Antibody drug conjugates

Abstract

The present invention relates to anti-cKIT antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

What is claimed is: 
     
         1 .- 33 . (canceled) 
     
     
         34 . A method of treating an cKIT positive cancer in a patient in need thereof, comprising administering to said patient an antibody drug conjugate of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutical composition thereof; wherein; 
         Ab is an antibody or antigen binding fragment thereof that specifically binds to human cKIT at domains 1-3 (SEQ ID NO.155), and n is an integer from 1 to 10. 
       
     
     
         35 . The method of  claim 34 , wherein said cancer is selected from the group consisting of gastrointestinal stromal tumors (GIST), small cell lung cancer (SCLC), acute myeloid leukemia (AML), melanoma, mast cell leukemia (MCL), mastocytosis, neurofibromatosis, breast cancer, non-small cell lung cancer (NSCLC) and pancreatic cancer. 
     
     
         36 . The method of  claim 35 , wherein the antibody drug conjugate or the pharmaceutical composition is administered in combination with another therapeutic agent. 
     
     
         37 . The method of  claim 36 , wherein the antibody drug conjugate or the pharmaceutical composition is administered in combination with a therapeutic selected from the group consisting of Imatinib, Sunitinib, Everolimus, NVP-LCL161, NVP-BEZ235, NVP-BKM120, NVP-BYL719, NVP-CCG168, NVP-115P990 and NVP-BVB808. 
     
     
         38 .- 47 . (canceled) 
     
     
         48 . The method of  claim 34 , wherein the antibody or antigen binding fragment thereof comprises:
 (i) a heavy chain variable region that comprises (a) a HCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO: 76, (b) a HCDR2 of SEQ ID NO: 77, (c) a HCDR3 of SEQ ID NO: 78; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 85, (e) a LCDR2 of SEQ ID NO: 86, and (f) a LCDR3 of SEQ ID NO: 87;   (ii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO: 22, (b) a HCDR2 of SEQ ID NO: 23, (c) a HCDR3 of SEQ ID NO: 24; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 31, (e) a LCDR2 of SEQ ID NO: 32, and (f) a LCDR3 of SEQ ID NO: 33;   (iii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO: 130, (b) a HCDR2 of SEQ ID NO: 131, (c) a HCDR3 of SEQ ID NO: 132; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 139, (e) a LCDR2 of SEQ ID NO: 140, and (f) a LCDR3 of SEQ ID NO: 141;   (iv) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO: 58, (b) a HCDR2 of SEQ ID NO: 59, (c) a HCDR3 of SEQ ID NO: 60; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 67, (e) a LCDR2 of SEQ ID NO: 68, and (f) a LCDR3 of SEQ ID NO: 69;   (v) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO: 40, (b) a HCDR2 of SEQ ID NO: 41, (c) a HCDR3 of SEQ ID NO: 42; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 49, (e) a LCDR2 of SEQ ID NO: 50, and (f) a LCDR3 of SEQ ID NO: 51;   (vi) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO: 94, (b) a HCDR2 of SEQ ID NO: 95, (c) a HCDR3 of SEQ ID NO: 96; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 103, (d) a LCDR2 of SEQ ID NO: 104, and (f) a LCDR3 of SEQ ID NO: 105;   (vii) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO: 112, (b) a HCDR2 of SEQ ID NO: 113, (c) a HCDR3 of SEQ ID NO: 114; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 121, (e) a LCDR2 of SEQ ID NO: 122, and (f) a LCDR3 of SEQ ID NO: 123; or   (viii) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO: 3, (b) a HCDR2 of SEQ ID NO: 4, (c) a HCDR3 of SEQ ID NO: 5; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 12, (e) a LCDR2 of SEQ ID NO: 13, and (f) a LCDR3 of SEQ ID NO: 14.   
     
     
         49 .- 50 . (canceled)