Anti-CLEVER-1 Antibody Formulation Stability
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Solution Overview
Problem
Anti-CLEVER-1 antibodies are prone to chemical denaturation and instability during storage, which affects their functionality and shelf-life, requiring a stable formulation to maintain their efficacy and colloidal stability.
Innovation Solution
A stable pharmaceutical formulation comprising 1-100 mg/ml of anti-CLEVER-1 antibody or antigen binding fragments with a histidine or Tris buffer, trehalose, proline, or mannitol as stabilizing agents, and polysorbate as a surfactant, maintaining a pH between 5.5-6.5 or 7.0-7.6, respectively, to prevent aggregation and denaturation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-CLEVER-1 antibody is stored in conventional formulation conditions, then the antibody maintains its basic structure, but it undergoes chemical denaturation and aggregation over time, reducing shelf-life and functionality
Solution Approach 1:
The patent optimizes multiple formulation parameters including pH (5.5-6.5 or 7.0-7.6), ionic strength, and temperature to enhance antibody stability. Specific buffer concentrations and compositions are tuned to prevent chemical denaturation and aggregation, directly resolving the contradiction between maintaining structure and extending shelf-life
Solution Approach 2:
Stabilizing agents such as trehalose, proline, and mannitol are introduced as intermediary substances that protect the antibody from degradation. These excipients act as molecular chaperones or osmolytes that prevent unwanted interactions between antibody molecules, thereby extending shelf-life without compromising stability
Solution Approach 3:
The patent develops a composite formulation system combining multiple components: buffers (histidine or Tris), stabilizing agents (trehalose, proline, mannitol), and surfactants (polysorbate). This multi-component composite approach synergistically addresses both structural integrity and long-term stability requirements
2Ease of manufacture
If the antibody formulation uses simple buffer systems, then the formulation is easy to prepare, but the antibody shows increased aggregation and denaturation during storage
Solution Approach 1:
The patent specifies precise buffer parameters including pH ranges (5.5-6.5 for histidine, 7.0-7.6 for Tris) and concentration ranges (5-50 mM) to achieve optimal colloidal stability. These parameter optimizations prevent aggregation while maintaining ease of preparation through straightforward buffering
3Reliability
If stabilizing agents are added to prevent denaturation, then the antibody maintains functionality, but the formulation complexity increases
Solution Approach 1:
The patent employs well-established pharmaceutical excipients (trehalose, proline, mannitol) as intermediary stabilizing agents that protect antibody functionality through proven mechanisms such as preferential exclusion or water structure modification. These are standard pharmaceutical materials that do not significantly increase formulation complexity
Solution Approach 2:
The patent optimizes the concentrations of stabilizing agents within specific ranges (e.g., trehalose at appropriate concentrations) to achieve maximum protective effect while minimizing formulation complexity. This parameter optimization ensures functionality preservation without excessive complexity
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 provides long-term stability, maintaining the antibody's functionality and biological activity, suitable for clinical use with extended shelf-life and reduced aggregation, making it effective for treating various diseases including cancer and immune-related conditions.
Implementation Method 1
5-50 mM of a histidine buffer in combination with 150-400 mM of trehalose, proline or mannitol as a stabilizing agent, wherein the pH of said pharmaceutical formulation is in the range of 5.5-6.5, or 5-50 mM of a Tris buffer in combination with 100-200 mM of sodium chloride as a stabilizing agent, wherein the pH of said pharmaceutical formulation is in the range of 7.0-7.6
Implementation Method 2
150-400 mM of trehalose, proline or mannitol as a stabilizing agent
Implementation Method 3
0.01-0.1% (w/v) of polysorbate as a non-ionic surfactant
Data Source
AI summary
The invention relates to stable formulations comprising an anti-CLEVER-1 antibody or antigen binding fragment(s) thereof, a buffer and a stabilizing agent. The present invention further relates to stable formulations of an anti-CLEVER-1 antibody or antigen binding fragments thereof for use in treatment of various diseases and disorders.