Antibody Optimization
The unique modular structure of HuCAL is the basis for a rapid access to human antibodies with optimized characteristics.
Features:
- Unique DNA restriction sites flanking all important segments of the antibodies
- Highly diversified affinity maturation cassettes of all six CDRs
- Rapid antibody optimization
- Optimization of affinity and biological activity
- No amino acid exchanges in frameworks lowering the risk of immunogenicity of optimized antibody
The HuCAL technology dramatically simplifies the optimization of an antibody’s binding characteristics. The complementarity-determining regions (CDRs), which mostly contribute to the binding to the target molecule, can easily be exchanged in a simple cloning step.
MorphoSys’s proprietary TRIM technology facilitates the targeted diversification of CDRs: Pre-assembled trinucleotides are used in the chemical synthesis of the CDR sequences, thereby ensuring complete control over the amino acid composition and avoidance of STOP codons. As a result, the CDR libraries are of substantially higher quality than using conventional approaches.
- The HuCAL technology dramatically simplifies the optimization of an antibody’s binding characteristics. The complementarity-determining regions (CDRs), which mostly contribute to the binding to the target molecule, can easily be exchanged in a simple cloning step.
HuCAL antibodies binding to a specific antigen are identified in a first round of screening. For optimization of the binding characteristics, CDRs diversified according to the natural repertoire of CDR sequences are inserted via the unique flanking restriction sites. This simple and efficient “mix and match”-process permits rapid affinity maturation of single antibodies (“lead optimization”) or even antibody pools (“pool maturation”). By sequential exchange of CDRs improvement factors in affinity of >3,000 fold compared to the non-optimized parental binders could be shown, resulting in antibodies exhibiting subnanomolar affinities.
- HuCAL antibodies binding to a specific antigen are identified in a first round of screening. For optimization of binding characteristics, new CDR sequences are inserted via unique flanking restriction enzymes. In further screening rounds, antibodies with improved binding characteristics are identified. Candidates chosen from optimization can be converted in various Ig formats.
- Optimization of antibodies does not only lead to antibodies with higher binding affinities. Optimization also improves the biological function of the antibodies, e. g. blocking of a rat protease.