Polyether Polymers with Alkoxymethyl Side Chains for Reduced Immunogenicity
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Solution Overview
Problem
Polyethylene glycol (PEG) based therapeutics face issues such as the development of anti-PEG antibodies leading to accelerated clearance, allergic reactions, and immunogenicity, which limit their long-term use in medical applications, particularly in cancer therapy and RNA delivery, due to its non-biodegradability and renal accumulation.
Innovation Solution
Development of polyether polymers with C1 to C3-alkyloxymethyl side chains, characterized by low dispersity and high end-group fidelity, which reduce interaction with anti-PEG antibodies and exhibit low immunogenicity, while maintaining biocompatibility and aqueous solubility similar to PEG.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PEG is used for drug delivery and therapeutic applications, then biocompatibility and aqueous solubility are improved, but immunogenicity and interaction with anti-PEG antibodies increase leading to accelerated clearance
Solution Approach 1:
The patent introduces side chains at specific positions along the PEG backbone (every 2-10 repeating units) to create localized modifications. These side chains consisting of 1-3 alkoxymethyl groups per repeating unit provide steric hindrance that prevents anti-PEG antibody binding while preserving the overall biocompatibility and aqueous solubility of the polymer
Solution Approach 2:
The invention creates a composite polymer structure combining modified PEG backbone with alkoxymethyl side chains. This composite architecture integrates the beneficial properties of PEG (biocompatibility, solubility) with the protective effect of the side chains (reduced immunogenicity), achieving a material that exhibits both characteristics simultaneously
2Reliability
If PEG chains are attached to drugs and nanocarriers, then stealth effect is achieved preventing immune system recognition, but anti-PEG antibodies cause accelerated clearance and allergic reactions
Solution Approach 1:
The side chains are strategically positioned along the PEG backbone at intervals of 2-10 repeating units, creating localized protective barriers that maintain the overall stealth effect while preventing antibody binding at critical locations
Solution Approach 2:
The patent converts the harmful immunogenicity of PEG into a beneficial property by introducing side chains that specifically block antibody binding sites. The side chains act as protective elements that transform the vulnerable PEG structure into an antibody-resistant configuration while preserving the stealth effect
3Duration of action of moving object
If PEG is used repeatedly in therapeutic treatments, then therapeutic efficacy is maintained, but anti-PEG antibodies accumulate causing accelerated blood clearance
Solution Approach 1:
The side chains are pre-installed on the PEG backbone before therapeutic application, providing preliminary protection against anti-PEG antibody formation. This preventive modification ensures that even upon repeated dosing, the polymer resists antibody binding and maintains circulation time
Solution Approach 2:
The invention modifies the chemical parameters of PEG by introducing alkoxymethyl side chains, changing the polymer's immunogenic properties. This parameter change (adding side chains) fundamentally alters the polymer-antibody interaction while preserving the therapeutic efficacy and circulation characteristics
Data Source
AI summary
Polyether polymers represented by the following formula [I]:—(CH2CHR—O—)m— (I)wherein 10 to 90% of the residues R are hydrogen and 10% to 90% of the residues R are independently from each other selected from the group made of, methoxymethyl, ethoxymethyl, n-propoxymethyl and iso-propoxymethyl; 1 to 100% of the residues R are methoxymethyl; up to 50% of the residues R may be selected from the group made of ethoxymethyl, n-propoxymethyl and iso-propoxymethyl; and m is in the range of from 10 to 1000 and the dispersity is 1.15 or less. A process for their preparation, conjugates thereof and the use thereof.