Case Study: High-Quality Lead Molecule Identification from a Human Synthetic VHH Phage Display Library We identified a VHH lead molecule that exhibited superior binding affinity, internalization, yield, and stability compared to a benchmark antibody.
FACS binding on human target X engineered cells FACS binding on human target X engineered cells
ELISA binding on Cyno target X protein 1.5 ELISA binding on Cyno target X protein
Internalization on target X engineered cells 4000 Internalization on target X engineered cells
12000
3000
8000
1.0
2000
4000
0.5
1000
0
0
0.0
10 -3 10 -2 10 -1 10 0
10 1
10 2
10 -3 10 -2 10 -1 10 0
10 1
10 2
10 -3 10 -2 10 -1 10 0
10 1
10 2
Abs (nM)
Abs (nM)
Abs (nM)
Benchmark Ab
WuXi Bio lead
Human target X binding FACS EC 50 (nM)
Cyno target X binding ELISA EC 50 (nM)
Internalization EC 50 (nM)
Ab
Yield (mg/L)
DSF T m 1
Benchmark Ab
1.3
1.5
1.6
NA
NA
WuXi Bio lead
0.6
1.4
1.7
490
63.4 °C
Cutting-Edge Hybridoma Platform
High-Throughput Screening
Immunization 4–12 weeks
Immunization & Fusion
Experience
• AAALAC-accredited, licensed animal facility • Diverse immunogen choices (DNA, mRNA, peptide, protein, and cell) • Proprietary immunization protocols • High-efficiency electrofusion • Semi-solid subcloning techniques
• ELISA and FACS binding assays • Reporter gene assays for functional screening • Internalization assays for ADC development
• Over 300 successful projects using the hybridoma antibody discovery platform • Proven expertise with diverse targets, including CD3, CD19, PD1, PD-L1, GPCR, and small molecules (payload)
Fusion & Screening 2–4 weeks
Subcloning 2 weeks
Hybridoma Sequencing 1-2 weeks
WuXi Biologics’ Proprietary Platforms for mAb Optimization with Improved Affinity Our proprietary optimization platforms average a 366-fold increase in mAb affinity across more than 50 affinity maturation projects. • Parsimonious or multi-site mutagenesis screening to identify hot-spot regions • Construct and design hot-spot combinatorial library with customized diversity at each targeted position • Extensive-diversity space with library size up to 10⁹ • Simultaneous PTM risk removal
Average affinity improvement across 54 projects
10 -12 10 -11 10 -10 10 -9 10 -8 10 -7 10 -6 10 -5 A inity Improvement 3.11E-6 Affinity improvement
366-fold
8.48E-9
About WuXi Biologics
WuXi Biologics is a leading contract research, development, and manufacturing organization (CRDMO) that provides end-to-end capabilities to healthcare organizations worldwide. With operations in China, the United States, Ireland, Germany, and Singapore, we enable our partners to effectively and efficiently bring biologics and vaccines to patients worldwide through our comprehensive and high-quality drug development model.
The world’s leading global single-source platform from concept to commercialization
wuxibiologics.com | PS_BD@wuxibiologics.com
12-3-2024
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