Stable Liquid Antibody Formulation with Surfactant and Sugar

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Solution Overview

Problem

Current formulations for anti-influenza virus antibodies lack stability across varying temperatures and long-term storage, making them unsuitable for effective prevention and treatment of diverse influenza virus subtypes.

Innovation Solution

A stable liquid pharmaceutical formulation comprising an anti-influenza virus antibody or a mixture of antibodies, combined with a surfactant, sugar or its derivative, and an amino acid, which maintains stability at 5°C, 25°C, and 40°C, and exhibits long-term storage stability up to 12 months.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If conventional liquid pharmaceutical formulations are used for anti-influenza virus antibodies, then the antibodies can be administered in liquid form, but the formulations lack stability across varying temperatures and long-term storage

Engineering Contradiction:
Improveantibody stabilityVSAvoidstorage duration
Core Design Contradiction:
Stability of the object's compositionVSDuration of action of stationary object

Solution Approach 1:

The patent optimizes multiple formulation parameters including pH (adjusted to specific ranges using buffers like phosphate or acetate), ionic strength (controlled through salt concentration), temperature conditions (stability demonstrated across 5°C, 25°C, and 40°C), and excipient concentrations (surfactant 0.01-1%, sugar 1-20%, amino acid 0.1-10 mM). These parameter optimizations collectively achieve both liquid form stability and long-term storage capability up to 12 months

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The formulation employs a composite system combining the anti-influenza virus antibody with multiple excipients: surfactants (e.g., polysorbate 80, poloxamer 188) to prevent aggregation, sugars or sugar derivatives (e.g., trehalose, sucrose, sorbitol) for stabilization, and amino acids (e.g., histidine, arginine) for pH buffering and chemical stability. This composite formulation approach enables simultaneous achievement of liquid stability and long-term storage

Inventive Principle:
Principle #40Composite materials

2Adaptability or versatility

If antibodies are formulated to maintain stability at multiple temperatures, then storage flexibility is improved, but formulation complexity increases

Engineering Contradiction:
Improvetemperature adaptabilityVSAvoidformulation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent develops a universal liquid formulation system that simultaneously provides stability across multiple temperature conditions (5°C refrigeration, 25°C room temperature, and 40°C elevated temperature). The same formulation composition with optimized excipient concentrations achieves multi-temperature adaptability without requiring temperature-specific formulations, thereby managing complexity while enhancing versatility

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If excipients are added to stabilize the antibody, then chemical and biological stability is improved, but predicting optimal excipient types and amounts becomes difficult

Engineering Contradiction:
Improveantibody reliabilityVSAvoidformulation development ease
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent establishes specific parameter ranges for excipients based on systematic optimization: surfactant concentration (0.01-1%, w/v), sugar concentration (1-20%, w/v), amino acid concentration (0.1-10 mM), and pH (5.5-7.0). These defined parameters provide a practical framework that improves reliability while making formulation development more predictable and manageable

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS12065482B2Stable liquid pharmaceutical formulation of anti-influenza virus antibody
Publication Date: 2024.08.20 CELLTRION INC

AI summary

A stable liquid pharmaceutical preparation of an anti-influenza virus antibody and, more specifically, a stable liquid pharmaceutical preparation that comprises: (A) an anti-influenza virus antibody or a mixture of two or more different types of anti-influenza virus antibodies; (B) a surfactant; (C) a sugar or a sugar derivative; and (D) an amino acid. The stable liquid pharmaceutical preparation for an anti-influenza virus antibody disclosed herein has excellent storage stability at low temperature (5° C.), room temperature (25° C.), and high temperature (40° C.) and excellent long-term (12 months) storage stability, and may be administered intravenously, intramuscularly, transdermally, subcutaneously, intraperitoneally, topically, or in combinations thereof.