PDL1 Antibodies with Optimized Affinity and Stability

The patent modifies key parameters of the antibody molecule including affinity for PDL1 (achieving KD values in the picomolar range), isoelectric point (pI between 6.0-8.0 to reduce aggregation), and half-life (optimized Fc region for extended circulation). These parameter changes transform existing antibodies into more potent therapeutic agents that effectively overcome immunosuppression.

The patent creates composite antibody structures by combining optimized variable regions (with improved affinity and specificity) with engineered constant regions (with optimized effector functions and pharmacokinetics). This composite approach integrates multiple beneficial properties into a single therapeutic molecule, resulting in superior immune response activation.

The patent simultaneously optimizes multiple parameters including affinity (KD), isoelectric point (pI), and hydrophobicity to achieve a balanced profile. High affinity is maintained through optimized CDR regions while the framework regions are engineered to ensure proper folding, solubility, and stability, preventing the trade-off between affinity and biophysical properties.

The patent applies local optimization by modifying specific regions of the antibody independently: CDR regions are optimized for high affinity binding to PDL1, while framework regions and Fc regions are optimized for structural stability, solubility, and appropriate half-life. This localized quality assignment allows high affinity without compromising overall biophysical properties.