High-Concentration Anti-IL-4Rα Liquid Composition With Low Viscosity
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Solution Overview
Problem
Existing high-concentration antibody formulations targeting human interleukin-4 receptor face challenges such as high viscosity, aggregation, and instability, making them difficult to manufacture and administer, leading to potential side effects and inefficiencies.
Innovation Solution
A liquid composition comprising an antibody against human interleukin-4 receptor alpha, formulated with specific buffers, protective agents, and surfactants, maintaining a pH of 5.4-6.4 and concentrations between 50-200 mg/ml, which includes a monoclonal antibody with defined CDR sequences, and optimized with trehalose and sodium chloride for stability and low viscosity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If humanized antibodies are used to reduce immunogenicity, then immunogenicity is reduced, but affinity and activity are decreased
Solution Approach 1:
The patent applies parameter changes by systematically varying the degree of humanization (from fully human to partially humanized variants) and selecting optimal combinations of CDR regions and framework structures. This allows tuning the balance between reducing immunogenicity and maintaining affinity/activity, finding the optimal parameter set for each therapeutic application.
Solution Approach 2:
The patent creates composite antibody structures by combining human framework regions with non-human CDR regions, or by combining different humanized variants with specific ligands or adjuvants. This composite approach allows the antibody to benefit from the low immunogenicity of human sequences while retaining the high affinity of non-human binding regions.
2Reliability
If affinity maturation is performed to increase binding affinity, then affinity is increased, but the risk of enhancing immunogenicity also increases
Solution Approach 1:
The patent applies local quality by performing affinity maturation primarily in the CDR regions while keeping the framework regions highly humanized. This localized approach allows affinity enhancement where it is most needed (in the binding sites) while maintaining low immunogenicity in the majority of the antibody structure.
Solution Approach 2:
The patent applies partial action by performing limited rounds of affinity maturation rather than exhaustive optimization. This partial approach achieves sufficient binding affinity for therapeutic effect while avoiding the accumulation of multiple non-human mutations that would increase immunogenicity risk.
3Object-affected harmful factors
If fully human antibodies are produced using transgenic animals, then immunogenicity is minimized, but production complexity and cost increase
Solution Approach 1:
The patent applies copying by creating fully human antibodies through in silico modeling and in vitro selection methods that replicate the natural antibody repertoire without requiring transgenic animals. Phage display libraries and other in vitro systems copy the diversity and specificity of natural human antibodies, eliminating the need for complex animal models.
Solution Approach 2:
The patent replaces the mechanical/biological system of transgenic animal production with in vitro biochemical and biophysical methods. Instead of relying on animal immune systems to produce antibodies, the patent uses controlled in vitro selection, phage display, and recombinant DNA technology to generate and select fully human antibody variants.
Data Source
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AI summary
The present invention provides a liquid composition comprising an antibody of human interleukin-4 receptor alpha. The liquid composition comprises the antibody at a concentration of 50-200 mg/ml; and a buffer, a protective agent, and a surfactant as adjuvants. The liquid composition has a pH of 5.4-6.4.