Acryloyloxyethylphosphorylcholine Containing Polymer Conjugates and Their Preparation

Abstract

The present invention relates to polymeric reagents and conjugates thereof, methods for synthesizing the polymeric reagents and conjugates, pharmaceutical compositions comprising the conjugates and methods of using the polymer conjugates including therapeutic methods where conjugates are administered to patients.

1 . A compound comprising a biologically active agent bonded to a phosphorylcholine containing polymer. 
     
     
         2 . The compound of  claim 1  wherein the phosphorylcholine containing polymer is covalently bonded to a biologically active agent. 
     
     
         3 . The compound of  claim 1  wherein the phosphorylcholine containing polymer is covalently bonded to a biologically active agent via linking group and an optional spacer group. 
     
     
         4 . The compound of  claim 1  wherein the phosphorylcholine containing polymer is covalently bonded to at least one of an amino group, a hydroxyl group, a sulfhydryl group and a carboxyl group of the biologically active agent. 
     
     
         5 . The compound of  claim 1  wherein the phosphorylcholine containing polymer is a linear polymer. 
     
     
         6 . The compound of  claim 1  wherein the phosphorylcholine containing polymer is a branched polymer. 
     
     
         7 . The compound of  claim 1  having formula (IIb), 
       
         
           
           
               
               
           
         
         where 
         each occurrence of Q is independently selected from the group consisting of H and C 1-4  alkyl; 
         each occurrence of T is independently selected from the group consisting of H, C 1-4  alkyl, and —C 1-4  alkyl —O—PC, where PC denotes a phosphorylcholine group, with the proviso that one or more T groups is —C 1-4  alkyl —O—PC; 
         each occurrence of E is independently selected from the group consisting of halo and Nu wherein Nu is a nucleophilic group; 
         Sp 1  is selected from the group consisting of: —C 1-12  alkyl-, —C 3-12  cycloalkyl-, —(C 1-8  alkyl)-(C 3-12  cycloalkyl)-(C 0-8  alkyl)-, —(CH 2 ) 1-12 O—, (—(CH 2 ) 1-6 —O—(CH 2 ) 1-6 —) 1-12 —, (—(CH 2 ) 1-4 —NH—(CH 2 ) 1-4 ) 1-12 —, (—(CH 2 ) 1-4 —O—(CH 2 ) 1-4 ) 1-12 —O—, (—(CH 2 ) 1-4 —O—(CH 2 ) 1-4 —) 1-12 O—(CH 2 ) 1-12 —, —(CH 2 ) 1-12 —(C═O)—O—, —(CH 2 ) 1-12 —O—(C═O)—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—O—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—O—(C 0-6  alkyl)-, —(CH 2 ) 1-12 —(C═O)—O—(CH 2 ) 1-12 —, —CH(OH)—CH(OH)—(C═O)—O— —CH(OH)—CH(OH)—(C═O)—NH—, —S-maleimido-(CH 2 ) 1-6 —, —S-maleimido-(C 1-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 1-3 alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-, —(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-(C═O)—O—, —(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 0-3 alkyl)-phenyl-(C 0-3 alkyl)-, —(C 0-3  alkyl)-phenyl-(C═O)—NH—, —(CH 2 ) 1-12 —NH—(C═O)—, —(CH 2 ) 1-12 —(C═O)—NH—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —S—(CH 2 )—(C═O)—NH-(phenyl)-, —(CH 2 ) 1-12 —(C═O)—NH—(CH 2 ) 1-12 —, —(CH 2 ) 2 —(C═O)—O—(CH 2 ) 2 —O—(C═O)—(CH 2 ) 2 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—N—(C 1-6  alkyl)-, acetal, ketal, acyloxyalkyl ether, —N═CH—, —(C 1-6  alkyl)-S—S—(C 0-6  alkyl)-, —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—O—, —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-4 —NH—(C═O)—(CH 2 ) 1-3 —, —S—S—(C 0-3  alkyl)-(phenyl)-, —S—S—(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —, —(C 1-3  alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —(C═O)—NH—, —S—S—(C 1-3 -alkyl)-, -(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—, —O—(C 1 -C 6  alkyl)-S(O 2 )—(C 1-6  alkyl)-O—(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═O)—, —(CH 2 ) 1-3 —(C═O)—NE-N═C—S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-5 —, —(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-5 —(C═O)—NH—, —(CH 2 ) 0-3 -(heteroaryl)-(CH 2 ) 0-3 —, -(CH 2 ) 0-3 -phenyl-(CH 2 ) 0-3 —, 
       
       
         
           
           
               
               
           
         
         n is 0 or 1, wherein when n is 0, Sp 1  is a bond; 
         m is an integer ranging from 2 to 2,000; 
         L is selected from the group consisting of C 1-4 alkyl, cycloalkyl, carboxyC 1-4 alkyl, carboxycycloalkyl, C 1-4 alkoxyC 1-4 alkyl and cyclic alkyl ether; 
         A is a biologically active agent; 
         Z is selected from the group consisting of: phosphate, phosphate ester, —(C═O)O—, carboxylic acid ester, thioester, amide, dislufide, amine, —NH(R 1 )—, amidine, hydrazone, —N═CH—, —NH—CH 2 , 
       
       
         
           
           
               
               
           
         
