Biologics and Biosimilars Characterization

与化学合成的小分子药物相反，生物制剂和生物仿制药（也称为生物治疗药物）是由细菌，酵母和哺乳动物细胞等活生物体产生的。因此，它们通常是非常大的分子（肽，小蛋白质，抗体，多糖等），可以表现出翻译后修饰和某些结构变化程度。

因此，通过结构表征确认治疗药物的身份，从初级氨基酸序列到高阶结构，以及杂质控制对于确保功效和患者安全至关重要。

布鲁克的质谱解决方案超出了传统的肽映射和完整的质量分析。这些解决方案将最终的性能，速度和多功能性与强大的功能流量软件相结合，可为生物制剂开发人员准备好访问正交特征方法。其中包括使用中间和中间的方法分析单克隆抗体（MAB）亚基分析，用于对序列变体的明确检测和表征以及修饰，包括脱氨酸，氧化和N末端剪辑：以及高阶结构研究，以详细介绍二硫化物的详细表征桥梁，构象表位，在抗体药物结合物（ADC）研究中计算准确的药物抗体比（DAR）时的结构变化。

二硫键（DSB）分析和Hydrogendeuterium Exchange（HDX）已成为可以采用的技术，可用于洞悉蛋白质结构。这些见解对于确定生物仿制药的结构相似性至关重要，或者对于监测药物开发过程中的蛋白质稳定性至关重要。治疗蛋白的三级结构是其活性和稳定性的关键。 

Research and development labs require technology capable of automated DSB analysis in biopharmaceuticals, based on a single digest of the unreduced protein and without prior knowledge of enzyme specificity or native DSBs. Due to the complexity of these proteins and the fact that they contain multiple disulfide bonds, analysis is challenging, often requiring several LC-MS runs with the tryptic digests from reduced and non-reduced protein and a manual comparison of these two analyses.

与化学合成的小分子药物相反，生物制剂和生物仿制药（也称为生物治疗药物）是由细菌，酵母和哺乳动物细胞等活生物体产生的。因此，它们通常是非常大的分子（肽，小蛋白质，抗体，多糖等），可以表现出翻译后修饰和某些结构变化程度。

因此，通过结构表征确认治疗药物的身份，从初级氨基酸序列到高阶结构，以及杂质控制对于确保功效和患者安全至关重要。

布鲁克的质谱解决方案超出了传统的肽映射和完整的质量分析。这些解决方案将最终的性能，速度和多功能性与强大的功能流量软件相结合，可为生物制剂开发人员准备好访问正交特征方法。These include monoclonal antibody (mAb) subunit analysis using middle up and middle down approaches for the unambiguous detection and characterization of sequence variants and modifications - including deamidation, oxidation and N-terminal clipping; as well as higher order structure studies for the detailed characterization of disulfide bridges, conformational epitopes, and structural changes upon perturbation; and calculating accurate drug antibody ratios (DAR) in antibody drug conjugate (ADC) studies.

二硫键（DSB）分析和Hydrogendeuterium Exchange（HDX）已成为可以采用的技术，可用于洞悉蛋白质结构。这些见解对于确定生物仿制药的结构相似性至关重要，或者对于监测药物开发过程中的蛋白质稳定性至关重要。治疗蛋白的三级结构是其活性和稳定性的关键。 

Research and development labs require technology capable of automated DSB analysis in biopharmaceuticals, based on a single digest of the unreduced protein and without prior knowledge of enzyme specificity or native DSBs. Due to the complexity of these proteins and the fact that they contain multiple disulfide bonds, analysis is challenging, often requiring several LC-MS runs with the tryptic digests from reduced and non-reduced protein and a manual comparison of these two analyses.

NMR is especially sensitive to changes to higher order structure at atomic resolution, making it ideally suited for similarity assessment of biologics and biosimilars. NMR allows for intact protein analysis, enabling structural evaluation of therapeutic drugs without modification, in conditions that are physiologically relevant. The selectivity and quantitative nature of magnetic resonance means that potency determination, impurity profiling and degradation studies (eg polysorbates) can be performed directly enabling fast and easy testing without the need for response factor calculations or the method redevelopment activities required by traditional LC methods, thereby saving time and reducing costs. In addition, benchtop time domain NMR (TD-NMR) is becoming an important technique for the analysis ofprotein aggregates和100％填充检查of vials and syringes.

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傅立叶变换红外（FT-IR）光谱法可用于分析水溶性和膜蛋白（例如核受体），这些核受体目前是药物研究和开发中的决定性靶标，与阿尔茨海默氏症，帕金森氏病，糖尿病，糖尿病，糖尿病和糖尿病，糖尿病和糖尿病，糖尿病和疾病有关肥胖。FT-IR通常应用于蛋白质二级结构阐明，构象变化的检测以及蛋白质动力学等诸如聚集，沉淀和结晶等蛋白质动力学的监测。红外蛋白质分析是一种快速且相对廉价的技术，用于配方优化，药物开发过程中的稳定性研究以及蛋白质药物的QC。

Surface Plasmon Resonance (SPR) is the gold standard methodology to characterize an interaction from a kinetic point of view. While solution-based approaches offer an equilibrium-based perspective on an interaction, the label-free and real-time analysis of SPR affords insight into the kinetics a key characteristic that enables more precise understanding of an interaction. Biologics demonstrating similar affinities using equilibrium-based methods like ELISA may have vastly different off-rates with subsequently different biological outcomes. SPR however enables the identification of biologics with the optimal half-life at your target protein.

SPR also allows researchers to identify antibodies that target different epitopes on a protein. Equally, conditional binding based on factors like pH, e.g. as in cancer tissue, or the effect of different buffers on the binding interaction can be investigated with ease. These approaches help to understand an interaction in a physiologically more translatable context.