Chimeric IL-10

Abstract

Disclosed are chimeric proteins having a cytokine fused to an enzymatically inactive polypeptide which increases the circulating half-life of the cytokine. The chimeric proteins are useful for treating, inhibiting, or preventing a variety of conditions, including septic shock, granulomatous disorders, Type I diabetes, and various cancers (e.g., multiple myeloma) in a patient.

1 . A method for treating, or inhibiting the onset of, an immunological disorder in a patient, the method comprising administering to the patient a therapeutically effective amount of a chimeric protein comprising interleukin-4 (IL-4) or interleukin-10 (IL-10) and a polypeptide that increases the circulating half-life of the IL-4- or IL-10-containing chimera relative to that of IL-4 or IL-10 alone.  
     
     
         2 . The method of  claim 1 , wherein the polypeptide comprises a hinge region of an IgG molecule.  
     
     
         3 . The method of  claim 1 , wherein the polypeptide comprises albumin, or a porcine or rodent glycosyltransferase or α-1,3-galactosyltransferase.  
     
     
         4 . The method of  claim 1 , wherein the polypeptide comprises the Fc region of an IgG molecule but lacks an IgG variable region.  
     
     
         5 . The method of  claim 4 , wherein the polypeptide further comprises a hinge region of an IgG molecule.  
     
     
         6 . The method of  claim 4 , wherein the Fc region is lytic.  
     
     
         7 . The method of  claim 4 , wherein the Fc region is non-lytic.  
     
     
         8 . The method of  claim 4 , wherein the Fc region includes a mutation that inhibits complement fixation and high affinity binding to an Fc receptor by the protein.  
     
     
         9 . The method of  claim 1 , wherein the chimeric protein is administered to the patient with a pharmaceutically acceptable carrier.  
     
     
         10 . The method of  claim 1 , wherein the immunological disorder comprises granuloma formation.  
     
     
         11 . The method of  claim 1 , wherein the immunological disorder is schistosomiasis.  
     
     
         12 - 21 . (canceled)  
     
     
         22 . A chimeric protein comprising interleukin-4 (IL-4) or interleukin-10 (IL-10) and a polypeptide that increases the circulating half-life of the IL-4- or IL-10-containing chimera relative to that of IL-4 or IL-10 alone.  
     
     
         23 . The chimeric protein of  claim 22 , wherein the polypeptide comprises a hinge region of an IgG molecule.  
     
     
         24 . The chimeric protein of  claim 22 , wherein the polypeptide comprises albumin, or a porcine or rodent glycosyltransferase or α-1,3-galactosyltransferase.  
     
     
         25 . The chimeric protein of  claim 22 , wherein the polypeptide comprises the Fc region of an IgG molecule but lacks an IgG variable region.  
     
     
         26 . The chimeric protein of  claim 25 , wherein the polypeptide further comprises a hinge region of an IgG molecule.  
     
     
         27 . The chimeric protein of  claim 25 , wherein the Fc region is lytic.  
     
     
         28 . The chimeric protein of  claim 25 , wherein the Fc region is non-lytic.  
     
     
         29 . The chimeric protein of  claim 25 , wherein the Fc region includes a mutation that inhibits complement fixation and high affinity binding to the Fc receptor by the protein.  
     
     
         30 . A composition comprising the chimeric protein of  claim 22  and a pharmaceutically acceptable carrier.