       
       —NH—C(R 1 )H—, —S—CH 2 —C(OH)(R 2 )—, —O—CH 2 —C(OH)(R 2 )—, —C(═O)O—CH 2 —C(OH)(R 2 )—, —NR 2 —CH 2 —C(OH)(R 2 )—, —S—CH 2 —C(SH)(R 2 )—, —O—CH 2 —C(SH)(R 2 )—, —C(═O)O—CH 2 —C(SH)(R 2 )—, —NR 2 —CH 2 —C(SH)(R 2 )—, 
       
         
           
           
               
               
           
         
       
       C(R 2 )H—NH—, —(C═O)—NH—(C═O)—NH—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—NH—, —(C═O)—NH—(C═O)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—O—, —(C═O)NH(C═S)—NH—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)—NH—, —(C═O)—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —NH—(C═O)—NH—, —O—(C═O)—NH—, —NH—(C═S)—NH—, —O—(C═S)—NH—, —S—CH 2 CH 2 —(C═O)—, —S—CH 2 CH(CH 3 )—(C═O)O—, —S—CH 2 CH 2 —(C═O)O—, —S—CH 2 CH(CH 3 )—(C═O)O—, —S—CH 2 CH 2 —(C═O)NH—, —S—CH 2 —CH 2 —(pyridyl)-, —S—CH 2 —CH 2 —SO 2 —, —S—CH 2 —CH 2 —SO 2 —, —S—CH 2 —(C═O)—O—, —S—CH 2 —(C═O)—NH—, —S—CH 2 —(C═O)—, and 
       
         
           
           
               
               
           
         
         R 1  is C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms; and 
         R 2  is H, C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms. 
       
     
     
         8 . The compound of  claim 1  having formula (IIIb), 
       
         
           
           
               
               
           
         
         where 
         each occurrence of Q is independently selected from the group consisting of H, methyl, and ethyl; 
         each occurrence of T is independently selected from the group consisting of H, —CH 3 , —CH 2 —CH 3 , and —CH 2 —CH 2 —O—PC, where PC denotes a phosphorylcholine group, with the proviso that one or more T groups is —CH 2 —CH 2 —O—PC; 
         each occurrence of E is independently selected from the group consisting of Br, Cl, I, —NH 2 , —NH(C 1-4  alkyl), —N(C 1-4  alkyl) 2 , —OH, —O—(C 1-4  alkyl), and —O— (C 1-4 haloalkyl); 
         Sp 1  is selected from the group consisting of —C 1-12  alkyl-, —C 3-12  cycloalkyl-, —(C 1-8  alkyl)-(C 3-12  cycloalkyl)-(C 0-8 alkyl)-, —(CH 2 ) 1-12 O—, (—(CH 2 ) 1-6 —O—(CH 2 ) 1-6 —) 1-12 —, (—(CH 2 ) 1-4 —NH—(CH 2 ) 1-4 ) 1-12 —, (—(CH 2 ) 1-4 —O—(CH 2 ) 1-4 ) 1-12 —O—, (—(CH 2 ) 1-4 —O—(CH 2 ) 1-4 ) 1-12 O—(CH 2 ) 1-12 —(CH 2 ) 1-12 —(C═O)—O—, —(CH 2 ) 1-12 —O—(C═O)—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—O—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—O—(C 0-6  alkyl)-, —(CH 2 ) 1-12 —(C═O)—O—(CH 2 ) 1-12 —, —CH(OH)—CH(OH)—(C═O)-o— —CH(OH)—CH(OH)—(C═O)—NH—, —S-maleimido-(CH 2 ) 1-6 —, —S-maleimido-(C 1-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-, —(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-(C═O)—O—, —(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 0-3 alkyl)-phenyl-(C 0-3 alkyl)-, —(C 0-3  alkyl)-phenyl-(C═O)—NH—, —(CH 2 ) 1-12 —NH—(C═O)—, —(CH 2 ) 1-12 —(C═O)—NH—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —S—(CH 2 )—(C═O)—NH-(phenyl)-, —(CH 2 ) 1-12 —(C═O)—NH—(CH 2 ) 1-12 —, —(CH 2 ) 2 —(C═O)—O—(CH 2 ) 2 —O—(C═O)—(CH 2 ) 2 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—N—(C 1-6  alkyl)-, acetal, ketal, acyloxyalkyl ether, —N═CH—, —(C 1-6  alkyl)-S—S—(C 0-6  alkyl)-, —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—O—, —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 14 —N11-(C═O)—(CH 2 ) 1-3 —, —S—S—(C 0-3  alkyl)-(phenyl)-, —S—S—(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —, —(C 1-3  alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —(C═O)—NH—, —S—S—(C 1-3 -alkyl)-, —(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—, —O—(C 1 -C 6  alkyl)-S(O 2 )—(C 1-6  alkyl)-O—(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═o)—, —(CH 2 ) 1-3 —(C═O)—NH—N═C—S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-5 —, —(CH 2 ) 1-3 —(c═o)—NH—(CH 2 ) 1-5 —(C═O)—NH—, —(CH 2 ) 0-3 -(heteroaryl)-(CH 2 ) 0-3 —, —(CH 2 ) 0-3 -phenyl-(CH 2 ) 0-3 —, 
       
       
         
           
           
               
               
           
         
         n is 0 or 1, wherein when n is 0, Sp 1  is a bond; 
         m is an integer ranging from 2 to 2,000; 
         L is selected from the group consisting of C 1-4 alkyl, cycloalkyl, carboxyC 1- 4alkyl, carboxycycloalkyl, C 1-4 alkoxyC 1-4 alkyl and cyclic alkyl ether; 
         A is a biologically active agent; 
         Z is selected from the group consisting of: phosphate, phosphate ester, —(C═O)O—, carboxylic acid ester, thioester, amide, dislufide, amine, —NH(R 1 )—, amidine, hydrazone, —N═CH—, —NH—CH 2 —, 
       
