Specific antibody-drug-conjugates (adcs) with ksp inhibitors and anti-cd123-antibodies

Abstract

The invention relates to specific Antibody-Drug-Conjugates (ADCs) with KSP inhibitors and anti-CD123-antibodies, to the use of these conjugates for the treatment and/or prophylaxis of diseases and to the use of these conjugates for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases. Such treatments can be carried out as monotherapy or else in combination with other medicaments or further therapeutic measures.

What is claimed is: 
     
         1 . An antibody or antigen-binding antibody fragment that binds to CD123, comprising a variable heavy chain comprising the variable CDR1 sequence of the heavy chain, as shown in SEQ ID NO: 202, the variable CDR2 sequence of the heavy chain, as shown in SEQ ID NO: 203, and the variable CDR3 sequence of the heavy chain, as shown in SEQ ID NO: 204; and a variable light chain comprising the variable CDR1 sequence of the light chain, as shown in SEQ ID NO: 206, the variable CDR2 sequence of the light chain, as shown in SEQ ID NO: 207, and the variable CDR3 sequence of the light chain, as shown in SEQ ID NO: 208. 
     
     
         2 . The antibody or antigen-binding antibody fragment of  claim 1 , wherein the variable heavy chain comprises a sequence at least 98% identical to SEQ ID NO: 201. 
     
     
         3 . The antibody or antigen-binding antibody fragment of  claim 2 , wherein the variable heavy chain comprises SEQ ID NO: 201. 
     
     
         4 . The antibody or antigen-binding antibody fragment of  claim 1 , wherein the variable light chain comprises a sequence at least 98% identical to SEQ ID NO: 205. 
     
     
         5 . The antibody or antigen-binding antibody fragment of  claim 1 , wherein the variable light chain comprises SEQ ID NO: 205. 
     
     
         6 . The antibody or antigen-binding antibody fragment of  claim 2 , wherein the variable light chain comprises a sequence at least 98% identical to SEQ ID NO: 205. 
     
     
         7 . The antibody or antigen-binding antibody fragment of  claim 3 , wherein the variable light chain comprises SEQ ID NO: 205. 
     
     
         8 . The antibody or antigen-binding antibody fragment of  claim 1 , comprising a heavy chain comprising SEQ ID NO: 209. 
     
     
         9 . The antibody or antigen-binding antibody fragment of  claim 1 , comprising a light chain comprising SEQ ID NO: 210. 
     
     
         10 . The antibody or antigen-binding antibody fragment of  claim 8 , comprising a light chain comprising SEQ ID NO: 210. 
     
     
         11 . A pharmaceutical composition comprising the antibody or antigen-binding antibody fragment of  claim 1 , and an inert non-toxic pharmaceutically suitable auxiliary. 
     
     
         12 . A method for treatment of a disease associated with CD123 expression, comprising administering to a patient in need thereof an effective amount of the antibody or antigen-binding antibody fragment of  claim 1 . 
     
     
         13 . A conjugate comprising the antibody or antigen-binding antibody fragment of  claim 1 , and a chemotherapeutic. 
     
     
         14 . The conjugate of  claim 13 , wherein the chemotherapeutic comprises an inhibitor of kinesin spindle protein. 
     
     
         15 . A conjugate comprising the antibody or antigen-binding antibody fragment of  claim 1 , comprising one or more chemical compound(s) as defined in formula (I), or a salt, a solvate, a salt of a solvate, or an epimer of one or more chemical compound(s) as defined in formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 X is —CH 2 — or —CH 2 —CH 2 —; 
 L is (—CH 2 —CH 2 —O-)m-CH 2 —CH 2 —; 
 m is 1 to 20; 
 n is 1 to 8; and 
 AK is the antibody or antigen-binding antibody fragment. 
 
     
     
         16 . The conjugate of  claim 15 , wherein X is —CH 2 —. 
     
     
         17 . The conjugate of  claim 16 , wherein m is 2 to 8. 
     
     
         18 . The conjugate of  claim 15 , wherein the conjugate has the structure: 
       
         
           
           
               
               
           
         
       
       wherein n is 1 to 8, and AK is the antibody or antigen-binding antibody fragment. 
     
     
         19 . The conjugate of  claim 15 , wherein n is 2 to 6. 
     
     
         20 . A method for treatment of a disease associated with CD123 expression, comprising administering to a patient in need thereof an effective amount of the antibody or antigen-binding antibody fragment of  claim 15 .