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 - 40 . (canceled) 
     
     
         41 . A compound comprising a biologically active agent bonded to a phosphorylcholine containing polymer wherein said polymer is branched, having 2 or more polymer arms. 
     
     
         42 . The compound according to  claim 41  wherein the biologically active agent is covalently bonded to the polymer. 
     
     
         43 . The compound according to  claim 42  wherein the polymer comprises one or more monomer units and wherein a first monomer units has the structure: 
       
         
           
           
               
               
           
         
       
       wherein Q is selected from the group consisting of H, methyl and ethyl and T is C 1-4 alkyl-O—PC where PC is a phosphorylcholine group. 
     
     
         44 . The compound according to  claim 43  wherein Q is methyl. 
     
     
         45 . The compound according to  claim 44  wherein T is —CH 2 —CH 2 —O—PC. 
     
     
         46 . The compound according to  claim 45  wherein each arm has from about 20 to about 2000 first monomer units. 
     
     
         47 . The compound according to  claim 46  wherein each arms has from about 100 to about 500 first monomer units. 
     
     
         48 . The compound according to  claim 46  wherein each arms has from about 500 to about 1000 first monomer units. 
     
     
         49 . The compound according to  claim 46  wherein the polymer has a second monomer unit in a molar ration to the first monomer unit. 
     
     
         50 . The compound according to  claim 49  wherein the molar ratio of the first monomer unit to the second monomer unit is about 1:50 to 50:1. 
     
     
         51 . The compound according to  claim 50  wherein the molar ratio is about 1:10 to 10:1. 
     
     
         52 . The compound according to  claim 51  wherein the molar ratio is about 1:5 to 1:1. 
     
     
         53 . The compound of  claim 45  wherein the biologically active agent is selected from the group consisting of a drug, a protein, a peptide, an oligonucleotide and a nucleic acid. 
     
     
         54 . The compound of  claim 46  wherein the polymer has 3, 4, 5, 6, 7, 8, or more polymer arms. 
     
     
         55 . The compound of  claim 47  wherein the polymer has 3 arms. 
     
     
         56 . The compound of  claim 47  wherein the polymer has 6 arms. 
     
     
         57 . The compound of  claim 47  wherein the polymer has more than 8 arms. 
     
     
         58 . The compound of  claim 47  wherein the biologically active agent is a protein. 
     
     
         59 . The compound of  claim 51  wherein the biologically active agent is a therapeutic protein. 
     
     
         60 . The compound of  claim 59  wherein the therapeutic protein is a human protein. 
     
     
         61 . The compound of  claim 60  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 protein or peptide. 
     
     
         62 . The compound of  claim 60  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. 
     
     
         63 . The compound of  claim 60  wherein the human protein is obtained by gene activation in a cell line. 
     
     
         64 . The compound according to  claim 60  wherein the therapeutic protein is selected from the group consisting of a cytokine, an enzyme, an antibody and an antibody fragment.