![]() ![]() The PK of mAb can also be influenced by anti-drug antibody (ADA) response and off-target binding, which require careful consideration during the discovery stage. Most mAbs display target mediated drug disposition (TMDD), which can have significant consequences on the study designs of preclinical and clinical studies. mAb charge can be important and variants with pI values of 1–2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. ![]()
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January 2023
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