Sandbox Reserved 1474: Difference between revisions
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IgG mAbs are typically chimeric, humanized, or fully human proteins. The longest t1/2lamdaz values are usually achieved when the antibody does not bind to tissue sites and is not prematurely cleared due to antigenicity. | IgG mAbs are typically chimeric, humanized, or fully human proteins. The longest t1/2lamdaz values are usually achieved when the antibody does not bind to tissue sites and is not prematurely cleared due to antigenicity. | ||
Ch-mAb7F9, a chimeric mAb is produced as a treatment medication for METH abuse. In vitro, it is shown only binds to (+)METH (KD=6.9nM), (+)AMP(kI=350nM), (+)MDMA(kI=6.7nM). | |||
===Preclinical characterization of Ch-mAb7F9 for human use=== | ===Preclinical characterization of Ch-mAb7F9 for human use=== | ||
====Cross reactions in vitro ligand binding studies==== | ====Cross reactions in vitro ligand binding studies==== | ||
It did not bind endogenous neurotransmitters or other medications and was not bound by protein C1q, thus it is unlikely to stimulate in vivo complement-dependent cytotoxicity. <ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use" /> | It did not bind endogenous neurotransmitters or other medications and was not bound by protein C1q, thus it is unlikely to stimulate in vivo complement-dependent cytotoxicity. <ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use" /> | ||
====Isothermal titration calorimetry potency studies==== | ====Isothermal titration calorimetry potency studies==== | ||
Isothermal titration calorimetry analysis of ch-mAb7F9 binding to METH provided thermodynamic and stoichiometry measurements.<ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use" /> | |||
<table><tr><td colspan='2'> Antibody thermodynamic values and stoichiometry for target binding.<br></td><td colspan='2'><math>Delta G(kJ/mol)</math>.<br></td></td><td colspan='2'><math>Delta H(kJ/mol)</math>.<br></td></td><td colspan='2'><math>-t DeltaS(kJ/mol)</math>.<br></td></tr> | |||
<tr id='Antibody'><td class="sblockLbl"><b>[Ch-mAb7F9]</b></td><td class="sblockDat">-43</td></tr> | |||
<tr id=''><td class="sblockLbl"><b> </b></td><td class="sblockDat"> </td></tr> | |||
<tr id=''><td class="sblockLbl"><b> </b></td><td class="sblockDat"> </td></tr> | |||
<tr id=''><td class="sblockLbl"><b> </b></td><td class="sblockDat"> </td></tr> | |||
</table> | |||
====Pharmacokinetics studies in rats==== | ====Pharmacokinetics studies in rats==== | ||
METH had little effect on ch-mAb7F9 disposition, ch-mAb7F9 substantially altered METH disposition. <ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use" /> | METH had little effect on ch-mAb7F9 disposition, ch-mAb7F9 substantially altered METH disposition. <ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use" /> | ||
