Anti-PD-1/IL-2 Immunoconjugate Formulation for Shelf-Life Stability
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Solution Overview
Problem
Existing formulations for anti-PD-1/IL-2 mutant protein immunoconjugates lack stability, which is crucial for maintaining drug efficacy and safety during shelf life.
Innovation Solution
A stable liquid formulation of anti-PD-1/IL-2 mutant protein immunoconjugate is developed, comprising specific buffering agents, stabilizers, and surfactants, with a pH range of 5.0 to 6.5, and optionally including EDTA, to ensure stability and quality control during storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing formulations are used for anti-PD-1/IL-2 mutant protein immunoconjugates, then the drug can be administered, but the formulation lacks stability during shelf life
Solution Approach 1:
The patent optimizes formulation parameters including pH (adjusted to 5.0-6.5 range), ionic strength, and excipient concentrations to achieve stable liquid formulations. Specific modifications to buffer composition and surfactant types are implemented to prevent aggregation and maintain protein structure integrity throughout shelf life.
Solution Approach 2:
The formulation employs a composite system combining multiple excipients including buffers (phosphate, acetate, or citrate), stabilizers (sugars or amino acids), and surfactants (polysorbate 20, 80, or 40) that work synergistically to protect the immunoconjugate protein from degradation, aggregation, and denaturation during storage.
2Duration of action of stationary object
If the formulation is optimized for stability, then shelf life is extended, but the formulation complexity increases
Solution Approach 1:
The selected excipients serve multiple functions simultaneously: phosphate buffer maintains pH while providing ionic strength, polysorbate surfactants prevent aggregation while stabilizing the protein surface, and added sugars or amino acids provide both stabilization and osmotic balance. This multi-functionality reduces the need for additional separate components.
Solution Approach 2:
The formulation is optimized with specific local considerations for the protein's critical regions, using surfactants that preferentially adsorb to hydrophobic patches on the protein surface and buffers that maintain the pH in the optimal range for the protein's charge distribution and conformational stability.
3Reliability
If the pH is adjusted to 5.0-6.5 for stability, then formulation stability improves, but the buffering agent selection becomes more restricted
Solution Approach 1:
The pH is specifically adjusted to the 5.0-6.5 range where the immunoconjugate exhibits maximum stability. Within this range, phosphate buffer is preferred as it provides effective buffering capacity, though acetate or citrate buffers can be used as alternatives. This parameter optimization ensures minimal aggregation and degradation while maintaining protein activity.
Data Source
Figure 1A~1F
Figure 2(A)~2(E)
Figure 2(F)~2
AI summary
The present invention relates to formulations comprising an immunoconjugate of a recombinant anti-programmed death receptor 1 (PD-1) antibody and a mutant interleukin-2 (IL-2) (also referred to as "αPD-1/IL2m"), particularly stable liquid formulations, as well as methods for preparing said formulations, and the use of said formulations for the treatment and/or prevention of diseases.