Lead Selection & Optimization

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 potency of the drug molecule. Titer and protein concentration determination are more robust to cell culture and media, making them desirable as replacement for enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC) in upstream and downstream processes. 

• Analyze a full 96-well plate of samples for IgG titer in as little as two minutes 
• Use crude and unpurified samples 
• Automate for walkaway high throughput analysis

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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^® BLI platform excels at these large-scale studies due to assay speed, throughput and exceptional reproducibility. 

• Sample plate format allows for use of crude and non-purified samples
• Automation capable Octet^® RH96 and RH16 allow for walk away high throughput analysis

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When screening crude samples with unknown concentrations, off-rate screening is a powerful tool for predicting sample properties. Library screening by ELISA does not enable ranking of antibodies based upon their affinities for an antigen. Using Octet^® BLI systems, clones with high affinities and low off-rates can be rapidly identified and selected for further characterization. Many biotechnology companies utilize the technology in automated affinity screening and off-rate screening of positive clones obtained from ELISA-based primary screens.

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Monitoring the binding of candidate molecules to targets is a critical process in lead molecule selection and can aid in the selection of desirable clones. Octet^® BLI systems generate highly-precise data on molecular binding affinities, specificities and association/dissociation rate constants and in a high throughput manner. 

• Accurately determine k_a, k_d, and K_D
• 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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Fragment-based drug design (FBDD) 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. The Octet^® SF3 system has 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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