Biomedical Engineering Reference
In-Depth Information
Variable
Constant
S
S
S
S
Figure
9.2.
Schematic of the monoclonal antibody structure.
The variable region, which includes the ends of both heavy and light chains, is the
antigen binding site. The variable region is further subdivided into hypervariable (HV)
and framework (FR) regions. The HV regions contain a high ratio of different amino
acids in a given location and are directly responsible for the antigen binding activity. The
FR regions have more stable amino acid sequences and form a beta sheet scaffold
structure to hold the HV regions in position to contact the antigen. On the other hand, the
constant regions do not directly participate in the antigen binding activity. Identifying
the type of chemical modifications and the associated molecular regions with respect to
the antigen binding activity helps design the preformulation studies and determine
stabilization strategies. An example summary of these types of results for an antibody
example is provided in Table 9.2. In this case, the forced degradation results for a
particular antibody under development may indicate that the variable region is suscep-
tible to aggregation at acidic pH, oxidation at elevated temperature, and in the presence of
trace metals, whereas the constant region is more susceptible to deamidation at alkaline
pH region and oxidation at elevated temperature. These results are critical to the
