Ludwig Institute for Cancer Research Limited

Vegenics Limited

Other

Vegenics Pty Limited

Peter Maccallum Cancer Institute

Helsinki University Licensing, Ltd.

Steven Alan Stacker

Marc Gregory Achen

Kari Alitalo

Andrew Frederick Wilks

Edouard Collins Nice

Christoph Renner

Andrew Allan Mercer

Stephen Bruce Fleming

Megan E Baldwin

Lyn Marie Wise

Bradley McColl

Robert B Oelrichs

Maria Luisa Macheda

Christopher M Hovens

Michael Maurice Halford

Clare Louise Parish

Richard A Hughes

Angela Cendron

Loreen J Savory

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.

Antibodies against human RYK and uses therefor

The invention also relates to a method for of enhancing the acceptance and/or healing of a skin graft in a subject comprising stimulating angiogenesis and lymphangiogenesis with an effective amount of an isolated VEGF-D polypeptide.

Method of enhancing the acceptance and/or healing of a skin graft

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.

Methods of stimulating wound healing by administration of vascular endothelial growth factor D (VEGF-D)

This invention relates to expression vectors comprising VEGF-D and its biologically active derivatives, cell lines stably expressing VEGF-D and its biologically active derivatives, and to a method of making a polypeptide using these expression vectors and host cells. The invention also relates to a method for treating and alleviating melanomas or tumors expressing VEGF-D and various diseases.

Expression vectors and cell lines expressing vascular endothelial growth factor D

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.

Methods of using VEGF-D polypeptides

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.

Mammalian cells that express VEGF-D polypeptides

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.

Chimeric anti-VEGF-D antibodies and humanized anti-VEGF-D antibodies and methods of using same

Disclosed herein are VEGF-D antibody diagnostic kits and methods of using such kits for the detection of VEGF-D in a biological sample.

Antibody diagnostic kits and methods of use

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.

Methods for treating neoplastic disease characterized by vascular endothelial growth factor D expression, for screening for neoplastic disease or metastatic risk, and for maintaining vascularization of tissue

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.

Methods and compositions for activating VEGF-D and VEGF-C

Vascular endothelial growth factor D(VEGF-D) antibodies and methods of use

Vascular endothelial growth factor D (VEGF-D) antibodies and vectors, and methods of use

The invention is based on the isolation of antibodies that were made to a polypeptide having the amino acid sequence for a truncated VEGF-D. One of these antibodies can interfere with the activity of VEGF-D mediated by VEGFR-2 and interfere with the binding of VEGF-D to VEGFR-3 but does not interfere with the activity of VEGF mediated by VEGFR-2 or bind to VEGF-C. The invention provides pharmaceutical and diagnostic compositions and methods utilizing these antibodies.

Antibodies to truncated VEGF-D and uses thereof

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.

Growing community of inventors

North Fitzroy, Australia

Steven Alan Stacker