Sterile chromatography resin and use thereof in manufacturing processes

A resin and process technology, applied in the field of sterile chromatography resin and its use in the manufacturing process, can solve the problems of reduced flow rate, contaminated product, increased pressure, etc.

Active Publication Date: 2016-11-02
GENZYME CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A known limitation of continuous chromatography is the presence of contaminating agents in the system (e.g., increased bioburden), which results in contaminated product, decreased production yield, and decreased flow rate (or increased pressure) in the system
For example, increased bioburden within the system can lead to complete shutdown of the system

Method used

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  • Sterile chromatography resin and use thereof in manufacturing processes
  • Sterile chromatography resin and use thereof in manufacturing processes
  • Sterile chromatography resin and use thereof in manufacturing processes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0264] Example 1.Gamma-irradiation on the effect of static binding capacity of different chromatography resins

[0265] A set of experiments was performed to test the effect of gamma-irradiation on the static binding capacity of three different Protein A affinity chromatography resins: GE Mab Select SuRe TM (a highly cross-linked agarose resin with a particle size of 85 μm and epoxy functional groups linking protein A to the agarose), JSR LifeSciences Amsphere ProA JWT203 (a porous polymethacrylate resin with ~50 μm particle size, and epoxy functional groups linking Protein A to polymethacrylate), and Kaneka KanCap A (a highly cross-linked cellulose with a particle size of 65–85 μm in which Protein A was reductively aminated attached to cellulose). Each of the three resins was treated with 15 kGy of γ-irradiation, except Mab Select SuRe TM , which was treated with an irradiation dose of 25kGy, while the control sample GE Mab Select SuRe TM The resin was left untreated, load...

Embodiment 2

[0268] Example 2. Effect of multiple Γ-irradiation on resin binding capacity in multiple chromatography cycles

[0269] The next set of experiments was performed to test the effect of gamma-irradiation on the binding capacity of the chromatography resin in multiple chromatography cycles. JSR LifeSciences Amsphere ProA JWT203 resin was used for these experiments because this resin showed minimal loss of binding capacity in Example 1 in response to gamma-irradiation. Gamma-irradiation of each resin in this example was performed in 50 mM phosphate, pH 7.0.

[0270] A first experiment was performed to test the effect of 15 kGy γ-irradiation on the ability of JSR LifeSciences Amsphere ProA JWT203 resin to bind anti-TGFβ antibody (IgG4) in multiple chromatography cycles. Multiple chromatography cycles were also performed using untreated JSR LifeSciences Amsphere ProA JWT203 resin as a positive control. At the end of each cycle, the resin was rinsed with 0.1N NaOH. The amount of a...

Embodiment 3

[0275] Example 3.Γ-irradiation on GE Mab Select SuRe TM The role of the binding capacity of the resin

[0276] A set of experiments was performed to determine the effect of γ-irradiation on another protein ligand chromatography resin (GE Mab Select SuRe TM Resin) binding capacity. The resin was exchanged into 50 mM sodium phosphate, pH 7.0, and then treated with 29 kGy γ-irradiation in 30-mL Nalgene bottles. The resin was then packed into a 0.66-cm diameter column (1 mL column) with a bed height of 3 cm. This column is then used to capture monoclonal IgG1 antibodies in the cell culture medium in multiple cycles of chromatography. Also used untreated GE Mab Select SuRe TM The resin was used for multiple chromatography cycles as a positive control. At the end of each cycle, the resin was rinsed with 0.1 N NaOH. The amount of IgGl in the eluate from each cycle was determined. Data show 29kGy γ-irradiation leads to GE Mab Select SuRe TM Immediate, about 25% to about 30% re...

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Abstract

Provided herein are methods of reducing bioburden of (e.g., sterilizing) a chromatography resin that include exposing a container including a composition including a chromatography resin and at least one antioxidant agent and / or chelator to a dose of gamma-irradiation sufficient to reduce the bioburden of the container and the chromatography resin, where the at least one antioxidant agent and / or chelator are present in an amount sufficient to ameliorate the loss of binding capacity of the chromatography resin after / upon exposure to the dose of gamma-irradiation. Also provided are reduced bioburden chromatography columns including the reduced bioburden chromatography resin, compositions including a chromatography resin and at least one chelator and / or antioxidant agent, methods of performing reduced bioburden column chromatography using one of these reduced bioburden chromatography columns, and integrated, closed, and continuous processes for reduced bioburden manufacturing of a purified recombinant protein.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 61 / 928,929, filed January 17, 2014, and U.S. Provisional Patent Application No. 62 / 001,498, filed May 21, 2014, each of which is incorporated by reference in its Incorporated into this article as a whole. technical field [0003] The present invention relates to methods of biotechnology and biomanufacture of recombinant proteins. Background technique [0004] Mammalian cells comprising nucleic acids encoding recombinant proteins are commonly used to produce therapeutically or commercially important proteins. In the current environment of diverse product pipelines, biotech companies are increasingly driven to develop innovative solutions for the highly flexible and cost-effective manufacturing of therapeutic protein drug substances. One of the strategies for efficient isolation of recombinant proteins is by processes involving sequential chrom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01D15/18B01D15/20A61L2/08
CPCB01D15/1864B01D15/20B01D15/327B01D15/34B01D15/362B01J39/26Y10T29/49826B01D15/363B01D15/3804B01J20/265B01J20/281B01J20/3441B01J41/12B01J41/20A61L2/081C07K1/16C07K1/18C07K1/22A61L2/08B01D15/18
Inventor R·戈达瓦特V·沃里库R·帕蒂尔K·康斯坦丁诺夫V·K·里卡拉
Owner GENZYME CORP
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