Method of purifying an antibody

Inventors

Kokke, Bastiaan Pieter Arjan • WIJK-BASTEN VAN, Everdina Josephina Wilhelmina • BEIJER DE, Thomas Antonius Bernardus • MARZÁ PÉREZ, Maria • Eppink, Michel Hendrikus Maria

Assignees

Byondis BV

Abstract

A method of purifying an antibody composition comprises application of anion exchange chromatography late in the purification process. An ultrafiltration/diafiltration-purified antibody composition is subjected to anion exchange chromatography (AEX) to form a pharmaceutically-pure antibody composition.

Core Innovation

The invention provides a method of purifying an antibody composition produced in eukaryotic cells by subjecting a UF/DF-purified antibody composition to anion exchange chromatography (AEX) to form a pharmaceutically-pure antibody composition. A key aspect is that the anion exchange chromatography is the last chromatographic purification step and is performed directly after the final UF/DF step.

The method addresses impurities associated with antibody manufacturing, including host cell proteins (HCP) and host cell DNA, and is used to obtain a pharmaceutically-pure antibody composition with reduced HCP and improved virus control. The resulting composition is described with low levels of impurities and low levels of product-related impurities such as aggregates/dimers.

The disclosure includes purification workflows that compare conventional sequencing of purification steps with an approach where AEX is placed after the final UF/DF step. Examples are provided for trastuzumab, showing that placing AEX after UF/DF yields reduced HCP while maintaining low product-related impurities, including aggregates and dimers, in the context of producing a pharmaceutically-pure antibody composition.

Claims Coverage

The document includes two independent method claims describing purification workflows that end with anion exchange chromatography (AEX) performed directly after the final UF/DF step. Across the independent claims, there are four main inventive features.

Across the independent claims, the central claim coverage is directed to sequencing AEX as the final chromatographic purification step directly after the final UF/DF step to obtain a pharmaceutically-pure antibody composition. The claims further include broader workflows with affinity capture, polishing, UF/DF, and final AEX, and specify Protein A affinity chromatography, a virus removal step, and polishing that includes ionic exchange chromatography (IEX).

Stated Advantages

Documented Applications