       
         
           
           
               
               
           
         
       
       —NH—C(R 1 ) H —, —S—CH 2 —C(OH)(R 2 )—, —O—CH 2 —C(OH)(R 2 )—, —C(═O)O—CH 2 —C(OH)(R 2 )—, —NR 2 —CH 2 —C(OH)(R 2 )—, —S—CH 2 —C(SH)(R 2 )—, —O—CH 2 —C(SH)(R 2 )—, —C(═O)O—CH 2 —C(SH)(R 2 )—, —NR 2 —CH 2 —C(SH)(R 2 )—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—, —(C═O)—NH—(C═O)—NH—. 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—NH—, —(C═O)—NH—(C═O)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—O—, —(C═O)—NH—(C═S)—NH—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)—NH—, —(C═O)—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —NH—(C═O)—NH—, —O—(C═O)—NH—, —NH—(C═S)—NH—, —O—(C═S)—NH—, —S—CH 2 CH 2 —(C═O)—, —S—CH 2 CH(CH 3 )—(C═O)— —S—CH 2 CH 2 —(C═O)O—, —S—CH 2 CH(CH 3 )—(C═O)O—, —S—CH 2 CH 2 —(C═O)NH—, —S—CH 2 —CH 2 —(pyridyl)-, —S—CH 2 —CH 2 —SO 2 —, —S—CH 2 —CH 2 —SO 2 —, —S—CH 2 —(C═O)—O—, —S—CH 2 —(C═O)—NH—, —S—CH 2 —(C═O)—, and 
       
         
           
           
               
               
           
         
         R 1  is C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms; and 
         R 2  is H, C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms. 
       
     
     
         9 . The compound of  claim 1  having formula (IVb), 
       
         
           
           
               
               
           
         
         where 
         each occurrence of Q is independently selected from the group consisting of H, methyl, and ethyl; 
         each occurrence of T is independently selected from the group consisting of H, —CH 3 , —CH 2 —CH 3 , and —CH 2 —CH 2 —O—PC, where PC denotes a phosphorylcholine group, with the proviso that one or more T groups is —CH 2 —CH 2 —O—PC; 
         each occurrence of E is independently selected from the group consisting of Br, Cl, I, —NH 2 , —NH(C 1-4  alkyl), —N(C 1-4 alkyl) 2 , —OH, —O—(C 1-4  alkyl), and —O—(C 1-4  fluoro-substituted alkyl); 
         Sp 1  is selected from the group consisting of —C 1-12  alkyl-, —C 3-12  cycloalkyl-, —(C 1-8  alkyl)-(C 3-12  cycloalkyl)-(C 0-8  alkyl)-, —(CH 2 ) 1-12 O—, (—(CH 2 ) 1-6 —O—(CH 2 ) 1-6 —) 1-12 —, (—(CH 2 ) 1-4 —NH—(CH 2 ) 1-4 ) 1-12 —, (—(CH 2 ) 1-4 ) 1-12 —O—, (—(CH 2 ) 1-4 —O—(CH 2 ) 1-4 —) 1-12 O—(CH 2 ) 1-12 —, —(CH 2 ) 1-12 —(C═O)—O—, —(CH 2 ) 1-12 —O—(C═O)—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—O—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—O—(C 0-6  alkyl)-, —(CH 2 ) 1-12 —(C═O)—O—(CH 2 ) 1-12 —, —CH(OH)—CH(OH)—(C═O)—O-—CH(OH)—CH(OH)—(C═O)—NH—, —S-maleimido-(CH 2 ) 1-6 —, —S-maleimido-(C 1-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 1-3  alkyl)-(C s-6  cycloalkyl)-(C 0-3  alkyl)-, —(C 1-3  alkyl)-(C 5-6  cyoloalkyl)-(C 0-3  alkyl)-(C═O)—O—, —(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 0-3 alkyl)-phenyl-(C 0-3 alkyl)-, —(C 0-3  alkyl)-phenyl-(C═O)—NH—, —(CH 2 ) 1-12 —NH—(C═O)—, —(CH 2 ) 1-12 —(C═O)—NH—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —S—(CH 2 )—(C═O)—NH-(phenyl)-, —(CH 2 ) 1-12 —(C═O)—NH—(CH 2 ) 1-12 —, —(CH 2 ) 2 —(C═O)—O—(CH 2 ) 2 —O—(C═O)—(CH 2 ) 2 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—N—(C 1-6  alkyl)-, acetal, ketal, acyloxyalkyl ether, —N═CH—, —(C 1-6  alkyl)-S—S—(C 0-6 , —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—O—, —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-4 —NH—(C═O)—(CH 2 ) 1-3 —, —S—S—(C 0-3  alkyl)-(phenyl)-, —S—S—(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —, —(C 1-3  alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —(C═O)—NH—, —S—S—(C 1-3 -alkyl)-, —(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—, —O—(C 1 -C 6  alkyl)-S(O 2 )—(C 1-6  alkyl)-O—(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═O)—, —(CH 2 ) 1-3 —(C═O)—NH—N═C—S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-5 —, —(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-5 —(C═O)—NH—, —(CH 2 ) 0-3 -(heteroaryl)-(CH 2 ) 0-3 —, —(CH 2 ) 0-3 -phenyl-(CH 2 ) 0-3 —, 
       
