Anti-PD-L1 Antibody Formulation for High-Concentration Stability
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Solution Overview
Problem
There is a significant unmet medical need for an optimal therapeutic to enhance T cell immunity by inhibiting the PD-L1/PD-1 interaction for the treatment of cancer and infection, as existing methods have not been effectively commercialized.
Innovation Solution
A stable aqueous pharmaceutical formulation comprising an antibody is developed, comprising an antibody concentration of about 40 mg/ml to about 125 mg/ml, a buffer, sucrose, and a surfactant, with a pH of about 5.0 to about 7.0, to enhance the stability and efficacy of anti-PDL1 antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If anti-PDL1 antibodies are formulated at high concentration (40-125 mg/ml), then therapeutic efficacy is improved, but formulation stability deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically optimizing multiple formulation parameters including pH (5.0-7.0), buffer type (acetate, histidine acetate, phosphate), sucrose concentration (20-240 mM), and surfactant concentration (0.005-0.06% w/v polysorbate). These parameter adjustments resolve the contradiction by finding the optimal combination that maintains both high antibody concentration and formulation stability.
Solution Approach 2:
The patent uses composite materials by combining multiple excipients (buffer + sucrose + surfactant) with the anti-PDL1 antibody. This composite formulation approach allows each component to contribute to overall stability: the buffer maintains pH, sucrose provides osmotic balance and stabilizes protein structure, and surfactant prevents aggregation, enabling high concentration formulation while maintaining stability.
2Reliability
If the formulation pH is adjusted to optimize antibody stability, then biological activity is maintained, but solubility may deteriorate
Solution Approach 1:
The patent systematically evaluates pH as a critical parameter, testing ranges from 5.0 to 7.0 and identifying optimal pH values (5.5-6.5) that balance biological activity and solubility. This parameter optimization resolves the contradiction by finding the pH window where the antibody remains both active and soluble.
Solution Approach 2:
The patent introduces buffer systems (acetate, histidine acetate, phosphate) as intermediaries that mediate between the antibody and the aqueous environment. These buffers maintain pH within the optimal range, preventing precipitation while preserving biological activity, thus resolving the solubility-activity contradiction.
3Stability of the object's composition
If sucrose concentration is increased to enhance formulation stability, then antibody protection is improved, but osmotic pressure increases
Solution Approach 1:
The patent optimizes sucrose concentration within a specific range (20-240 mM), identifying optimal levels that provide sufficient stability protection without excessive osmotic pressure. This parameter optimization balances the protective benefits of sucrose with the need to maintain physiological compatibility.
Solution Approach 2:
The patent applies local quality by using sucrose specifically for its stabilizing effect on antibody structure without requiring uniform high concentration throughout the formulation. The sucrose provides localized protection at the antibody-solvent interface, preventing aggregation and denaturation while maintaining overall osmotic balance.
Data Source
AI summary
The invention provides stable aqueous pharmaceutical formulations comprising an anti-PDL1 antibody. The invention also provides methods for making such formulations and methods of using such formulations.