Medvet Science Pty Ltd

Christopher James Bagley

Angel Francisco Lopez

Joanna Woodcock

Michael William Parker

Jamie Rossjohn

William John McKinstry

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

A therapeutic agent capable of of binding to the F'-G&#x2032; loop of domain 4 of the commonChain of the receptor for GM-CSF, IL-3, and IL-5. The amino acid Tyrwhich is located in the F&#x2032;-G&#x2032; loop is critical in the high affinity binding and stimulation of function of GM-CSF, IL-3 and IL-5 to the commonchain of the receptors. Other receptors for cytokines also show hydrophobic amino acids in analogous positions and it is probable that they too play a pivotal role in binding of respective cytokines to them and in modulating function. Agents capable of binding to the F&#x2032;-G&#x2032; loops are suggested and should be of therapeutic value.

Therapeutic agents as cytokine antagonists and agonists

A therapeutic agent capable of of binding to the F&prime;-G&prime; loop of domain 4 of the common,Chain of the receptor for GM-CSF, IL-3, and IL-5. The amino acid Tyr,which is located in the F&prime;-G&prime; loop is critical in the high affinity binding and stimulation of function of GM-CSF, IL-3 and IL-5 to the common,chain of the receptors. Other receptors for cytokines also show hydrophobic amino acids in analogous positions and it is probable that they too play a pivotal role in binding of respective cytokines to them and in modulating function. Agents capable of binding to the F&prime;-G&prime; loops are suggested and should be of therapeutic value.

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Fullarton, Australia

Christopher James Bagley