Anti-Prolactin Receptor Antibody Formulation Viscosity Control
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Solution Overview
Problem
Current anti-prolactin receptor 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 isotonic and low viscosity, using organic or inorganic salts for buffering, along with sugars and surfactants 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 concentrations are used in antibody formulations, then dosage volume is reduced and treatment efficiency is improved, but phase separation, gelation, and crystallization occur leading to formulation instability
Solution Approach 1:
The patent applies parameter changes by systematically optimizing pH, ionic strength, and excipient concentrations to stabilize high-concentration antibody formulations. Specific pH ranges (5.5-6.5) and buffer compositions are identified to prevent phase separation and maintain solubility at concentrations up to 150 mg/mL
Solution Approach 2:
The patent uses excipients as intermediary substances to mediate between high antibody concentration and formulation stability. Surfactants (e.g., polysorbate 80), sugars (e.g., sucrose, trehalose), and amino acids (e.g., arginine, glycine) act as mediators that prevent aggregation and phase separation while enabling high protein concentrations
2Quantity of substance
If high protein concentrations are used in antibody formulations, then injection volume is reduced, but viscosity increases making processing and injection difficult
Solution Approach 1:
The patent employs parameter changes by optimizing formulation pH and ionic strength to decouple concentration from viscosity. By maintaining pH in the 5.5-6.5 range and controlling salt concentrations, the patent achieves low viscosity even at 150 mg/mL antibody concentration, enabling ease of processing and injection
Solution Approach 2:
The patent uses specific excipients as intermediaries to reduce viscosity at high concentrations. Amino acids like arginine and glycine, along with sugars, act as viscosity-modulating agents that enable high antibody concentrations while maintaining fluidity for easy injection
3Stability of the object's composition
If high concentrations of stabilizers are used to maintain protein stability, then formulation stability is improved, but osmolality increases causing injection pain and tissue damage
Solution Approach 1:
The patent applies parameter changes by optimizing the types and concentrations of stabilizers to achieve protein stability at lower osmolality. By selecting specific excipients and controlling their concentrations within defined ranges, the patent maintains protein stability while keeping formulations substantially isosmotic to reduce injection pain
Solution Approach 2:
The patent converts the potential harm of high stabilizer concentrations into a benefit by carefully selecting excipients that provide both stabilization and osmolality control. The same excipients that stabilize the antibody (sugars, amino acids) are used at optimized concentrations to maintain isotonicity, turning a potential source of tissue damage into a benefit for patient comfort
4Stability of the object's composition
If salt concentrations are increased to buffer the formulation, then pH stability is improved, but osmolality increases leading to hypertonic solutions and injection pain
Solution Approach 1:
The patent applies parameter changes by optimizing buffer composition and concentration to achieve pH stability with minimal impact on osmolality. By selecting specific buffer systems and controlling ionic strength, the patent maintains pH stability while keeping formulations substantially isosmotic
Solution Approach 2:
The patent uses excipients that serve multiple functions simultaneously. Sugars and amino acids provide both pH buffering capacity and osmolality control, while also acting as protein stabilizers. This multi-functionality reduces the need for additional salts that would increase osmolality and cause injection pain
Data Source
AI summary
Provided are a wide concentration range, especially high concentration anti-prolactin receptor antibody formulations that are substantially isosmotic and of low viscosity.