Since the first antibody drug was approved by FDA in 1986, the development of antibody drugs could divided into four generations: the first generation is mouse-derived antibody, the second generation is chimeric antibody, the third generation is humanized antibody, and the fourth generation is fully human antibody.
The first generation murine antibody exhibits a genuine downside in human treatment, as it triggers the human anti-mouse antibody (HAMA) response of the human immune system.
To resolve this issue, new genetic recombination methodologies have been developed into chimeric antibodies similar to human molecules in 1984. These antibodies were prepared by connecting constant regions of human antibodies to the variable region from the murine antibodies with around 65% similarity to human DNA sequence. But they still induced heterologous response, and their clinical application is limited.
Subsequently, the need for an less immunogenic alternative boosted the development of humanized antibodies (only the region that interacts with the antigen epitope is from mouse origin), which has more than 90% of human DNA.
Taking advantage of the advanced phage display technology in 1990s, high-quality monoclonal human antibodies were generated. They completely eliminate the adverse effects of heterologous response and show promising application prospects in clinical treatment and diagnosis.
Humanized and fully human antibody constitute the majority of today’s approved therapeutic antibodies. Based on the statistics from 2014 to 2018, humanized antibody accounts for 30%-57% in all aproved antibody drugs annually and the rest is mainly human antibodies. While, among fully human antibodies, nearly 30% come from phage display library.
Based on phage display technology, Sanyou bio developed antibody engineering core technology platform and extended its deep humanization and affinity maturation service to customers. Sanyou bio's antibody expert team has more than 50 cases of experience in deep humanization design, of which more than 40 cases are in the clinical declaration stage and 7 in the clinical trial stage.
By now, Sanyou bio has cooperated with many antibody drug R&D companies, such as I-MAB BIOPHARMA, Generon, SANHOME and developed more than 20 projects raised by many senior scientists from antibody drug R&D companies.
Antibody design based on 3D structure
Apply original structure simulation core algorithm
Apply unique humanized antibody database
Massive humanization design data
Sanyou bio antibody engineering platform has the world's first-class phage display technology and 108 super-large CDR mutation libraries which is first class in the worldwide.
Sanyou bio antibody humanization can reach 95%. It can maintain specificity and affinity to the maximum extent, while almost eliminating the immunogenicity and toxicity of mouse-derived antibodies. In addition, Sanyou bio also provides additional services such as antibody function analysis, antibody stability detection, antibody expression and so on.
Sanyou bio antibody engineering technology platform are established by more than 10 experienced R&D team members and also supported by several senior scientific consultants. In addition, there are powerful instruments and equipments.
Sanyou bio affinity maturation platform integrates high-capacity of phage display antibody libraries, random mutation, site-directed mutagenesis, combinatorial mutations, and also combined with advanced structural simulations of antibodies, amino acid composition analysis, high-throughput screening, pressure screening, affinity kinetic analysis, physicochemical analysis, stabilization research, and so on. Through a strategy of “optimal step modification” and “gradual modification,” the affinity of antibodies could be extremely promoted.
Step 1: Sequence comparison
◆ Apply bioinformatics analysis to label the framework regions (FW) and complementary determining regions (CDRs) of antibodies
◆ Use BLAST program and database to compare and analyze mouse and human antibodies
◆ Determine the FW sequence of humanized antibody
Step 2: 3D modeling
◆ Construct 3D advanced structural model of antibody using protein structure simulation
◆ Design point mutations based on unique technology and experience without affecting antibody affinity
◆ Check the Hot-Spot sequence to remove glycosylation, deamidation, oxidation, free cysteine and other sites
Step 3: Full-length construction
◆Select IgG subtypes, design full-length antibodies, and optimize codon according to customer needs
◆Synthesis of antibody gene and construction of eukaryotic expression vector for full-length antibody
◆Transient transfection and expression of antibody by CHO cells, affinity purification by AKTA, etc.
Step 4: Affinity activity analysis
◆Analysis of antibody purity by SDS-PAGE
◆Analysis of antigen-antibody binding activity by Fortebio/Biacore and ELISA
Step 5: Druggability analysis
◆Analysis of the physicochemical properties of antibodies using SEC, DSF/DSC, etc.
◆Analysis of biological activity using biological activity assay
★ Sanyou bio's antibody expert team provide optimal design scheme for customers, relieve your worries.
★ Sanyou bio's antibody engineering platform provide high-throughput screening , and thus is quite efficient and requires much less test time.
★ Sanyou bio's antibody engineering platform extends multiple additional services , more choices, more effective and lower cost .