Lyophilized Anti-PD-1 Antibody Formulation for Shelf-Life Stability
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Solution Overview
Problem
Existing antibody therapeutics for targeting the PD-1 pathway in human subjects face challenges due to immunogenicity and the need for stable formulations that maintain bioactivity during storage and transportation, particularly for treating cancers and chronic infections.
Innovation Solution
Development of lyophilized formulations of anti-human PD-1 antibodies or antigen binding fragments, comprising histidine buffer, polysorbate 80, and sucrose, with a pH between 5.0 and 6.0, allowing reconstitution at concentrations of 25 mg/mL to 100 mg/mL, and including specific CDR sequences for enhanced stability and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If antibody therapeutics are stored in liquid form, then they maintain bioactivity, but they have limited shelf-life and require cold chain storage
Solution Approach 1:
The patent applies freeze-drying (lyophilization) to convert the antibody formulation from liquid to solid frozen state, then to dry solid state. This phase transition enables long-term storage at ambient temperatures while maintaining bioactivity, resolving the contradiction between shelf-life and bioactivity stability.
Solution Approach 2:
The patent creates a composite lyophilized formulation containing the anti-PD-1 antibody combined with excipients (sucrose, histidine, polysorbate 80). This composite material provides both long-term stability during storage and maintains bioactivity upon reconstitution, addressing the contradiction between shelf-life and reliability.
2Quantity of substance
If antibody formulations are concentrated to high doses, then treatment effectiveness improves, but formulation stability during storage deteriorates
Solution Approach 1:
The lyophilization process enables the formulation to be stored in a stable frozen/dry state at high antibody concentrations (25-100 mg/mL). The phase transition to solid frozen state prevents aggregation and degradation that would occur in liquid form at such high concentrations, thus maintaining both quantity and stability.
Solution Approach 2:
The composite formulation includes stabilizing excipients (sucrose at 7%, histidine buffer, polysorbate 80 at 0.02%) that protect the high-concentration antibody from aggregation and degradation during storage. This composite structure enables both high concentration and long-term stability.
3Productivity
If lyophilized formulations are reconstituted at high concentrations, then administration efficiency improves, but formulation complexity increases
Solution Approach 1:
The lyophilized formulation serves multiple functions: it provides long-term stable storage, enables high-concentration reconstitution for efficient administration, and includes all necessary excipients in a single冻干 cake. This multi-functionality improves productivity without proportionally increasing complexity.
Solution Approach 2:
The formulation is prepared in advance with all excipients and stabilizers incorporated during the lyophilization process. This preliminary action eliminates the need for separate stabilization steps and simplifies the overall formulation process, enabling high-concentration reconstitution without excessive complexity.
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 formulations provide stable, bioactive antibodies that can be administered at high or low concentrations, effectively treating various cancers and chronic infections with improved shelf-life and reduced immunogenicity.
Implementation Method 1
stable formulations of antibodies against human programmed death receptor PD-1... lyophilized formulations
Data Source
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AI summary
The present invention relates to stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof. The present invention further provides methods for treating various cancers and chronic infections with stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof.