Anti-IL-33 Antibody Formulation Stability
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Solution Overview
Problem
There is a need for stable and suitable pharmaceutical formulations of anti-human interleukin-33 (hIL-33) antibodies that maintain stability during storage and are suitable for administration, as existing formulations face challenges with degradation, aggregation, and chemical modifications.
Innovation Solution
A stable liquid pharmaceutical formulation comprising a human antibody specific to hIL-33, combined with a buffer, an amino acid, a thermal stabilizer, and an organic cosolvent, such as acetate, arginine, sucrose, and polysorbate 80, which maintains the antibody's stability and bioactivity over time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If therapeutic antibodies are formulated in liquid solution, then they become suitable for administration to patients, but they are prone to degradation, aggregation and undesired chemical modifications during storage
Solution Approach 1:
The patent applies parameter changes by systematically optimizing multiple formulation parameters including pH (using acetate or histidine buffers at specific concentrations), ionic strength (using amino acids like arginine or glutamic acid), viscosity (using thermal stabilizers like sucrose), and surfactant content (using organic cosolvents like polysorbate 80). This multi-parameter optimization resolves the contradiction by finding the specific combination that maintains both administerability and storage stability.
Solution Approach 2:
The patent creates a composite formulation system combining the antibody with multiple excipients serving different functions: buffers for pH control, amino acids for ionic strength and stability, thermal stabilizers for aggregation prevention, and surfactants for surface tension control. This composite approach allows each component to address specific stability issues while maintaining overall administerability.
2Quantity of substance
If the concentration of antibody in the formulation is increased, then the therapeutic efficacy is improved, but the viscosity of the solution increases making administration difficult
Solution Approach 1:
The patent uses parameter changes by incorporating thermal stabilizers like sucrose at optimized concentrations (1-20% w/v) and adjusting the pH and ionic strength to specific ranges. These parameter adjustments allow the formulation to maintain low viscosity even at high antibody concentrations (1-200 mg/ml), thereby resolving the contradiction between concentration and viscosity.
3Reliability
If excipients are added to maintain stability, then degradation and aggregation are reduced, but the formulation complexity increases
Solution Approach 1:
The patent applies universality by selecting excipients that perform multiple functions: acetate or histidine buffers maintain pH stability while also providing ionic strength; amino acids like arginine or glutamic acid provide both ionic strength and act as viscosity modifiers; sucrose serves as both a thermal stabilizer and a viscosity controller. This multi-functionality reduces the number of separate components needed, thereby reducing formulation complexity while maintaining stability.
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 retains at least 90% of the native antibody form after two months at 5°C and 97.5% after nine months at -20°C, with low viscosity and minimal high molecular weight species, ensuring effective and stable administration.
Implementation Method 1
a thermal stabilizer; In some cases, the thermal stabilizer is sucrose at a concentration of from 1% w/v to 10 % w/v
Implementation Method 2
the organic cosolvent is a surfactant at a concentration of from 0.01% w/v to 0.15% w/v. In some embodiments, the surfactant is polysorbate 80
Implementation Method 3
the amino acid is arginine or glutamic acid at a concentration of from 30 mM to 110 mM
Data Source
AI summary
The present invention provides pharmaceutical formulations comprising an antibody that specifically binds to human interleukin-33 (hlL-33). The formulations may contain, in addition to an anti-IL-33 antibody, a buffer, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months and after being subjected to thermal and other physical stresses.