Anti-LAG3 Antibody Formulation Stability via pH and Excipient Optimization
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Solution Overview
Problem
Therapeutic antibodies, such as those targeting LAG-3 and PD-1, face challenges in maintaining stability and efficacy due to sequence-specific degradation pathways and variability in amino acid sequences, making it difficult to predict optimal solution conditions for storage and shelf-life.
Innovation Solution
Formulations incorporating excipients like histidine, arginine, and sucrose, along with a buffer at pH 5-8, stabilize anti-LAG3 and anti-PD-1 antibodies, enhancing their stability and co-formulations show improved stability compared to individual antibodies, suitable for both liquid and lyophilized forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic antibodies are stored in solution, then they maintain biological activity, but they undergo sequence-specific degradation and lose stability over time
Solution Approach 1:
The patent applies parameter changes by optimizing formulation conditions including pH (5-8), ionic strength, temperature (refrigeration), and excipient concentrations to minimize degradation rates and extend the shelf-life of therapeutic antibodies while maintaining their stability and biological activity over extended storage periods
Solution Approach 2:
The patent uses excipients as intermediary substances that mediate between the antibody and the storage environment. These excipients protect the antibody from degradation pathways while maintaining solution stability, effectively acting as protective intermediaries that extend shelf-life without compromising reliability
2Productivity
If antibody concentration is increased to reduce dosing volume, then dosing efficiency improves, but viscosity increases and stability decreases
Solution Approach 1:
The patent employs parameter changes by adjusting pH to 5-8 and optimizing ionic strength through salt concentration control to maintain low viscosity even at high antibody concentrations (≥100 mg/mL), thereby enabling improved dosing efficiency while preserving solution stability and preventing aggregation
Solution Approach 2:
Excipients serve as intermediary substances that enable high antibody concentrations to be maintained in solution without excessive viscosity increase or stability loss. These intermediaries facilitate the coexistence of high concentration and stability by modifying the solution's physical properties
3Reliability
If different amino acid sequences are used to improve antibody efficacy, then binding affinity increases, but solution stability becomes unpredictable and requires individual formulation optimization
Solution Approach 1:
The patent establishes a universal formulation platform with pH 5-8 buffer systems and specific excipient combinations that can be applied across multiple antibody therapeutics with different amino acid sequences. This multi-functional approach maintains solution stability for diverse antibodies without requiring complete re-optimization for each individual molecule, reducing formulation complexity while preserving high binding affinity
Data Source
AI summary
The present invention provides formulations of anti-LAG3 antibodies, and co-formulations of anti-PD-1 antibodies and anti-LAG3 antibodies, and their use in treating various disorders.