Treatment

Abstract

The invention provides an antibody or fragment thereof that specifically binds to human Lrg1.

1 .- 45 . (canceled) 
     
     
         46 . A method of revascularisation of a tissue in which the vasculature is malformed comprising administering to an individual an antagonist of Lrg1. 
     
     
         47 . The method according to  claim 46 , wherein the antagonist of Lrg1 is administered in conjunction with a pro-angiogenic agent. 
     
     
         48 . The method according to  claim 47 , wherein the pro-angiogenic agent is selected from VEGF, bFGF, PLGF and angiopoietin 2. 
     
     
         49 . The method according to  claim 46 , wherein the method of revascularisation is a disease where tissues are affected by hypoxia. 
     
     
         50 . The method according to  claim 46 , wherein the method of revascularisation is selected from ischemia, ischemic heart disease, diabetes, ischemic stroke, vascular dementia, transient ischemic attack, mitral valve disease, chronic atrial fibrillation, cardiomyopathies, acute limb ischemia, peripheral limb ischemia, thrombosis, blood vessel occlusion, thoracic outlet syndrome, atherosclerosis, hypoglycaemia, tachycardia, hypotension, sickle cell disease, frostbite, arteriovenous malformations, blood vessel rupture and anemia. 
     
     
         51 . The antagonist of Lrg1 according to  claim 46 , which comprises an antibody that binds Lrg1, a double-stranded RNA that inhibits Lrg1 gene expression, an aptamer that targets Lrg1, or a peptide or peptidomimetic that blocks Lrg1 function by binding Lrg1. 
     
     
         52 . The antagonist of Lrg1 according to  claim 51 , which is an antibody or fragment thereof that specifically binds to human Lrg1 and which comprises at least one CDR selected from SEQ ID NOs: 21 to 26. 
     
     
         53 . An antibody or fragment thereof according to  claim 52 , which comprises at least one CDR selected from SEQ ID NOs: 23 and 26. 
     
     
         54 . An antibody or fragment thereof according to  claim 52 , wherein the antibody or fragment thereof comprises the CDRs of SEQ ID NOs: 23 and 26. 
     
     
         55 . An antibody or fragment thereof according to  claim 52 , wherein the antibody or fragment thereof comprises the CDRs of:
 (a) SEQ ID NOs: 21, 22 and 23; or   (b) SEQ ID NOs: 24, 25 and 26.   
     
     
         56 . An antibody or fragment thereof according to  claim 52 , wherein the antibody or fragment thereof comprises the CDRs of SEQ ID NOs: 21, 22, 23, 24, 25 and 26. 
     
     
         57 . An antibody or fragment thereof according to  claim 52 , 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;   (b) a fragment of at least 7 amino acids of (a), wherein the antibody or fragment retains the ability to specifically bind to Lrg1; or   (c) a variant of (a) having at least 70% amino acid sequence identity to a sequence of (a), wherein the antibody or fragment retains the ability to specifically bind to Lrg1.   
     
     
         58 . An antibody or fragment thereof according to  claim 52 , wherein the antibody comprises:
 (a) a light chain variable region amino acid sequence of SEQ ID NO: 2, 15, 17 or 19;   (b) a fragment of at least 7 amino acids of (a), wherein the antibody or fragment retains the ability to specifically bind to Lrg1; or   (c) a variant of (a) having at least 70% identity amino acid identity to a sequence of (a), wherein the antibody or fragment retains the ability to specifically bind to Lrg1.   
     
     
         59 . An antibody or fragment thereof according to  claim 52 , 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.   
     
     
         60 . An antibody or fragment thereof according to  claim 52 , which comprises an Fc region which is an IgG1, IgG2, IgG3 or IgG4 region. 
     
     
         61 . An antibody or fragment thereof according to  claim 52 , conjugated to an additional moiety. 
     
     
         62 . An antibody or fragment thereof according to  claim 52 , wherein the antibody or fragment thereof comprises a Fab fragment, a F(ab′)2 fragment, a Fab′ fragment, a Fv fragment, or a scfv.