       
         
           
           
               
               
           
         
         n is 0 or 1, wherein when n is 0, Sp 1  is a bond; 
         m is an integer ranging from 2 to 2,000; 
         L is selected from the group consisting of C 1-4 alkyl, cycloalkyl, carboxyC 1-4 alkyl, carboxycycloalkyl, C 1-4 alkoxyC 1-4 alkyl and cyclic alkyl ether; 
         A is a biologically active agent; 
         Z is selected from the group consisting of: phosphate, phosphate ester, —(C═O)O—, carboxylic acid ester, thioester, amide, dislufide, amine, —NH(R 1 )—, amidine, hydrazone, —N═CH—, —NH—CH 2 —, 
       
       
         
           
           
               
               
           
         
       
       —NH—C(R 1 )H—, —S—CH 2 —C(OH)(R 2 )—, —O—CH 2 —C(OH)(R 2 )—, —C(═O)O—CH 2 —C(OH)(R 2 )—, —NR 2 —CH 2 —C(OH)(R 2 )—, —S—CH 2 —C(SH)(R 2 )—, —O—CH 2 —C(SH)(R 2 )—, —C(═O)O—CH 2 —C(SH)(R 2 )—, —NR 2 —CH 2 —C(SH)(R 2 )—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—, —(C═O)—NH—, —(C═O)—NH—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—NH—, —(C═O)—NH—(C═O)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—O—, —(C═O)—NH—(C═S)—NH—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)—NH—, —(C═O)—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —NH—(C═O)—NH—, —O—(C═O)—NH—, —NH—(C═S)—NH—, —O—(C═S)—NH—, —S—CH 2 CH 2 —(C═O)—, —S—CH 2 CH(CH 3 )—(C═O)NH—, —S—CH 2 CH 2 —(C═O)O—, —S—CH 2 CH(CH 3 )—(C═O)O—, —S—CH 2 CH 2 —(C═O)NH—, —S—CH 2 —CH 2 —(pyridyl)-, —S—CH 2 —CH 2 —SO 2 —, —S—CH 2 —(C═O)—O—, —S—CH 2 —(C═O)—NH—, —S—CH 2 —(C═O)—, and 
       
         
           
           
               
               
           
         
         R 1  is C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms; and 
         R 2  is H, C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms. 
       
     
     
         10 . The compound of  claim 1  having formula (Vb), 
       
         
           
           
               
               
           
         
         where 
         each occurrence of Q is independently selected from the group consisting of H, methyl, and ethyl; 
         each occurrence of T is independently selected from the group consisting of H, —CH 3 , —CH 2 —CH 3 , and —CH 2 —CH 2 —O—PC, where PC denotes a phosphorylcholine group, with the proviso that one or more T groups is —CH 2 —CH 2 —O—PC; 
         each occurrence of E is independently selected from the group consisting of Br, Cl, I, —NH 2 , —NH(C 1-4 —N(C 1-4 alkyl) 2 , —OH, —O—(C 1-4  alkyl), and —O—(C 1-4  fluoro-substituted alkyl); 
         Sp 1  is selected from the group consisting of: —C 1-12  alkyl-, —C 3-12  cycloalkyl-, —(C 1-8  alkyl)-(C 3-12  cycloalkyl)-(C 0-8  alkyl)-, —(CH 2 ) 1-12 O—, (—(CH 2 ) 1-6 —O—(CH 2 ) 1-6 —) 1-12 —, (—(CH 2 ) 14 —NH—(CH 2 ) 14 ) 1-12 —, (—(CH 2 ) 1-4 —O—(CH 2 ) 1-4 ) 1-12 —O—, (—(CH 2 ) 1-4 —O—(CH 2 ) 1-4 —) 1-12 O—(CH 2 ) 1-12 —, —(CH 2 ) 1-12 —(C═O)—O—, —(CH 2 ) 1-12 —O—(C═O)—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—O—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—O—(C 0-6  alkyl)-, —(CH 2 ) 1-12 —(C═O)—O—(CH 2 ) 1-12 —, —CH(OH)—CH(OH)—(C═O)—O-—CH(OH)—CH(OH)—(C═O)—NH—, —S-maleimido-(CH 2 ) 1-6 —, —S-maleimido-(C 1-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 1-3 alkyl)-(C 5-6  cycloalkyl)-(C 0-3 alkyl)-, —(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3 alkyl)-(C═O)—O—, —(C 1-3  alkyl)-(C 5-6  cycloalkyl)-(C 0-3  alkyl)-(C═O)—NH—, —S-maleimido-(C 0-3 alkyl)-phenyl-(C 0-3 alkyl)-, —(C 0-3  alkyl)-phenyl-(C═O)—NH—, —(CH 2 ) 1-12 —NH—(C═O)—, —(CH 2 ) 1-12 —(C═O)—NH—, -(phenyl)-(CH 2 ) 1-3 —(C═O)—NH—, —S—(CH 2 )—(C═O)—NH-(phenyl)-, —(CH 2 ) 1-12 —(C═O)—NH—(CH 2 ) 1-12 —, —(CH 2 ) 2 —(C═O)—O—(CH 2 ) 2 —O—(C═O)—(CH 2 ) 2 —(C═O)—NH—, —(C 1-6  alkyl)-(C═O)—N—(C 1-6  alkyl)-, acetal, ketal, acyloxyalkyl ether, —N═CH—, —(C 1-6  alkyl)-S—S—(C 0-6  alkyl)-, —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—O—, —(C 1-6  alkyl)-S—S—(C 1-6  alkyl)-(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 14 —NH—(C═O)—(CH 2 ) 1-3 —, —S—S—(C 0-3  alkyl)-(phenyl)-, —S—S—(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —, —(C 1-3  alkyl)-(phenyl)-(C═O)—NH—(CH 2 ) 1-5 —(C═O)—NH—, —S—S—(C 1-3 -alkyl)-, -(C 1-3 -alkyl)-(phenyl)-(C═O)—NH—, —O—(C 1 -C 6  alkyl)-S(O 2 )—(C 1-6  alkyl)-O—(C═O)—NH—, —S—S—(CH 2 ) 1-3 —(C═O)—, —(CH 2 ) 1-3 —(C═O)—NH—N═C—S—S—(CH 2 ) 1-3 —(C═O)—NH—(CH 2 ) 1-5 —, —(CH 2 ) 1-3 —(C═O)—NR—(CH 2 ) 1-5 —(C═O)—NH—, —(CH 2 ) 0-3 —(heteroaryl)-(CH 2 ) 0-3 —, —(CH 2 ) 0-3 -phenyl-(CH 2 ) 0-3 —, 
       
