Pegylation of therapeutic agents

A method for determining the type of biocompatible polymer, the extent of modification, and the conditions for modification of a therapeutic agent with a biocompatible polymer to prevent host-mediated inactivation of said therapeutic agent when covalently modified by said biocompatible polymer, comprising:

• (a) selecting a biological activity;
• (b) assaying the selected biological activity of step (a) of a first modified therapeutic agent after said first modified therapeutic agent has been administered to a subject, wherein said first modified therapeutic agent is covalently modified with a biocompatible polymer;
• (c) assaying the selected biological activity of step (a) of said first modified therapeutic agent after at least one booster dose of said first modified therapeutic agent has been administered to said subject;
• (d) assaying the selected biological activity of step (a) of a second modified therapeutic agent after said second modified therapeutic agent has been administered to a subject, wherein said second modified therapeutic agent is covalently modified with a biocompatible polymer and wherein at least one condition selected from the group consisting of the type of biocompatible polymer, the extent of modification, and the conditions for modification differs from the conditions of said first modified therapeutic agent;
• (e) assaying the selected biological activity of step (a) of said second modified therapeutic agent after at least one booster dose of said second modified therapeutic agent has been administered to said subject;
• (f) comparing the selected biological activity of step (a) of said first modified therapeutic agent with the selected biological activity of step (a) of said second modified therapeutic agent to determine the relative bioavailability of said first modified therapeutic agent and said second therapeutic agent;
• and
• (g) selecting the type of biocompatible polymer, the extent of modification, and the conditions for modification that prevent host-mediated inactivation of said therapeutic agent when covalently modified by said biocompatible polymer based upon the comparison of step (f), wherein said biological activity is selected from the group consisting of an enzyme catalyzing a reaction, a molecule binding a receptor or antibody, mediating a receptor-mediated response such as ion influx/efflux or generation of second messengers, antagonizing or blocking a receptor-mediated response, induction of apoptosis and release or uptake of a neurotransmitter or hormone.