalanine;
- FPhe represents fluorophenylalanine;
- Nal represents napthylalanine;
- MeOPhe represents methoxy phenylalanine;
- 4,4-BPA represents 4,4biphenylalanine;
- Pal represents pyridylalanine;
- tBuPhe represents t-butyl phenylalanine;
- NO2Phe represents nitro phenylalanine;
- 4BrPhe represents bromo phenylalanine;
- HLeu represents homoleucine;
- and Ahp represents aminoheptanoic acid.
Dependencies are inferred from the claim text.