Anti-PD-1 Antibody Formulation Stability via Trehalose and Buffers
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Solution Overview
Problem
Existing anti-PD-1 antibodies are unstable and difficult to formulate into a clinically feasible preparation, hindering their therapeutic effectiveness in cancer immunotherapy.
Innovation Solution
A stable pharmaceutical formulation of anti-PD-1 antibodies or antigen-binding fragments is developed, comprising specific CDR region sequences, a buffer, and stabilizers like trehalose, with optional surfactants, to enhance stability and prevent degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If new anti-PD-1 antibodies are developed to achieve high affinity and long half-life, then therapeutic effectiveness is improved, but formulation stability deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically optimizing formulation conditions including pH (tested ranges 4.0-6.0), temperature (storage at 2-8°C vs 25°C), concentration (1mg/ml to 60mg/ml), and excipient types to achieve stable formulation of the novel anti-PD-1 antibodies while maintaining their high affinity and long half-life therapeutic properties
Solution Approach 2:
The patent uses excipients as intermediary substances to stabilize the antibody formulation. Specifically, buffers (acetate, citrate, succinate, phosphate) stabilize pH, saccharides (trehalose, sucrose, lactose) prevent aggregation, and surfactants (polysorbate 20, polysorbate 80, polyoxyethylene hydrogenated castor oil) prevent surface adsorption and aggregation, thereby maintaining formulation stability without compromising therapeutic effectiveness
2Reliability
If antibody concentration is increased to improve therapeutic efficacy, then treatment effectiveness is improved, but aggregation and degradation increase
Solution Approach 1:
The patent converts the potential harm of high concentration into a benefit by using stabilizers to prevent aggregation and degradation. The formulation achieves high concentration (up to 60mg/ml) for improved therapeutic efficacy while saccharides and surfactants prevent the harmful aggregation and deamidation that would normally occur at high concentrations
Solution Approach 2:
The patent creates a composite formulation system combining the anti-PD-1 antibody with multiple excipients (buffers, saccharides, surfactants) that work synergistically to maintain stability at high concentrations, enabling both high treatment effectiveness and low aggregation/degradation rates
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 effectively suppresses antibody aggregation and deamidation, maintaining stability for extended periods, allowing for safe storage and effective use in treating PD-1 mediated cancers such as breast, lung, and melanoma.
Implementation Method 1
The pharmaceutical formulation further contains at least one stabilizer, and optionally a surfactant
Implementation Method 2
The stable pharmaceutical formulation of the present invention contains an anti-PD-1 antibody or an antigen-binding fragment thereof and a buffer
Data Source
AI summary
A stable anti-PD-1 antibody pharmaceutical preparation and an application thereof in a medicine. The anti-PD-1 antibody pharmaceutical preparation comprises an anti-PD-1 antibody, a buffer, and can further comprise at least one type of stabilizer, and optionally can further comprise a surfactant. The anti-PD-1 antibody pharmaceutical preparation of the present invention can effectively suppress antibody aggregation and deamidation, thereby preventing degradation of an antibody product, resulting in a stable injectable pharmaceutical preparation.