Anti-IL-23p19 Antibody Formulation for High-Concentration Stability

The patent introduces multiple excipients as intermediary substances to mediate between the antibody molecules. Sucrose (5-10%) acts as a stabilizing agent that prevents aggregation, while polysorbate 80 (0.01-0.1%) serves as a surfactant that reduces surface tension and prevents interfacial aggregation. These intermediary substances enable high antibody concentrations (50-150 mg/ml) to be maintained without the physical instability and aggregation that would normally occur at such concentrations.

The patent systematically optimizes multiple formulation parameters simultaneously: pH (adjusted to 5.5-6.5 using histidine buffer), temperature (storage at 2-8°C), ionic strength (10-150 mM NaCl), and excipient concentrations. By changing these parameters within specific ranges, the formulation achieves a state where high antibody concentration is compatible with long-term physical stability. The histidine buffer system specifically controls pH to minimize antibody denaturation and aggregation.

Polysorbate 80 serves as a viscosity-modulating intermediary in the formulation. At concentrations of 0.01-0.1%, it acts as a surfactant that reduces interfacial tension and prevents protein-protein interactions that would increase viscosity. This allows the formulation to maintain acceptable viscosity levels even at high antibody concentrations of 50-150 mg/ml, enabling subcutaneous injection with volumes of 0.5-2.0 ml.

The patent controls viscosity by optimizing the balance between antibody concentration, buffer composition (10-150 mM NaCl in histidine buffer), and excipient concentrations. The formulation achieves a viscosity range of 5-50 cP at 25°C, which is suitable for subcutaneous injection. This is accomplished by maintaining pH 5.5-6.5 and using sucrose-polysorbate 80 combinations that prevent excessive protein crowding and aggregation.

The patent applies humanization by selectively replacing only the non-human portions of the antibody sequence. The CDR regions (residues 24-34, 50-56, 89-97 in light chain; 31-35, 50-65, 95-102 in heavy chain) that provide antigen-binding specificity are retained from the non-human parent antibody, while the framework regions are replaced with human sequences. This local modification approach maintains therapeutic efficacy against IL-23p19 while reducing immunogenicity by eliminating most non-human amino acid sequences.

The patent creates a humanized version of the anti-IL-23p19 antibody by copying the essential functional elements (CDR sequences) from the non-human parent antibody and integrating them into a human antibody framework. The humanized antibody sequences are designed to mimic the binding characteristics of the original non-human antibody while presenting a more 'self-like' structure to the human immune system, thereby reducing the risk of immune rejection and anti-drug antibody formation.