ANTIBODY THAT BINDS TO VEGF-A AND ANG2 AND METHODS OF USE

Claims

1. An antibody that binds to human VEGF-A and to human ANG2, wherein the antibody comprises a VH domain comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3, (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 21, and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and a VL domain comprising (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 22, (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 23, and (e) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8, and (g) the VH domain comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 19; and (z) the VL domain comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 20, wherein the antibody comprises a human heavy chain framework with (i) FR1 comprising amino acid residues H3, D26, F27, E29 and Y30, (ii) FR3 comprising amino acid residues R66 and R94; and a human light chain framework with (i) FR1 containing amino acid residues 12 and Y3, (ii) FR2 containing amino acid residues L46 and F49, (iii) FR3 containing amino acid residue E57, In this case, the numbering of the VH and VL domains is carried out in accordance with the Kabatu numbering system.

2. The antibody of claim 1, wherein the Fab fragment of the antibody binds (i) to human VEGF-A121 with K D less than 50 pM as measured by KinExA, and (ii) with human ANG2 with K D less than 50 pM measured using KinExA.

3. The antibody of claim 1 or 2, wherein a 20 mM His / HisHCl solution at pH 6.0 containing 180 mg / ml of the Fab fragment of the antibody has a viscosity of less than 20 cP at 20°C, as determined by dynamic light scattering using the latex bead DLS method described in Example 8.

4. The antibody according to any one of claims 1-3, wherein the antibody is a Fab fragment.

5. An isolated nucleic acid encoding an antibody according to any one of claims 1-4.

6. A host cell containing the nucleic acid according to claim 5.

7. A method for producing an antibody that binds to human VEGF-A and human ANG2, comprising culturing the host cell of claim 6 so as to produce the antibody.

8. The method of claim 7, wherein the host cell is a CHO cell.

9. A pharmaceutical composition comprising an antibody according to any one of claims 1-4 and a pharmaceutically acceptable carrier.

10. A delivery port device comprising an antibody according to any one of claims 1-4.

11. An antibody according to any one of claims 1-4 for use as a medicinal product for the treatment of a vascular disease.