التفاصيل البيبلوغرافية
| العنوان: |
Characterization of Critical Quality Attributes of an Anti-PCSK9 Monoclonal Antibody. |
| المؤلفون: |
Cruz, Thayana A.1,2,3, Larson, Nicholas R.3, Wei, Yangjie3, Subelzu, Natalia3, Wu, Yaqi3, Schöneich, Christian3, Castilho, Leda R.1,2, Middaugh, Charles Russell3 middaugh@ku.edu |
| المصدر: |
Biologics. Sep2024, Vol. 4 Issue 3, p294-313. 20p. |
| مصطلحات موضوعية: |
*MONOCLONAL antibodies, *CLONING, *BIOPHARMACEUTICS, *SOLUBILITY, *MEDICAL care |
| مستخلص: |
During early development of biopharmaceuticals, suboptimal producing clones and production conditions can result in limited quantities of high-purity products. Here we describe a systematic approach, which requires minimal amounts of protein (~10 mg) to assess critical quality attributes of a monoclonal antibody (mAb). A commercial anti-PCSK9 IgG2 (evolocumab, Repatha®) and an early-stage biosimilar candidate were compared head-to-head using a range of high-throughput physicochemical and in-vitro binding analytical methods. Overall, both mAbs were shown to be highly pure and primarily monomeric, to share an identical primary structure, and to have similar higher-order structural integrity, apparent solubility, aggregation propensity, and physical stability profiles under temperature and pH stress conditions. Low levels of dimers were detected for the innovator (1.2%) and the biosimilar candidate mAb (0.3%), which also presented fragments (1.2%). Regarding charge heterogeneity, the amount of the main charge isoform was 53.6% for the innovator and 61.6% for the biosimilar candidate mAb. Acidic species were 38% for the innovator and 30% for the biosimilar candidate. Variations in the relative content of a few N-glycan species were found. The in-vitro binding affinity to PCSK9 was monitored, and no differences were detected. The mathematical approach called "error spectral difference" (ESD), proposed herein, enabled a quantitative comparison of the biophysical datasets. The workflow used in the present work to characterize CQAs at early stages is helpful in supporting the development of biosimilar mAb candidates. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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