Conjugates of an il-2 moiety and a polymer

Abstract

Conjugates of an interleukin-2 (“IL-2”) moiety and one or more nonpeptidic, water-soluble polymers are provided. Typically, the non-peptidic, water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided, among other things, are compositions comprising conjugates, methods of making conjugates, methods of administering compositions to an individual, nucleic acid sequences, expression systems, host cells, and methods for preparing IL-moieties.

What is claimed is: 
     
         1 . A conjugate comprising an interleukin-2 (IL-2) moiety covalently attached to a single poly(ethylene glycol) polymer via a stable linkage, wherein the IL-2 moiety has an amino acid sequence selected the group consisting of SEQ ID NOs: 1-4 and sequences having at least 95 percent sequence identity to any one of SEQ ID NOs: 1-4. 
     
     
         2 . The conjugate of  claim 1 , wherein the poly(ethylene glycol) is terminally capped with an end-capping moiety. 
     
     
         3 . The conjugate of  claim 2 , wherein the end-capping moiety is methoxy. 
     
     
         4 . The conjugate of  claim 1 , wherein the IL-2 moiety is covalently attached to the single polyethylene glycol moiety via a spacer moiety. 
     
     
         5 . The conjugate of  claim 4 , wherein the spacer is not a carbamate-containing spacer. 
     
     
         6 . The conjugate of  claim 1 , wherein the poly(ethylene glycol) polymer has a weight average molecular weight in a range of from about 29,000 daltons to about 120,000 daltons. 
     
     
         7 . The conjugate of  claim 1 , wherein the single poly(ethylene glycol) polymer has a weight average molecular weight selected from the group consisting of about 30,000 daltons, about 35,000 daltons, about 40,000 daltons, about 45,000 daltons, about 50,000 daltons, about 55,000 daltons, about 60,000 Daltons, about 65,000 daltons, about 70,000 daltons, and about 75,000 daltons. 
     
     
         8 . The conjugate of  claim 7 , wherein the single poly(ethylene glycol) polymer has a weight average molecular weight of about 30,000 daltons or about 40,000 daltons. 
     
     
         9 . The conjugate of  claim 1 , wherein the IL-2 moiety is a recombinant IL-2 moiety. 
     
     
         10 . The conjugate of  claim 9 , wherein the recombinant IL-2 moiety is  E. coli -derived. 
     
     
         11 . The conjugate of  claim 1 , wherein the IL-2 moiety is a native protein. 
     
     
         12 . The conjugate of  claim 9 , wherein the IL-2 moiety has been modified to substitute an amino acid residue to thereby provide facile attachment to the single poly(ethylene glycol) polymer. 
     
     
         13 . The conjugate of  claim 12 , wherein the amino acid residue that has been substituted is a naturally-occurring amino acid. 
     
     
         14 . The conjugate of  claim 12 , wherein the amino acid residue that has been substituted is a non-naturally occurring amino acid. 
     
     
         15 . The conjugate of  claim 1 , wherein the IL-2 moiety has an amino acid sequence of SEQ ID NO: 2 or has at least 95 percent sequence identity to SEQ ID NO:2. 
     
     
         16 . The conjugate of  claim 15 , wherein the IL-2 moiety has an amino acid sequence having greater than 97 percent sequence identity to SEQ ID NO:2. 
     
     
         17 . The conjugate of  claim 4 , wherein the single poly(ethylene glycol) polymer is covalently attached via the spacer moiety to a lysine of the interleukin-2 moiety. 
     
     
         18 . The conjugate of  claim 17 , wherein the spacer comprises an amide group. 
     
     
         19 . A composition comprising a plurality of conjugates of  claim 1 , wherein each of the conjugates comprising the plurality of conjugates has the single poly(ethylene glycol) attached at the same location on the IL-2 moiety. 
     
     
         20 . A pharmaceutical composition comprising the plurality of conjugates of  claim 19  and a pharmaceutically acceptable excipient. 
     
     
         21 . The pharmaceutical composition of  claim 20  in a form suitable for parenteral administration. 
     
     
         22 . The pharmaceutical composition of  claim 21  in a solid form suitable for reconstitution in a diluent prior to administration. 
     
     
         23 . A method of administering comprising administering to a patient by parenteral administration the pharmaceutical composition of  claim 20 .