IDENTIFICATION AND METHOD FOR USING THE PRE-LIGAND ASSEMBLY DOMAIN OF THE IL-17 RECEPTOR

The invention provides isolated Pre-Ligand Assembly Domain (PLAD) polypeptides comprising an amino acid sequence of a domain (e.g., a Fibronectin Ill-like domain) of an IL-17 Receptor (IL-17R) family member, wherein the PLAD polypeptide inhibits multimerization of a receptor complex comprising an IL-17R family member. Also provided are isolated PLAD-binding polypeptides, e.g., antibodies and avimers, which specifically bind to a PLAD polypeptide described herein. Related chimeric proteins, conjugates, nucleic acids, vectors, and host cells are provided herein. Further provided are methods of treating an inflammatory or autoimmune disease, methods of inhibiting IL-17-mediated signal transduction, methods of inhibiting IL-17 ligand binding, methods of inhibiting multimerization of IL-17R complexes, and methods of inhibiting the production of at least one cytokine, chemokine, matrix metalloproteinase, or other molecule associated with IL-17 signal transduction are provided. 1. An isolated polypeptide selected from the group consisting of(a) an isolated polypeptide comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 3 or 4;(b) an isolated polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 3 or 4;(c) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 3 or 4;(d) the isolated polypeptide of any of (a)-(c), comprising the amino acid sequence of SEQ ID NO: 5 or 6;(e) the isolated polypeptide of (d), comprising the amino acid sequence of SEQ ID NO: 7 or 8;(f) the isolated polypeptide of any of claims (a)-(e), comprising the amino acid sequence of SEQ ID NO: 9 or 10; and(g) the isolated polypeptide of (f), comprising the amino acid sequence of any of SEQ ID NOs: 11-14,wherein the polypeptide inhibits multimerization of a receptor complex comprising an IL-17 Receptor (IL-17R) family member, provided that the polypeptide does not comprise SEQ ID NO: 1 or 2.28.-. (canceled)9. The isolated ...

Pre-ligand assembly domain of the IL-17 receptor

The invention provides isolated Pre-Ligand Assembly Domain (PLAD) polypeptides comprising an amino acid sequence of a domain (e.g., a Fibronectin Ill-like domain) of an IL-17 Receptor (IL-17R) family member, wherein the PLAD polypeptide inhibits multimerization of a receptor complex comprising an IL-17R family member. Also provided are isolated PLAD-binding polypeptides, e.g., antibodies and avimers, which specifically bind to a PLAD polypeptide described herein. Related chimeric proteins, conjugates, nucleic acids, vectors, and host cells are provided herein. Further provided are methods of treating an inflammatory or autoimmune disease, methods of inhibiting IL-17-mediated signal transduction, methods of inhibiting IL-17 ligand binding, methods of inhibiting multimerization of IL-17R complexes, and methods of inhibiting the production of at least one cytokine, chemokine, matrix metalloproteinase, or other molecule associated with IL-17 signal transduction are provided.

Pre-Ligand assembly domain of the IL-17 receptor

The invention provides isolated Pre-Ligand Assembly Domain (PLAD) polypeptides which inhibit multimerization of a receptor complex comprising an IL-17R family member. Related PLAD-binding polypeptides, chimeric proteins, conjugates, nucleic acids, vectors, host cells, and methods are provided herein.

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