{"id":18218,"date":"2026-03-16T16:23:37","date_gmt":"2026-03-16T16:23:37","guid":{"rendered":"https:\/\/www.richterbiologics.eu\/beyond-the-monoclonal-the-ascendance-of-single-domain-antibodies-and-fragments-in-biopharma\/"},"modified":"2026-03-16T16:23:39","modified_gmt":"2026-03-16T16:23:39","slug":"beyond-the-monoclonal-the-ascendance-of-single-domain-antibodies-and-fragments-in-biopharma","status":"publish","type":"post","link":"https:\/\/www.richterbiologics.eu\/de\/beyond-the-monoclonal-the-ascendance-of-single-domain-antibodies-and-fragments-in-biopharma\/","title":{"rendered":"Beyond the monoclonal: the ascendance of single-domain antibodies and fragments in biopharma"},"content":{"rendered":"\t\t
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\n\t\t\t\t\tRichter BioLogics discusses the company capabilities, capacities and expertise in producing VHH\/nanobodies for clinical and commercial purposes.<\/span>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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or decades, full-length monoclonal antibodies (mAbs) have dominated the biopharma landscape, serving as the gold standard for targeted therapeutics. However, a significant paradigm shift is currently underway. As the industry pivots towards smaller indication scopes and moves away from the traditional blockbuster model, production demands are shifting to smaller batch sizes. This makes standard Chinese hamster ovary (CHO) expression systems becoming less attractive for a growing list of products. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Consequently, in fields of oncology, rare diseases, autoimmune and infectious diseases, and as diagnostic\/imaging tools, the focus is sharpening on smaller, more agile modalities. Fragment-based formats, including specifically nanobodies (single-domain antibodies or VHHs), Fabs and single-chain variable fragments (scFvs), represent the next frontier in protein engineering. A key advancement driving this transition is the development of multi-domain VHH constructs. By combining multiple VHH units (bivalent or trivalent) into a continuous polypeptide chain, these formats achieve higher avidity and multi-specificity while retaining the stability of classic VHHs. Furthermore, they allow for the seamless integration of functional payloads, such as enzymes or toxins. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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This transition is not merely a trend; it is a necessary development driven by the limitations of conventional mAbs and the unique capabilities of these smaller molecules.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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The strategic advantage of antibody fragments<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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The dominance of mAbs has been challenged by their inherent physical limitations, specifically their structural complexity and approximate size of 150kDa. These factors can hinder tissue penetration, particularly within dense solid tumours, and complicate stability profiles. <\/p>

VHHs and antibody fragments in general offer a compelling alternative. Their reduced size of approximately 15kDa (for single-domain VHHs) allows for exceptional tissue penetration, granting access to epitopes that conventional antibodies cannot reach. Furthermore, their superior stability and high specificity make them powerful tools for next-generation cancer immunotherapies and advanced diagnostic imaging. <\/p>

However, the therapeutic potential of a molecule is irrelevant if it cannot be manufactured efficiently, safely and at scale needed. This is where the industry faces its most critical challenge: establishing robust production pipelines for these formats. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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This is precisely the area in which Richter BioLogics excels, with its extraordinary capabilities, capacities and expertise in producing VHH\/nanobodies for clinical and commercial purposes.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Richter BioLogics overcomes manufacturing hurdles with specialised expression systems<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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Producing complex proteins at high titres without compromising quality requires more than standard manufacturing protocols \u2013 it demands a specialised toolbox tailored to the molecule\u2019s unique properties.<\/p>

As pioneers in this field, having produced single-domain VHH\/nanobody molecules years before they became a dominant trend, Richter BioLogics has established and implemented a comprehensive production ecosystem over the last years.<\/p>

Its experience confirms that a one-size-fits-all approach is insufficient for different molecule types, including antibody fragments. Instead, success relies on leveraging different expression systems that ensure high yields and purity specifically for fragments. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Three platforms have proven essential in our manufacturing strategy for various protein products, including VHH\/nanobodies:<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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