Antibody animal species selection

Animal Species Selection Almost all pharmaceutical companies select animal species for preclinical studies on the basis of the results of the responsiveness of a test animal to the biological activity of a biopharmaceutical and its production of neutralizing antibodies. Such considerations are specifically applicable to biopharmaceuticals but not to new chemical entities (NCEs). This survey finding suggests that most pharmaceutical companies in Japan understand and implement the animal species selection in good accordance with ICH S6. 

Common haptens used for labeling DNA probes for BISH assays are biotin, DIG, DNP, FITC, and Texas Red. Based on the size of your DNA targets, you may choose from a direct detection or an indirect detection for BISH assays. In general, an indirect detection system can provide better sensitivity compared to a direct detection system. For an indirect detection, you need to select a combination of two antibodies raised with two different animal species, such as a mouse anti-DIG antibody and a rabbit anti-DNP antibody, so that enzyme-labeled anti-mouse antibody and anti-rabbit antibody can be applied for signal detection. If a direct BISH detection is going to be applied, anti-hapten antibodies raised in the same animal species that are labeled with either AP or HRP enzyme molecules... 

Tissue Cross-Reactivity Studies for Monoclonal Antibodies Predictive Value and Use for Selection of Relevant Animal Species for Toxicity Testing... 

The sera of certain animal species contain substances which are not antibodies, although they bind to hepatitis B surface antigen. They are probably glycoproteins and can be selectively removed from sera by reaction with purified hepatitis B surface antigen. 

Pharmacological activity in the test species is an essential component in providing the rationale for species selection. This is usually accomplished by in vitro comparison of binding affinity (or functional activity) of the antibody to animal and human cells. For example, the ability of the test antibody to block a human mixed lymphocyte reaction can be compared with its ability to block mixed lymphocyte reactions in the test species. 

Primates may be needed when it becomes clearer that the parameters of interest (hematology, blood chemistry, histopathology, etc.) can only be studied in species that are phylogenetically closer to H. sapiens. This is often the case when candidate drugs are proteins (e.g. animal-derived monoclonal antibodies), and antibody formation may be major issue and may dictate the choice of species. For example, it may be known that only the chimpanzee does not develop neutralizing antibodies to the drug, which would lead one to select that species as the nonclinical model. 

Variations between species using different enzyme substrates have been shown for cholinesterase (Myers 1953 Evans 1990) and other enzymes (e.g., angiotensin converting enzyme Evans 1989). For alkaline phosphatase, the majority of methods employ 4-nitrophenylphosphate as the substrate, but there are two main alternative buffers—diethanolamine and 2-aminopropanol—that can cause interspecies differences (Masson and Holmgren 1992). For isoenzymes, the majority of laboratories currently use a variety of electrophoretic separation methods although selective inhibition of isoenzymes with antibodies is being used increasingly, there are problems associated with protein specificity and relative isoenzyme concentrations in animal samples. 

More sensitive is the polymerase chain reaction (PCR). Using two PCR primers, even small amounts of DNA can be detected, due to selective amplification (Newton and Graham, 1997). Thus, PCR allows the unambiguous identification of animal and plant species in food or feedstuffs. Moreover, the unique specificity, selectivity, and sensitivity of PCR affords the analysis of complex matrices (Meyer et al., 1993). In addition, primers (in contrast to antibodies) as starting points for PCR are independent of commercial sources and easily accessible to everyone. 

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