METHODS FOR ACHIEVING SUPERHYDROPHILIC LOW IMMUNOGENICITY DRUG-POLYMER CONJUGATES
A method for selectively isolating lower immunogenic biomolecule-polymer conjugates from an initial source of biomolecule-polymer conjugate, the method comprising eluting the initial source of biomolecule-polymer conjugate through a hydrophobic interaction chromatography (HIC) medium at an eluent salt concentration greater than 0.15 M, and selectively isolating more hydrophilic conjugate species that pass through the HIC column at the salt concentration greater than 0.15 M while leaving more hydrophobic conjugate species bound to the HIC medium, wherein the more hydrophilic conjugate species being isolated have a lower immunogenicity than the hydrophobic conjugate species bound to the HIC column. The polymer may be, for example, PEG, polypeptide, or zwitterionic, and the biomolecule may be, for example, a protein or oligopeptide, such as an antibody, antibody fragment, enzyme, enzyme active site, or metalloprotein, or the biomolecule is a nucleic acid or oligonucleotide, such as an RNA (e.g., mRNA) or DNA (e.g., plasmid or vector).