IL-17RA-IL-17RB ANTAGONISTS AND USES THEREOF
The present invention relates to Interleukin-17 ligand and receptor family members and the discovery that IL-17 receptor A and IL-17 receptor C form a heteromeric receptor complex that is biologically active. Antagonists of the IL-17RA-IL-17RB heteromeric receptor complex are disclosed, as well as various methods of use.
1 - 15 . (canceled)
16 . A method of inhibiting IL-17RA-IL-17RB heteromeric receptor complex activation, comprising exposing a cell expressing at least IL-17RA and IL-17RB to an IL-17RA-IL-17RB antagonist such that activation of an IL-17RA-IL-17RB heteromeric receptor complex by IL-25 is partially or fully inhibited.
17 . The method of claim 16 , wherein the IL-17RA-IL-17RB antagonist is an antigen binding protein.
18 . The method of claim 17 , wherein the antigen binding protein binds the IL-17RA-IL-17RB heteromeric receptor complex or a subunit thereof.
19 . The method of any one of claims 16 - 18 wherein formation of an IL-17RA-IL-17RB heteromeric receptor complex is partially or fully inhibited.
20 . The method of any one of claims 16 - 18 wherein release of at least one proinflammatory mediator is partially or fully inhibited.
21 . The method of claim 20 , wherein the proinflammatory mediator is selected from the group consisting of: IL-5, IL-6, IL-8, IL-13, CXCL1, CXCL2, GM-CSF, G-CSF, M-CSF, IL-1β, TNFα, RANK-L, LIF, PGE2, IL-12, MMP3, MMP9, GROα, and NO.
22 . A method of inhibiting IL-17RA-IL-17RB heteromeric receptor complex activation in vivo, comprising exposing a cell expressing at least IL-17RA and IL-17RB to an IL-17RA-IL-17RB antagonist such that activation of an IL-17RA-IL-17RB heteromeric receptor complex by IL-25 is partially or fully inhibited.
23 . The method of claim 22 , wherein the IL-17RA-IL-17RB antagonist is an antigen binding protein.
24 . The method of claim 23 , wherein the antigen binding protein binds the IL-17RA-IL-17RB heteromeric receptor complex or a subunit thereof.
25 . The method of claim 22 , wherein formation of an IL-17RA-IL-17RB heteromeric receptor complex is partially or fully inhibited.
26 . The method of claim 23 , wherein formation of an IL-17RA-IL-17RB heteromeric receptor complex is partially or fully inhibited.
27 . The method of claim 24 , wherein formation of an IL-17RA-IL-17RB heteromeric receptor complex is partially or fully inhibited.
28 . The method of claim 22 , wherein release of at least one proinflammatory mediator is partially or fully inhibited.
29 . The method of claim 23 , wherein release of at least one proinflammatory mediator is partially or fully inhibited.
30 . The method of claim 24 , wherein release of at least one proinflammatory mediator is partially or fully inhibited.
31 . The method of claim 25 , wherein release of at least one proinflammatory mediator is partially or fully inhibited.
32 . The method of any one of claims 28 - 31 , wherein the proinflammatory mediator is selected from the group consisting of: IL-5, IL-6, IL-8, IL-13, CXCL1, CXCL2, GM-CSF, G-CSF, M-CSF, IL-1β, TNFα, RANK-L, LIF, PGE2, IL-12, MMP3, MMP9, GROα, and NO.
33 . The method of claim 22 , wherein the IL-17RA-IL-17RB antagonist is administered to an individual afflicted with an autoimmune or inflammatory disease.
34 . The method of claim 23 , wherein the IL-17RA-IL-17RB antagonist is administered to an individual afflicted with an autoimmune or inflammatory disease.
35 . The method of claim 24 , wherein the IL-17RA-IL-17RB antagonist is administered to an individual afflicted with an autoimmune or inflammatory disease.
36 . The method of claim 25 , wherein the IL-17RA-IL-17RB antagonist is administered to an individual afflicted with an autoimmune or inflammatory disease.
37 . The method of any one of claims 33 - 36 , wherein the autoimmune or inflammatory disease is selected from the group consisting of Acute Respiratory Disorder Syndrome (ARDS), respiratory distress syndrome, bronchitis, and airway hyperresponsiveness associated with viral-induced conditions such as respiratory syncytial virus (RSV), parainfluenza virus (PIV), rhinovirus (RV) and adenovirus.
38 . The method of any one of claims 33 - 36 , wherein the IL-17RA-IL-17RB antagonist partially or fully reduces or ameliorates the signs and/or symptoms of the autoimmune or inflammatory disease.
39 . The method of claim 37 , wherein the IL-17RA-IL-17RB antagonist partially or fully reduces or ameliorates the signs and/or symptoms of the autoimmune or inflammatory disease.