High-Concentration Anti-BLYS Formulation for Stable Subcutaneous Delivery
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Solution Overview
Problem
Existing pharmaceutical formulations of antigen binding proteins, such as antibodies, are limited by solubility and stability issues, restricting intravenous administration and necessitating lower concentrations for subcutaneous or intramuscular injections, which are less convenient and require multiple doses.
Innovation Solution
A pharmaceutical formulation comprising a buffering agent, tonicity agent, and optionally a stabilizer and nonionic surfactant, achieving concentrations of 150 to 250 mg/mL with a pH of 5.0 to 7.0, stabilizing the antigen binding protein for subcutaneous use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If intravenous administration is used, then the antibody can be administered, but the amount is limited by solubility and stability in liquid formulation
Solution Approach 1:
The patent changes the concentration parameter from traditional IV concentrations to high concentration formulations (150-250 mg/mL), fundamentally altering how the antibody is administered. This high concentration enables subcutaneous delivery while maintaining stability through optimized formulation components.
Solution Approach 2:
The patent introduces specific formulation intermediaries including buffering agents (histidine, arginine), tonicity agents (NaCl), stabilizers (polysorbate 80), and nonionic surfactants that mediate between the high concentration antibody and the biological system, enabling stability and compatibility.
2Ease of operation
If subcutaneous injection is used, then patient compliance and ease of administration improve, but high protein concentration is required which creates solubility and stability issues
Solution Approach 1:
The patent optimizes multiple parameters including pH (5.0-7.0), concentration (150-250 mg/mL), ionic strength, and additive composition to create a formulation that is both highly concentrated for subcutaneous delivery and stable enough for storage and administration.
Solution Approach 2:
The patent creates a composite formulation system combining antibody with multiple excipients (buffering agents, tonicity agents, stabilizers, surfactants) that work synergistically to maintain protein stability at high concentrations while enabling subcutaneous administration.
3Quantity of substance
If high concentration formulation is achieved, then subcutaneous injection convenience improves, but viscosity increases and stability challenges arise
Solution Approach 1:
The patent systematically adjusts formulation parameters including pH, ionic strength, temperature, and composition to optimize protein solubility and reduce aggregation at high concentrations, managing viscosity and stability through controlled parameter optimization.
Solution Approach 2:
The patent employs intermediary substances including polysorbate 80 as a stabilizer, NaCl as a tonicity agent, and buffering agents that mediate the interactions between high concentration protein molecules, preventing aggregation and maintaining formulation stability.
Data Source
AI summary
The present invention relates to pharmaceutical formulations of a pharmaceutically active antigen binding protein, for example a monoclonal antibody. Such formulations comprise, in addition to the antigen binding protein, a buffering agent and a tonicity agent.