TACI-Immunoglobulin Fusion Protein Formulation Stability

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Solution Overview

Problem

Therapeutic proteins like TACI-immunoglobulin fusion proteins face challenges with stability, bioavailability, and patient-friendly dosage forms, particularly due to poor storage stability and the need for effective formulation to prevent aggregation and degradation.

Innovation Solution

Development of stable formulations for TACI-immunoglobulin fusion proteins with a pH ranging from 4.5 to 5.5, using buffers like acetate and excipients such as trehalose, and preservatives like benzyl alcohol and benzalkonium chloride, to maintain stability over extended periods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If therapeutic proteins are stored in conventional formulations, then they can be administered to patients, but they suffer from poor storage stability and aggregation

Engineering Contradiction:
Improvestorage stabilityVSAvoidprotein stability
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent applies parameter changes by optimizing the pH of the formulation to a specific range (pH 4.5 to 5.5) to enhance protein stability. This pH optimization prevents aggregation and degradation of the TACI-immunoglobulin fusion protein, directly resolving the storage stability issue while maintaining protein reliability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses an intermediary substance (buffer) to mediate between the protein and the formulation environment. The buffer system at optimized pH acts as a mediator that stabilizes the protein structure and prevents aggregation, thereby improving both storage stability and reliability.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If the formulation pH is adjusted to optimize stability, then protein aggregation is prevented, but the formulation complexity increases

Engineering Contradiction:
Improveprotein stabilityVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent resolves the contradiction by implementing a specific pH parameter change (to 4.5-5.5 range) that simultaneously achieves protein stability and manageable formulation complexity. This targeted parameter adjustment prevents aggregation while maintaining a relatively simple buffer system.

Inventive Principle:
Principle #35Parameter changes

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 formulations ensure long-term stability and bioactivity of TACI-immunoglobulin fusion proteins, preventing aggregation and degradation, and are suitable for pharmaceutical use in treating autoimmune diseases and lymphoproliferative disorders.

Implementation Method 1

a buffer buffering the formulation at a pH ranging between 4.5 and 5.5

Methodology Applied
Scientific EffectpH buffering:

Implementation Method 2

using buffers like acetate and excipients such as trehalose, and preservatives like benzyl alcohol and benzalkonium chloride, to maintain stability over extended periods

Methodology Applied
Scientific EffectProtein stabilization:

Data Source

PatentUS8637021B2Formulations for TACI-immunoglobulin fusion proteins
Publication Date: 2014.01.28 ARES TRADING SA

AI summary

The invention relates to formulations of TACI-Immunoglobulin fusion proteins.