Eureka’s Adaptive Library Panning for Human Antibody (ALPHA) Phage Display Platform achieves optimal results through highly adaptable matrix panning. After initial panning, Eureka’s adjustable library selection and panning strategies maximize the diversity and affinity of binders. We employ multiple panning methods customized according to the target antigen profile, including plastic panning, panning in solution and cell panning. Positive phage antibodies are ranked according to antigen binding affinity via competitive phage binding.
Eureka’s proprietary ALPHA Phage Display Platform is an integrated system, designed and developed specifically for fully-human antibody drug discovery. It is broadly applicable – from discovery of target- specific human antibody fragments to characterization of full-length antibody drug candidates. The platform has been applied to multiple drug discovery projects and has successfully generated high- affinity antibody candidates against both novel and validated human targets. The platform’s core component is a fully-human phage library containing more than 60 billion unique human antibody fragments. The library is one of the largest in the world, and features three extended systems:
1. Naïve Human Libraries (scFv and Fab formats)
Constructed from DNA extracted from human PMBCs and spleens from healthy donors. This system encompasses all human heavy and light chain subfamilies, and each heavy chain sub-family was independently constructed. Our sub-family specific libraries and panning strategy facilitate increased diversity of positive binders, particularly in cases where antibodies from certain subfamilies dominate panning results.
2. Semi-Synthetic Human Libraries (scFv and Fab formats)
Features completely randomized, TRIMER technology-based, synthetic heavy chain CDR3 region screening, where all amino acids (with the exception of cysteine) are equally likely to be presented. Each HCDR3 region length is built as an independent library with length coverage ranging from 5 to 24 amino acids. Our panning strategy involves a combined approach utilizing three libraries with sequential lengths, in order to maximize HCDR3 length coverage for positive
binders.
3. Naïve Human Libraries from Disease Patient PBMCs (scFv and Fab formats)
Constructed from PBMCs isolated from patients with various diseases. Currently available libraries cover patients with autoimmune diseases such as Systemic lupus erythematosus (SLE) and Rheumatoid arthritis (RA). These libraries have broad applications and are particularly suitable for human antigen targets, especially targets expressed in adult tissues. Libraries currently under construction include those from cancer patients and patients with infectious diseases, to specifically address cancer targets and other indications.
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