Polypeptide-polymer conjugates and methods of use thereof

Abstract

The present invention provides polypeptide-polymer conjugates. A subject polypeptide-polymer conjugate is useful in a variety of applications, which are also provided.

1 .- 13 . (canceled) 
     
     
         14 . A treatment method comprising administering to an individual in need thereof an effective amount of a pharmaceutical composition comprising: a) a pharmaceutically acceptable excipient; and b) a conjugate of the formula:
   [X—(Y)Y n ] 10-50 —Z,
   wherein X is a biologically active polypeptide having a molecular weight of from about 5 kDa to about 50 kDa;   Y is an optional linker moiety, wherein n is 0 or an integer from 1 to about 10; and   Z is a biocompatible polymer having a molecular weight of at least about 450,000 Daltons,   wherein the polypeptide is covalently linked to the polymer directly or via the linker moiety.   
     
     
         15 . The method of  claim 14 , wherein the polymer is a linear polymer comprising multiple subunits selected from hyaluronic acid, acrylic acid, ethylene glycol, methacrylic acid, acrylamide, hydroxyethyl methacrylate, mannitol, maltose, glucose, arabinose, taurine, betaine, modified celluloses, hydroxyethyl cellulose, ethyl cellulose, methyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, modified starches, hydrophobically modified starch, hydroxyethyl starch, hydroxypropyl starch, amylose, amylopectin, oxidized starch, and copolymers thereof. 
     
     
         16 . The method of  claim 14 , wherein the biologically active polypeptide is a receptor, a ligand for a receptor, a growth factor, an angiogenic factor, a polypeptide that induces cell differentiation, an antibody, or a polypeptide that inhibits cell proliferation. 
     
     
         17 . The method of  claim 14 , wherein the polymer is linear poly(acrylic acid). 
     
     
         18 . The method of  claim 14 , wherein the polymer is hyaluronic acid. 
     
     
         19 . The method of  claim 14 , wherein the conjugate has the formula:
   [X—(Y)n] 10-25 —Z.
   
     
     
         20 . The method of  claim 14 , wherein the conjugate has the formula:
   [X—(Y)n] 25-50 —Z
   
     
     
         21 . The method of  claim 14 , wherein the biocompatible polymer has a molecular weight of at least 1×10 6  Daltons. 
     
     
         22 . The method of  claim 14 , wherein the biologically active polypeptide has a molecular weight of from about 10 kDa to about 50 kDa. 
     
     
         23 . The method of  claim 14 , wherein the biologically active polypeptide has a molecular weight of from about 10 kDa to about 25 kDa. 
     
     
         24 . The method of  claim 14 , wherein the biologically active polypeptide has a molecular weight of from about 25 kDa to about 50 kDa. 
     
     
         25 . A treatment method comprising administering to an individual in need thereof an effective amount of implantable device comprising a conjugate of the formula:
   [X—(Y)n] 10-50 —Z,
   where X is a biologically active polypeptide having a molecular weight of from about 5 kDa to about 50 kDa;   Y is an optional linker moiety, wherein n is 0 or an integer from 1 to about 10; and   Z is a biocompatible polymer having a molecular weight of at least about 450,000 Daltons,   wherein the polypeptide is covalently linked to the polymer directly or via the linker moiety.   
     
     
         26 . A treatment method comprising administering to an individual in need thereof an effective amount of an implantable drug delivery device comprising a conjugate of the formula:
   [X—(Y)n] 10-50 —Z,
   where X is a biologically active polypeptide having a molecular weight of from about 5 kDa to about 50 kDa;   Y is an optional linker moiety, wherein n is 0 or an integer from 1 to about 10; and   Z is a biocompatible polymer having a molecular weight of at least about 450,000 Daltons,   wherein the polypeptide is covalently linked to the polymer directly or via the linker moiety.