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Lead Selection & Optimization

  • Determine titer or perform kinetics screens in minutes rather than hours

Octet HTX and RED384 System

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.

Titer determination on the octet plateform

Titer determination on the Octet platform

Titer and protein concentration determination is a critical process in the development of biologics drug molecules. The active protein concentration can be used to determine the potency of the drug molecule. While ELISA and especially HPLC are commonplace techniques for titer and protein concentration determination, techniques that are more robust to cell culture and media are especially desirable as they can be easily adopted in both upstream and downstream processes during the development of the drug molecule.

  • A full plate (96 samples) of IgG titer can be analyzed 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
Epitope binning section

Epitope binning and cross-competition assays

In early drug development, cross-competition studies are necessary to characterize hundreds of antibody clones . Since monoclonal antibodies in different bins bind to distinct antigen epitopes and display diverse functional characteris­tics, epitope binning studies can increase the likelihood of choosing a lead antibody with the desired biological activity.

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. The Octet system excels at these large-scale studies due to assay speed, throughput, and exceptional reproducibility.

  • Sample plate format allows for the use of crude and non-purified samples
  • Automation capable Octet HTX and Red 384 allow for walk away high through-put analysis
Sensorgrams of Evaluated

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.

kinetic Characterization

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
Fragment Screening

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.

Resources of Lead Selection & Optimization

Application Note Enhancing Efficiency and Economics in Process Development and Manufacturing of Biotherapeutics

Analytical techniques that measure protein quantity and quality are used in nearly all stages of research, process development and manufacturing of biotherapeutics. UV spectroscopy, ELISA and HPLC have been in use for decades for protein quantitation in physiologi- cal and process samples, and continue to be the workhorses despite their many limitations. Read more

Application Note Fragment Based Drug Discovery on Pioneer Systems Using Next Generation SPR Analysis

Fragment-based drug design (FBDD) has become an increasingly popular platform for the identification of lead candidates in drug discovery programs.

Read more

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