Aflibercept Composition Tolerating Truncation Variants
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Solution Overview
Problem
Existing pharmaceutical formulations of aflibercept face challenges in maintaining stability and efficacy due to the presence of truncation variants, which are difficult to remove and affect the quality control of the active ingredients.
Innovation Solution
A composition comprising aflibercept with a truncation variant (T100) is developed, where the content of the truncation variant is controlled to be less than or equal to 20%, using peptide mass fingerprinting analysis, and the composition is formulated with pharmaceutically acceptable carriers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If truncation variants are removed from aflibercept production, then product purity is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent changes the acceptance parameter for truncation variants from complete removal to controlled presence (≤20% by mass). This parameter change allows the variant to be retained in the final product within specified limits, thereby simplifying the manufacturing process and reducing purification complexity while maintaining product quality and efficacy requirements.
2Reliability
If truncation variants are completely removed, then product quality is improved, but production cost increases
Solution Approach 1:
The patent establishes a quality parameter that accepts truncation variants at levels ≤20% by mass, rather than requiring complete removal. This parameter change reduces the intensity of purification processes, thereby lowering production costs and energy consumption while maintaining acceptable product quality and therapeutic efficacy.
3Manufacturing precision
If strict quality control is implemented to remove all variants, then medicinal requirements are met, but production time increases
Solution Approach 1:
The patent modifies the quality control parameter to accept truncation variants within 20% by mass, which reduces the stringency of purification and analysis procedures. This parameter change shortens production time by eliminating excessive purification steps while still meeting medicinal requirements for product quality and safety.
Data Source
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AI summary
Provided is a composition comprising aflibercept and a variant thereof, wherein the variant is a truncation variant with a truncated VEGF binding portion of aflibercept, and wherein the content of the truncation variant is less than or equal to about 20% by mass percentage. Also provided is a pharmaceutical formulation comprising the composition. Further, provided are a method for detecting the variant and use of the variant in quality inspection or quality control of an aflibercept-containing product.