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MorphoSys’s HuCAL (Human Combinatorial Antibody Library) technology is a unique and innovative concept for the in vitro generation of highly specific and fully human antibodies. 

The collection of several billion distinct fully human antibodies allows for the rapid selection of antibodies with high affinity and specificity. The recombinant antibody technology of HuCAL enables the generation of therapeutic and diagnostic antibodies, including those binding to difficult antigens.

HuCAL antibodies are produced in bacteria, and the technology enables in vitro selection to isolate antibodies with the desired characteristics. HuCAL is generated by de novo gene synthesis, and the large library is screened with a technique called phage display to identify the antibody with a high affinity to the investigated antigen.

The structural diversity of the human antibody repertoire is 95 percent composed of seven heavy chain and seven light chain variable region genes. The combination of these genes gives rise to 49 frameworks in the HuCAL master library displaying several billion distinct fully human antibodies.

Further fine-tuning of the antibodies is made possible with MorphoSys’s proprietary TRIM technology that facilitates the targeted diversification of CDRs. Pre-assembled trinucleotides are used in the chemical synthesis of the CDR sequences, thereby ensuring complete control over amino acid composition while avoiding stop codons. TRIM allows synthesizing any combination of amino acids at each single position of the variable region in a ratio reflecting exactly the one found in humans. As a result, these CDR libraries are of substantially higher quality than those developed using more conventional approaches.