Salt-Free Antibody Formulations for Low Viscosity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current protein and antibody formulations face challenges with high viscosity, osmolality, and protein aggregation, which complicates processing and administration, especially for subcutaneous injections, and requires a balance of stabilizers to maintain stability and osmolality without causing injection pain.
Innovation Solution
Development of low viscosity, substantially isosmotic antibody and protein formulations without inorganic salts, using histidine, sugars, and non-ionic surfactants like polysorbate, which maintain stability and osmolality, allowing for increased concentrations of stabilizers and reduced injection pain, and are suitable for both liquid and lyophilized forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high protein concentration is used in antibody formulations, then dosage volume is reduced and stability is improved, but viscosity increases significantly making processing and injection difficult
Solution Approach 1:
The patent changes the chemical composition parameters of the formulation by introducing specific excipients (histidine buffer at pH 5.0-6.0, non-ionic surfactants like polysorbate 80, and sugar alcohols like mannitol or sorbitol) to modify the physical properties of the protein solution, thereby reducing viscosity while maintaining high protein concentration
Solution Approach 2:
The patent creates a composite formulation system combining protein, buffer, surfactant, and sugar alcohol components that work synergistically to maintain solubility and reduce viscosity at high concentrations, enabling both high dosage strength and ease of administration
2Stability of the object's composition
If high concentrations of stabilizers are added to maintain protein stability, then protein aggregation is reduced, but osmolality increases causing injection pain and tissue damage
Solution Approach 1:
The patent changes the type of stabilizer used from traditional high-osmolality agents to sugar alcohols (mannitol, sorbitol) that provide stabilization with lower osmolality contribution, and adjusts pH to 5.0-6.0 to optimize protein stability while controlling osmolality
Solution Approach 2:
The patent uses sugar alcohols as temporary stabilizing agents that fulfill their protective function during storage and administration, after which they are safely metabolized or excreted, providing stable protection without long-term osmolality issues
3Ease of operation
If liquid formulation is used for convenience of administration, then ease of injection is improved, but protein aggregation and phase separation occur at high concentrations
Solution Approach 1:
The patent adjusts multiple formulation parameters including pH (5.0-6.0), ionic strength, and excipient concentrations to shift the phase behavior of the protein solution, ensuring that the liquid formulation remains stable and monophasic at high protein concentrations suitable for convenient administration
Solution Approach 2:
The patent introduces non-ionic surfactants as intermediary substances that mediate between protein molecules, preventing aggregation and phase separation while maintaining the liquid state and ease of administration
Data Source
Figure 1
Figure 2
AI summary
Provided are salt-free antibody and other protein formulations that are substantially isosmotic and of low viscosity. Also provided are methods for the treatment of diseases using the disclosed formulations.