Anti-PRLR Antibody Formulations with Low Viscosity
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Solution Overview
Problem
Current anti-Prolactin receptor (PRLR) antibody formulations face challenges with high protein concentrations, including phase separation, gelation, crystallization, and increased viscosity, which complicate processing and injection, and often require high concentrations of stabilizers that can lead to injection pain due to hypertonic solutions.
Innovation Solution
Development of anti-PRLR antibody formulations with a wide concentration range that are substantially isosmotic and low viscosity, using excipients like histidine, polysorbate, sugars, and arginine to maintain osmolality and stability, while minimizing salt concentrations to reduce tissue damage and improve processing and injection ease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high protein concentration is used in antibody formulations, then dosage volume for intramuscular or subcutaneous administration is reduced, but phase separation, gelation, crystallization, and increased viscosity occur
Solution Approach 1:
The patent modifies formulation parameters including pH (adjusted to specific ranges), ionic strength (controlled through buffer selection and concentration), and excipient ratios to prevent phase separation and maintain stability at high antibody concentrations up to 100 mg/mL
Solution Approach 2:
The patent employs composite formulation systems combining multiple excipients (buffers, surfactants, sugars, amino acids) working synergistically to stabilize high-concentration antibody formulations and prevent aggregation, gelation, and crystallization
2Quantity of substance
If high protein concentration is used in antibody formulations, then processing and injection become difficult due to high viscosity, but dosage volume is reduced
Solution Approach 1:
The patent controls viscosity by adjusting formulation parameters including pH, ionic strength, and excipient concentrations, achieving optimal balance between high antibody concentration and acceptable viscosity for processing and injection
Solution Approach 2:
The patent uses surfactants and amino acids as intermediary substances that reduce protein-protein interactions and lower viscosity, facilitating easier processing through ultrafiltration and sterile filtration while maintaining high antibody concentration
3Stability of the object's composition
If high concentrations of stabilizers are used to maintain protein stability, then long-term stability is improved, but injection pain occurs due to hypertonic solutions
Solution Approach 1:
The patent optimizes osmolality by adjusting stabilizer concentrations and selecting appropriate excipients, achieving isotonic formulations that provide long-term protein stability without causing injection pain or tissue damage
Solution Approach 2:
The patent uses sugars and amino acids as intermediary stabilizers that provide both protein stabilization and osmotic balance, replacing high concentrations of sodium chloride with alternative stabilizers that maintain stability while keeping formulations isotonic
4Stability of the object's composition
If high protein concentration is used in antibody formulations, then stabilizer concentration must be increased to achieve long-term stability, but osmolality increases causing tissue damage
Solution Approach 1:
The patent employs composite stabilization systems using combinations of surfactants, sugars, and amino acids that work synergistically to provide long-term protein stability at high concentrations without requiring excessively high stabilizer levels that would increase osmolality
Solution Approach 2:
The patent optimizes pH and ionic strength parameters to enhance protein stability through electrostatic repulsion and reduced aggregation, allowing lower stabilizer concentrations while maintaining long-term stability at high antibody concentrations
Data Source
AI summary
Provided are a wide concentration range, especially high concentration, substantially salt-free anti-prolactin receptor antibody formulations that are substantially isosmotic and of low viscosity.