Antibody modeling approaches

To guide model development, the observed data were first examined graphically to determine general characteristics and to look for trends with respect to dose, time, and the impact of anti-mAb antibodies. Models were developed using NONMEM (Version 5). Two different model types were developed the first model (MODEL 1, see Appendix 45.1) used an analytical solution (closed-form) where the nonlinearity was accounted for by allowing the model parameters to be a function of mAb dose and the titer of anti-mAb antibody, while the second model (MODEL 2, see Appendix 45.2) used differential equations to allow a more mechanistic approach to characterize the nonlinearity. For each model, three estimation methods were evaluated first-order (FO), first-order conditional estimation (FOCE), and FOCE with interaction. Various forms of between-subject variability models were evalu-... 

Different approaches have been used to probe the role of chemokines and their receptors in experimental models of arthritis for instance, peptide antagonists or immunization of the host to promote the generation of endogenous neutralizing Abs via the use of chemokine plasmid DNA vaccination (Table 4 and Ref. 50), injection of neutralizing antibodies (Table 5), or mice that lack specific chemokine or chemokine receptors (Table 6). 

In the pharmaceutical sciences, the nonequilibrium thermodynamics approach has been particularly important in the design of osmotic drug delivery devices, as discussed in Chapter 11. It has also been used to describe the convective transport of a binding antibody in an in vitro model of a solid tumor [8], As our appreciation of the roles of convection and osmosis in drug delivery increases, the nonequilibrium thermodynamics approach may find wider appeal. 

Model selections, in which phage antibodies with defined specificity are mixed with nonspecific phage and the enrichment and yield for a selection procedure is measured, provides a rapid experimental approach for studying such complex selection procedures. In order to compare different selection approaches on complex preparations, and to determine the best selection parameters for each approach, an extensive study of various in vitro and in vivo model selections was recently carried out by our group [73]. 

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