Conjugates Comprising a Biodegradable Polymer and Uses Therefor

Abstract

Biologically active agents covalently linked to a polymer. The polymer is preferably a biodegradable polymer are provided. The biologically active agent is preferably a protein, such as an extracellular soluble protein, e.g., an extracellular enzyme. The enzyme can be an apyrase, e.g., NTPDase. Conjugates of the invention can be used as therapeutics in subjects. For example, a conjugate comprising an apyrase can be used for treating and preventing thrombosis, atherosclerotic plaque complications and vascular disorders.

1 - 49 . (canceled) 
     
     
         50 . A conjugate comprising a protein and a biodegradable polymer, wherein the activity of the protein is higher relative to that of the protein in the absence of the biodegradable polymer; and/or the half-life of the protein is longer relative to that of the protein in the absence of the biodegradable polymer; and wherein the biodegradable polymer is a polyketal or polyacetal. 
     
     
         51 . The conjugate of  claim 50 , wherein the activity of the protein is at least 10 fold higher relative to that of the protein in the absence of the biodegradable polymer. 
     
     
         52 . The conjugate of  claim 50 , wherein the half-life of the protein is at least 10 fold longer relative to that of the protein in the absence of the biodegradable polymer. 
     
     
         53 . The conjugate of  claim 50 , wherein the biodegradable polymer is negatively charged. 
     
     
         54 . The conjugate of  claim 50 , wherein the biodegradable polymer is positively charged. 
     
     
         55 . The conjugate of  claim 50 , wherein the biodegradable polymer has a molecular weight from about 2 kDa to about 250 kDa. 
     
     
         56 . The conjugate of  claim 50 , wherein the biodegradable polymer has a molecular weight from about 20 kDa to about 100 kDa. 
     
     
         57 . The conjugate of  claim 50 , wherein the biodegradable polymer is a polyketal. 
     
     
         58 . The conjugate of  claim 50 , wherein the biodegradable polymer is a polyacetal. 
     
     
         59 . The conjugate of  claim 50 , wherein the biodegradable polymer is a polyacetal; and the polyacetal is poly(hydroxymethylethylene hydroxymethylacetal). 
     
     
         60 . The conjugate of  claim 50 , wherein the protein is conjugated to the biodegradable polymer through a covalent bond. 
     
     
         61 . The conjugate of  claim 50 , comprising a tether between the protein and the biodegradable polymer. 
     
     
         62 . The conjugate of  claim 61 , wherein the tether is a derivative of a compound chosen from the group consisting of ethylene glycol-bis-succinimidylsuccinate, succinic acid or succinic anhydride, diaminohexane, glyoxlic acid, short chain polyethylene glycol, and glycine. 
     
     
         63 . The conjugate of  claim 50 , further comprising a targeting agent. 
     
     
         64 . A pharmaceutical preparation comprising a conjugate of any one of  claims 50 - 63  and a pharmaceutically acceptable carrier.