Chimeric IL-10 proteins and uses thereof

Abstract

Disclosed are chimeric proteins having IL-10 fused to an enzymatically inactive polypeptide which increases the circulating half-life of IL-10. The chimeric polypeptides are useful for treating or preventing septic shock, inhibiting the development of Type I diabetes, and treating multiple myeloma in a patient.

1 . A method for treating, or inhibiting the onset of, septic shock, Type I diabetes, or multiple myeloma in a patient, the method comprising administering to the patient a therapeutically effective amount of a chimeric protein comprising interleukin-10 (IL-10) and a polypeptide that increases the circulating half-life of the IL-10-containing chimera relative to that of 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 . A chimeric protein comprising interleukin-10 (IL-10) and a polypeptide that increases the circulating half-life of the IL-10-containing chimera relative to that of IL-10 alone.  
     
     
         11 . The chimeric protein of  claim 10 , wherein the polypeptide comprises a hinge region of an IgG molecule.  
     
     
         12 . The chimeric protein of  claim 10 , wherein the polypeptide comprises albumin, or a porcine or rodent glycosyltransferase or α-1,3-galactosyltransferase.  
     
     
         13 . The chimeric protein of  claim 10 , wherein the polypeptide comprises the Fc region of an IgG molecule but lacks an IgG variable region.  
     
     
         14 . The chimeric protein of  claim 13 , wherein the polypeptide further comprises a hinge region of an IgG molecule.  
     
     
         15 . The chimeric protein of  claim 13 , wherein the Fc region is lytic.  
     
     
         16 . The chimeric protein of  claim 13 , wherein the Fc region is non-lytic.  
     
     
         17 . The chimeric protein of  claim 13 , wherein the Fc region includes a mutation that inhibits complement fixation and high affinity binding to an Fc receptor by the protein.  
     
     
         18 . A composition comprising the chimeric protein of  claim 10  and a pharmaceutically acceptable carrier.