Abstract: The present invention relates to antibodies and antigen-binding fragments thereof that bind RYK, in particular human RYK and their use in regulating RYK-associated activities. Specifically there is provided an isolated monoclonal antibody or antigen-binding fragment or derivative thereof that specifically binds to the extracellular domain of human RYK, in particular, the antibody or antigen-binding fragment thereof, binds specifically to the WIF domain of human RYK. Preferably, the antibodies of the present invention modulate RYK-associated activity, which includes RYK mediated signal transduction activity and modulation of the interaction of Wnts with RYK and, preferably, modulate Wnt induced signaling. In particular, the antibodies inhibit the binding of Wnt5a and inhibit Wnt induced phosphorylation of Dishevelled (Dvl) 2 and/or Dvl3 proteins.

Abstract: The present invention relates to antibodies and antigen-binding fragments thereof that bind RYK, in particular human RYK and their use in regulating RYK-associated activities. Specifically there is provided an isolated monoclonal antibody or antigen-binding fragment or derivative thereof that specifically binds to the extracellular domain of human RYK, in particular, the antibody or antigen-binding fragment thereof, binds specifically to the WIF domain of human RYK. Preferably, the antibodies of the present invention modulate RYK-associated activity, which includes RYK mediated signal transduction activity and modulation of the interaction of Wnts with RYK and, preferably, modulate Wnt induced signaling. In particular, the antibodies inhibit the binding of Wnt5a and inhibit Wnt induced phosphorylation of Dishevelled (Dvl) 2 and/or Dvl3 proteins.

Abstract: Disclosed herein are various uses for VEGF-D polypeptides. Exemplary uses include methods of stimulating endothelial cell proliferation, methods of stimulating vascular permeability, methods of stimulating angiogenesis and methods of activating VEGFR-2 and VEGFR-3 using VEGF-D polypeptides.

Abstract: Disclosed herein are mammalian cells transformed or transfected with a VEGF-D nucleic acid consisting of a nucleotide sequence encoding continuous portions of VEGF-D polypeptides.

Abstract: Methods for Activating endothelial growth factors VEGF-C or VEGF-D with plasmin, and methods of treatment comprising administering a pharmaceutical compositions comprising plasmin. Also disclosed are methods of screening for inhibitors of activation of the growth factors by plasmin, and method of treatment by blocking activation of VEGF-C/D activation by plasmin. Further disclosed are methods for screening for other proteases that activate VEGF-CD, and for inhibitors of such activation. The invention further includes inhibitors of plasmin activity and methods of treating patients in need thereof with said inhibitors.

Abstract: A method for treating and alleviating disease characterized by the expression of VEGF-D involving screening to find an organism with tumor cells expressing VEGF-D and administering an effective amount of a VEGF-D antagonist; a method for screening for neoplastic diseas, where detection of VEGF-D on or in a sample such as tumor cells, blood vessel endothelial cells or lymph vessel endothelial cells indicates neoplastic disease; a method for promoting and maintaining vascularization of normal tissue in an organism involving administering a vascularization promoting amount of VEGF-D or a fragment or analog thereof to the organism; a method for screening tumors for metastatic risk involving detecting expression of VEFG-D by a tumor which indicates metastatic risk; and a method of detecting micro-metastasis of neoplastic disease involving detection of VEGF-D on or in a tissue sample which indicates metastasis of a neoplastic disease.

Abstract: Methods for activating endothelial growth factors VEGF-C or VEGF-D with plasmin, and methods of treatment comprising administering a phamarceutical compositions comprising plasmin. Also disclosed are methods for screening for inhibitors of activation of the growth factors by plasmin, and method of treatment by blocking activation of VEGF-C/D activation by plasmin. Further disclosed are methods for screening for other proteases that activate VEGF-C/D, and for inhibitors of such activation. The invention further includes inhibitors of plasmin activity and methods of treating patients in need thereof with said inhibitors.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: Proprotein convertase inhibitor has been found to block proteolytic processing and activation of VEGF-C and VEGF-D and inhibit angiogenesis and/or lymphangiogenesis. Method and composition are disclosed for inhibiting angiogenesis and/or lymphangiogenesis, and for treating conditions associated with excessive angiogenesis, such as tumors and/or retinopathies, as well as conditions associated with lymphangiogenesis, such as the metastatic spread of malignancies, macular degeneration, inflammatory mediated diseases, rheumatoid arthritis, diabetic retinopathy and psoriasis in a patient. The inventive method and composition utilize proprotein convertase antagonist selected from the group consisting of an anti-proprotein convertase antibody, an antisense nucleic acid molecule against a polynucleotide coding for a proprotein convertase, and an siRNA for inhibiting proprotein convertase expression, as well as proprotein convertase inhibitors.

