Anti-IL-6 Antibody Formulation Stability via Excipient Optimization
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Solution Overview
Problem
There is a need for a stable aqueous pharmaceutical formulation of anti-IL-6 antibodies that minimizes the formation of aggregates, acidic species, and oxidized species, while maintaining potency and stability over time, suitable for therapeutic use in treating IL-6 mediated diseases.
Innovation Solution
The formulation comprises about 5 mg/mL to 120 mg/mL of an anti-IL-6 antibody, with specific concentrations of methionine, trehalose, arginine, histidine, and polysorbate 80, and a pH range of 5.0 to 7.0, which reduces the formation of aggregates and oxidized species, and maintains potency over 12 months of storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibody formulations are used, then the formulation can be stored and administered, but aggregates, acidic species, and oxidized species form over time, reducing stability and potency
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range (5.0-7.0) and antibody concentration (5-120 mg/mL) to minimize aggregate formation and maintain stability. This resolves the contradiction by adjusting formulation parameters to prevent harmful aggregate generation while ensuring reliable storage and administration.
Solution Approach 2:
The patent introduces excipients such as methionine, trehalose, arginine, histidine, and polysorbate 80 as intermediary substances that protect the antibody from aggregation and oxidation. These mediators stabilize the formulation by preventing direct harmful interactions between antibody molecules, thereby reducing aggregate formation while maintaining reliability.
2Duration of action of stationary object
If conventional antibody formulations are used, then the formulation can be stored, but oxidized species accumulate over time, reducing potency
Solution Approach 1:
Methionine is introduced as an antioxidant intermediary that protects the antibody from oxidation during storage. This resolves the contradiction by providing a protective mediator that prevents oxidized species formation, enabling long-term storage without potency loss from oxidation.
Solution Approach 2:
The patent optimizes the pH range (5.0-7.0) to minimize oxidation of the antibody. By controlling this critical parameter, the formulation maintains stability over extended storage periods while preventing the generation of oxidized harmful species.
3Quantity of substance
If high concentration of antibody is formulated, then therapeutic dose can be delivered in smaller volume, but aggregate formation increases
Solution Approach 1:
Polysorbate 80 is introduced as a surfactant intermediary that prevents aggregate formation at high antibody concentrations. This resolves the contradiction by providing steric stabilization that allows formulation of high concentrations (5-120 mg/mL) without excessive aggregate generation, enabling small-volume therapeutic dosing.
Solution Approach 2:
The patent optimizes the pH range (5.0-7.0) to minimize electrostatic interactions that lead to aggregation at high concentrations. This parameter optimization allows formulation of high antibody concentrations while controlling aggregate formation through reduced intermolecular attraction.
4Reliability
If pH is adjusted to stabilize antibody, then potency is maintained, but formulation may become incompatible with therapeutic applications
Solution Approach 1:
The patent optimizes the pH range (5.0-7.0) to balance potency stability with therapeutic compatibility. This resolves the contradiction by selecting a pH range that maintains antibody structure and activity while avoiding extreme values that would cause formulation incompatibility or adverse effects upon administration.
Solution Approach 2:
Buffering excipients such as histidine and arginine are introduced as intermediaries that maintain pH within the optimal range without requiring extreme pH values. These mediators provide pH stability while ensuring formulation compatibility with therapeutic applications by keeping the pH within physiological tolerable limits.
Data Source
AI summary
Provided herein are stable aqueous anti-IL-6 antibody formulations that have reduced aggregate formation and oxidation. The anti-IL-6 antibody formulations are suitable for treating IL-6 mediated diseases and disorders.