Bispecific heterodimeric diabodies and uses thereof

Abstract

Bispecific heterodimeric diabody molecules and uses thereof in the treatment of cancer. The bispecific heterodimeric diabody molecules comprise two polypeptide chains that associate to form two epitope binding sites recognizing the P-cadherin tumor cell associated antigen and the CD3 T cell antigen.

1 .- 57 . (canceled) 
     
     
         58 . An antibody that binds to P-cadherin, comprising:
 a. a P-CAD VL CDR1 sequence comprising X L1.1 -X L1.6 -X L1.7 -X L1.8 -X L1.9 -X L1.10 -X L1.11 -X L1.2 -X L1.13 ,   b. a P-CAD VL CDR2 sequence comprising X L2.1 -X L2.2 -X L2.3 -X L2.4 -X L2.5 -X L2.6 -X L2.7 ,   c. a P-CAD VL CDR3 X L3.1 -X L3.2 -X L3.3 -X L3.4 -X L3.5 -X L3.6 -X L3.7 -X L3.8 -X L3.9 -X L3.10 -X L3.11 ,   d. a P-CAD VH CDR1 sequence comprising X H1.1 -X H1.2 -X H1.3 -X H1.4 -X H1.5 -X H1.6 -X H1.7 -X H1.8 -X H1.9 -X H1.10  or X H1.5 , X H1.6 -X H1.7 -X H1.8 -X H1.9 -X H1.10 ,   e. a P-CAD VH CDR2 sequence comprising X H2.1 -X H2.2 -X H2.3 -X H2.4 -X H2.5 -X H2.6 -X H2.7 -X H2.8 -X H2.9 -X H2.10  or X H2.1 -X H2.2 -X H2.3 -X H2.4 -X H2.5 -X H2.6 -X H2.7 -X H2.8 -X H2.9 -X H2.10 -X H2.11 -X H2.12 -X H2.13 -X H2.14 -X H2.15 -X H2.16 -X H2.17 , and   f. a P-CAD VH CDR3 sequence comprising X H3.1 -X H3.2 -X H3.3 -X H3.4 -X H3.5 -X H3.6 -X H3.7 -X H3.8 -X H3.9 ,   
       wherein X L3.3  is W, X H1.8  is G, X H2.5  is Y, X H3.1  is I, and X H3.7  is F. 
     
     
         59 . The antibody of  claim 58 , wherein X L1.8  is G, X L2.2  is N, X L2.3  is N, X L3.2  is T, X H2.6  is N, X H2.16  is Q, X H3.5  is N and X H3.9  is I. 
     
     
         60 . The antibody of  claim 58 , comprising a P-CAD VL CDR1, a P-CAD VL CDR2, and a P-CAD VL CDR3 of a light chain variable region comprising the sequence of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 or 23 and/or a P-CAD VH CDR1, a P-CAD VH CDR2, and a P-CAD VH CDR3 of a heavy chain variable region comprising the sequence of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 or 24. 
     
     
         61 . The antibody of  claim 58 , comprising:
 a. a P-CAD VL CDR1 comprising the sequence of SEQ ID NO: 35 or 36,   b. a P-CAD VLCDR2 comprising the sequence of SEQ ID NO: 37 or 38,   c. a P-CAD VL CDR3 comprising the sequence of SEQ ID NO: 39, 40, 41, 42, 43 or 44,   d. a P-CAD VH CDR1 comprising the sequence of SEQ ID NO: 25 or 33,   e. a P-CAD VH CDR2 comprising the sequence of SEQ ID NO: 26 or 34, and   f. a P-CAD VH CDR3 comprising the sequence of SEQ ID NO: 27, 28, 29, 30, 31 or 32.   
     
     
         62 . The antibody of  claim 61 , comprising:
 a. a P-CAD VL CDR1 comprising the sequence of SEQ ID NO: 35 or 36,   b. a P-CAD VL CDR2 comprising the sequence of SEQ ID NO: 37 or 38,   c. a P-CAD VL CDR3 comprising the sequence of SEQ ID NO: 39, 40, 41, 42, 43 or 44,   d. a P-CAD VH CDR1 comprising the sequence of SEQ ID NO: 25,   e. a P-CAD VH CDR2 comprising the sequence of SEQ ID NO: 26, and   f. a P-CAD VH CDR3 comprising the sequence of SEQ ID NO: 27, 28, 29, 30, 31 or 32.   
     
     
         63 . The antibody of  claim 62 , comprising:
 a. a P-CAD VL CDR1 comprising the sequence of SEQ ID NO: 35,   b. a P-CAD VL CDR2 comprising the sequence of SEQ ID NO: 37,   c. a P-CAD VL CDR3 comprising the sequence of SEQ ID NO: 42,   d. a P-CAD VH CDR1 comprising the sequence of SEQ ID NO: 25,   e. a P-CAD VH CDR2 comprising the sequence of SEQ ID NO: 26, and   f. a P-CAD VH CDR3 comprising the sequence of SEQ ID NO: 29.   
     
     
         64 . The antibody of  claim 58 , comprising a light chain variable region comprising the sequence of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23, and/or a heavy chain variable region comprising the sequence of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 or 24. 
     
     
         65 . The antibody of  claim 64 , comprising a light chain variable region amino acid comprising the sequence of SEQ ID NO: 5, and/or a heavy chain variable region comprising the sequence of SEQ ID NO: 6. 
     
     
         66 . The antibody of  claim 64 , comprising a light chain variable region comprising the sequence of SEQ ID NO: 7, and/or a heavy chain variable region comprising the sequence of SEQ ID NO: 8. 
     
     
         67 . The antibody of  claim 64 , comprising a light chain variable region comprising the sequence of SEQ ID NO: 9 and/or a heavy chain variable region comprising the sequence of SEQ ID NO: 10. 
     
     
         68 . The antibody of  claim 64 , comprising a light chain variable region comprising the sequence of SEQ ID NO: 15 and/or a heavy chain variable region comprising the sequence of SEQ ID NO: 16. 
     
     
         69 . (canceled) 
     
     
         70 . A pharmaceutical composition comprising a therapeutically effective amount of the antibody of  claim 58  vand a pharmaceutically acceptable carrier. 
     
     
         71 .- 76 . (canceled)