Administering anti-placental growth factor antibodies

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 monocloncal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

1 . An antibody or a fragment thereof that specifically binds to placental growth factor and that neutralizes the activity of placental growth factor. 
     
     
         2 . A method of suppressing inflammation in a mammal by administering to a mammal in need of suppressing inflammation an antibody or a fragment thereof of  claim 1 , such that said inflammation is suppressed, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         3 . The method according to  claim 2  wherein said inflammation is an inflammatory disorder or inflammatory disease. 
     
     
         4 . A method of suppressing development of inflammation-associated edema in a mammal by administering to a mammal likely to develop inflammation-associated edema an antibody or a fragment thereof of  claim 1 , such that development of inflammation-associated edema is suppressed, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         5 . A method of reducing inflammation in a mammal by administering to a mammal suffering from inflammation an antibody or a fragment thereof of  claim 1 , such that said inflammation is reduced, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         6 . The method according to  claim 5  wherein said inflammation is an inflammatory disorder or inflammatory disease. 
     
     
         7 . A method of reducing development of inflammation-associated edema in a mammal by administering to a mammal likely to develop inflammation-associated edema an antibody or a fragment thereof of  claim 1 , such that development of inflammation-associated edema is reduced, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         8 . A method of suppressing pathological angiogenesis or pathological arteriogenesis in an eye of a mammal, by administering to said mammal an antibody or fragment thereof of  claim 1 , thereby suppressing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         9 . The method according to  claim 8  further suppressing bleeding of new blood vessels pathologically grown in or on said eye. 
     
     
         10 . The method according to  claim 8  further suppressing vitreous hemorrhage, retinal detachment or uncontrolled glaucoma. 
     
     
         11 . A method of suppressing retinopathy, a choroidal disorder or an intraocular disorder, by suppressing pathological angiogenesis in or on the eye of a mammal by administering to said mammal an antibody or fragment thereof of  claim 1 , thereby suppressing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         12 . The method according to  claim 11  wherein said retinopathy is selected from the group consisting of ischemic retinopathy, retinopathy of prematurity, diabetic retinopathy, proliferative diabetic retinopathy and sickle cell retinopathy. 
     
     
         13 . The method according to  claim 11  wherein said retinopathy is caused by central retinal vein occlusion or by stenosis of a carotid artery. 
     
     
         14 . 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, by suppressing pathological angiogenesis in or on the eye of a mammal by administering to said mammal an antibody or fragment thereof of  claim 1 , thereby suppressing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         15 . A method of reducing pathological angiogenesis or pathological arteriogenesis in an eye of a mammal, by administering to said mammal an antibody or fragment thereof of  claim 1 , thereby reducing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         16 . 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 an antibody or fragment thereof of  claim 1 , thereby reducing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         17 . The method according to  claim 16  wherein said retinopathy is selected from the group consisting of ischemic retinopathy, retinopathy of prematurity, diabetic retinopathy, proliferative diabetic retinopathy and sickle cell retinopathy. 
     
     
         18 . 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, by reducing pathological angiogenesis in or on the eye of a mammal by administering to said mammal an antibody or fragment thereof of  claim 1 , thereby reducing pathological angiogenesis or pathological arteriogenesis in said eye of said mammal, said antibody being optionally selected from the group consisting of a monoclonal antibody, a human antibody, a human monoclonal antibody, a humanized antibody, and a humanized monoclonal antibody; and said antibody fragment being optionally selected from the group consisting of a Fab, F(ab)′2 or scFv fragment. 
     
     
         19 . A method of treating pathological angiogenesis or arteriogenesis by administering to a subject suffering from said pathological angiogenesis or arteriogenesis an antibody or a fragment thereof of  claim 1 , thereby treating said pathological angiogenesis or arteriogenesis, wherein said antibody is optionally a monoclonal antibody, a human antibody or humanized antibody, and wherein said antibody fragment is optionally a Fab, F(ab′) 2  F(ab)′2 or scFv fragment.