Polymeric drug conjugates with tether groups for controlled drug delivery

Abstract

Described herein is a cyclodextrin containing polymer conjugate.

1 . A linear, cyclodextrin containing polymer conjugate, comprising a therapeutic agent covalently attached to a polymer through a tether, wherein the tether comprises a self-cyclizing moiety. 
     
     
         2 . The polymer conjugate of  claim 1 , wherein the tether further comprises a selectivity-determining moiety. 
     
     
         3 . The polymer conjugate of  claim 2 , wherein the selectivity-determining moiety is attached via a bond to the self-cyclizing moiety between the self-cyclizing moiety and the polymer. 
     
     
         4 . The polymer conjugate of  claim 3 , wherein the bond between the selectivity-determining moiety and the self-cyclizing moiety is selected from the group consisting of an amide, a carbamate, a carbonate, an ester, a thioester, a urea, and a disulfide bond. 
     
     
         5 . The polymer conjugate of  claim 3 , wherein the bond between the selectivity-determining moiety and the self-cyclizing moiety is an ester bond. 
     
     
         6 . The polymer conjugate of  claim 3 , wherein cleavage of the bond between the selectivity-determining moiety and the self-cyclizing moiety results in cyclization of the self-cyclizing moiety, thereby releasing the therapeutic agent from the polymer. 
     
     
         7 . The polymer conjugate of  claim 6 , wherein cyclization of the self-cyclizing moiety forms a five- or six-membered ring. 
     
     
         8 . The polymer conjugate of  claim 7 , wherein the five- or six-membered ring is a heterocycle comprising at least one heteroatom selected from the group consisting of a nitrogen, an oxygen, and a sulfur. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . The polymer conjugate of claim  12 , wherein the cyclodextrin moieties and the linker groups alternate in the copolymer. 
     
     
         14 . The polymer conjugate of claim  12 , wherein each linker group independently comprises an alkyl chain, a polyethylene glycol (PEG) chain, polysuccinic anhydride, poly-L-glutamic acid, poly(ethyleneimine), an oligosaccharide, or an amino acid chain. 
     
     
         15 . The polymer conjugate of claim  12 , wherein each linker group comprises PEG. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The polymer conjugate of  claim 1 , wherein the therapeutic agent is an anti-cancer, anti-fungal, anti-bacterial, anti-mycotic, or anti-viral therapeutic. 
     
     
         19 - 22 . (canceled) 
     
     
         22 . The polymer conjugate of  claim 1 , wherein the therapeutic agent is attached to the self-cyclizing group through the amino group of the therapeutic agent. 
     
     
         23 . The polymer conjugate of  claim 1 , wherein the tether comprises an amino acid or peptide, or derivative thereof. 
     
     
         24 . The polymer conjugate of  claim 1 , wherein the therapeutic agent makes up at least 5% by weight of the polymer conjugate. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The polymer conjugate of  claim 1 , wherein the polymer conjugate has a molecular weight of 10,000-500,000 amu. 
     
     
         28 . A pharmaceutical composition comprising a polymer conjugate of  claim 1 , and a pharmaceutically acceptable excipient, or a pharmaceutically acceptable salt thereof. 
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein upon administration to a subject, the therapeutic agent is delivered to the subject for a period of from about 1 to about 2,000 hours, e.g., about 1 to about 800 hours. 
     
     
         30 . The polymer conjugate of  claim 1 , wherein the polymer comprises a copolymer comprising beta-cyclodextrin moieties and PEG groups that alternate in the copolymer, the therapeutic agent is an anti-cancer agent, and the tether comprises a self-cyclizing moiety and a selectivity-determining moiety. 
     
     
         31 . A pharmaceutical composition comprising the polymer conjugate of  claim 30 , and a pharmaceutically acceptable excipient, or a pharmaceutically acceptable salt thereof.