Anti-ROBO4 antibodies and uses therefor
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) an HVR-L1 comprising sequence A1-A11, wherein A1-A11 is RASQDVSTAVA (SEQ ID NO:1)
(ii) an HVR-L2 comprising sequence B1-B7, wherein B1-B7 is SASFLYS (SEQ ID NO:2)
(iii) an HVR-L3 comprising sequence C1-C9, wherein C1-C9 is QQSYTTPPT (SEQ ID NO:3)
(iv) an HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GFTINGYYIH (SEQ ID NO:17)
(v) an HVR-H2 comprising sequence E1-E18, wherein E1-E18 is GFIYPAGGDTDYADSVKG (SEQ ID NO:18); and
(vi) an HVR-H3 comprising sequence F1-F17 wherein F1-F17 is ARLIGNKFGWSSYGMDY (SEQ ID NO:19).
2. An isolated anti-Robo4 antibody 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. An isolated anti-Robo4 antibody 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. An isolated anti-Robo4 antibody 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 QQSRSDHPT (SEQ ID NO:20); and
(ii) a heavy chain variable domain comprising
an HVR-H1 comprising SEQ ID NO:17,
an HVR-H2 comprising SEQ ID NO:18, and
an HVR-H3 comprising SEQ ID NO:19.
5. The antibody of any one of claims 1 - 3 and 4 , wherein the antibody is humanized.
6. The antibody of any one of claims 1 - 3 and 4 , wherein the antibody is selected from the group consisting of a Fab, a Fab′, and a (Fab′) 2 .
7. The antibody of any one of claims 1 - 3 and 4 , further comprising a cytotoxic agent.
8. The antibody of claim 7 , 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.
9. The antibody of claim 8 , further comprising a detectable label.
10. The antibody of claim 9 , 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.
11. The antibody of claim 9 , wherein the detectable label is covalently attached to the antibody at a cysteine residue.
12. The antibody of claim 11 , wherein the cysteine residue is at position 118 of the heavy chain Fc region according to EU numbering.