Anti-IL-17 Antibody Liquid Formulation for Stable Isotonic Injection
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Solution Overview
Problem
Existing anti-IL-17 monoclonal antibody drugs face issues such as instability, high manufacturing costs, complex use, osmotic pressure risks, and poor patient compliance due to hypertonic solutions, necessitating the development of stable, isotonic, and convenient liquid formulations.
Innovation Solution
A liquid formulation comprising anti-IL-17 antibodies at high concentrations (20-200 mg/mL) with citrate buffer (10-50 mM), sucrose (20-120 mg/mL) or arginine (50-250 mM), and polysorbate 80 (0.1-5 mg/mL), maintaining a pH of 6.0±0.5, without antioxidants or viscosity reducers, suitable for subcutaneous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-IL-17 monoclonal antibody drugs use conventional formulations (Cosentyx or Taltz), then the antibody can be stabilized, but the osmotic pressure becomes hypertonic causing red blood cell atrophy and tissue cell dehydration
Solution Approach 1:
The patent changes the osmotic pressure parameter from hypertonic to isotonic by adjusting the concentration of compatible solutes (sucrose, arginine, or a combination) to match human blood plasma osmotic pressure (280-320 mOsm/kg), thereby eliminating red blood cell atrophy and tissue cell dehydration while maintaining antibody stability
Solution Approach 2:
The patent introduces compatible solutes (sucrose, arginine) as intermediary substances that mediate between the antibody molecules and the biological environment, providing osmotic balance and protecting cells from hypertonic damage without interfering with antibody function
2Productivity
If anti-IL-17 monoclonal antibody drugs use high concentration formulations, then dosing frequency is reduced, but viscosity increases making injection difficult
Solution Approach 1:
The patent changes the viscosity parameter by selecting appropriate compatible solutes and their concentrations, ensuring the formulation remains within acceptable viscosity ranges (1-10 cP) even at high antibody concentrations (50-200 mg/mL), thereby maintaining easy injectability while achieving reduced dosing frequency
Solution Approach 2:
The patent applies different properties to different components of the formulation: the antibody provides therapeutic activity, the compatible solute provides osmotic balance and viscosity control, and the buffer system provides pH stability, allowing each component to optimize its local function without compromising overall performance
3Reliability
If anti-IL-17 monoclonal antibody drugs use lyophilized formulations, then storage stability is improved, but manufacturing cost increases and manufacturing process becomes complicated
Solution Approach 1:
The patent extracts the reconstitution step from the overall process by developing a ready-to-use liquid formulation that eliminates the need for lyophilization and reconstitution, thereby simplifying manufacturing while maintaining storage stability through appropriate formulation design (pH control, compatible solutes, antioxidants)
Solution Approach 2:
The patent adopts a single-use liquid formulation that eliminates the need for complex lyophilization equipment and multi-step manufacturing processes, reducing manufacturing cost and complexity while maintaining adequate stability through formulation design rather than through lyophilization
4Reliability
If anti-IL-17 monoclonal antibody drugs use formulations with antioxidants, then oxidation stability is improved, but the formulation becomes more complex
Solution Approach 1:
The patent extracts the antioxidant function from a separate additive by incorporating oxidation protection directly into the formulation design through pH control (maintaining pH 6.0-7.5), selection of oxidation-resistant excipients, and formulation composition, thereby achieving oxidation stability without adding complex antioxidant agents
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation achieves stability at high concentrations, low viscosity, and isotonic osmotic pressure, enhancing drug efficacy and patient compliance by allowing single-dose administration.
Implementation Method 1
citrate buffer at a concentration ranging from 10 mM to 50 mM, and the liquid formulation has a pH value of 6.0±0.5
Implementation Method 2
sucrose at a concentration ranging from 20 mg/mL to 120 mg/mL or arginine at a concentration ranging from 50 mM to 250 mM
Implementation Method 3
polysorbate 80 at a concentration ranging from 0.1 mg/mL to 5 mg/mL
Implementation Method 4
an osmotic pressure which is close to isotonic
Data Source
AI summary
Provided is a liquid preparation containing an anti-IL-17 antibody at a concentration of 20 mg/mL to 200 mg/mL, a citrate buffer at a concentration of 10 mM to 50 mM, a sucrose at a concentration of 20 mg/mL to 120 mg/mL or arginine at a concentration of 50 mM to 250 mM, and polysorbate 80 at a concentration of 0.1 mg/mL to 5 mg/mL. In addition, the liquid preparation has a pH of 6.0±0.5, wherein the anti-IL-17 antibody is an anti-IL-17A/F monoclonal antibody. The liquid preparation can be a stable subcutaneous injection preparation, and can be used to treat IL-17A and/or IL-17F related diseases, such as psoriasis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, osteoarthritis or inflammatory bowel disease.