Heparosan Polymers and Methods of Making and Using Same for the Enhancement of Therapeutics

Abstract

Compositions, methods, and systems are disclosed for the development and use of heparosan as a therapeutic modifying agent or vehicle which can modulate drug cargo pharmacokinetics and behavior within a mammalian patient.

What is claimed is: 
     
         1 . A pharmaceutical drug delivery composition for treating a disease condition in a mammalian patient, the pharmaceutical composition comprising:
 one or more heparosan-drug conjugates, wherein each conjugate comprises:
 at least one heparosan polymer; and 
 at least one therapeutic drug conjugated to the at least one heparosan polymer, wherein the at least one therapeutic drug treats a mammalian disease condition; and 
 a pharmaceutically acceptable carrier; and 
   wherein the pharmaceutical drug delivery composition is a sterile pharmaceutical formulation in a unit dosage format.   
     
     
         2 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one therapeutic drug remains active when conjugated to the at least one heparosan polymer. 
     
     
         3 . The pharmaceutical drug delivery composition of  claim 2 , wherein the at least one therapeutic drug does not increase immunoreactivity of the at least one heparosan polymer. 
     
     
         4 . The pharmaceutical drug delivery composition of  claim 2 , wherein the at least one therapeutic drug is not an adjuvant. 
     
     
         5 . The pharmaceutical drug delivery composition of  claim 1 , wherein each heparosan-drug conjugate comprises a single heparosan polymer conjugated to the at least one therapeutic drug. 
     
     
         6 . The pharmaceutical drug delivery composition of  claim 1 , wherein each heparosan-drug conjugate comprises a plurality of heparosan polymers conjugated to the at least one therapeutic drug. 
     
     
         7 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer has a mass in a range of from about 600 Da to about 800 kDa. 
     
     
         8 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer is unsulfated and unepimerized. 
     
     
         9 . The pharmaceutical drug delivery composition of  claim 1 , further defined as comprising a plurality of heparosan-drug conjugates, and wherein the plurality of heparosan polymers present in the conjugates is polydisperse in size. 
     
     
         10 . The pharmaceutical drug delivery composition of  claim 1 , further defined as comprising a plurality of heparosan-drug conjugates, and wherein the plurality of heparosan polymers present in the conjugates is substantially monodisperse in size. 
     
     
         11 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer has a linear polymer chain. 
     
     
         12 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer has a branched geometry. 
     
     
         13 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer has a half-life of at least 15 hours within extracellular compartments of the mammalian patient. 
     
     
         14 . The pharmaceutical drug delivery composition of  claim 1 , wherein at least one of:
 (a) the pharmaceutical drug delivery composition exhibits increased retention in blood and/or lymphatic circulation of a mammalian patient when compared to therapeutic drug alone;   (b) the pharmaceutical drug delivery composition exhibits reduced occurrence of accumulation in healthy organs and/or tissues of a mammalian patient when compared to therapeutic drug alone;   (c) the pharmaceutical drug delivery composition exhibits higher accumulation in tumors and/or diseased tissues of a mammalian patient when compared to therapeutic drug alone; and   (d) the at least one heparosan polymer is further characterized as being substantially non-targeting.   
     
     
         15 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer comprises an activated group on the at least one heparosan polymer to effect the conjugation of the at least one heparosan polymer to the therapeutic drug, and wherein the reactive group is selected from the group consisting of an aldehyde, alkyne, ketone, maleimide, thiol, azide, amino, carbonyl, sulfhydryl, hydrazide, phosphate, sulfate, nitrate, carbonate, ester, squarate, chelator, and combinations thereof. 
     
     
         16 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer and the at least one therapeutic drug are covalently conjugated. 
     
     
         17 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one heparosan polymer and the at least one therapeutic drug are non-covalently conjugated. 
     
     
         18 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one therapeutic drug is selected from the group consisting of a chemotherapy agent, an antineoplastic agent, a steroid, an antibiotic, an anti-inflammatory agent, an agent that has an action on a central nervous system of the mammalian patient, an antihistaminic, an antiallergic agent, an antipyretic, a respiratory agent, an antimicrobial agent, an antihypertensive agent, a calcium antagonist, an antipsychotic, an agent for Parkinson's disease, a vitamin, an antitumor agent, a cholinergic agonist, a mydriatic, an antidepressant agent, an antidiabetic drug, an anorectic agent, an antimalarial agent, a polypeptide therapeutic, a cytokine, a hormone, an enzyme, an antibody, an antibody fragment, an antiulcerative agent, an anticancer agent, a vaccine antigen, a polynucleotide, a nutrient, a small molecule, and combinations thereof. 
     
     
         19 . The pharmaceutical drug delivery composition of  claim 1 , wherein the at least one therapeutic drug is selected from the group consisting of a cytokine, a hormone, an enzyme, an antibody, an antibody fragment, and combinations thereof. 
     
     
         20 . A pharmaceutical drug delivery composition for treating a disease condition in a mammalian patient, the pharmaceutical composition comprises:
 one or more heparosan-drug conjugates, wherein each conjugate comprises:
 at least one heparosan polymer; and 
 at least one therapeutic drug covalently conjugated to the at least one heparosan polymer, wherein the at least one therapeutic drug treats a mammalian disease condition, wherein the at least one therapeutic drug remains active when conjugated to the at least one heparosan polymer; and 
 a pharmaceutically acceptable carrier; and 
   wherein the pharmaceutical drug delivery composition is a sterile pharmaceutical formulation in a unit dosage format.   
     
     
         21 . A pharmaceutical drug delivery composition for treating a disease condition in a mammalian patient, the pharmaceutical composition comprises:
 one or more heparosan-drug conjugates, wherein each conjugate comprises:
 at least one heparosan polymer; and 
 at least one therapeutic drug non-covalently conjugated to the at least one heparosan polymer, wherein the at least one therapeutic drug treats a mammalian disease condition, wherein the at least one therapeutic drug remains active when conjugated to the at least one heparosan polymer; and 
 a pharmaceutically acceptable carrier; and 
   wherein the pharmaceutical drug delivery composition is a sterile pharmaceutical formulation in a unit dosage format.