Creative Biolabs provides full-service for completely evaluating your bispecific antibodies (BsAbs) in vivo and in vitro, so as to help you solve complex problems in the preclinical tests. According to the client’s requirements and specific characteristics of a BsAb, experts from Creative Biolabs are able to design and perform the standard animal and cellular studies to obtain metabolism and pharmacokinetics (DMPK), preliminary efficacy, and toxicity information about your BsAbs.
As is well known, drug discovery is highly connected with in vitro and in vivo experimental models. In order to measure the efficacy and safety during drug development, a range of models, ranging from test tube experiments to cell cultures, animals, and healthy human subjects, are utilized at different stages. Besides, the absorption, distribution, metabolism and excretion (ADME) parameters gained from in vitro and in vivo models, are crucial for a decision to advance, hold or terminate a drug candidate. Therefore, suitable selection and application of the correct model, as well as proper data interpretation, are extremely essential in decision making and successful development of drug candidates.
Figure 1. The schematic diagram of co-clinical trial project. Synchronizing preclinical with clinical trials in parallel in human patients and mouse models allows real-time integration of information (Nardella, C., 2011).
In vitro assays have many unique advantages in screening chemical entities in the discovery stage. First, it is a convenient and rapid way to determine the potency and drug-like properties of chemical entities. Second, in vitro assays need limited amounts of the tested compound. Third, these assays are usually performed to answer special questions, which may be unable to be solved in animal studies. Fourth, human-based in vitro assays offer a more accurate estimation of human clinical outcomes than animal tests do at the preclinical stage.
Transporters serve as an essential role in drug disposition, drug–drug interactions and drug toxicity. The measurement of a drug candidate’s status as a transporter substrate and/or inhibitor needs a transporter assay. Creative Biolabs provides various in vitro experimental models for this purpose, including immortalized cell lines, transfected cell lines, hepatocytes, and membrane vesicles.
Primarily, the organ perfusion model closely mimics in vivo drug absorption, transport, metabolism and excretion. Liver perfusion model is the most explored one among a variety of organ perfusion models. However, bovine blood, bovine serum albumin, and bovine or human erythrocytes can also be used to mimic in vivo conditions, due to the hemoglobin and ideal protein binding conditions they offer. Ex vivo studies are assays in which a drug is dosed to animals and then the organ tissues are removed and used for determination of the variations in expression levels of enzymes or transporters upon drug treatment.
Results from In vivo models are multi-factorial, including the combined effects of permeability, distribution, metabolism and excretion, and also a measurable set of pharmacokinetic information and toxicology endpoints. Currently, rat as the first animal species for measuring drug exposure is commonly used, because they are inexpensive and need small amount of the tested compound. Human based in vitro assays can offer closer estimations of the human clinical outcomes, especially for properties that are known to have species differences.
An increasing number of engineered mouse models are used for measuring the roles of CYP enzymes in drug metabolism and toxicity. Human CYP gene(s) have taken the place of mouse Cyp gene(s) in the mouse genome, leading to our understanding of the specific involvement of the given mouse and/or human CYP(s) in a number of aspects of ADME.
Based on the well-established models, Creative Biolabs offers high throughput ADME screening, including:
We also provide DMPK studies, including:
With our well-established preclinical research platform, the experienced scientists at Creative Biolabs are dedicated to helping you develop BsAbs using a full range of the in vivo and in vitro models. Creative Biolabs also provides various other services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
1. Nardella, C.; et al. The APL paradigm and the “co-clinical trial” project. Cancer Discov. 2011, 1(2): 108-16.
2. Chapman, K.; et al. Preclinical development of monoclonal antibodies: considerations for the use of non-human primates. MAbs. 2009, 1(5): 505-516.