       
         
           
           
               
               
           
         
         n is 0 or 1, wherein when n is 0, Sp 1  is a bond; 
         m is an integer ranging from 2 to 2,000; 
         L is selected from the group consisting of C 1-4 alkyl, cycloalkyl, carboxyC 1-4 alkyl, carboxycycloalkyl, C 1-4 alkoxyC 1-4 alkyl and cyclic alkyl ether; 
         A is a biologically active agent; 
         Z is selected from the group consisting of: phosphate, phosphate ester, —(C═O)O—, carboxylic acid ester, thioester, amide, dislufide, amine, —NH(R 1 )—, amidine, hydrazone, —N═CH—, —NH—CH 2 —, 
       
       
         
           
           
               
               
           
         
       
       —NH—C(R 0 )H—, —S—CH 2 —C(OH)(R 2 )—-O—CH 2 —C(OH)(R 2 )—, —C(═O)o-CH 2 —C(OH)(R 2 )—, —NR 2 —CH 2 —C(OH)(R 2 )—, —S—CH 2 —C(SH)(R 2 )—, —O—CH 2 —C(SH)(R 2 )—, —C(═O)O—CH 2 —C(SH)(R 2 )—, —NR 2 —CH 2 —C(SH)(R 2 )—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—, —(C═O)—NH—(C═O)—NH—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—NH—, —(C═O)—NH—(C═O)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═O)—O—, —(C═O)—NH—(C═S)—NH—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)NH—, —(C═O)—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —C(R 2 )H—NH—(C═S)—O—, 
       
         
           
           
               
               
           
         
       
       —NH—(C═O)—NH—, —O—(C═O)—NH—, —NH—(C═S)—NH—, —O—(C═S)—NH—, —S—CH 2 CH 2 —(C═O)—, —S—CH 2 CH(CH 3 )—(C═O)— —S—CH 2 CH 2 —(C═O)O—, —S—CH 2 CH(CH 3 )—(C═O)O—, —S—CH 2 CH 2 —(C═O)NH—, —S—CH 2 —CH 2 — (pyridyl)-, —S—CH 2 —CH 2 —SO 2 —, —S—CH 2 —CH 2 —SO 2 —, —S—CH 2 —(C═O)—O—, —S—CH 2 —(C═O)—NH—, —S—CH 2 —(C═O)—, and 
       
         
           
           
               
               
           
         
         R 1  is C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms; and 
         R 2  is H, C 1-6  alkyl, C 3-6  cycloalkyl, or an aryl group having 5-8 endocyclic atoms. 
       
     
     
         11 . The compound of  claim 7  having formula (VIb), 
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 9  having formula (VIIIb) 
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound according to any of  claims 7  to  12 , wherein Q is methyl. 
     
     
         14 . The compound according to any of  claims 7  to  12 , wherein E is bromo. 
     
     
         15 . The compound according to any of  claims 7  to  12 , wherein T is PC. 
     
     
         16 . The compound according to any one of  claims 7  to  12  wherein Sp 1  is selected from the group consisting of a bond and 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of any one of  claims 7  to  12  wherein Z is independently selected from the group consisting of —NH—, —N═CH—, —NH—CH 2 — and 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 1 , wherein the phosphorylcholine containing polymer has a molecular weight between about 0.5 kDa and about 200 kDa. 
     
     
         19 . The compound of  claim 1 , wherein the phosphorylcholine containing polymer has a molecular weight between about 5 kDa and about 40 kDa. 
     
     
         20 . The compound of  claim 1 , wherein the phosphorylcholine containing polymer has a molecular weight between about 10 kDa and about 20 kDa. 
     
     
         21 . The compound of  claim 1 , wherein said biologically active agent further comprises an Sp 2  group. 
     
     
         22 . The compound of  claim 1  wherein the biologically active agent is a protein. 
     
     
         23 . The compound of  claim 22  wherein the biologically active agent is a therapeutic protein. 
     
     
         24 . The compound of  claim 22  wherein the protein is a human protein. 
     
     
         25 . The compound of  claim 24  wherein the human protein is obtained by heterologous gene expression in a cell selected from the group consisting of a bacterium, a yeast cell, a mammalian cell in culture, an insect cell in culture, a plant cell in culture, an avian cell in culture, a cell of a transgenic avian, a cell of a transgenic mammal, and a cell of a transgenic plant. 
     
