Anti-VLA-1 Antibody Formulation for Subcutaneous Delivery

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Solution Overview

Problem

Current treatments for inflammatory and autoimmune disorders, such as rheumatoid arthritis, are inadequate in effectively targeting VLA-1 integrin, leading to insufficient therapeutic outcomes.

Innovation Solution

Development of an aqueous pharmaceutical composition containing high concentrations of anti-VLA-1 antibodies, specifically formulated with 165 mg/mL to 190 mg/mL of anti-VLA-1 antibodies, histidine, sorbitol, and polysorbate, optimized for subcutaneous delivery to provide therapeutic effects for inflammatory and autoimmune disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high concentration of anti-VLA-1 antibody is formulated for subcutaneous delivery, then therapeutic effectiveness is improved, but formulation stability and injectability become challenging

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidformulation stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent optimizes multiple formulation parameters including antibody concentration (100-200 mg/mL), pH (5.0-7.0), ionic strength, and excipient ratios to achieve a stable formulation that maintains therapeutic effectiveness while ensuring subcutaneous injectability. This systematic parameter optimization resolves the contradiction between high concentration requirements and formulation stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The formulation employs a composite system combining the anti-VLA-1 antibody with multiple excipients (surfactants, buffers, and stabilizers) to create a synergistic formulation. This composite approach enhances overall formulation stability while maintaining the high antibody concentration needed for therapeutic effectiveness.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If high concentration of anti-VLA-1 antibody is formulated, then dosing volume is reduced, but viscosity and injectability worsen

Engineering Contradiction:
Improveantibody concentrationVSAvoidinjectability
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent carefully controls ionic strength, pH, and the presence of excipients to modulate the physical properties of the formulation. These parameter adjustments reduce viscosity and improve flow characteristics, enabling easy subcutaneous injection even at high antibody concentrations of 100-200 mg/mL.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Excipients such as surfactants and buffers act as intermediaries that modify the physical properties of the antibody solution. These additives reduce intermolecular interactions that cause viscosity increases, thereby maintaining injectability while preserving high antibody concentration.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If conventional antibody concentrations are used, then formulation stability is maintained, but therapeutic effectiveness is insufficient

Engineering Contradiction:
Improveformulation stabilityVSAvoidtherapeutic effectiveness
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent systematically optimizes formulation parameters including pH, ionic strength, and excipient concentrations to extend the stability profile of high-concentration antibody formulations. This enables the use of therapeutically effective high concentrations (100-200 mg/mL) while maintaining long-term formulation stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The formulation uses a composite system with multiple stabilizing excipients that work synergistically to prevent aggregation and degradation of the antibody at high concentrations. This composite approach enables both high therapeutic effectiveness and long-term stability.

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP2814468B1Anti-VLA1 (CD49a) antibody pharmaceutical compositions
Publication Date: 2019.06.19 SANTARUS INC
  • EP2814468B1 patent drawingFigure 1A
  • EP2814468B1 patent drawingFigure 1B
  • EP2814468B1 patent drawingFigure 1C

AI summary

Formulations of anti-VLA-1 antibodies are described.