Abzyme will partner with your company to solve typical issues encountered in antibody drug development, such as protein expression, thermostability, folding, target affinity, on-target/off-tumor toxicities and more.
Conditionally-active Antibodies: The tumor microenvironment is acidic compared to physiological pH, due to its poor vascular perfusion, regional hypoxia, and fermentative glycolysis in the tumor. Abzyme offers 3 strategies to restrict the activity of your therapeutic to the tumor microenvironment by taking advantage of this pH differential. First, we can optimize the binding profile of your antibody for a specific pH range, so as to have a high on-rate at low pH and high off-rate at neutral pH or vice versa. Specific binding at this pH can essentially render this antibody inactive in normal tissues and active in the tumor microenvironment. Such specific activity would minimize on-target, off-tumor toxicity and increase the antibody’s mean residence time by reducing binding to non-therapeutic targets. This allows the therapeutic dose to be much lower. On the other hand, fine tuning candidate antibodies to bind specifically at high pH and dissociate at low pH can increase the antibody’s plasma half-life by facilitating antibody recycling via neonatal Fc receptors in the acidic endosome. A second alternative would be to fuse a pH-dependent anti-albumin VHH to your therapeutic, so that its activity is limited in normal tissues, but activated inside the tumor, where albumin no longer binds to the VHH. Finally, the third strategy is to fuse an anti-albumin VHH with a linker that can be cleaved with a tumor-specific protease, so that your therapeutic can be free to bind its antigen only inside the tumor microenvironment. The anti-albumin antibodies are available for licensing or can be engineered to your biologic as a service.
Expression, Thermostability and Folding: Good expression, thermostability and proper folding are key attributes for successful biologic manufacturing and storage. Abzyme will work with your company to improve the attributes of your existing antibodies while retaining their binding affinity. Starting from the gene encoding the original antibody, a self-diversifying antibody library will be built. From the highly diversified library, we will isolate well-expressed, well-displayed, and thermostable clones with high affinity.
Target Affinity: While an antibody may bind to the correct epitope and has neutralizing properties, sometimes the affinity is not optimal for therapeutic applications. Abzyme will work with you to improve or moderate your antibody affinities to suit your therapeutic applications.
Humanization: Antibody humanization may reduce the immunogenicity of an antibody while preserving its therapeutic qualities. The process requires both bioinformatic analysis and physical experiments. Abzyme’s humanization approach allows rapid selection of humanized antibody variants with attributes optimized for therapeutic applications.