Medvet Science Pty Ltd

St. Vincent's Institute of Medical Research

Central Adelaide Local Health Network Inc.

William John McKinstry

Angel Francisco Lopez

Michael William Parker

Joanna Woodcock

Christopher James Bagley

Jamie Rossjohn

Timothy Robert Hercus

Guido Hansen

The present invention relates generally to the field of crystallography. More particularly, the present invention provides crystalline forms of a complex between granulocyte macrophage-colony stimulating factor (GM-CSF) and its receptor (GM-CSFR). The present invention further provides methods for the design and selection of modulators of GM-CSF/GM-CSFR interaction and signaling as well as signaling of other cytokines.

Crystalline composition of GM-CSF/GM-CSFR

The present invention provides a cytokine-binding domain or portion thereof which binds to at least one cytokine and is capable of transducing a cytokine signal through a single cytokine receptor, said domain comprising a portion of the B'-C&#x2032; loop of domain 4 of a &#x3b2;chain or analogous structure of a cytokine receptor. In another aspect of the invention there is provided a method of identifying a compound having cytokine agonist or antagonist activity, said method including subjecting a potential cytokine agonist and/or cytokine antagonist compound to a cytokine binding domain or portion thereof wherein said domain binds to at least one cytokine and is capable of transducing a cytokine signal through a single cytokine receptor, said domain comprising a portion of the B&#x2032;-C&#x2032; loop of domain 4 of a &#x3b2;chain or analogous structure of the cytokine receptor; and determining the presence of an agonist or antagonist response of the compound on the activity of a cytokine. In a preferred aspect there is provided a method fo identifying a GM-CSF, IL-3 and IL-5 agonist or antagonist, said method including: subjecting a potential agonist or antagonist to a GM-CSF, IL-3 and IL-5 binding domain or portion thereof wherein said domain binds to at least one of the cytokines and is capable of transducing a cytokine signal through a single cytokine receptor, said domain comprising a portion of the B&#x2032;-C&#x2032; loop of domain 4 of a &#x3b2;chain or analogous structure of the cytokine receptor; and determining the presence of a agonist or antagonist response from the compound on the activity of GM-CSF, IL-3 and IL-5.

Cytokine binding domain of cytokine receptors

Growing community of inventors

North Carlton, Australia

William John McKinstry