Targeted drug phosphorylcholine polymer conjugates

Abstract

The present invention provides random copolymers containing phosphorylcholine and one or more functional agents, and methods of preparing such random copolymers.

1 - 15 . (canceled) 
     
     
         16 . A random copolymer comprising a first monomer and a second monomer, wherein the first monomer comprises a phosphorylcholine, and the second monomer is linked to a first functional agent, wherein the first and the second monomer are distributed randomly throughout the polymer. 
     
     
         17 . The random copolymer of  claim 16 , further comprising an initiator fragment linked to a second functional agent. 
     
     
         18 . The random copolymer of  claim 17 , wherein the first functional agent is different from the second functional agent. 
     
     
         19 . The random copolymer of  claim 17 , wherein the initiator fragment is branched and the random copolymer has multiple polymer arms. 
     
     
         20 . The random copolymer of  claim 17 , wherein the initiator fragment is selected from the group consisting of an alkane, a cycloalkane, an alkyl carboxylic acid, an ester of an alkyl carboxylic acid, a cycloalkylcarboxylic acid, an ester of a cycloalkylcarboxylic acid, an ether, a cyclic alkyl ether, an alkyl aryl group, an alkyl amide, an alkyl-aryl carboxylic acid, and an ester of an alkyl-aryl carboxylic acid. 
     
     
         21 . The random copolymer of  claim 16 , wherein the first monomer comprises 2-(methacryloyloxy)ethyl (2-(trimethylammonio)ethyl) phosphate. 
     
     
         22 . The random copolymer of  claim 16 , which has multiple polymer arms. 
     
     
         23 . The random copolymer of  claim 22 , wherein the polymer has 2, 3, 4, 5, 6, 7, 8 or 9 polymer arms. 
     
     
         24 . The random copolymer of  claim 16 , which comprises from about 100 to about 1,000 repeat units of the first monomer, and from about 100 to about 1,000 repeat units of the second monomer. 
     
     
         25 . The random copolymer of  claim 16 , which comprises from about 10 to about 5,000 repeat units of the first monomer, and from about 10 to about 5,000 repeat units of the second monomer. 
     
     
         26 . The random copolymer of  claim 25 , wherein the second monomers are present relative to the first monomers in a ratio of 100:1, 50:1, 40:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50 or 1:100. 
     
     
         27 . The random copolymer of  claim 25 , which has a weight average molecular weight of from about 1000 to about 200,000 Daltons, as determined by a light scattering technique. 
     
     
         28 . The random copolymer of  claim 27 , which has a polydispersity less than about 1.5, as determined by gel permeation chromatography. 
     
     
         29 . The random copolymer of  claim 16 , wherein the second monomer is linked to the first functional agent through a cleavable linker. 
     
     
         30 . The random copolymer of  claim 29 , wherein the cleavable linker is selected from the group consisting of a hydrolyzable linker, an enzymatically cleavable linker, a pH sensitive linker, a disulfide linker, and a photolabile linker. 
     
     
         31 . The random copolymer of  claim 16 , wherein the second monomer is linked to the first functional agent through a non cleavable linker. 
     
     
         32 . The random copolymer of  claim 16 , wherein the second monomer is linked to the first functional agent through a linker which comprises a triazole ring. 
     
     
         33 . The random copolymer of  claim 16 , wherein the first functional agent is selected from the group consisting of a bioactive agent, a detection agent, an imaging agent, a labeling agent, and a diagnostic agent. 
     
     
         34 . The random copolymer of  claim 33 , wherein the first functional agent is a bioactive agent. 
     
     
         35 . The random copolymer of  claim 34 , wherein the bioactive agent is a therapeutic protein. 
     
     
         36 . The random copolymer of  claim 34 , wherein the bioactive agent is an antibody or antibody fragment. 
     
     
         37 . The random copolymer of  claim 34 , wherein the bioactive agent is a drug. 
     
     
         38 . A method of making a random copolymer, the method comprising the step of contacting a mixture of a first monomer and a second monomer with an initiator under conditions sufficient to prepare a random copolymer via free radical polymerization, wherein the first monomer comprises a phosphorylcholine, and the second monomer is linked to a functional agent.