Abstract: The present invention provides modified VEGF-D polypeptide variants that are resistant to serine protease processing and methods of making and using the same, as well pharmaceutical compositions comprising the peptide or a polynucleotide encoding the same. The VEGF-D variants comprise a VEGF homology domain, and at least one of (1) a C-terminal propeptide that is not cleavable by a serine protease, and (2) an N-terminal propeptide that is not cleavable by a serine protease. The VEGF-D variants can be made using site-directed mutagenesis. The VEGF-D variants are useful for the treatment of diseases such as cardiovascular disease and primary and secondary lymphedema, and for the prevention of stenosis and restenosis of blood vessels.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: Isolated nucleic acid molecule comprising an antisense nucleic acid sequence which is antisense to a polynucleotide that encodes a VEGF-D polypeptide, vectors and host cells including the same. Also disclosed are methods of inhibiting VEGF-D function or expression in a mammal, for example, in treating cancer, comprising administering to the mammal in need thereof a vector of the present invention.

Abstract: Monomeric monocyclic peptide inhibitors and dimeric bicyclic peptide inhibitors based on exposed loop fragments of a growth factor protein, such as loop 1, 2 or 3 of VEGF-D, and methods of making them are described as well as pharmaceutical compositions containing them and methods utilizing them.

Abstract: The present invention relates to materials and methods for modulating angiogenesis and lymphangiogenesis. The compositions of the invention provide chimeric and/or humanized VEGF-D antibody substances, antibodies, polypeptides and fragments thereof useful for modulating angiogenesis and lymphangiogenesis in a subject.

Abstract: Methods for activating endothelial growth factors VEGF-C or VEGF-D with plasmin, and methods of treatment comprising administering a phamarceutical compositions comprising plasmin. Also disclosed are methods for screening for inhibitors of activation of the growth factors by plasmin, and method of treatment by blocking activation of VEGF-C/D activation by plasmin. Further disclosed are methods for screening for other proteases that activate VEGF-C/D, and for inhibitors of such activation. The invention further includes inhibitors of plasmin activity and methods of treating patients in need thereof with said inhibitors.

Abstract: The present invention relates to materials and methods for modulating angiogenesis. The compositions of the invention provide antibody substances specific for two or more PDGF/VEGF family members, which are useful for modulating angiogenesis and lymphangiogenesis in a subject.

Abstract: Proprotein convertase inhibitor has been found to block proteolytic processing and activation of VEGF-C and VEGF-D and inhibit angiogenesis and/or lymphangiogenesis. Method and composition are disclosed for inhibiting angiogenesis and/or lymphangiogenesis, and for treating conditions associated with excessive angiogenesis, such as tumors and/or retinopathies, as well as conditions associated with lymphangiogenesis, such as the metastatic spread of malignancies, macular degeneration, inflammatory mediated diseases, rheumatoid arthritis, diabetic retinopathy and psoriasis in a patient. The inventive method and composition utilize proprotein convertase antagonist selected from the group consisting of an anti-proprotein convertase antibody, an antisense nucleic acid molecule against a polynucleotide coding for a proprotein convertase, and an siRNA for inhibiting proprotein convertase expression, as well as proprotein convertase inhibitors.

Abstract: A method for treating and alleviating disease characterized by the expression of VEGF-D involving screening to find an organism with tumor cells expressing VEGF-D and administering an effective amount of a VEGF-D antagonist; a method for screening for neoplastic diseas, where detection of VEGF-D on or in a sample such as tumor cells, blood vessel endothelial cells or lymph vessel endothelial cells indicates neoplastic disease; a method for promoting and maintaining vascularization of normal tissue in an organism involving administering a vascularization promoting amount of VEGF-D or a fragment or analog thereof to the organism; a method for screening tumors for metastatic risk involving detecting expression of VEFG-D by a tumor which indicates metastatic risk; and a method of detecting micro-metastasis of neoplastic disease involving detection of VEGF-D on or in a tissue sample which indicates metastasis of a neoplastic disease.