Inhibitors of placental growth factor for the treatment of pathological angiogenesis, pathological arteriogenesis, inflammation, tumor formation and/or vascular leakage

Abstract

The present invention relates to the field of pathological angiogenesis and arteriogenesis and, in particular, to a stress-induced phenotype in a transgenic mouse (PIGF −/− ) that does not produce Placental Growth Factor (PIGF) and that demonstrates an impaired vascular endothelial growth factor (VEGF)-dependent response PIGF deficiency has a negative influence on diverse pathological processes of angiogenesis, arteriogenesis and vascular leakage comprising ischemic retinopathy, tumor formation, pulmonary hypertension, vascular leakage (edema formation) and inflammatory disorders. The invention thus relates to molecules that can inhibit the binding of PIGF to its receptor (VEGFR-1), such as monoclonal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

1 . A method of suppressing pathological angiogenesis or pathological arteriogenesis in an eye of a mammal, said method comprising administering to said mammal a molecule capable of neutralizing the activity of placental growth factor thereby suppressing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal. 
   
   
       2 . The method according to  claim 1  further suppressing bleeding of new blood vessels pathologically grown in or on said eye. 
   
   
       3 . The method according to  claim 1  further suppressing vitreous hemorrhage, retinal detachment or uncontrolled glaucoma. 
   
   
       4 . A method of suppressing retinopathy, a choroidal disorder or an intraocular disorder, said method comprising suppressing pathological angiogenesis in or on the eye of a mammal by administering to said mammal a molecule capable of neutralizing the activity of placental growth factor thereby suppressing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal. 
   
   
       5 . The method according to  claim 4  wherein said retinopathy is selected from the group consisting of ischemic retinopathy, retinopathy of prematurity, diabetic retinopathy, proliferative diabetic retinopathy and sickle cell retinopathy. 
   
   
       6 . The method according to  claim 4  wherein said retinopathy is caused by central retinal vein occlusion or by stenosis of a carotid artery. 
   
   
       7 . A method of suppressing venous dilatation or arterial tortuosity of blood vessels in or on an eye, or capillary outgrowth in the vitreous chamber, or the formation of neovascular vitreous tufts, said method comprising suppressing pathological angiogenesis in or on the eye of a mammal by administering to said mammal a molecule capable of neutralizing the activity of placental growth factor thereby suppressing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal. 
   
   
       8 . The method according to  claim 1  wherein said molecule is an antibody or a fragment thereof capable of neutralizing the activity of placental growth factor. 
   
   
       9 . The method according to  claim 8  wherein said antibody is a monoclonal antibody. 
   
   
       10 . The method according to  claim 8  wherein said antibody is a human or humanized antibody. 
   
   
       11 . The method according to  claim 8  wherein said antibody fragment is a Fab, F(ab)′2 or scFv fragment. 
   
   
       12 . A method of reducing pathological angiogenesis or pathological arteriogenesis in an eye of a mammal, said method comprising administering to said mammal a molecule capable of neutralizing the activity of placental growth factor thereby reducing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal. 
   
   
       13 . A method of reducing retinopathy, a choroidal disorder or an intraocular disorder, said method comprising reducing pathological angiogenesis in or on the eye of a mammal by administering to said mammal a molecule capable of neutralizing the activity of placental growth factor thereby reducing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal. 
   
   
       14 . The method according to  claim 4  wherein said retinopathy is selected from the group consisting of ischemic retinopathy, retinopathy of prematurity, diabetic retinopathy, proliferative diabetic retinopathy and sickle cell retinopathy. 
   
   
       15 . A method of reducing venous dilatation or arterial tortuosity of blood vessels in or on an eye, or capillary outgrowth in the vitreous chamber, or the formation of neovascular vitreous tufts, said method comprising reducing pathological angiogenesis in or on the eye of a mammal by administering to said mammal a molecule capable of neutralizing the activity of placental growth factor thereby reducing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal. 
   
   
       16 . The method according to  claim 12  wherein said molecule is an antibody or a fragment thereof capable of neutralizing the activity of placental growth factor. 
   
   
       17 . The method according to  claim 16  wherein said antibody is a monoclonal antibody. 
   
   
       18 . The method according to  claim 16  wherein said antibody is a human or humanized antibody. 
   
   
       19 . The method according to  claim 16  wherein said antibody fragment is a Fab, F(ab)′2 or scFv fragment.