Antibody Developability Prediction

Antibody developability prediction estimates key developability properties of an antibody from its sequence. It facilitates developability assessment and optimization early in the antibody design process.

Features

• Comprehensive prediction: Predicts multiple critical developability properties including expression yield, thermostability, aggregation, viscosity, etc.
• State-of-the-art algorithm: Powered by advanced deep learning techniques including large language models and geometric deep learning. Achieves superior performance over baseline models.
• Convenient usage: Only need the antibody sequence as input. No need for structure modeling or complex setup.

Inputs

To submit an Antibody Developability Prediction job, open the Project Editor and select "Antibody Developability Prediction" from the "Antibody Engineering" dropdown menu.

• Antibody: Input antibody in FASTA format. You can either enter the sequence directly or upload a FASTA file by clicking "". The antibody should contain both heavy and light chains labeled as _H and _L.

  >antibody_H
  EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
  >antibody_L
  DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK
  

• Job Name: Name of the job. Must be unique within the project.

Job submission form: Antibody Developability Prediction

Models & Parameters

You can leverage two BioGeometry proprietary models for this job: GeoDevPred+ and GeoDevPred-v2 (default). We recommend using GeoDevPred-v2 for its superior performance.

Parameter of the GeoDevPred+ model include:

• Prediction targets: Developability properties to predict. Select one or multiple from below. Defaults to all.
  • Stability:
    • Fab Tm by DSF (°C): Thermostability of the Fab (antigen-binding fragment), observed using differential scanning fluorimetry (DSF). Higher is better.
    • Accelerated Stability SEC Slope: Stability of the antibody, measured by size-exclusion chromatography (SEC) slope under accelerated stress conditions. Lower is better.
  • Expression:
    • HEK Titer (mg/L): Expression yield in human embryonic kidney (HEK) 293 cells. Higher is better.
    • Normalized Yeast Surface Expression (%): Expression yield in yeast surface display. Higher is better.
  • Solubility:
    • HIC Retention Time (min): Antibodies with more hydrophobic characteristics have a longer hydrophobic interaction chromatography (HIC) retention time. Lower is better.
    • SGAC-SINS AS100 ((NH₄)₂SO₄ mM): Salt-Gradient Affinity-Capture Self-Interaction Nanoparticle Spectroscopy quantify the interaction between antibodies bound to the surface of gold nanoparticles by measuring the phonon wavelength. Higher is better.
    • SMAC Retention Time (min): Antibodies are injected onto a pre-packed Zenix HPLC column and their retention times are calculated. The longer the Solvent-Modified Affinity Chromatography (SMAC) retention time, the lower their colloidal stability. Lower is better.
    • AC-SINS ∆λmax (nm): The Affinity-capture Self-interaction Nanoparticle Spectroscopy (AC-SINS) assay tests how likely an antibody is to self-interact. It uses gold nanoparticles that are coated with anti-Fc antibodies. When a dilute solution of antibodies is added, they rapidly become immobilised on the gold beads. If these antibodies subsequently attract one another, it leads to shorter interatomic distances and longer absorption wavelengths that can be detected by spectroscopy. Lower is better.
    • CSI-BLI Delta Response (nm): Clone Self-Interaction by Bio-layer Interferometry quantifies the degree to which clones of an antibody self-associate. Lower is better.
    • CIC Retention Time (Min): HPLC-based Cation-Interaction Chromatography (CIC) technique helps to understand the 'charge variance' in antibodies. Longer retention time indicates that the antibody species exhibits lesser charge variance and is more uniform, which can be critical for stability and efficiency over time.
  • Viscosity:
    • Viscosity at 150 mg/mL (cP): Thickness or resistance to flow of an antibody solution at a high concentration (150 mg/mL). Lower viscosity is generally better for manufacturing and for the end-user, because it allows for easier syringeability and less discomfort for the patient upon injection.
  • Polyspecificity:
    • PSR SMP Score (0-1): The poly-specificity reagent (PSR) binding assay provides Normalized Median Fluorescence Intensity (MFI) values for IgG-presenting yeast that have been incubated with a polyspecificity reagent, indicating antibody specificity. Lower is better.
    • BVP ELISA: Baculovirus Particle (BVP) ELISA measures the binding capacity of an antibody to baculovirus particles. Lower is better.
    • ELISA: In this protocol, the ELISA score measures an antibody's binding affinity to six different antigens (cardiolipin, KLH, LPS, ssDNA, dsDNA, and insulin) individually coated onto the ELISA plates. Lower is better.
    • Immunogenicity: The degree to which an antibody is able to stimulate an immune response. Lower is better.

Parameter of the GeoDevPred-v2 model include:

• Prediction targets: Developability properties to predict. Select one or multiple from below. Defaults to all.

  • HEK Titer (mg/L): Expression yield in human embryonic kidney (HEK) 293 cells. Higher is better.
  • Fab Tm by DSF (°C): Thermostability of the Fab (antigen-binding fragment), observed using differential scanning fluorimetry (DSF). Higher is better.
  • HIC Retention Time (min): Antibodies with more hydrophobic characteristics have a longer hydrophobic interaction chromatography (HIC) retention time. Lower is better.
  • Accelerated Stability SEC Slope: Stability of the antibody, measured by size-exclusion chromatography (SEC) slope under accelerated stress conditions. Lower is better.
  • AC-SINS ∆λmax (nm): The Affinity-capture Self-interaction Nanoparticle Spectroscopy (AC-SINS) assay tests how likely an antibody is to self-interact. It uses gold nanoparticles that are coated with anti-Fc antibodies. When a dilute solution of antibodies is added, they rapidly become immobilised on the gold beads. If these antibodies subsequently attract one another, it leads to shorter interatomic distances and longer absorption wavelengths that can be detected by spectroscopy. Lower is better.
  • Viscosity at 150 mg/mL (cP): Thickness or resistance to flow of an antibody solution at a high concentration (150 mg/mL). Lower viscosity is generally better for manufacturing and for the end-user, because it allows for easier syringeability and less discomfort for the patient upon injection.
  • SMAC Retention Time (min): Antibodies are injected onto a pre-packed Zenix HPLC column and their retention times are calculated. The longer the Solvent-Modified Affinity Chromatography (SMAC) retention time, the lower their colloidal stability. Lower is better.

Results

The results are summarized in a CSV file, which can be downloaded by clicking the "" button.

It contains the following columns:

• name: Name of the input antibody.
• VH_sequence: Sequence of the heavy chain variable domain of the input antibody.
• VL_sequence: Sequence of the light chain variable domain of the input antibody.
• {property}: Predicted value of the target property. One column for each selected property.
• {property}_percentile: Predicted value of the target property. One column for each selected property. Higher value indicates better developability regarding the specific property.