     
         26 . The compound of  claim 24  wherein the human protein is obtained by gene activation in a cell line. 
     
     
         27 . The compound according to  claim 1  wherein the biologically active agent is a selected from the group consisting of a cytokine, an enzyme, an antibody and an antibody fragment. 
     
     
         28 . The compound according to  claim 27  wherein the cytokine, the enzyme, the antibody and the antibody fragment are human. 
     
     
         29 . The compound according to  claim 27  or  28  wherein the cytokine, the enzyme and antibody or antibody fragment are obtained by heterologous gene expression in a cell selected from the group consisting of a bacterium, a yeast cell, a mammalian cell in culture, an insect cell in culture, a plant cell in culture, an avian cell in culture, a cell of a transgenic avian, a cell of a transgenic chicken, a cell of a transgenic quail, a cell of a transgenic goat, a cell of a transgenic cow and a cell of a transgenic plant. 
     
     
         30 . The compound according to  claim 1  wherein the biologically active agent is selected from the group consisting of factor VIII, b-domain deleted factor VIII, factor VIIa, factor IX, anticoagulants; hirudin, alteplase, tpa, reteplase, tpa, tpa—3 of 5 domains deleted, insulin, insulin lispro, insulin aspart, insulin glargine, long-acting insulin analogs, hgh, glucagons, tsh, follitropin-beta, fsh, gm-csf, pdgh, ifn alpha, ifn beta, ifn alpha2, ifn alpha2a, ifn alpha2b, ifn alpha2c, inf-aphal, ifn beta, inf-beta 1b, ifn-beta 1a, ifn-gamma, il-2, il-11, hbsag, ospa, murine mab directed against t-lymphocyte antigen, murine mab directed against tag-72, tumor-associated glycoprotein, fab fragments derived from chimeric mab directed against platelet surface receptor gpII(b)/III(a), murine mab fragment directed against tumor-associated antigen cal 25, murine mab fragment directed against human carcinoembryonic antigen, cea, murine mab fragment directed against human cardiac myosin, murine mab fragment directed against tumor surface antigen psma, murine mab fragments (fab/fab2 mix) directed against hmw-maa, murine mab fragment (fab) directed against carcinoma-associated antigen, mab fragments (fab) directed against nca 90, a surface granulocyte nonspecific cross reacting antigen, chimeric mab directed against cd20 antigen found on surface of b lymphocytes, humanized mab directed against the alpha chain of the il2 receptor, chimeric mab directed against the alpha chain of the il2 receptor, chimeric mab directed against tnf-alpha, humanized mab directed against an epitope on the surface of respiratory synctial virus, humanized mab directed against her 2, human epidermal growth factor receptor 2, human mab directed against cytokeratin tumor-associated antigen anti-ctla4, infliximab gemtuzumab ozogamicin, ranibizumab, chimeric mab directed against cd 20 surface antigen of b lymphocytes dornase-alpha dnase, beta glucocerebrosidase, tnf-alpha, il-2-diptheria toxin fusion protein, tnfr-lgg fragment fusion protein laronidase, dnaases, alefacept, darbepoetin alpha (colony stimulating factor), tositumomab, murine mab, alerntuzumab, rasburicase, agalsidase beta, teriparatide, parathyroid hormone derivatives, adalimumab (Igg1), anakinra, biological modifier, nesiritide, human b-type natriuretic peptide (hbnp), colony stimulating factors, pegvisomant, human growth hormone receptor antagonist, recombinant activated protein c, ornalizumab, immunoglobulin e (Ige) blacker, Ibritumomab tiuxetan, ACTH, glucagon, somatostatin, somatotropin, thymosin, parathyroid hormone, pigmentary hormones, somatomedin, erythropoietin, luteinizing hormone, chorionic gonadotropin, hypothalmic releasing factors, etanercept, antidiuretic hormones, prolactin, thyroid stimulating hormone, humanized anti-HER 2  monoclonal antibody, anti-glycoprotein IIb/IIIa receptor, humanized anti-CD25 monoclonal antibody, murine anti-17-IA cell surface antigen IgG2a antibody, murine anti-idiotype (GD3 epitope) IgG antibody, chimeric anti-EGFR IgG antibody, humanized anti-αVβ3 integrin antibody, humanized anti CD52 IgG1 antibody, humanized anti-CD33 IgG antibody, chimeric anti-CD2O IgG1 antibody, humanized anti-CD22 IgG antibody, humanized anti-ICAM3 antibody, primate anti-CD80 antibody, murine anti-CD20 antibody, humanized anti-CD40L antibody, primatized anti-CD4 antibody, primatized anti-CD23 antibody, humanized anti-CD3 IgG, humanized anti-complement factor 5 (CS) antibody, humanized anti-TNF-α antibody, humanized anti-TNF-α Fab fragment, primatized anti-CD4 IgG1 antibody, human anti-CD4 IgG antibody, humanized anti-TNF-α IgG4 antibody, humanized anti-α4β7 antibody, humanized anti-CD4 IgG antibody, humanized anti-CD40L IgG antibody, humanized anti-VLA-4 IgG antibody, human anti-TGF-β 2  antibody, monoclonal anti-EGF receptor (EGFr) antibody, anti-VEGF human monoclonal antibody, agalsidase, alefacept, aspariginase, amdoxovir (DAPD), antide, becaplermin, botulinum toxin including types A and B and lower molecular weight compounds with botulinum toxin activity, calcitonins, cyanovirin, denileukin diffitox, erythropoietin (EPO), EPO agonists, dornase alpha, erythropoiesis stimulating protein (NESP), coagulation factors such as Factor V, Factor VII, Factor VIIa, Factor VIII, Factor IX, Factor X, Factor XII, Factor XIII, von Willebrand factor; ceredase, cerezyme, alpha-glucosidase, collagen, cyclosporin, alpha defensins, beta defensins, desmopressin, exendin-4, cytokines, cytokine receptors, granulocyte colony stimulating factor (G-CSF), thrombopoietin (TPO), alpha-1 proteinase inhibitor, elcatonin, granulocyte macrophage colony stimulating factor (GM-CSF), fibrinogen, filgrastim, growth hormones human growth hormone (hGH), somatropin, growth hormone releasing hormone (GHRH), GRO-beta, GRO-beta antibody, bone morphogenic proteins such as bone morphogenic protein-2, bone morphogenic protein-6, OP-1; acidic fibroblast growth factor, basic fibroblast growth factor, CD-40 ligand, heparin, human serum albumin, low molecular weight heparin (LMWH), interferon alpha, interferon beta, interferon gamma, interferon omega, interferon tau, consensus interferon; interleukins and interleukin receptors such as interleukin-1 receptor, interleukin-2, interleukin-2 fusion proteins, interleukin-1 receptor antagonist, interleukin-3, interleukin-4, interleukin-4 receptor, interleukin-6, interleukin-8, interleukin-12, interleukin-13 receptor, interleukin-17 receptor; lactoferrin and lactoferrin fragments, luteinizing hormone releasing hormone (LHRH), insulin, pro-insulin, insulin analogues, amylin, C-peptide, somatostatin, somatostatin analogs including octreotide, vasopressin, follicle stimulating hormone (FSH), imiglucerase, influenza vaccine, insulin-like growth factor (IGF), insulintropin, macrophage colony stimulating factor (M-CSF), plasminogen activators such as alteplase, urokinase, reteplase, streptokinase, pamiteplase, lanoteplase, and teneteplase; nerve growth factor (NGF), osteoprotegerin, platelet-derived growth factor, tissue growth factors, transforming growth factor-1, vascular endothelial growth factor, leukemia inhibiting factor, keratinocyte growth factor (KGF), glial growth factor (GGF), T Cell receptors, CD molecules/antigens, tumor necrosis factor (TNF) (e.g., TNF-α and TNF-β), CTLA4, CTLA4 receptor, CTLA4-Fc fusion, monocyte chemoattractant protein-1, endothelial growth factors, parathyroid hormone (PTH), glucagon-like peptide, somatotropin, thymosin alpha 1, rasburicase, thymosin alpha 1 inhibitor, thymosin beta 10, thymosin beta 9, thymosin beta 4, alpha-1 antitrypsin, phosphodiesterase (PDE) compounds, VLA-4 (very late antigen-4), VLA-4 inhibitors, bisphosphonates, respiratory syncytial virus antibody, cystic fibrosis transmembrane regulator (CFTR) gene, deoxyribonuclease (Dnase), bactericidal/permeability increasing protein (BPI), and anti-CMV antibody, etanercept (a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kD TNF receptor linked to the Fc portion of IgG1), abciximab, adalimumab, afelimomab, alemtuzumab, antibody to B-lymphocyte, atlizumab, basiliximab, bevacizumab, biciromab, bertilimumab, CDP-484, CDP-57I, CDP-791, CDP-860, CDP-870, cetuximab, clenoliximab, daclizumab, eculizumab, edrecolomab, efalizumab, epratuzumab, fontolizumab, gavilimomab, gemtuzumab ozogamicin, ibritumomab tiuxetan, infliximab, inolimomab, keliximab, labetuzumab, lerdelimumab, olizumab, radiolabeled lym-1, metelimumab, mepolizumab, mitumomab, muromonad-CD3, nebacumab, natalizumab, odulimomab, omalizumab, oregovomab, palivizumab, pemtumomab, pexelizumab, rhuMAb-VEGF, rituximab, satumomab pendetide, sevirumab, siplizumab, tositumomab, I 131 tositumomab, trastuzumab, tuvirumab, visilizumab, tacrine, memantine, rivastigmine, galantamine, donepezil, levetiracetam, repaglinide, atorvastatin, alefacept, tadalafil, vardenafil, sildenafil, fosamprenavir, oseltamivir, valacyclovir and valganciclovir, abarelix, adefovir, alfuzosin, alosetron, amifostine, amiodarone, aminocaproic acid, aminohippurate sodium, aminoglutethimide, aminolevulinic acid, aminosalicylic acid, amlodipine, amsacrine, anagrelide, anastrozole, aprepitant, aripiprazole, aminosalicylic acid, asparaginase, atazanavir, atomoxetine, anthracyclines, bexarotene, bicalutamide, bleomycin, bortezomib, buserelin, busulfan, cabergoline, capecitabine, carboplatin, carmustine, cephalexin, chlorambucin, cilastatin sodium, cisplatin, cladribine, clodronate, cyclophosphamide, cyproterone, cytarabine, camptothecins, 13-cis retinoic acid, all trans retinoic acid; dacarbazine, dactinomycin, daptomycin, daunorubicin, deferoxamine, dexamethasone, diclofenac, diethylstilbestrol, docetaxel, doxorubicin, dutasteride, eletriptan, emtricitabine, enfitvirtide, eplerenone, epirubicin, estramustine, ethinyl