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Purified immunoglobulin fusion proteins and methods of their purification

A technology of immunoglobulin and fusion protein, which is applied to the preparation method of peptide, chemical equipment and method, fusion polypeptide, etc.

Inactive Publication Date: 2011-11-09
BIOGEN MA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention solves the problem of purifying antibody-based biologicals, such as LT-β-R-Ig fusion proteins, from impurities produced during the process of expressing the biologicals in mammalian cells, such as CHO cell culture, such that the resulting compositions are Is the protein suitable for pharmaceutical use in terms of mass production and purity

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  • Purified immunoglobulin fusion proteins and methods of their purification
  • Purified immunoglobulin fusion proteins and methods of their purification
  • Purified immunoglobulin fusion proteins and methods of their purification

Examples

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Embodiment 1

[0212] Example 1: Development of a High Resolution Hydrophobic Interaction Chromatography Method Capable of Removing Multiple Product-Related Impurities During the Purification of Antibody-Based Biologicals (Cycle 1)

[0213] For Phase 1 clinical production, a HIC process step capable of removing two monomeric but inactive product-associated impurities from the antibody-based product was developed. During subsequent development, efforts were made to improve capacity and robustness while maintaining chromatographic resolution. A development study will be described in which alternative HIC resins and binding salts are explored, and parameters critical to separation efficiency are identified through a design of experiments approach. A second HIC step with a different resolution was used downstream of the same process to remove a third product-related impurity. Issues and challenges faced in establishing robust methods suitable for production-scale clinical preparation will be di...

Embodiment 2

[0253] Example 2: Purification of Bioactive LT-β-R-IG Fusion Protein: Cycle 2

[0254] The following example describes a method of purifying an Ig-fusion biologic, the LT-β-R-Ig fusion protein, from a feedstock containing a high percentage of product-related impurities, ie about 50% product-related impurities. As noted above, the starting material for LT-β-R-Ig contains different types of impurities, namely aggregated species and two distinct, disulfide-disordered forms of the product—termed inactivation of LT-β-R— 1 and inactivated-2 forms. Because these impurities are closely associated with LT-β-R-Ig (the product), purification of the desired product poses challenges.

[0255]The production method of LT-β-R-Ig was originally developed for early clinical research and was modified to increase the production rate to a level sufficient for commercialization. To achieve this, cell culture productivity was increased by 4 times. However, this change was accompanied by an increa...

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Abstract

The invention provides methods and compositions for separating impurities during the manufacture of immunoglobulin (Ig) fusion proteins. Examples of impurities which may be removed in accordance with the methods of the invention include inactive forms of the Ig fusion protein and / or aggregates.

Description

Background of the invention [0001] Given the growing acceptance of biologics as approved therapies, detailed characterization of these classes of drugs is important. Unforeseen product decomposition or the presence of impurities can compromise therapeutic efficacy and patient safety. Examples of impurities found during the production of biological products may include aggregates of the product. Aggregates are undesirable in pharmaceutical compositions because they can be immunogenic and pose safety concerns for in vivo use. Aggregates can also reduce the stability of the product in vivo by neutralizing antibodies produced in the patient. [0002] In addition, it is possible to make inactive proteins during the production process. Inactive proteins may be caused by incorrect folding during production. For example, US Patent Application 2002 / 0039580 (Browning et al.) describes two forms, an active and an inactive form, of a lymphotoxin beta receptor immunoglobulin (LTβR-Ig) ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/715C07K1/20C12N15/62C07K1/16
CPCC07K14/7151C07K2319/30A61K47/48507A61K47/48415C07K2319/32A61K47/6811A61K47/6835A61P37/00A61P37/06
Inventor 贾斯廷·麦丘乔纳森·罗梅罗沃纳·梅尔斯蒂芬·诺塔尼科拉戴维·埃文斯理查德·麦克尼文
Owner BIOGEN MA INC
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