Aflibercept Formulation With Controlled Truncation Variant Content

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Solution Overview

Problem

Existing pharmaceutical compositions 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 variant is controlled to be less than or equal to 20%, and the preparation process includes specific culture conditions and analytical methods to ensure stability and efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional purification methods are used to remove truncation variants, then the purity of aflibercept is improved, but the production process complexity and cost increase

Engineering Contradiction:

Improvepurity of afliberceptVSAvoidproduction process complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent changes the acceptance criterion parameter from traditional high purity requirements to allowing truncation variant content up to 20%. This parameter change eliminates the need for complex additional purification steps while maintaining medicinal requirements, thereby resolving the contradiction between purity and process complexity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the harmful effect of truncation variants (which were previously considered impurities requiring removal) into an acceptable feature by establishing that variants at ≤20% content do not affect medicinal requirements. This approach simplifies the production process while maintaining product quality

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Reliability

If additional purification steps are added to remove truncation variants, then the quality control is improved, but the production time and cost increase

Engineering Contradiction:

Improvequality controlVSAvoidproduction time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent changes the quality control parameter by accepting truncation variant content up to 20% as long as it meets medicinal requirements. This eliminates time-consuming purification steps while maintaining reliable quality control through analytical methods that detect and quantify variants

Inventive Principle:

Principle #35Parameter changes

3Object-affected harmful factors

If strict quality control standards are enforced to eliminate all variants, then the product safety is improved, but the manufacturing cost increases

Engineering Contradiction:

Improveproduct safetyVSAvoidmanufacturing cost

Core Design Contradiction:

Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent changes the quality threshold parameter from complete elimination of variants to accepting up to 20% truncation variant content. This parameter adjustment maintains product safety by ensuring variants do not affect medicinal requirements while significantly reducing manufacturing costs by eliminating complex purification steps

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260103739A1Composition comprising aflibercept and a variant thereof, and related methods and uses

Publication Date: 2026.04.16 QILU PHARMA CO LTD

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, and a method for preparing the same. 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.