BIOLOGICS
Combined technology for antibody drugs
arYla is the
combination of the HuCAL technology and a solid-phase technology, and enables the individual design of each CDR (complementary determining regions) cassette for a variety of properties, such as high affinity and low immunogenicity. It is applicable to all HuCAL antibodies. HuCAL is a fully synthetic human Fab library that is based on modular consensus frameworks and CDRs, and represents the structural diversity of the human antibody repertoire. Further fine-tuning of antibodies can be achieved with a DNA engineering platform (Slonomics) that is based on the synthesis and ligation of double-stranded oligonucleotides with
technology platforms of MorphoSys and of Sloning BioTechnology, which was acquired by MorphoSys last year. The company plans to use the technology to accelerate antibody optimisation, with the goal of generating superior therapeutic and diagnostic candidates faster and more cost-effectively than is currently possible. arYla will be used to optimise a range of properties critical to the successful development of a therapeutic or diagnostic antibody. “We see many therapeutic and diagnostic antibody programmes in our industry in which shortcomings in the antibody hinder the development of a successful product,” says Moroney. “arYla gives us a unique and proprietary means of optimising antibody properties, which we expect to lead to better products faster than is possible today. We intend to apply the technology in our own programmes and within existing as well as new partnerships, and are seeing considerable interest in the pharmaceutical industry.” With the arYla technology, MorphoSys combines its extensive experience in design and selection of therapeutic antibodies with the library synthesis capabilities of Sloning BioTechnology. The new technology enables individualised antibody libraries to be made both quickly and with high precision. arYla can now be used to make diverse, customised sub-libraries based on an existing lead compound, incorporating many millions of pre-defined variations at precisely determined
24 sp2 November/December 2011 steps can be done in parallel.
“It was definitely the combination of their platform with ours and the potential benefits their system can bring to antibody library design that made Sloning a great acquisition for us,” states Moroney. “The technology can be used, in combination with HuCAL or alone, to ‘fine tune’ monoclonal antibodies and to generate ‘intelligent libraries.’ Applied to antibodies, Slonomics becomes arYla, a platform providing high-quality, ratio-controlled, combinatorial libraries for optimising antibodies on their functional, expression or biophysical properties.”
complementary regions. Two distinct hairpin double-stranded oligonucleotides, anchors and splinkers, are the starting materials for the generation of small sub-fragments, called the elongation blocks (E-blocks). Repeated reaction cycles of immobilisation, washing and restriction and ligation result in E-blocks that are then assembled to form larger fragments of 462 base-pair constructs, reflecting every possible permutation.
sites within the antibody structure. “In this way, antibodies optimised for a multitude of properties, including affinity, specificity, humanness, solubility, stability, production yield and others, can rapidly be identified,” says Moroney. Sloning BioTechnology, a pioneer in the development of new synthetic biology technologies, was acquired by MorphoSys in October 2010. The acquisition has made MorphoSys the sole provider of Sloning’s Slonomics technology, which dramatically improves the assembly and quality of protein libraries. MorphoSys developed the arYla technology by integrating the Slonomics technology into its HuCAL antibody technology platform to improve the generation of drug candidates. Slonomics is based on the synthesis and ligation of stable double-stranded oligonucleotides with complementary regions. It can be used to ‘fine tune’ monoclonal antibodies in their critical domains such as the antigen-binding domain.
Slonomics is an enhanced DNA engineering method that is not based on stepwise or multiplexed polymerase cycling assembly, which is known to be error-prone due to the high error rate. Instead, it is a ligation-based strategy that generates double-stranded DNA building blocks through repeated reaction cycles of ligation, immobilisation, washing and restriction. Slonomics is an automated, robotic process, and the building blocks are used for multiple reactions, which means all
Strong uptake in diagnostics MorphoSys is currently experiencing a strong uptake of its technology in the diagnostics market: “Trends towards personalised medicine and the need to segment patient populations to improve clinical trial outcomes are creating more demand for diagnostic antibodies in the drug development process, which is good for us,” says Moroney. “Our business segment for research and diagnostic antibodies, AbD Serotec, increasingly benefits from these trends.” “New technologies will remain an important part of the life sciences industry. Strategic alliances and acquisitions will continue to be a vital part of the sector, and we see a significant number of technology deals in the antibody sector. We are always interested in gaining access to technologies that could complement our technology portfolio. In some cases, a licence agreement might be the best way to gain this access, whereas an acquisition might be the better option in others,” he says. “We expect to enter new HuCAL-based deals in infectious diseases as well as Slonomics- and arYla-based alliances. Additionally, from 2012/2013 on, we are looking to partner our own compounds Several years from now, the first HuCAL- based product is likely to enter the market, and we will benefit from product royalties, which represents pure profit for us. This could further transform the company and will strengthen our ability to invest in proprietary products,” he concludes.
Further information Dr Simon Moroney MorphoSys AG Lena-Christ-Strasse 48 82152 Martinsried/Planegg Germany Tel: +49 89 899270 Email:
info@morphosys.com
Web:
www.morphosys.com
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