Specific antibody drug conjugates (adcs) having ksp inhibitors

Abstract

Specific binder-drug conjugates (ADCs) of kinesin spindle protein inhibitors, effective metabolites of these ADCs, processes for preparing these ADCs, the use of these ADCs for the treatment and/or prevention of diseases and to the use of these ADCs for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases, are described.

1 . An antibody-drug conjugate of formula (I): 
       
         
           
           
               
               
           
         
         or a salt, solvate, or salt of a solvate thereof; 
         wherein: 
         n is 1-8, 
         AK is an anti-CD123 antibody,
 or an anti-CXCRS antibody, 
 or an antigen-binding fragment of these antibodies, 
 
         wherein the antibody or the antigen-binding fragment is attached via a sulfur atom of a cysteine side group. 
       
     
     
         2 . The antibody-drug conjugate of  claim 1 , wherein n is 2-8. 
     
     
         3 . The antibody-drug conjugate of  claim 1  or  2 , wherein n is 4-8. 
     
     
         4 . A pharmaceutical composition comprising at least one antibody-drug conjugate according to any one of  claims 1  to  3 , in combination with an inert, non-toxic, pharmaceutically suitable auxiliary. 
     
     
         5 . A method for treating a disease in a subject comprising administering to the subject a therapeutically effective amount of an antibody-drug conjugate of any one of  claims 1  to  3 , or a salt, solvate, or salt of a solvate thereof. 
     
     
         6 . A method for treating a hyperproliferative and/or angiogenic disorder in a subject comprising administering to the subject a therapeutically effective amount of an antibody-drug conjugate of any one of  claims 1  to  3 , or a salt, solvate, or salt of a solvate thereof. 
     
     
         7 . A method for treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an antibody-drug conjugate of any one of  claims 1  to  3 , or a salt, solvate, or salt of a solvate thereof. 
     
     
         8 . A method for treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an antibody-drug conjugate of any one of  claims 1  to  3  in combination with one or more therapeutic approaches for cancer immunotherapy or with one or more active compounds directed against a molecular target of cancer immunotherapy. 
     
     
         9 . An anti-CD123 antibody comprising a variable region of the heavy chain (VH) comprising the variable CDR1 sequence of the heavy chain (H-CDR1), as shown by SEQ ID NO: 12, the variable CDR2 sequence of the heavy chain (H CDR2), as shown by SEQ ID NO: 13 and the variable CDR3 sequence of the heavy chain (H-CDR3), as shown by SEQ ID NO: 14, and a variable region of the light chain (VL) comprising the variable CDR1 sequence of the light chain (L CDR1), as shown by SEQ ID NO: 16, the variable CDR2 sequence of the light chain (L-CDR2), as shown by SEQ ID NO: 17 and the variable CDR3 sequence of the light chain (L-CDR3), as shown by SEQ ID NO: 18, or an antigen-binding fragment thereof. 
     
     
         10 . A method for treating cancer in a subject comprising administering to the subject a therapeutically effective amount of the anti-CD123 antibody of  claim 9 .