Anti-robo4 antibodies and uses therefor

Abstract

The invention provides anti-Robo4 antibodies, and compositions comprising the antibodies and methods of using these antibodies, including diagnostic and therapeutic methods.

1 . An isolated anti-Robo4 antibody comprising:
 (i) HVR-L1 comprising SEQ ID NO:1   (ii) HVR-L2 comprising SEQ ID NO:2   (iii) HVR-L3 comprising SEQ ID NO:3   (iv) HVR-H1 comprising SEQ ID NO:4   (v) HVR-H2 comprising SEQ ID NO:5;   (vi) HVR-H3 comprising SEQ ID NO:6.   
     
     
         2 . The antibody of  claim 1 , comprising a light chain variable domain comprising an amino acid sequence selected from the group consisting of: SEQ ID NOS:72-97 as shown in  FIGS. 1A and 2A . 
     
     
         3 . The antibody of  claim 1 , comprising a heavy chain variable domain comprising an amino acid sequence selected from the group consisting of: SEQ ID NOS:140-165 as shown in  FIGS. 1B and 2B . 
     
     
         4 - 5 . (canceled) 
     
     
         6 . The antibody of  claim 1 , comprising
 (i) a light chain variable domain comprising   an HVR-L1 comprising SEQ ID NO:1,   an HVR-L2 comprising SEQ ID NO:2, and   an HVR-L3 comprising SEQ ID NO:3; and   (ii) a heavy chain variable domain comprising   an HVR-H1 comprising SEQ ID NO:4,   an HVR-H2 comprising SEQ ID NO:5, and   an HVR-H3 comprising SEQ ID NO:6.   
     
     
         7 . The antibody of  claim 1 , wherein the antibody is humanized. 
     
     
         8 . The antibody of  claim 1 , wherein the antibody is selected from the group consisting of a Fab, a Fab′, and a (Fab′) 2 . 
     
     
         9 . The antibody of  claim 1 , further comprising a cytotoxic agent. 
     
     
         10 . The antibody of  claim 9 , wherein the cytotoxic agent is selected from the group consisting of: N 2 ′-deacetyl-N- 2 ′(3-mercapto-1-oxopropyl)-maytansine (DM1), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and combinations thereof. 
     
     
         11 . The antibody of  claim 10 , further comprising a detectable label. 
     
     
         12 . The antibody of  claim 11 , wherein the detectable label is selected from the group consisting of: biotin, a fluorescent dye, a radionuclide, chelating agent 1, 4, 7, 10-tetraazacyclododecane-N,N′, N″, N′″-tetraacetic acid (DOTA), a microbubble, a perfluorocarbon nanoparticle emulsion, a metallic particle, and combinations thereof. 
     
     
         13 . The antibody of  claim 11 , wherein the detectable label is covalently attached to the antibody at a cysteine residue. 
     
     
         14 . The antibody of  claim 13 , wherein the cysteine residue is at position 118 of the heavy chain Fc region according to EU numbering. 
     
     
         15 - 27 . (canceled)