Soluble zcytor14, anti-zcytor14 antibodies and binding partners and methods of using in inflammation

Abstract

The present invention relates to blocking, inhibiting, reduceing, antagonizing or neutralizing the activity of IL-17F, IL-17A, or both IL-17A and IL-17F polypeptide molecules. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. ZcytoR14 is a common receptor for IL-17A and IL-17F. The present invention includes soluble ZcytoR14, anti-ZcytoR14 antibodies and binding partners, as well as methods for antagonizing IL-17F, IL-17A or both IL-17A and IL-17F using such soluble receptors, antibodies and binding partners.

1 . An isolated soluble receptor comprising at least one ZcytoR14 subunit, wherein the ZcytoR14 subunit comprises a polypeptide having an amino acid sequence of SEQ ID NO:3.  
     
     
         2 . The isolated soluble receptor of  claim 1 , wherein the soluble receptor further comprises an IL-17RA subunit (SEQ ID NO:21).  
     
     
         3 . The isolated soluble receptor of  claim 2  wherein the ZcytoR14 subunit and the IL-17RA subunit are linked together by a polypeptide linker.  
     
     
         4 . The isolated soluble receptor of  claim 2  wherein the soluble receptor comprises the extracellular domain of IL-17RA (SEQ ID NO:21).  
     
     
         5 . The isolated soluble receptor of  claim 2  wherein the ZcytoR14 subunit and the IL-17RA subunit each further comprise an immunoglobulin moiety.  
     
     
         6 . A method for producing a soluble receptor comprising a ZcytoR14 subunit and an IL-17RA subunit, the method comprising: (a) introducing into a host cell a first DNA sequence comprised a DNA sequence that encodes the ZcytoR14 subunit and the DNA that encodes an immunoglobulin moiety; (b) introducing into the host cell a second DNA construct comprised of a DNA sequence that encodes the IL-17RA subunit and a DNA sequence that encodes an immunoglobulin moiety; (c) growing the host cell in an appropriate growth medium under physiological conditions to allow production of a fusion protein comprising both the ZcytoR14 and the IL-17RA subunit; and (d) isolating the polypeptide from the host cell.  
     
     
         7 . A method for producing a soluble receptor comprising a ZcytoR14 subunit and an IL-17RA subunit, the method comprising: (a) introducing into a host cell a first DNA sequence comprised a DNA sequence that encodes the ZcytoR14 subunit and the DNA that encodes an immunoglobulin moiety; (b) introducing into the host cell a second DNA construct comprised of a DNA sequence that encodes the IL-17RA subunit and a DNA sequence that encodes an immunoglobulin moiety; (c) growing the host cell in an appropriate growth medium under physiological conditions to allow the production of a dimerized heterodimeric fusion protein comprising both the ZcytoR14 and the IL-17RA subunit; and (d) isolating the dimerized polypeptide from the host cell.  
     
     
         8 . A host cells transformed or transfected with a DNA construct that encodes a ZcytoR14 subunit and an IL-17RA subunit.  
     
     
         9 . The isolated soluble receptor of  claim 2 , wherein said soluble receptor reduces the pro-inflammatory activity of either IL-17A (SEQ ID NO:14) or IL-17F (SEQ ID NO:16).  
     
     
         10 . The soluble receptor of  claim 5 , wherein said soluble receptor reduces the pro-inflammatory activity of both IL-17A (SEQ ID NO:14) and IL-17F (SEQ ID NO:16).  
     
     
         11 . The soluble receptor of  claim 2  further comprising PEGylation.