F-MAB

Elute the antigen (-f mAb) by heating beads for 5 min at 95 C with an equal volume of SDS sample buffer and run on an SDS-containing 10% polyacrylamide reducing gel. Run pre-stained markers on these gels because they will transfer to blots and assist in determining the size of the proteins. 

Die Reduktion von Benzoldiazoniumchlorid zu Phenylhydrazin ist sowohl in verdiinnter Salzsaure (an Quecksilber)2 wie auch in Natronlauge (an Graphit)3 in technischem MaB-stab durchfiihrbar. Die Ausbeuten sind mit 72% an Quecksilber und 90% d.Th. an Graphit giinstiger als bei der chemischen Reduktion2,3. Da diese Reaktion ausfiihrlich in ds. Handb., Bd. X/2, S. 222 f. besprochen wurde, soil an dieser Stelle nicht naher darauf einge-gangen werden. 

Despite the differences between the estimated derivatives values, the computed profiles of the specific MAb production rate are quite similar. Upon inspection of the data, it is seen that during the batch period (up to t=2I2 h), qM is decreasing almost monotonically. It has a mean value of about 0.5 /ug/(l(f cells-h). Throughout the dialyzed continuous operation of the bioreactor, the average qM is about 0.6 fxg/(l(f cells-h) and it stays constant during the steady state around time... 

McKey, D. and Beckerman, S. (1993). Chemical ecology, plant evolution and traditional manioc cultivation systems. In Man and theBiosphereSeries, vol. 13 Tropical Forests People andPood, ed. C. M. Hadlik, A. Hadlik, O. F. Linares, etflZ. pp. 321-338. Paris UNESCO-MAB/Parthenon Publishing. 

Marin MAB, Nome F, Zanette D, Zucco C, Romsted LS. J Phys Chem 1995 99 10879-10882. 

Prepare immunoabsorbent beads by linking 5-15 mg of purified MAb or polyclonal antibody to mouse or rat F[ab ]2 to Sepharose 4B (about 3 mL of swollen gel). Alternatively, use protein A/G-beads for mouse antibodies (see Note 14)... 

Due to their high molecular mass (and other reasons), the vast majority of mAbs that have been approved or are currently in clinical development are administered by intravenous (IV) infusion. This route allows the total dose to be available in the circulation, as F (the systemically available fraction of the dose) is, by definition, 1. In consequence, maximum concentrations in serum are rapidly observed, and are higher compared to those achieved by other routes. Therefore, adverse reactions after IV administration occur more often but are generally reversible. In addition, IV infusions represent the most inconvenient (they often require hospitalization) as well as time- and cost-consuming means of administration. Consequently, ex-travascular routes have been chosen as alternatives, including subcutaneous administration (SC e. g., adalimumab, efalizumab) and intramuscular administration (IM e.g., palivizumab) (Table 3.4). 

The mechanism of absorption after SC or IM administration is thought to occur via the lymphatic system. The mAbs enter the lymphatic system by convective flow of interstitial fluid into the porous lymphatic vessels. The molecular mass cut-off of these pores is >100-fold the molecular mass of mAbs. From the lymphatic vessels, the mAbs are transported unidirectionally into the venous system. As the flow rate of the lymphatic system is relatively low, mAbs are absorbed over a long time period after administration. The resulting time of maximum concentration (tmax) is much later (typically 1-8 days), and the systemically available fraction (F) is equal or lower (typically 0.5-1.0) compared to the IV administration of mAbs. For example, SC injection of 40 mg adalimumab results in a tmax of approximately 5 days, and F is approximately 64%. 

The pharmacokinetic parameters of approved mAbs with regard to absorption, maximum concentration (Cmax) and tmax after single dose administration, systemically available fractions (F), and the commonly used dosing regimens and routes of administration are summarized in Table 3.4. 

In contrast to antibacterial antibiotic therapy, inhibition of viral replication is usually difficult to achieve. Therefore preventive strategies, such as vaccination, are frequendy more successful and clinically important. However, vaccines are not available for all viruses furthermore, some viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), are ubiquitously present and usually not very pathogenic unless in an immunocompromised host. One strategy to combat viral infecdons in the immunocompromised host is the application of neutralizing mAbs. One such mAh is directed to the F protein of the respiratory syncytial virus (RSV), which afflicts premature newborns with often severe pulmonary infections this mAh appears to be useful in such situations (91). Other mAbs to viral antigens are in development. 

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