Somatic Hypermutation (SHM)
The basis for AnaptysBio’s proprietary technology is Somatic HyperMutation (SHM) – the natural process that occurs in a specific cell type of the immune system (B-cells) during the selection and maturation of antibodies. This process is the means by which the body generates potent antibodies to fight disease.
SHM is a controlled process of introducing changes into the binding region of the antibody gene sequence catalyzed by a molecule called Activation-Induced Cytidine Deaminase (AID). In scientific terms, AID initiates the process of SHM by deaminating deoxycytidine (dC) residues to become deoxyuridines (dU) within the IgV (variable) region of the immunoglobulin locus. DNA repair enzymes and other molecules then play a role in introducing additional changes in the binding region sequence of the antibody.
Following a process known as Recombination, B cells generate a large number of antibodies with different binding characteristics; through subsequent SHM an even greater, more potent and diverse, assortment of antibodies is created. Only those B cells expressing antibodies with stronger binding to the disease target survive and go on to generate large quantities of therapeutically useful antibodies.
SHM-Platform™ Description
The SHM-Platform™ is a powerful next generation antibody platform designed to generate therapeutic antibodies with characteristics that meet increasingly more challenging product design goals. The platform utilizes the key components of SHM coupled with high-throughput selection using flow cytometry to create best-in-class antibodies directed at novel, validated and previously difficult disease targets. The use of SHM results in a characteristic pattern of amino acid changes that are preferentially located in the binding regions of antibodies and resemble those that occur naturally, suggesting that the resulting antibodies will be well tolerated. This novel approach has been referred to as “naturalizing” antibodies.
For antibody discovery and optimization, AnaptysBio applies the SHM-Platform™ to its proprietary library of fully human, full length, bivalent antibody genes expressed in mammalian cells to evolve and select antibodies with the desired binding characteristics to the target of interest. For affinity maturation, AnaptysBio applies the SHM-Platform™ to evolve a specific antibody into multiple new versions with improved binding characteristics.
The SHM-Platform™ is robust, fast, and is not subject to the traditional royalty stacking obligations normally associated with antibody discovery and optimization.
Advantages
Increased probability of generating antibodies that:
Meet ever more challenging design goals
Are well tolerated
Are functional
Are manufacturable
Possess desirable, specific cross-reactivity
Points of Differentiation
Uniquely versatile platform
Same platform for de novo antibody discovery/optimization as well as affinity maturation of existing antibodies
Can evolve and select antibodies using the intended final therapeutic format (e.g., full length, fragment, etc.)
Natural method of generating antibody diversity
No in vivo selection bias
Evolving, non-static library of antibody genes
Simultaneous co-evolution of heavy and light antibody genes