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Extending a Large Molecule Model for Pregnancy in MoBi

Learn how to extend a large molecule base model for pregnancy scenarios in MoBi by configuring FcRn recycling, fetal, and maternal extension modules.

By Sophie Fischer

To extend a base large molecule model for pregnancy scenarios with FcRn-mediated placental transfer in MoBi, you must incorporate three extension modules: the FcRn Recycling Extension -Pregnancy Module, the Fetal Extension Module, and the Maternal Extension Module. Because these modules use default compound names upon import, you must rename the placeholder name (WT IgG) to your drug name and update related reaction formulas to match your specific drug (e.g., Efgartigimod) before compiling the final simulation.

1. Rename the Core Molecule and Complex

Start by updating the default WT IgG molecule to the name of your compound used in the PKSim base model.

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Right-click the default WT IgG molecule.
Step #1: Right-click the default WT IgG molecule.
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Select Rename.
Step #2: Select Rename.
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Change name and click OK.
Step #3: Change name and click OK.
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Click OK on the Rename Related Entities dialog to automatically update dependencies.
Step #4: Click OK on the Rename Related Entities dialog to automatically update dependencies.
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Next, rename the WT IgG-FcRn complex following the same steps.

2. Update Reaction Names

You also need to rename the individual reactions so that they clearly indicate your specific molecule instead of the default generic name.

Go through the list and replace WT IgG with your drug's name for each relevant reaction:

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Rename the FcRn binding tissue WT IgG reaction.
First, open the reaction and then click on the three dots next to the reaction name and change WT IgG to your compound name.
Step #6: Rename the FcRn binding tissue WT IgG reaction.First, open the reaction and then click on the three dots next to the reaction name and change WT IgG to your compound name.
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Rename the following three reactions
- FcRn binding WT IgG in interstitial
- FcRn binding WT IgG in endosomal space
- FcRn binding WT IgG in plasma
as described in step 6.

3. Update Parameters in Reaction BB

Ensure that parameter formulas reference to the right molecule.

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Switch to the Parameters tab in the reaction panel.
Step #8: Switch to the Parameters tab in the reaction panel.
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Select the Total amount of drug-FcRn-Complex parameter.
Step #9: Select the Total amount of drug-FcRn-Complex parameter.
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Rename WT IgG-FcRn_Complex in the conditions panel with your compound name, e.g. Efgartigimod-FcRn_Complex.
Step #10: Rename WT IgG-FcRn_Complex in the conditions panel with your compound name, e.g. Efgartigimod-FcRn_Complex.
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Repeat that renaming in the conditions tab for Total amount of drug.
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The conditions in the parameter tab need to be updated for:
- FcRn binding WT IgG in interstitial
- FcRn binding WT IgG in endosomal space
- FcRn binding WT IgG in plasma
for both the Total amount of drug and Total amount of drug-FcRn-Complex following the steps described above.
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Delete the Molcule BB from the FcRn recycling extension - pregnancy module

3. Update the reactions within the Fetal Extension Module

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Under the Fetal module, double-click the Fetal FcRn compensation for growing Fetus reaction.
Step #14: Under the Fetal module, double-click the Fetal FcRn compensation for growing Fetus reaction.
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Click the concentration alias field in the properties table and update the path reference to the right molecule name, e.g. Efgartigimod-FcRn_Complex Concentration.
Step #15: Click the concentration alias field in the properties table and update the path reference to the right molecule name, e.g. Efgartigimod-FcRn_Complex Concentration.

4. Create the Pregnancy Simulation

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Create your simulation by adding all the needed modules
Step #16: Create your simulation by adding all the needed modules