Research Capabilities

MedImmune Cambridge has the discovery capabilities to identify specific features of the antibody to create a human monoclonal antibody therapeutic with the desired characteristics. Target selectivity, cross reactivity, binding affinity and potency, efficacy, mechanism of action, manufacturability and formulation, and route of administration are some of the areas where we have the expertise to characterise antibody molecules. Applying knowledge of the biology of a system in both health and disease, the Research team has a unique opportunity to design, isolate and characterise distinct human antibody therapeutics with superior performance characteristics for the treatment of important diseases.

• Target Generation and Quality
• High Throughput Screening
• Mode of Action Expertise
• High Capacity DNA sequence analysis
• Antibody Expression and Conversion
• Lead Optimisation
• Biology

Target Generation and Quality

We have considerable expertise in cloning and expression of target antigens across multiple target classes. This is coupled with effective protein purification strategies, and comprehensive protein analysis and modification technologies. In particular, accumulated knowledge and expertise in the generation of the key classes of antibody targets - cell surface receptors and extracellular proteins - has been exploited to understand the formats that are optimal for the selection of antibodies from Phage Display and Ribosome Display antibody libraries.
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High Throughput Screening

Functional high throughput screening capability allows our scientists to focus rapidly only on antibodies with the desired biological activity, not those that merely bind to the target. Automation is key to our ability to run high capacity screens, and in addition, we have a range of data analysis tools that use visual or statistical methods to analyse the results and identify isolation strategies that are delivering the antibodies of highest value. Affinity determination, specificity screening and epitope categorisation are standard components of the characterisation process. These capabilities ensure the delivery of panels of lead antibodies, which generate more choice during the subsequent development process.
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Mode of Action Expertise

An in-depth understanding of the clinical candidate antibody's mode of action is determined to define the antibody characteristics. We will engineer the appropriate antibody format to deliver a desired effector function, for example, complement recruitment.
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High Capacity DNA sequence analysis

A central part of the primary characterisation of antibodies is their unique DNA sequence. Therefore we have invested in a high capacity sequencing capability and, in particular, proprietary sequence analysis tools, specifically designed for antibody sequence determination and comparison. Expertise in sequence analysis allows, for example, identification of glycosylation sites that could affect downstream development.
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Antibody Expression and Conversion

High throughput expression of antibody fragments in both bacterial and mammalian systems is a key part of the antibody isolation process. In particular, the expertise to derive purified antibody preparations compatible with diverse assay requirements has been gained. For lead antibodies of interest for further development, the capability to convert scFv antibodies into whole IgG format in medium throughput is in place.
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Lead Optimisation

A "toolbox" of protein optimisation strategies based on both Phage Display and Ribosome Display technologies, to improve affinity and other characteristics, are applied when required. Concurrent with the affinity maturation of lead antibodies, antibodies of germline sequences are generated; these have a minimised risk of triggering unwanted immunogenic responses.
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Biology

The Biology group is a multidisciplinary team that uses a wide range of techniques to add value to its antibody drugs at all stages of drug discovery and development. At the initiation of a project the scientists in the biology team provide data that supports the rationale behind the target antigen, often using clinical samples to understand the disease mechanism and to correlate disease severity with antigen levels. The biology team also supports the isolation and identification of the therapeutic antibodies by profiling scFv and/or IgG in a panel of cellular assays. These assays reflect the biology of the target and the disease mechanism ensuring that an appropriate assay cascade is implemented to identify the most effective drug candidate.

To understand its mode of action, the drug's pharmacology is then investigated within the team. The pharmacology strategy is ultimately defined to ensure enough biological information is produced to seek to predict efficacy in the clinic. These studies are designed to ensure an appropriate balance between drug safety and efficacy, therefore determining the drug's therapeutic window. Through a combination of in-house capabilities, external collaborators and contract research organisations, our biology is able to deliver the required pre-clinical pharmacology package for the drug.

To support all these aspects, the drug discovery biology team is made up of cell biologists, pharmacologists, tissue culture specialists, biological services teams, cellular pathologists and toxicologists. By combining these skills within our therapeutic area organisation, the biology team supports the identification of the most appropriate drug candidate and is capable of delivering the pre-clinical pharmacology package necessary to support clinical trial applications.
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