High-Concentration Anti-IL-13 Formulation With Low Viscosity

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Solution Overview

Problem

Formulating high concentration anti-IL-13 antibodies poses challenges due to instability, increased viscosity, and particulate formation, which complicates administration and manufacturing, especially for subcutaneous use.

Innovation Solution

A formulation comprising anti-IL-13 antibody in a histidine buffer with polyol and surfactant at high concentrations maintains stability and low viscosity, using specific amino acid sequences and excipients like sucrose and polysorbate 20.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If high concentration antibody formulation is used, then dosage volume is reduced, but viscosity increases making administration difficult

Engineering Contradiction:

Improveantibody concentrationVSAvoidadministration ease

Core Design Contradiction:

Quantity of substanceVSEase of operation

Solution Approach 1:

The patent changes the pH parameter of the formulation to a specific range (5.0-6.5, preferably 5.5-6.0) to reduce intermolecular interactions between antibodies. This pH optimization allows high concentration formulations (100-200 mg/mL) to maintain lower viscosity, enabling subcutaneous administration while delivering high doses of antibody.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If high concentration antibody formulation is used, then dosage volume is reduced, but manufacturing complexity increases

Engineering Contradiction:

Improveantibody concentrationVSAvoidmanufacturing ease

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent optimizes formulation parameters including pH (5.0-6.5), buffer concentration (10-100 mM histidine), and excipient concentrations to prevent aggregation and maintain stability at high antibody concentrations. This enables manufacturing of high concentration formulations without excessive complexity.

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If high concentration antibody formulation is used, then number of injections is reduced, but particulate formation increases

Engineering Contradiction:

Improveantibody concentrationVSAvoidformulation stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent optimizes pH to 5.0-6.5 and includes specific excipients (surfactants at 0.01-0.5%, sugars at 1-10%, amino acids at 0.1-10%) to prevent intermolecular interactions and aggregation. These parameter changes maintain formulation stability at high concentrations while reducing particulate formation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses surfactants (e.g., polysorbate 20, polysorbate 80, poloxamer 188) as intermediary substances that prevent direct intermolecular interactions between antibodies. These surfactants act as mediators that reduce aggregation and maintain stability in high concentration formulations.

Inventive Principle:

Principle #24Intermediary (Mediator)

4Stability of the object's composition

If conventional surfactants are used to reduce particulate formation, then stability improves, but viscosity increases

Engineering Contradiction:

Improveparticulate reductionVSAvoidviscosity

Core Design Contradiction:

Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent optimizes surfactant concentration to a specific range (0.01-0.5%, preferably 0.03-0.1%) and combines it with pH optimization (5.0-6.5) to achieve the right balance. This prevents excessive viscosity increase while maintaining particulate reduction benefits.

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 formulation achieves extended physical and chemical stability with low viscosity, enabling effective subcutaneous administration and maintaining antibody potency for extended periods.

Implementation Method 1

surfactants (e.g., a polysorbate)... surfactants further do not reduce the increased viscosity caused as a result of numerous intermolecular interactions from the macromolecular nature of antibodies

Methodology Applied

Scientific EffectSurfactant: Surfactant