Bispecific Antibody Formulation for Aggregation and Charge Control

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Solution Overview

Problem

Existing stable solution formulations for bispecific antibodies that bind to FIX and/or FIXa and FX do not effectively suppress aggregate formation and charge heterogeneity.

Innovation Solution

A solution formulation of pH 4.5 to 6.5 containing 20 to 180 mg/mL bispecific antibody, 10 mM to 40 mM histidine/aspartate buffer, 0.2 to 1 mg/mL Poloxamer 188, and 100 mM to 300 mM arginine is developed to stabilize the antibody and prevent aggregate formation and charge heterogeneity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional solution formulations (using histidine/arginine or histidine/aspartate buffer) are used for bispecific antibodies, then the formulations can be prepared with high antibody concentration, but aggregate formation and charge heterogeneity are not effectively suppressed

Engineering Contradiction:

Improveantibody concentrationVSAvoidaggregate formation and charge heterogeneity

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by optimizing the pH range (4.5-6.5) and using specific concentrations of histidine/aspartate buffer (10-40 mM), Poloxamer 188 (0.2-1 mg/mL), and arginine (100-300 mM) to achieve both high antibody concentration (20-180 mg/mL) and suppression of aggregate formation and charge heterogeneity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite formulation system combining multiple components (histidine/aspartate buffer, Poloxamer 188, and arginine) working synergistically to stabilize the bispecific antibody at high concentrations while preventing aggregation and charge heterogeneity

Inventive Principle:

Principle #40Composite materials

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 excellent stability by suppressing aggregate formation and charge heterogeneity, ensuring the bispecific antibody's effectiveness in treating hemophilia A.

Implementation Method 1

10 mM to 40 mM histidine/aspartate buffer

Methodology Applied

Scientific EffectBuffering:

Implementation Method 2

Poloxamer 188 at 0.2 to 1 mg/mL

Methodology Applied

Scientific EffectSteric stabilization:

Implementation Method 3

100 mM to 300 mM arginine

Methodology Applied

Scientific EffectElectrostatic interactions:

Data Source

PatentEP3449940B1Antibody-containing preparation

Publication Date: 2025.11.19 CHUGAI PHARMA CO LTD

Figure 1(a)~1(b)
Figure 2(a)~2(d)

AI summary

The present invention relates to stable antibody-containing solution formulations in which aggregate formation of Emicizumab (ACE910) which is a bispecific antibody functionally substituting for FVIII, is suppressed. Specifically, the present invention relates to the above-mentioned antibody-containing solution formulations of pH 4.5 to 6.5 that contain the aforementioned bispecific antibody at 20 to 180 mg/mL, 10 mM to 40 mM histidine-aspartate buffer, Poloxamer 188 at 0.2 to 1 mg/mL, and 100 mM to 300 mM arginine.