Basedon "integratedR&Dplatformforinnovativeantibodydrugs" and "super-trillioninnovativeantibodydiscoveryplatform". Sanyou Bio can customize the
screening strategies for the best antibody candidates suitable for gene therapy. SanyouBio also
providesall-in-one R&D servicesfromtargettogenetherapeuticantibody.
Service Overview
Basedon"integratedR&Dplatformforinnovativeantibodydrugs"and"super-trillioninnovativeantibodydiscoveryplatform".
SanyouBio can customize the screening strategies for the best antibody candidates suitable for gene therapy
SanyouBio also providesall-in-one R&D servicesfromtargettogenetherapeuticantibody.
Service Contents
Service
Service Contents
Provided by Clients
Deliverables (and standards)
Delivery Cycle (month)
Antibody services
1. Material preparation
2. Antibody production
3. Antibody engineering
4. Nucleotide conjugation
5. In vivo/in vitro drug efficacy screening
1.Target ID
2. Project objectives
3. Nucleic acid targets and linkers
1. Data report: stage reports and project data package
2. In vivo and in vitro drug efficacy
3. Pharmacokinetics
9–13 (fully validated candidates)
Segments of gene therapeutic drug R&D stages
Material preparation
1. Human/monkey antigen and receptor
2. Antibody control (benchmark)
3. Human and monkey cell lines
Target ID
1. SDS-PAGE > 85%
2. ELISA activity identification: consistent with the literature
3. FACS activity identification: the expression of target antigen is 10 times higher than background
1
Antibody production
1. Humanized antibody library, mouse/alpaca immune library
2. Affinity maturation (if required)
3. Antibody humanization (if required)
Raw materials
1. Deliver ≥ 20 sequence-specific leads with human-monkey cross-activity
2. Improved affinity up to 5~20 times after engineering with humanization > 90%
3. Humanized antibody function is similar to or better than that of the parental antibody
1. 1–2
2. 1
3. 2
Nucleotide conjugation
1. Antibody conjugation
2. Post-conjugation molecule quality assessment
Purified qualified antibody
1. Qualified AOC
2. Data report
1
In vitro model screening
1. Internalization
2. Target antigen knockdown (qPCR)
3. ADCC, CDC
Purified qualified antibody
1. Functional screening: deliver ≥ 3 equivalent or better candidates
2. Data report: data report on functional screening
1–2
In vivo model screening
1. Two animal models for validation
2. PK
3. Tissue-specific target knockdown
Selected AOC
1. Functional screening: deliver ≥ 3 equivalent or better candidates
2. Data report: the screening of efficacy in animals
2–4
Service Highlights
1. Integrated platform for innovative antibody drug discovery
10 functional modules and 25+ sub-platforms covering the whole procedure of drug discovery
Project with comprehensive arrangement; PCC can be completed in 12 months
2. Distinctive capability for multi-route antibody discovery
Trillion-capacity antibody library; thousands of leads can be obtained for common targets
Diversified antibody sources: human recombinant library, semi-synthetic trillion-capacity VHH library, mouse immune library, alpaca immune VHH library, polypeptide library, and common light chain library
Full coverage of antibody types: full human antibody, single domain antibody, common light chain bispecific antibody, mouse monoclonal antibody, and rat monoclonal antibody
Antibody types: IgG, Fab, VHH
3. Extensive project experience
20+ scientists expertized in various fields with the capability of systematic review of specific project
100+ projects experience and high success rate
4. Customized service
Combination of innovative target / linker / intracellular nucleic acid
Integrated service platform in the antibody development
Case Presentations
1. In Vitro Efficacy Evaluation based on MOA of Gene Therapeutic Antibody
1.1. Cellular binding and epitope analysis
Cellular binding methods: Utilization of flow cytometry to detect the binding of different candidate to over-expressed cell lines.
Cellular binding results: The candidates exhibit a superior or similar binding activity to the benchmark.
Fig. 1A Cellular binding activity assay
Epitope analysis methods: Competition method with biotinylated of benchmark to group epitopes.
Epitope analysis results: All candidates can competitively inhibit the binding of Target Ab to the antigen, which indicated that the candidates recognize the same epitope.
Fig. 1B Cell competitive binding assay
1.2. Endocytosis Efficacy assay
Test method
Instruments
Suitability
Principle
Fab-Zap method
Microplate reader
primary screening
secondary antibody conjugated with saporin enters the cells through internalization and subsequently induces proliferation blockage
Double fluorescence membrane-breaking method
Flow cytometer
Secondary screening
The antibody triggers the internalization process at 37 °C, and the amount of
endocytosed antibody can be detected by double fluorescence and membrane- breaking staining
pH Rodo method
Microplate reader
primary screening
Antibodies labeled with pH-sensitive dyes are engulfed by target cells and acidified in the endosome to release fluorescent signals
Confocal microscopy
Confocal microscope
Secondary screening
Real time detection of drug transport and endocytosis by laser scanning confocal microscope
Fluorescence quenching method
Flow cytometry
primary screening
The antibody triggers the internalization process at 37 °C, and the amount of
endocytosed antibody can be detected by quenching extracellular fluorescence and membrane-breaking staining
Fig. 1C Fab-Zap endocytic activity assay
2. In Vivo Efficacy Evaluation based on MOA of Gene Therapeutic Antibody
2.1. In vivo imaging system
SanyouBio has been equipped with the IVIS Lumina III Imaging System to observe the progress of tumor growth and metastasis, and to analyze the tissue distribution of drugs.
Fig. 2A In vivo imaging by IVIS Lumina III Imaging System
2.2. Pharmacokinetics
Provide one-stop services for the high-quality preparation of antigen/antibody and the development and verification of antibody PK in multi-species (rat, mouse, rabbit, dog, and minipig).
Service
Animal type
Monoclonal antibodies
Rats, mice, rabbits, dogs, and minipigs
Multi-specific antibodies
Rats, mice, rabbits, dogs, and minipigs
Recombinant proteins
Rats, mice, rabbits, dogs, and minipigs
ADC molecules
Rats, mice, rabbits, dogs, and minipigs
Anti-drug antibody detection
Rats, mice, rabbits, dogs, and minipigs
Fig. 2B Sanyou Bio animal PK services and PK data display
2.3. Animal efficacy assessment
A mature prefabricated Cell Line Derived (CDX) Tumor Model for assessment of gene therapeutic antibodies in vivo.
Figure 2C. A431 (head and neck cancer cell line, EGFRhigh) CDX Tumor Model and its efficacy assessment in vivo.
Fig. 2C Head and neck cancer A431 tumor model and efficacy assessment
Core Services
Provide comprehensive solutions to satisfy unmet medical needs based on the specificity and internalization property of antibodies that bind to the intracellular target siRNA / ASO / tRNA / Crispr.