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IL-23 dual-epitope equilibrium neutralization

Explore independent engagement of two IL-23 epitopes using measured SPR affinities. Report the equilibrium result only; the relaxation axis has no biological time interpretation. Compare six fixed presets covering the unbound reference, bivalent parental antibodies, their equimolar mixture, and 1+1 or 2+2 dual-epitope formats. Antibody excess and negligible target depletion are assumed; no fitted bioassay, disease, or clinical prediction is made.

Biparatopic targeting of IL-23 enables dual-epitope engagement and enhanced neutralization potency ↗

mAbs

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MODEL IN MOTION 18 sec

How does antibody concentration change free IL-23 under independent dual-epitope engagement?

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No-antibody normalized IL-23 baseline

Equilibrium comparison: the chart coordinate is numerical equilibration, not biological time; no kinetic time course is modeled. Baseline no-antibody condition. The local paper source reports IL-23 dose-response curves and EC50 fold shifts, but no machine-readable baseline EC50 table; the runtime keeps baseline_signal_ec50_nM at 1.0 by default.

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Scenario details

No-antibody normalized IL-23 baseline

Equilibrium comparison: the chart coordinate is numerical equilibration, not biological time; no kinetic time course is modeled. Baseline no-antibody condition. The local paper source reports IL-23 dose-response curves and EC50 fold shifts, but no machine-readable baseline EC50 table; the runtime keeps baseline_signal_ec50_nM at 1.0 by default.

Readouts

Equilibrium EC50 fold shift · dimensionless
Reciprocal of the free IL-23 fraction under independent epitope binding; not a fitted assay or clinical prediction.
Equilibrium free il 23 fraction · dimensionless
Fraction with neither epitope occupied, assuming antibody excess and negligible target depletion.

Study purpose

  • How does this defined antibody format change the predicted independent-binding equilibrium?

Assumptions

  • Only the equilibrium endpoint is scientifically interpreted; numerical relaxation is not an assay time course.
  • Table 1 SPR affinities are not the paper fitted statistical model.

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Simulation time
h
h
2 → 168

Time between reported samples.

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0.05 → 1

2 changes · Variation 1

Biology

Explore independent engagement of two IL-23 epitopes using measured SPR affinities. Report the equilibrium result only; the relaxation axis has no biological time interpretation.

Explore independent engagement of two IL-23 epitopes using measured SPR affinities. Report the equilibrium result only; the relaxation axis has no biological time interpretation.

Model details

11 parameters · 4 states · 4 equations · 10 derived outputs

Classification & API access
Therapeutic
Guselkumab/ustekinumab-derived experimental biparatopic antibodies
Modality
Monoclonal antibody
Target
IL-23A, p19, IL-12B, p40
Disease / scope
Recombinant human IL-23 binding (no disease model)
ParameterDefaultUnitDescription
Gsk guselkumab monovalent il 23 dissociation constantKd_guselkumab_nM0.0801nMAffinity of the guselkumab-derived anti-IL-23A/p19 paratope. Converted from pM to nM for runtime concentration units.
Gsk ustekinumab monovalent il 23 dissociation constantKd_ustekinumab_nM0.0648nMAffinity of the ustekinumab-derived anti-IL-12B/p40 paratope. Converted from pM to nM for runtime concentration units.
Baseline il 23 bioassay EC50baseline_signal_ec50_nM1nMSet to a measured no-antibody IL-23 EC50 to convert fold shift into absolute predicted EC50. Default 1.0 makes predicted_ec50_nM equal to fold shift.
Numerical relaxation rateequilibration_rate101/hFast relaxation rate used to embed the paper algebraic equilibrium equations in the ODE engine without changing their steady-state solution.
Fraction of molecules carrying guselkumab derived paratopeguselkumab_molecule_fraction0.5—For bivalent antibody mixtures this is the guselkumab molecule fraction. For 1+1 or 2+2 biparatopic formats use 1.0 because every molecule carries this paratope.
Guselkumab derived paratope valencyguselkumab_valency2—Use 2 for bivalent GSK-Guselkumab or 2+2 bpAb, 1 for 1+1 bpAb, and 0 for no guselkumab-derived paratope.
Total binding domain dose for optimal ratio calculationoptimization_domain_dose_nM6nMLegacy provenance-only input. Optimization now derives the actual binding-domain total from treatment concentration, fractions and valencies; this value does not alter predictions.
Total target concentrationtarget_total_nM1nMUsed to report free IL-23 in normalized concentration units. Does not alter the EC50 fold-shift equation.
Total antibody concentration in neutralization assaytotal_antibody_nM3nMTotal molecule concentration of antibody treatment. For mixtures, split by molecule fractions; for biparatopic molecules, all molecules carry both paratope classes.
Fraction of molecules carrying ustekinumab derived paratopeustekinumab_molecule_fraction0.5—For bivalent antibody mixtures this is the ustekinumab molecule fraction. For 1+1 or 2+2 biparatopic formats use 1.0 because every molecule carries this paratope.
Ustekinumab derived paratope valencyustekinumab_valency2—Use 2 for bivalent GSK-Ustekinumab or 2+2 bpAb, 1 for 1+1 bpAb, and 0 for no ustekinumab-derived paratope.

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