Peter Maccallum Cancer Institute

Maria Luisa Macheda

Steven Alan Stacker

Edouard Collins Nice

Michael Maurice Halford

Clare Louise Parish

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.

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St. Albans, Australia

Maria Luisa Macheda