Bio-Rad Laboratories Inc, Hercules, Calif, has published new findings on the generation and characterization of drug-target complex-specific antibodies for pharmacokinetic analysis of biotherapeutics.1
The findings discuss antibodies that recognize a drug only when bound to its target. Called Type 3 antibodies, such antibodies differ from other anti-idiotypic antibodies that specifically detect free antibody drug by binding the paratope of the drug (Type 1), or total drug by binding outside the paratope of the drug (Type 2).
Bio-Rad researchers have demonstrated the utility of Type 3 and Type 4 antibodies for pharmacokinetic assays.
Pharmacokinetic assays form part of the totality of evidence required for approval of an original biologic or biosimilar drug, and anti-idiotypic antibodies are critical reagents used in these types of ligand binding assays. By describing the generation and characterization of Type 3 specificities for the development of ligand binding assays, the authors demonstrate the advantages of such antibodies as tools for drug quantification.
The paper describes the successful generation of Type 3 antibodies directed against several approved antibody drugs, using Bio-Rad’s innovative custom antibody generation service, based on the Human Combinatorial Antibody Library (HuCAL) technology and Cys-Display, a modified phage display method. Such recombinant production ensures a consistent and secure batch-to-batch supply, which is important for assay reproducibility.
Stefan Harth, Bio-Rad Laboratories.
Using Type 3 antibodies, Bio-Rad’s team demonstrated increased sensitivity and specificity across several assay formats, and quantified the detection of drugs produced as monovalent antibody fragments, such as ranibizumab, which is difficult to achieve with commonly used ligand binding assays, such as bridging assays. Additionally, the team introduced a derivative of the Type 3 specificity, termed Type 4, providing an alternative when the drug target is not easily available or costly to produce, or when selection of Type 3 is not possible.
“Drug development relies on ligand binding assays, and the robustness, accuracy,and reproducibility of these assays depends on the quality of critical reagents used,”says Stefan Harth, Bio-Rad’s R&D team leader for custom antibodies and lead author on the paper.“This paper is important in characterizing drug-target complex-specific reagents as useful tools in those assays, demonstrating several advantageous properties, to ultimately improve the accuracy of conclusions and accelerate the drug development process.”
Amanda Turner, Bio-Rad Laboratories.
“The reagents discussed in the paper represent a valuable addition to the ligand binding assay toolbox, and the reagents offer bioanalysts options for more sophisticated pharmacokinetic assay design to support biotherapeutic development,”says Amanda Turner, product manager for Bio-Rad’s life science group. “The original Type 3 and Type 4 reagents enable simple and robust assays that support the development of simplified rapid tests for therapeutic drug monitoring.”
For further information, visit Bio-Rad Laboratories.
Reference
- Harth S, Ten Haaf A, Loew C, Frisch C, Knappik A. Generation by phage display and characterization of drug-target complex-specific antibodies for pharmacokinetic analysis of biotherapeutics. MAbs. Epub ahead of print, December 5, 2018:1–13; doi: 10.1080/19420862.2018.1538723.
Featured image: Bio-Rad researchers describe Type 4 antibodies for use in ligand binding assays when Type 3 antibodies are unavailable or are too costly to produce.
