HuCAL Concept

The HuCAL (Human Combinatorial Antibody Library) technology is a unique and innovative concept for the in vitro generation of highly specific and fully human antibodies. HuCAL provides a seamless transition from a rapidly generated antibody fragment with outstanding binding characteristics to a fully human antibody drug candidate. It is the system of choice for a broad range of purposes reaching from target validation to drug development. Of course, HuCAL is also a direct source of antibodies for all kinds of diagnostic and therapeutic applications.

Features

• Rapid generation of fully human antibodies in a high-throughput fashion
• Proven success with difficult antigens (e.g. non-immunogenic or toxic antigens)
• High affinity that can be further increased through targeted optimization
• High expression yields in E.coli

In the HuCAL libraries the structural diversity of the human antibody repertoire is represented by seven heavy chain and seven light chain variable region genes. The combination of these genes gives rise to 49 frameworks in the master library. By superimposing highly variable genetic cassettes (CDRs = complementarity determining regions) on these frameworks, the vast human antibody repertoire is perfectly reproduced. The genes, which comprise HuCAL were 100% prepared by chemical synthesis. No Polymerase Chain Reaction (PCR) is required at any stage in the development or use of HuCAL.

The use of MorphoSys’s proprietary trinucleotide mutagenesis technology (TRIM) allows the synthesis of any desired combination of amino acids at each single position of the variable regions. Therefore, in HuCAL libraries, the length and amino acid composition of the CDR regions are retained according to the natural antibody sequences derived from humans. Each of these CDR cassettes can be specifically and easily exchanged in order to facilitate the optimization of a specific antibody.

The structural types of the human antibody repertoire can be reproduced with seven heavy chain and seven light chain variable region genes. The combination of these genes gives rise to 49 frameworks in the master library. By superimposing highly variable genetic cassettes (CDRs) on these frameworks, the entire human antibody repertoire can be mimicked.

The diversity of the HuCAL antibody libraries makes HuCAL an extremely powerful tool for antibody generation. The modular gene structure of HuCAL allows easy switching between different antibody formats. Monomeric Fab fragments can be converted via one cloning step into a dimeric format, which is, for example, ideally suited for application in immunohistochemistry (see also AgX). When inserted into a standard immunoglobulin expression vector, fully human IgG antibodies can be produced ready for assessment as therapeutics.

At present, leading research-based pharmaceutical and biotechnology companies such as e.g. Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Merck & Co. Inc., Schering-Plough and Shionogi have integrated HuCAL into their R&D processes. MorphoSys is committed to supporting and further developing this platform, providing its users with ongoing access to the most advanced antibody technology available.