The discovery of fully human antibodies mainly employs three techniques: transgenic mice, phage display, and single B cell screening. Among them, transgenic animals and phage display are the mainstream technologies in the development of fully human antibody drugs. Based on a human antibody library, phage display technology has become an important means of obtaining fully human antibodies due to its low cost and short time frame.
ProBio's self-constructed human Fab naïve library is sourced from over 1000 healthy donors of different races, blood types, and genders. It boasts a high capacity exceeding 10^11, high diversity, and can provide fully human lead antibody molecules in as fast as one month.
High-quality library
- >1000 donors
- Library capacity >1×10^11
- Insert rate: >95%, in-frame rate:>85%, sequence diversity: >95%
Fast turnaround time
- No need for humanization
- Obtained fully human Ab leads as fast as 1 month
Diverse screening strategies
- Combine two different selection methods to improve screening accuracy
- Dual screening validation of single clone ELISA and soluble ELISA to reduce the risk of false positives
One-stop solution
- Antibody optimization: affinity maturation, Fc engineering, developability assessment
- Antibody validation: in vitro bioassay, in vivo pharmacology, developability assessment
Service Introduction
Key Indicators of Human Fab Naïve Library
| Source | ~1000 healthy donors | Material | Human PBMC |
| Library | Fab phage library | Total Size (cfu) | 1.0x1011 (in expansion) |
| Insertion rate | >95% | In-frame rate | >85% |
| Diversity rate | >95% | CDR3 diversity | Normal distribution |
| Tag | His & c-Myc | Affinity with SPR | 1E-8~1E-10 |
Panning and Screening Strategies
Up to 2 panning strategies to maximize the success rate
Two step validation: monoclonal phage ELISA and soluble ELISA
One-stop Discovery Solution
ProBio offers comprehensive downstream service packages, click the keywords below to learn more about service details.
- Antibody affinity maturation
- Antibody developability optimization
- Antibody Fc engineering
- In vitro bioassay
- In vivo pharmacology study
- Developability assessment
Service workflow
ProBio selected antibody molecules targeting CLDN18.2 from our human Fab naïve library using a combination of ELISA and FACS screening, reverse screening and epitope identification against homologous family member Claudin 18.1, and ADCC/CDC assays. As a result, 11 superior antibody molecules were identified with the following characteristics:
| Criteria | Lead | BMK-IMAB362 |
|---|---|---|
| ELISA EC50 | 0.07 | 1.53 |
| FACS EC50 with Claudin18.2 | 0.71 | 3.97 |
| FACS EC50 with Claudin18.1 | NA | NA |
| Affinity with SPR | 2.70E-09 | 3.93E-08 |
| ADCC | 0.38 | 0.76 |
| CDC | 1.12 | 6.96 |
| Epitope binning | / | same |
| In vivo assay | ongoing | |
Screening the antibody leads targeting PD-L1 with ProBio‘s human Fab naïve library. The leads were narrow down to 4 dominant antibody molecules with ELISA&FACS EC50, species cross-reactivity screening, blocking screening with the natural receptor PD1, and epitope binning:
| Criteria | Lead(best) | BMK1-Avelumab | BMK2-Tencentriq |
|---|---|---|---|
| ELISA EC50 | 0.2 | 0.7 | / |
| FACS EC50 | 0.01 | 0.07 | / |
| Affinity with SPR | 3.05E-10 | 8.34E-10 | / |
| Cross-reactivity with Mouse | 0.02 | 0.04 | / |
| Cross-reactivity with Cyno | 0.11 | 0.13 | / |
| Epitope binning | / | Similar and different | Similar and different |
| PD1/PD-L1 blockade assay | 0.16 | 1.41 | 0.38 |
| In vivo assay | ongoing | ||
