Anti-PD-1 Antibody Formulation for Stable High-Concentration Injection
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Solution Overview
Problem
Existing anti-human PD-1 antibody formulations face challenges in maintaining bioactivity, stability, and high concentration delivery, particularly for subcutaneous administration, due to issues like high viscosity, aggregation, and methionine oxidation.
Innovation Solution
Formulations comprising specific concentrations of anti-human PD-1 antibodies, buffers, stabilizers, and antioxidants, such as sucrose, trehalose, and polysorbate 80, are developed to maintain stability and reduce oxidation, ensuring high concentration delivery without increased viscosity or aggregation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If anti-human PD-1 antibody concentration is increased for subcutaneous delivery, then therapeutic efficacy is improved, but viscosity increases making injection difficult
Solution Approach 1:
The patent modifies the chemical composition parameters of the formulation by incorporating specific excipients including surfactants (polysorbate 80, polysorbate 20), stabilizers (trehalose, sucrose, mannitol, arginine), and buffers (histidine, acetate). These parameter changes in the formulation composition enable the antibody to be delivered at high concentrations (≥100 mg/mL) while maintaining acceptable viscosity and injectability characteristics for subcutaneous administration
2Duration of action of stationary object
If antibody is stored and transported for extended periods, then distribution is improved, but bioactivity decreases due to degradation
Solution Approach 1:
The patent incorporates stabilizing excipients (trehalose, sucrose, mannitol, arginine) and antioxidants (methionine, ascorbic acid, tocopherol) into the formulation before storage. These preliminary protective measures prevent degradation pathways during storage and transport, thereby maintaining antibody bioactivity over extended periods while enabling wide distribution
Solution Approach 2:
The formulation includes antioxidants (methionine, ascorbic acid, tocopherol) and controls pH using buffers (histidine, acetate) to create a chemically inert environment that protects the antibody from oxidation and degradation during storage and transport, thereby maintaining bioactivity over extended periods
3Stability of the object's composition
If formulation stability is enhanced through stabilizers, then shelf-life is improved, but formulation complexity increases
Solution Approach 1:
The patent optimizes the concentrations and combinations of excipients to achieve the necessary stability profile. By carefully controlling the parameters of each component (surfactants, stabilizers, buffers, antioxidants) within specific ranges, the formulation achieves adequate shelf-life and stability without excessive complexity in the formulation composition
Data Source
AI summary
The invention relates to stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof. In some embodiments the formulations of the invention comprise between 5-200 mg/mL anti-PD-1 antibody, or antigen binding fragment thereof. The invention further provides methods for treating various cancers with stable formulations of the invention. In some embodiments of the methods of the invention, the formulations are administered to a subject by intravenous or subcutaneous administration.