Anti-NGF Antibody Formulation Stability via Surfactant and Carbohydrate Excipients
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Solution Overview
Problem
Therapeutic antibodies, such as those targeting human nerve growth factor (NGF), face challenges in maintaining stability during storage due to degradation, aggregation, and chemical modifications, requiring a suitable formulation that balances antibody concentration, viscosity, and stability for effective administration.
Innovation Solution
A pharmaceutical formulation comprising a human antibody that specifically binds to hNGF, combined with a non-ionic surfactant like polysorbate 20 and a carbohydrate like sucrose, in specific concentrations and pH levels, to create a stable and administerable solution for treating conditions associated with NGF activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If therapeutic antibodies are formulated in liquid solution for administration, then they become suitable for patient administration, but they are prone to degradation, aggregation and chemical modifications during storage
Solution Approach 1:
The patent introduces multiple excipients as intermediary substances that mediate between the antibody and the storage environment. Specifically, surfactants (polysorbate 20 or polysorbate 80) act as intermediaries to prevent aggregation at air-liquid and container-liquid interfaces, while carbohydrates (sucrose, trehalose, or lactose) serve as intermediaries to stabilize the antibody structure through preferential exclusion and hydrogen bonding, thereby preventing degradation during storage
Solution Approach 2:
The patent optimizes multiple formulation parameters simultaneously: pH (adjusted to 4.5-6.0 using acetate or citrate buffers), excipient concentrations (surfactant at 0.01-1.0%, carbohydrate at 1-20%, antibody at 1-100 mg/mL), and ionic strength. This multi-parameter optimization creates a formulation space where the antibody remains stable in liquid solution without requiring freezing or lyophilization, thus maintaining ease of administration while preventing degradation
2Quantity of substance
If the concentration of antibody in the formulation is increased to improve therapeutic efficacy, then the treatment effectiveness improves, but the viscosity of the solution increases making administration difficult
Solution Approach 1:
The patent employs parameter changes by adjusting the pH to an optimized range (4.5-6.0) and incorporating specific excipients that interact with the antibody to prevent self-association. The surfactants reduce surface tension and prevent interfacial aggregation, while the carbohydrates provide steric stabilization. These parameter changes allow the formulation to maintain low viscosity even at high antibody concentrations (1-100 mg/mL), enabling both high therapeutic efficacy and ease of administration
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 maintains high stability of the antibody, with over 90% retention of native form after storage for several months, and exhibits low to moderate viscosity, enabling effective treatment of conditions like osteoarthritis and neuropathic pain.
Implementation Method 1
The formulations of the invention may comprise excipients in addition to the anti-hNGF antibody. For example, in certain embodiments, the formulation may comprise (i) a human antibody that specifically binds to hNGF; (ii) a non-ionic surfactant; and (iii) at least one carbohydrate. The non-ionic surfactant may be selected from the group consisting of polysorbate 20, polysorbate 80, polyoxyethylene sorbitan monooleate, and polyethylene glycol.
Implementation Method 2
The carbohydrate can be a sugar such as, e.g., sucrose, glucose, mannitol, sorbitol, lactose or trehalose. In one embodiment, the sugar is sucrose.
Data Source
AI summary
The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human nerve growth factor (hNGF). The formulations may contain, in addition to an anti-hNGF antibody, at least one non-ionic surfactant, at least one sugar, and acetate. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.