Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2
Co-formulation of multiple drug products is an efficient and convenient approach to simultaneously deliver multiple biotherapeutics with the potentially added benefit of a synergistic therapeutic effect. However, co-formulation also increases the risk of heteromeric interactions, giving rise to uniq...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2338301 |
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| author | Sophia Liu Yuetian Yan Cody M. Secor Zachary R. Oberholtzer Donna J. Skow Mushhood Sheikh Youmi Moon Yue Fu Cristinel Sandu Shunhai Wang Ning Li Jennifer B. Nguyen Michael P. Rosconi Erica A. Pyles |
| author_facet | Sophia Liu Yuetian Yan Cody M. Secor Zachary R. Oberholtzer Donna J. Skow Mushhood Sheikh Youmi Moon Yue Fu Cristinel Sandu Shunhai Wang Ning Li Jennifer B. Nguyen Michael P. Rosconi Erica A. Pyles |
| author_sort | Sophia Liu |
| collection | DOAJ |
| description | Co-formulation of multiple drug products is an efficient and convenient approach to simultaneously deliver multiple biotherapeutics with the potentially added benefit of a synergistic therapeutic effect. However, co-formulation also increases the risk of heteromeric interactions, giving rise to unique impurities with unknown efficacy and immunogenicity. Therefore, it is critical to develop methods to evaluate the risk of heteromers as an impurity that could affect potency, efficacy, and/or immunogenicity. The most direct strategy to evaluate antibody heteromers is via specific enrichment. However, the fact that antibody heterodimers generated from the co-formulated cocktail share highly similar molar mass and size properties as homodimers natively present in each individual antibody drug product poses a unique purification challenge. Here, we report the path to successful enrichment of heterodimers from co-formulated REGEN-COVⓇ and discuss its potential impacts on drug quality. |
| format | Article |
| id | doaj-art-1494bc863c804d3eb9523d2ed2f12fcb |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-1494bc863c804d3eb9523d2ed2f12fcb2025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2338301Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2Sophia Liu0Yuetian Yan1Cody M. Secor2Zachary R. Oberholtzer3Donna J. Skow4Mushhood Sheikh5Youmi Moon6Yue Fu7Cristinel Sandu8Shunhai Wang9Ning Li10Jennifer B. Nguyen11Michael P. Rosconi12Erica A. Pyles13Protein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USAAnalytical Chemistry, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USAProtein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USAProtein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USATherapeutic Proteins, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USATherapeutic Proteins, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USAProtein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USAProtein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USATherapeutic Proteins, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USAAnalytical Chemistry, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USAAnalytical Chemistry, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USAProtein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USAProtein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USAProtein Biochemistry, Regeneron Pharmaceuticals, Inc ., Tarrytown, NY, USACo-formulation of multiple drug products is an efficient and convenient approach to simultaneously deliver multiple biotherapeutics with the potentially added benefit of a synergistic therapeutic effect. However, co-formulation also increases the risk of heteromeric interactions, giving rise to unique impurities with unknown efficacy and immunogenicity. Therefore, it is critical to develop methods to evaluate the risk of heteromers as an impurity that could affect potency, efficacy, and/or immunogenicity. The most direct strategy to evaluate antibody heteromers is via specific enrichment. However, the fact that antibody heterodimers generated from the co-formulated cocktail share highly similar molar mass and size properties as homodimers natively present in each individual antibody drug product poses a unique purification challenge. Here, we report the path to successful enrichment of heterodimers from co-formulated REGEN-COVⓇ and discuss its potential impacts on drug quality.https://www.tandfonline.com/doi/10.1080/19420862.2024.2338301Heterodimersco-formulated biotherapeuticsmonoclonal antibodiesSARS-COV-2REGEN-COVⓇ; enrichmentSEC-HIC, MMC |
| spellingShingle | Sophia Liu Yuetian Yan Cody M. Secor Zachary R. Oberholtzer Donna J. Skow Mushhood Sheikh Youmi Moon Yue Fu Cristinel Sandu Shunhai Wang Ning Li Jennifer B. Nguyen Michael P. Rosconi Erica A. Pyles Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2 mAbs Heterodimers co-formulated biotherapeutics monoclonal antibodies SARS-COV-2 REGEN-COVⓇ; enrichment SEC-HIC, MMC |
| title | Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2 |
| title_full | Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2 |
| title_fullStr | Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2 |
| title_full_unstemmed | Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2 |
| title_short | Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2 |
| title_sort | enrichment strategy and initial characterization of heterodimers enriched from a co formulated cocktail of therapeutic antibodies against sars cov 2 |
| topic | Heterodimers co-formulated biotherapeutics monoclonal antibodies SARS-COV-2 REGEN-COVⓇ; enrichment SEC-HIC, MMC |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2338301 |
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