Polyether Bioconjugates That Avoid Anti-PEG Immune Response
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing PEGylated therapeutics face issues such as immunogenicity, anti-PEG antibody responses, crystallization, and high dispersity, which limit their effectiveness and safety in medical applications.
Innovation Solution
Development of polyether polymers with specific side chains and controlled molecular weight distribution, designed to minimize interaction with anti-PEG antibodies and reduce immunogenicity, while maintaining solubility and biocompatibility, using a process that ensures high end-group fidelity and low dispersity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If PEG is used for therapeutic applications, then solubility and biocompatibility are improved, but immunogenicity and anti-PEG antibody responses increase
Solution Approach 1:
The patent applies composite materials by combining polyethylene oxide backbone with glycidyl ether side chains to create a copolymer structure. This composite approach maintains the beneficial solubility and biocompatibility of PEG while introducing structural variations that reduce immunogenicity and prevent anti-PEG antibody recognition, thus resolving the contradiction between therapeutic effectiveness and immune response
Solution Approach 2:
The invention implements local quality by introducing glycidyl ether side chains at specific positions along the polyethylene oxide backbone. This localized modification strategy preserves the overall PEG structure's solubility and biocompatibility while creating specific regions with reduced antigenicity, allowing the polymer to maintain therapeutic benefits while minimizing immune recognition
2Reliability
If PEG is used for drug delivery, then stealth effect and circulation time are improved, but crystallization and high dispersity occur
Solution Approach 1:
The copolymer structure combining polyethylene oxide with glycidyl ether units creates a composite material that disrupts the regular crystalline packing of pure PEG. This structural heterogeneity prevents crystallization while maintaining the amorphous state necessary for stealth effect and prolonged circulation, thereby resolving the contradiction between reliability and compositional stability
Solution Approach 2:
The invention changes the structural parameters of PEG by incorporating side chains, which alters the polymer's physical properties. This parameter modification prevents crystallization and reduces dispersity while preserving the hydrodynamic properties that provide stealth effect and extended circulation time in biological systems
3Reliability
If PEG chains are attached to drugs, then therapeutic efficacy is improved, but manufacturing precision and end-group fidelity decrease
Solution Approach 1:
The patent changes the chemical parameters of the polymer structure by introducing glycidyl ether side chains, which enables more precise control during polymerization. This parameter modification allows for better manufacturing precision and end-group fidelity while maintaining the therapeutic efficacy provided by PEGylation
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The new polymers effectively replace PEG in pharmaceutical applications, reducing immunogenicity and crystallization, and ensuring uniform molecular behavior for improved therapeutic efficacy and safety.
Implementation Method 1
The increased spatial requirements of the side chains impede or disable interaction with anti-PEG antibodies according to the specific lock and key principle
Implementation Method 2
a process for the preparation of a polyether polymer by anionic ring-opening copolymerization
Implementation Method 3
the side chains have limited spatial requirements. In poly(ethylene oxides) with C2 and C3 alkoxymethyl side chains, the side chains are more sterically demanding, but the polymers are less hydrophilic
Data Source
Figure 1~2
Figure 3
Figure 4
AI summary
The present invention concerns immunological inactive polyether polymers represented by the following formula [I]: -[CH2-CHR-O]n- (I), wherein at least 3 % of the residues R comprise ethylene oxide side chains, oligo(ethylene oxide) side chains and/or glycerol ether side chains and R may also be hydrogen or a C1 to C3-alkyloxymethyl side chain. The invention further concerns a process for the preparation of the polymers. Finally, the invention concerns the use of the polymers for the preparation of conjugates, especially bioconjugates and the conjugates themselves as alternative for PEGylated therapeutics. The conjugates may comprise bioactive compounds and/or lipids. They are especially useful for the preparation of vaccines, lipid particles, especially lipid nanoparticles and may be used for the preparation of vaccines against COVID-19.