Multifunctional Chromatography Medium for Biologic Purification

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Solution Overview

Problem

Current purification processes for protein therapeutics, particularly monoclonal antibodies, face challenges in effectively removing antibody fragments and aggregates due to the lack of robust chromatographic technology, leading to increased operational costs and complexity in downstream processing.

Innovation Solution

A multifunctional chromatography medium with defined pore diameter distribution and conjugated ligands is developed, allowing for the separation of target biologics from process- and product-related impurities in a single flow-through mode, utilizing silica beads or monoliths with specific pore sizes and ligands that bind impurities while allowing the biologic to flow through unbound.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If ion-exchange and hydrophobic interaction chromatography are used to remove antibody fragments and aggregates, then product purity is improved, but device complexity and operational costs increase due to multiple processing steps

Engineering Contradiction:

Improveproduct purityVSAvoidprocess complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent combines multiple chromatographic functions (ion-exchange, hydrophobic interaction, and size-exclusion) into a single mixed-mode chromatography medium. The porous beads contain both ion-exchange ligands and hydrophobic ligands, enabling simultaneous removal of antibody fragments and aggregates through one processing step rather than multiple sequential steps.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The chromatography medium is designed with universal applicability for removing different types of impurities (process-related and product-related) through multiple mechanisms. The same medium can operate in capture, polish, or continuous mode, and handles various impurity types including aggregates, fragments, and host cell proteins through its mixed-mode ligands.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Manufacturing precision

If multiple chromatography steps are used to achieve high purity, then product purity is improved, but productivity decreases due to increased processing time and operational complexity

Engineering Contradiction:

Improveantibody purityVSAvoidprocessing throughput

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

Multiple chromatographic separation functions are merged into a single medium that can remove both aggregates and fragments simultaneously. This eliminates the need for sequential processing steps, reducing total processing time while maintaining high purity levels through the combined action of ion-exchange and hydrophobic interaction mechanisms.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The medium enables continuous chromatography operations where the chromatography resin is continuously regenerated and reused. The system operates in a continuous flow-through mode with periodic regeneration, maintaining continuous productive action without interrupting the purification process, thereby increasing overall throughput.

Inventive Principle:

Principle #20Continuity of useful action

3Ease of manufacture

If conventional chromatography media are used, then ease of manufacture is maintained, but manufacturing precision deteriorates due to inability to effectively remove antibody fragments

Engineering Contradiction:

Improvemedia fabricationVSAvoidfragment removal efficiency

Core Design Contradiction:

Ease of manufactureVSManufacturing precision

Solution Approach 1:

The chromatography medium uses composite porous beads that combine multiple ligand types (ion-exchange and hydrophobic ligands) within a single porous matrix. This composite structure enables the medium to address the technical challenge of fragment removal while maintaining compatibility with conventional chromatography manufacturing processes and operational procedures.

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

This solution enables efficient removal of impurities, achieving high antibody yield and purity, with up to 80% yield and 97% monomeric purity, while reducing operational costs and simplifying the purification process by operating in continuous flow-through mode.

Implementation Method 1

the pore diameter distribution is configured to exclude a target biologic

Methodology Applied

Scientific EffectSize exclusion: Filter (physical)

Implementation Method 2

one or more ligands conjugated to the surface of the pores capable of capturing process-related impurities and product-related impurities

Methodology Applied

Scientific EffectAdsorption: Adsorption

Data Source

PatentUS20250091034A1Chromatography medium for purifying target biologics

Publication Date: 2025.03.20 NORTH CAROLINA STATE UNIV

AI summary

The present disclosure provides materials and methods related to the purification of a biologic. The present disclosure provides materials and methods related to the purification of a biologic. In particular, the present disclosure provides a multifunctional chromatography medium comprising porous beads or particles having a defined pore diameter distribution and one or more ligands conjugated to the surface of the pores capable of removing process-related impurities and product-related impurities from a target biologic.