IL-21 Derivatives and variants

Abstract

The invention provides derivatives of IL-21 or variants thereof, methods of producing such variants, new variants of IL-21, and various methods of using such molecules.

1 . A derivative of interleukin 21 (IL-21) or an IL-21 variant comprising at least one polymeric molecule or lipophilic substituent.  
     
     
         2 . The derivative of  claim 1 , wherein the polymeric molecule is one or more PEG groups.  
     
     
         3 . The derivative of  claim 2 , wherein the polymeric molecule is one or more PEG groups having a weight of at least about 5 kDa.  
     
     
         4 . The derivative of  claim 3 , wherein the derivative comprises one or more PEG groups having a weight of at least about 30 kDa.  
     
     
         5 . The derivative of  claim 1 , wherein the polymeric molecule or lipophilic derivative is conjugated to the amino acid sequence of the IL-21 or IL-21 variant at the C-terminus.  
     
     
         6 . The derivative of  claim 1 , wherein the polymeric molecule or lipophilic derivative is conjugated to the interior of the amino acid sequence of the IL-21 or IL-21 variant.  
     
     
         7 . The derivative of  claim 1 , wherein the polymeric molecule or lipophilic derivative is conjugated to the amino acid sequence of the IL-21 or IL-21 variant at the N-terminus.  
     
     
         8 . The derivative of  claim 1 , wherein the IL-21 or IL-21 variant is an IL-21.  
     
     
         9 . The derivative of  claim 1 , wherein the IL-21 or IL-21 variant is an IL-21 variant.  
     
     
         10 . The derivative of  claim 9 , wherein the polymeric molecule or lipophilic derivative is conjugated to the IL-21 variant at an amino acid that does not naturally occur in human IL-21.  
     
     
         11 . A variant of interleukin 21 (IL-21) comprising an N-terminal addition of a sequence of 1-10 amino acids comprising a Ser, Tyr, Lys, or Cys residue.  
     
     
         12 . A variant of human interleukin 21 (hIL-21) comprising an addition of a serine residue at the N-terminus of the human IL-21 amino acid sequence (Ser-hIL-21).  
     
     
         13 . The IL-21 variant of  claim 12 , wherein the IL-21 variant is derivatized by conjugation of a polymeric group or lipophilic substituent to the N-terminal Ser residue of hIL-21.  
     
     
         14 . An isolated DNA comprising a sequence that codes for the expression of Ser-hIL-21.  
     
     
         15 . A method of producing an IL-21 variant derivative comprising derivatizing Ser-hIL-21 with a polymeric molecule under conditions suitable for producing a derivative of Ser-hIL-21.  
     
     
         16 . A method of treating cancer comprising administering to a patient in need thereof an effective amount of a derivative according to  claim 13 .  
     
     
         17 . A method of treating infection comprising administering to a patient in need thereof an effective amount of a derivative according to  claim 13.