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Antibody discovery

1. Phage display method

Antibody sequences that bind to specific target molecules can be enriched/selected from antibody libraries. By combining our unique screening technologies with our antibody library, we are able to obtain highly functional antibodies.

Human antibody library

We have constructed one of the world’s largest repertoire of human naïve antibody library. This system enables us to obtain antibodies against autoantigens with high affinity. In addition, this large repertoire contains diverse antibody sequences; therefore it allows us to obtain antibodies that recognize different epitopes on the target antigen.
Generally, naïve antibody repertoire in the immune systems of living organisms is considered to contain antibodies with low specificity and affinity. However, our well-designed naïve antibody library containing huge repertoire allows us to obtain optimal antibodies against a variety of target molecules.

Camel antibody library

Unlike common IgG antibodies, camel (VHH) antibodies comprise only heavy chains. Owing to their low molecule weights, camel antibodies are easier to manufacture. Moreover, they have excellent thermal stability. These single-chain antibodies are easily fused with other proteins and can be engineered to suit various applications.
We have constructed libraries containing VHH antibody sequences based on lymphocytes collected from the spleens of many camels. In addition, we have constructed VHH libraries of γ2 and γ3 with two different hinge lengths along with an IgM-derived μ library.

Phage library screening

The use of living cells for antibody screening ensures that antibodies accurately recognizing the native conformation of proteins on the cell surface can be identified from a massive library of antibodies. Our proprietary screening method using organic solvents (isolation of antigen/antibody complexes through organic solvent method) (patent number: JP4870348) enables us to obtain unique antibodies with high specificity.
Apart from antibodies against cell surface proteins, we have developed optimal screening methods for developing antibodies against target molecules that are difficult to obtain using the conventional immunization method. Using these specific screening methods, we can obtain antibodies against a variety of targets, including small molecules and carbohydrate moieties as well as general proteins.

2. Hybridoma method

In the hybridoma method, animals are immunized with a target molecule and antibody producing cells obtained from these animals are used to prepare hybridomas. This is a classic and highly reliable method.
Membrane proteins, which represent the major targets of antibody drugs, are often conserved across animal species. Therefore, it is difficult to obtain functional antibodies against these proteins by an ordinary immunization method. However, combing the cutting-edge knowledge acquired through many joint studies with the University of Tokyo and our know-how on adjuvant and administration methods, we have developed antibodies with high specificity and affinity against membrane proteins.

Antibody engineering

1. Hybridoma sequencing

Accurately determining the antibody sequences of hybridomas obtained by immunizing animals is critical for downstream manipulation, including amino acid sequence modification and humanization. Our specific primers are designed to accurately determine antibody variable regions from initiation points.

2. Antibody design

Antibody sequences obtained from hybridomas or phage libraries can be used to engineer antibodies in various ways, including humanization/chimerization (when the hybridoma method is used), isotype conversion, and conversion to antibody fragments such as Fab and scFv. These sequences can also be applied to CAR-T. Antibodies converted in various forms can be used in diverse modalities according to medical needs.

Target discovery

1. Transcriptome analysis

One of the most important tasks in drug development is to efficiently select target proteins. Using the information obtained from the world-leading transcriptome database of the Laboratories for Systems Biology and Medicine (LSBM) developed by Professor Hiroyuki Aburatani (Research Center for Advanced Science and Technology, University of Tokyo), we are able to mine proper target molecules and to develop antibodies for the diagnosis and treatment of cancer.

2. Reverse transcriptomeanalysis

Antibody sequences recognizing the accurate structures of various target proteins on the cell surface can be isolated from an antibody library using cells related to a particular disease (for example, cancer) during screening. Many sequences obtained in this manner can be used for diagnostic and therapeutic purposes, such as to identify target molecules and to generate further useful candidate antibodies.

Functional protein expression

To obtain an antibody with high specificity and affinity, it is critical to express the target molecule with native conformation and proper function. To achieve this, we employ budded virus technology, which was developed under the leadership of Professor Takao Hamakubo at the Research Center for Advanced Science and Technology at the University of Tokyo and was then transferred to us. This technology allows us to express large amounts of target proteins with native conformation in budded baculovirus particles and to directly use them as antigens. Thus, target molecules that were previously difficult to express can now be used as antigens.