Design and selection of medicaments that modulate the function and activity of interleukin 13

Abstract

The present invention relates generally to the field of medicaments in the form of therapeutic molecules including inflammatory modulators and their design and selection. More specifically, the present invention relates to a target site on Interleukin 13 (IL-13) by which a GAG molecule or polyanionic glycoconjugate or anionic polysaccharide modulates IL-13 activity or function, said target site selected from the list consisting of amino acids located in the AB loops and/or helix D of human IL-13 or its homolog or derivative, and the use of said IL-13 target site to design a medicament for modulating physiological processes. Therapeutic and prophylactic compositions comprising the designed medicaments are also contemplated.

1 . A method of screening for a medicament which inhibits IL-13 activity for modulating an inflammatory process in a subject, said method comprising the step of determining whether said medicament binds to a of polyanionic glycoconjugate-binding site on IL-13. 
     
     
         2 . The method of  claim 1  wherein the polyanionic glycoconjugate is a glycosaminoglycan (GAG). 
     
     
         3 . The method of  claim 2  wherein the polyanionic glycoconjugate-binding site comprises a conformation of amino acid residues within the AB loop and/or helix D of human IL-13 or the equivalent in a non-human IL-13. 
     
     
         4 . The method of  claim 3  wherein the polyanionic glycoconjugate-binding site is selected from the list consisting of:
 (i) a conformation of amino acid residues comprising Q22, Q24 and K25 in the AB loop of IL-13 or its equivalent in a non-human IL-13; 
 (ii) a conformation of amino acid residues comprising K97, D98, R102, K104, K105; R108, E109 and R111 in helix D of human IL-13 or its equivalent in non-human IL13; and 
 (iii) a conformation of amino acid residues comprising Q22, Q24 and K25 in the AB loop and K97, D98, R102, K104, K105, R108, E109 and R111 in helix D of IL-13 or its equivalent in non-human IL-13 or its equivalent in non-human IL-13. 
 
     
     
         5 . The method of  claim 4  wherein the polyanionic glycoconjugate-binding site is Q22, Q24 and K25 of the AB loop and K97, D98, R102, K104, K105, R108, E109 and R111 of human IL-13 or its equivalent in non-human IL-13. 
     
     
         6 . The method of  claim 1  wherein the inflammatory process is selected from inflammation, fibrosis, chronic graft rejection, cancer and stem cell differentiation and proliferation. 
     
     
         7 . The method of  claim 6  wherein the inflammation is allergic inflammatory disease. 
     
     
         8 . The method of  claim 7  wherein the allergic inflammatory disease is selected from asthma, allergic rhinitis, chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). 
     
     
         9 . (canceled) 
     
     
         10 . A method of treatment or prophylaxis of an inflammatory process in a subject, said method comprising administering to a subject an IL-13 activity modifier which interacts with a polyanionic glycoconjugate-binding site on IL-13 selected from the group consisting of an amino acid in the AB loop and an amino acid in helix D of human IL-13 or the equivalent in non-human IL-13. 
     
     
         11 . The method of  claim 10  wherein the polyanionic glycoconjugate is a glycosaminoglycan (GAG). 
     
     
         12 . The method of  claim 11  wherein the polyanionic glycoconjugate-binding site is selected from the group consisting of:
 (i) a conformation of amino acid residues comprising Q22, Q24 and K25 in the AB loop of IL-13 or its equivalent in a non-human IL-13; 
 (ii) a conformation of amino acid residues comprising K97, D98, HI02, K104, K105, R108, E109 and R111 in helix D of human IL-13 or its equivalent in non-human IL13; and 
 (iii) a conformation of amino acid residues comprising Q22, Q24 and K25 in the AB loop and K97; D98, H102, K104, K195, R108, E109 and R111 in helix D of IL-13 or its equivalent in non-human IL-13 or its equivalent in non-human IL-13. 
 
     
     
         13 . The method of  claim 12  wherein the polyanionic glycoconjugate-binding site is Q22, Q24 and K25 of the AB loop and K97, D98, H102, K104, K105, R108, E109 and R111 of human IL-13 or its equivalent in non-human IL-13. 
     
     
         14 . The method of  claim 10  wherein the modifier is selected from the group consisting of a GAG, heparin and pentosan polysulfate (PPS) and a fraction or derivative thereof. 
     
     
         15 . The method of  claim 10  wherein the inflammatory process is selected from the group consisting of inflammation, fibrosis, chronic graft rejection, cancer and stem cell differentiation and proliferation. 
     
     
         16 . The method of  claim 15  wherein the inflammation is allergic inflammatory disease. 
     
     
         17 . The method of  claim 16  wherein the allergic inflammatory disease is selected from the group consisting of asthma, allergic rhinitis, chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). 
     
     
         18 . (canceled)