estradiol, etoposide, exemestane, ezetimibe, fentanyl, fexofenadine, fludarabine, fludrocortisone, fluorouracil, fluoxymesterone, flutamide, fluticazone, fondaparinux, fulvestrant, gamma-hydroxybutyrate, gefitinib, gemcitabine, epinephrine, L-Dopa, hydroxyurea, icodextrin, idarubicin, ifosfamide, imatinib, irinotecan, itraconazole, goserelin, laronidase, lansoprazole, letrozole, leucovorin, levamisole, lisinopril, lovothyroxine sodium, lomustine, mechlorethamine, medroxyprogesterone, megestrol, melphalan, memantine, mercaptopurine, mequinol, metaraminol bitartrate, methotrexate, metoclopramide, mexiletine, miglustat, mitomycin, mitotane, mitoxantrone, modafinil, naloxone, naproxen, nevirapine, nicotine, nilutamide, nitazoxanide, nitisinone, norethindrone, octreotide, oxaliplatin, palonosetron, pamidronate, pemetrexed, pergolide, pentostatin, pilcamycin, porfimer, prednisone, procarbazine, prochlorperazine, ondansetron, palonosetron, oxaliplatin, raltitrexed, rosuvastatin, sirolimus, streptozocin, pimecrolimus, sertaconazole, tacrolimus, tamoxifen, tegaserod, temozolomide, teniposide, testosterone, tetrahydrocannabinol, thalidomide, thioguanine, thiotepa, tiotropium, topiramate, topotecan, treprostinil, tretinoin, valdecoxib, celecoxib, rofecoxib, valrubicin, vinblastine, vincristine, vindesine, vinorelbine, voriconazole, dolasetron, granisetron, formoterol, fluticasone, leuprolide, midazolam, alprazolam, amphotericin B, podophylotoxins, nucleoside antivirals, aroyl hydrazones, sumatriptan, eletriptan; macrolides such as erythromycin, oleandomycin, troleandomycin, roxithromycin, clarithromycin, davercin, azithromycin, flurithromycin, dirithromycin, josamycin, spiromycin, midecamycin, loratadine, desloratadine, leucomycin, miocamycin, rokitamycin, andazithromycin, and swinolide A; fluoroquinolones such as ciprofloxacin, ofloxacin, levofloxacin, trovafloxacin, alatrofloxacin, moxifloxicin, norfloxacin, enoxacin, gatifloxacin, gemifloxacin, grepafloxacin, lomefloxacin, sparfloxacin, temafloxacin, pefloxacin, amifloxacin, fleroxacin, tosufloxacin, prulifloxacin, irloxacin, pazufloxacin, clinafloxacin, and sitafloxacin; aminoglycosides such as gentamicin, netilmicin, paramecin, tobramycin, amikacin, kanamycin, neomycin, and streptomycin, vancomycin, teicoplanin, rampolanin, mideplanin, colistin, daptomycin, gramicidin, colistimethate; polymixins such as polymixin B, capreomycin, bacitracin, penems; penicillins including penicllinase-sensitive agents like penicillin G, penicillin V; penicillinase-resistant agents like methicillin, oxacillin, cloxacillin, dicloxacillin, floxacillin, nafcillin; gram negative microorganism active agents like ampicillin, amoxicillin, and hetacillin, cillin, and galampicillin; antipseudomonal penicillins like carbenicillin, ticarcillin, azlocfllin, mezlocillin, and piperacillin; cephalosporins like cefpodoxime, cefprozil, ceftbuten, ceftizoxime, ceftriaxone, cephalothin, cephapirin, cephalexin, cephradrine, cefoxitin, cefamandole, cefazolin, cephaloridine, cefaclor, cefadroxil, cephaloglycin, cefuroxime, ceforanide, cefotaxime, cefatrizine, cephacetrile, cefepime, cefixime, cefonicid, cefoperazone, cefotetan, cefmetazole, ceftazidime, loracarbef, and moxalactam, monobactams like aztreonam; and carbapenems such as imipenem, meropenem, and ertapenem, pentamidine isetionate, albuterol sulfate, lidocaine, metaproterenol sulfate, beclomethasone diprepionate, triamcinolone acetamide, budesonide acetonide, salmeterol, ipratropium bromide, flunisolide, cromolyn sodium, and ergotamine tartrate; taxanes such as paclitaxel; SN-38, tyrphostines and mimetics thereof. 
     
     
         31 . The compound according to  claim 1 , wherein said biologically active agent is selected from the group consisting of:
 erythropoietin, granulocyte colony stimulating factor (G-CSF), interferon alpha, interferon beta, human growth hormone, and imiglucerase.   
     
     
         32 . The compound of  claim 31  where the biologically active agent is human erythropoietin. 
     
     
         33 . The compound of  claim 31  where the biologically active agent is human granulocyte colony stimulating factor. 
     
     
         34 . The compound of  claim 31  where the biologically active agent is interferon alpha. 
     
     
         35 . The compound of any one of  claims 32  to  34  wherein the biologically active agent is avian derived. 
     
     
         36 . The compound of  claim 35  wherein the biologically active agent is chicken derived. 
     
     
         37 . The compound according to any of the Examples. 
     
     
         38 . A pharmaceutical composition comprising a compound according to  claim 1 . 
     
     
         39 . A method of increasing the biological half-life of a biologically active agent comprising bonding a phosphorylcholine group to a biologically active agent. 
     
     
         40 . A method of treating a condition responsive to a biological agent comprising administering to a patient in need thereof a compound according to  claims 1 ,  37 , or  39 .