Lead Selection & Optimization

  • Determine titer or perform kinetics screens in minutes rather than hours
  • Achieve automated and increased throughput and unattended run time in sample analysis with the Advanced Workflow Engineering Solutions (AWES)



Octet HTX and RED384 System Automation Bundles

Overview for Lead Selection & Optimization

Lead selection and optimization is a critical process in the identification, selection and optimization of molecules that meet predefined requirements and can then be progressed to the next step of development. While biologics lead selection mainly involves the screening of lead biological molecules to select those with desired functional and biophysical characteristics, optimization further helps improve these properties and may be performed through various means including affinity maturation and other techniques. Technologies that can aid in integrating the selection and optimization workflow should help in improving the speed and efficiency of the process.

  • Off-rate screening on Octet systems

    Library screening by ELISA does not enable ranking of antibodies based upon their affinities for an antigen. With the Octet system, clones with high affinities and low off-rates can be rapidly identified and selected for further characterization. Many biotechnology companies utilize the Octet system in automated affinity screening and off-rate screening of positive clones obtained from ELISA-based primary screens.

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    Fragment screening

    Fragment-based drug design has become an increasingly popular platform for the identification of lead candidates in drug discovery programs. The detection and characterization of fragment binding events is facilitated by sensitive biophysical technologies capable of detecting low affinity interactions of low molecular weight compounds. Surface plasmon resonance (SPR) has become one of the core technologies used in the identification of these low-affinity fragment compounds. SPR-based biosensors such as the Pioneer FE have the necessary sensitivity and throughput to provide complete fragment screens on libraries of several thousand compounds in just a few weeks per target.

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  • Kinetic characterization and clone selection

    The evaluation of kinetics information of drug candidate molecules by monitoring their binding properties to target molecules is a critical process in lead molecule selection and can aid in the selection of desirable clones. Integrated systems that can generate highly-precise data on molecular binding affinities, specificities, and association/dissociation rate constants and in a high throughput manner are desirable.

    • Accurately determine ka, kd, and KD
    • Screen up to 96 clones simultaneously in 96 or 384-well plates
    • Perform analysis directly in crude samples—no need for sample purification

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    Phage display screening

    The development of phage display revolutionized antibody drug discovery. The method is often used to isolate highly specific therapeutic antibody leads to develop anti-cancer or anti-inflammatory therapeutics. A typical phage library contains about 109–1011 variants, making it very difficult and time consuming to find the right candidate with traditional screening technologies. The automated QPix 400 Series Microbial Colony Picking Systems can screen 3000 clones per hour in white or fluorescent light and select clones based on user-defined parameters such as compactness, axis ratio, size, proximity and fluorescence levels.

    • Enables higher throughput while freeing up manual labor and increasing the walk-away time
    • Provides consistent, objective colony picking instead of subjective, manual picking
    • Accommodates a broad range of different applications such as fluorescence screening and liquid handling
    • Tracks data electronically, allowing for well-documented data control

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  • Isotyping and epitope binning

    Epitope binning studies rely on the sequential binding of two antibodies to an antigen, and are performed using dozens of antibody pairs in cross-competition matrices. While ELISA assays are sometimes used for epitope binning experiments, they remain labor and time intensive and can produce highly variable results. The Octet system excels at these large-scale studies due to assay speed, throughput, and exceptional reproducibility. View related articles.

    • Analyze a full plate (96-samples) of IgG titer in as little as two minutes
    • Sample plate format allows for the use of crude and non-purified samples
    • Automation capable Octet HTX and RED384 allow for walkaway high throughput analysis

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    Hybridoma-screening

    Antikörper-Discovery bezieht sich in der Regel auf das Screening und die Identifizierung von monoklonalen Antikörpern (mAbs), die zur Diagnose und Behandlung von Krankheiten gegen ein spezifisches Epitop gerichtet sind. Ein gängiger Ansatz bei der Generierung von monoklonalen Antikörpern umfasst die Fusion prämitotischer Krebszellen mit postmitotischen und terminal differenzierten Antikörper-exprimierenden B-Zellen aus der Milz. Die daraus resultierende fusionierte Zelle wird Hybridoma genannt und bietet die Vorteile, mAbs zu produzieren und sich gleichzeitig durch Teilung selbst zu erneuern. Screening hybridomas for binding specificity or productivity can be automated using the ClonePix 2 and the Octet HTX systems.

    • XP Media and CloneMedia provide a simple (no extra supplements required), yet comprehensive solution from hybridoma generation to production
    • XP Media and CloneMedia perform significantly better than competitor X on all stages of the hybridoma workflow
    • The use of automation for imaging, screening, and picking of clones drastically shortens the time needed to identify desirable clones
    • CloneMedia, CloneDetect reagent, and the ClonePix 2 System allow for the automated selection of high-producing clones in one convenient step
    • The Octet HTX system provides ample throughput for rapid binding and specificities analysis of multiple clones

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Resources for Lead Selection & Optimization

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