Antibody which binds Lrg1 and methods of use

1. An antibody or fragment thereof that specifically binds to human Lrg1 and which comprises CDRs of SEQ ID NOs: 21, 22, 23, 24, 25, and 26.

2. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof comprises:

(a) a heavy chain variable region amino acid sequence of SEQ ID NO: 1, 5, 7, 9, 11, or 13; or

(b) a variant of (a) having at least 70% amino acid sequence identity to a sequence of (a), wherein the antibody or fragment comprises CDRs of SEQ ID Nos: 21, 22, and 23, and retains the ability to specifically bind to Lrg1.

3. The antibody or fragment thereof according to claim 1 , wherein the antibody comprises:

(a) a light chain variable region amino acid sequence of SEQ ID NO: 2, 15, 17, or 19; or

(b) a variant of (a) having at least 70% identity amino acid identity to a sequence of (a), wherein the antibody or fragment comprises CDRs of SEQ ID Nos: 24, 25, and 26, and retains the ability to specifically bind to Lrg1.

4. The antibody or fragment thereof according to claim 1 , wherein the antibody comprises:

(a) the heavy chain variable region of SEQ ID NO: 1 and the light chain variable region of SEQ ID NO: 2; or

(b) the heavy chain variable region of SEQ ID NO: 1 and the light chain variable region of SEQ ID NO: 15; or

(c) the heavy chain variable region of SEQ ID NO: 1 and the light chain variable region of SEQ ID NO: 17; or

(d) the heavy chain variable region of SEQ ID NO: 1 and the light chain variable region of SEQ ID NO: 19; or

(e) the heavy chain variable region of SEQ ID NO: 5 and the light chain variable region of SEQ ID NO: 2; or

(f) the heavy chain variable region of SEQ ID NO: 5 and the light chain variable region of SEQ ID NO: 15; or

(g) the heavy chain variable region of SEQ ID NO: 5 and the light chain variable region of SEQ ID NO: 17; or

(h) the heavy chain variable region of SEQ ID NO: 5 and the light chain variable region of SEQ ID NO: 19; or

(i) the heavy chain variable region of SEQ ID NO: 7 and the light chain variable region of SEQ ID NO: 2; or

(j) the heavy chain variable region of SEQ ID NO: 7 and the light chain variable region of SEQ ID NO: 15; or

(k) the heavy chain variable region of SEQ ID NO: 7 and the light chain variable region of SEQ ID NO: 17; or

(l) the heavy chain variable region of SEQ ID NO: 7 and the light chain variable region of SEQ ID NO: 19; or

(m) the heavy chain variable region of SEQ ID NO: 9 and the light chain variable region of SEQ ID NO: 2; or

(n) the heavy chain variable region of SEQ ID NO: 9 and the light chain variable region of SEQ ID NO: 15; or

(o) the heavy chain variable region of SEQ ID NO: 9 and the light chain variable region of SEQ ID NO: 17; or

(p) the heavy chain variable region of SEQ ID NO: 9 and the light chain variable region of SEQ ID NO: 19; or

(q) the heavy chain variable region of SEQ ID NO: 11 and the light chain variable region of SEQ ID NO: 2; or

(r) the heavy chain variable region of SEQ ID NO: 11 and the light chain variable region of SEQ ID NO: 15; or

(s) the heavy chain variable region of SEQ ID NO: 11 and the light chain variable region of SEQ ID NO: 17; or

(t) the heavy chain variable region of SEQ ID NO: 11 and the light chain variable region of SEQ ID NO: 19; or

(u) the heavy chain variable region of SEQ ID NO: 13 and the light chain variable region of SEQ ID NO: 2; or

(v) the heavy chain variable region of SEQ ID NO: 13 and the light chain variable region of SEQ ID NO: 15; or

(w) the heavy chain variable region of SEQ ID NO: 13 and the light chain variable region of SEQ ID NO: 17; or

(x) the heavy chain variable region of SEQ ID NO: 13 and the light chain variable region of SEQ ID NO: 19.

5. The antibody or fragment according to claim 1 , which binds to Lrg1 with an affinity of 1 nM or less.

6. The antibody or fragment according to claim 1 , which comprises an Fc region which is an IgG1, IgG2, IgG3 or IgG4 region.

7. The antibody or fragment thereof according to claim 1 conjugated to an additional moiety.

8. A composition comprising an antibody or fragment thereof according to claim 1 and at least one pharmaceutically acceptable diluent or carrier.

9. A method of treating a disease or condition comprising administering to an individual an antibody or fragment thereof according to claim 1 , wherein the disease or condition is a solid tumor with Lrg-1 mediated vasculoproliferation or a vasculoproliferative condition mediated by Lrg-1.

10. The method according to claim 9 , wherein the solid tumor is selected from a brain, breast, kidney, colorectal, lung, prostate, head and neck, stomach, pancreatic, skin, cervical, bone, ovarian, testicular, and liver tumor.

11. The method according to claim 9 , wherein the vasculoproliferative condition comprises neovascularisation, vascular endothelial cell proliferation, angiogenesis, telangiectasia, or microaneurysms.

12. The method according to claim 9 , wherein the vasculoproliferative condition is a vasculoproliferative condition of the eye.

13. The method according to claim 9 , wherein the treatment further comprises the administration of an antiangiogenic compound.

14. The method according to claim 9 , wherein the treatment of cancer further comprises the administration of a cytotoxic compound or immunotherapeutic agent.

15. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment comprises a Fab fragment, a F(ab′) 2 fragment, a Fab′ fragment, a Fv fragment or a scfv.