Heterotandem bicyclic peptide complexes

Abstract

The present invention relates to heterotandem bicyclic peptide complexes which comprise a first peptide ligand, which binds to a component present on a cancer cell, conjugated via a linker to a second peptide ligand, which binds to a component present on an immune cell. The invention also relates to the use of said heterotandem bicyclic peptide complexes in preventing, suppressing or treating cancer.

1 - 16 . (canceled) 
     
     
         17 . A method of preventing, suppressing or treating a cancer, which comprises administering to a patient in need thereof a heterotandem bicyclic peptide complex comprising:
 (a) a first peptide ligand which binds to a component present on a cancer cell; conjugated via a linker to   (b) a second peptide ligand which binds to a component present on an immune cell; wherein each of said peptide ligands comprise a polypeptide comprising 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, characterized in that said heterotandem bicyclic peptide complex comprises the following first and second peptide ligands:   
     
     
         18 . The method of  claim 17 , wherein the immune cell is selected from: white blood cells, lymphocytes, CD8 cells, CD4 cells, dendritic cells, follicular dendritic cells and granulocytes. 
     
     
         19 . The method of  claim 17 , wherein the second peptide ligand comprises a CD137 binding bicyclic peptide ligand. 
     
     
         20 . The method of  claim 19 , wherein the CD137 binding bicyclic peptide ligand is selected from any of the peptides of SEQ ID NOS: 67 to 84. 
     
     
         21 . The method of  claim 17 , wherein the first peptide ligand comprises a Nectin-4 binding bicyclic peptide ligand. 
     
     
         22 . The method of  claim 21 , wherein the Nectin-4 binding bicyclic peptide ligand is selected from any of the peptides of SEQ ID NOS: 52 to 66. 
     
     
         23 . The method of  claim 21 , wherein the heterotandem bicyclic peptide complex is selected from BCY11468, BCY11618, BCY11776, BCY11860, BCY12020, BCY12661 and BCY12969. 
     
     
         24 . The method of  claim 17 , wherein the first peptide ligand comprises an EphA2 binding bicyclic peptide ligand. 
     
     
         25 . The method of  claim 24 , wherein the EphA2 binding bicyclic peptide ligand is selected from any of the peptides of SEQ ID NOS: 10 to 51. 
     
     
         26 . The method of  claim 24 , wherein the heterotandem bicyclic peptide complex is selected from BCY13035, BCY13040, BCY13253, BCY13254, BCY13340 and BCY13342. 
     
     
         27 . The method of  claim 17 , wherein the first peptide ligand comprises a PD-L1 binding bicyclic peptide ligand. 
     
     
         28 . The method of  claim 27 , wherein the PD-L1 binding bicyclic peptide ligand is selected from any of the peptides of SEQ ID NOS: 1 to 9. 
     
     
         29 . The method of  claim 27 , wherein the heterotandem bicyclic peptide complex is selected from BCY12375 and BCY12021. 
     
     
         30 . The method of  claim 17 , wherein the molecular scaffold is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA). 
     
     
         31 . The method of  claim 17 , wherein the pharmaceutically acceptable salt is selected from the free acid or the sodium, potassium, calcium, or ammonium salt. 
     
     
         32 . The method of  claim 17 , wherein the linker is PEG5: 
       
         
           
           
               
               
           
         
       
     
     
         33 . The method of  claim 20 , wherein the CD137 binding bicyclic peptide ligand is SEQ ID NO: 77. 
     
     
         34 . The method of  claim 25 , wherein the EphA2 binding bicyclic peptide ligand is SEQ ID NO: 33. 
     
     
         35 . The method of  claim 26 , wherein the heterotandem bicyclic peptide complex is BCY13340. 
     
     
         36 . The method of  claim 18 , wherein the lymphocytes are selected from T lymphocytes or T cells, B cells, or natural killer cells.