双抗深度报告(一):双抗概念、分类及技术平台梳理.pdf

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1 / 19 | 2021 4 6 陈梦洁 S0300520100001 010-64814022 12 HER2 ADC 2021-03-13 2021-03-22 ADC 2021-03-25 2021-03-29 bsAb Bispecific Antibody DNA Fc IgG Fc IgG Fc Fc IgG HL Fc FcRn ADCC CDC ADCP Fc IgG Fc Fc IgG Fc IgG KiH CrossMab YBODY FIT-ig IgG BiTE Fc Affimed TandAbs Nanobody -1% 12% 26% 39% 53% 20-04 20-07 20-10 20-12 21-03 沪深300 医药生物 2 / 19 . 4 . 5 Fc IgG . 5 Fc IgG . 6 Fc IgG . 7 Knob-in-Hole KiH . 9 CrossMab / . 9 YBODY scFv . 10 DVD-Ig N VL VH .11 FIT-Ig .11 HCAb HBICE . 12 Fc IgG . 13 HLE BiTE Fc . 13 DART Fc . 14 TandAbs . 15 Bi-Nanobody . 16 . 17 1 . 4 2 Fc IgG Fc IgG . 5 3 FcRn . 5 4 Fc IgG . 6 5 Fc IgG . 7 6 . 7 7 . 8 8 Fc IgG . 8 9 KiH . 9 10 KiH CrossMab . 10 11 YBODY . 10 12 DVD-ig .11 13 FIT-ig .11 14 HBICE . 12 15 Fc IgG . 13 16 Blincyto . 13 17 BiTE . 14 18 BiTE HLE BiTE . 14 19 DART . 14 3 / 19 20 TandAbs . 15 21 TandAbs . 15 22 Nanobody . 16 23 Nanobody . 16 4 / 19 bsAb Bispecific Antibody T CD3 T TCR T T Nature Review Drug Discovery 2019 3 CD3 1 lookfordiagnosis 1 2 3 PD-1 CTLA-4 5 / 19 EGFR/cMET EGFR EGFR cMET EGFR/cMET Fc DNA Fc 1 Fc IgG 2 Fc IgG Fc 2 Fc IgG Fc IgG Fc IgG Fc IgG KiH CrossMAB DVD-ig Orthogonal Fab IgG BiTE Nanobody DART Catumaxomab Blincyto CMC Fc ADCC CDC ADCP CMC Fc BioValley Fc IgG Fc IgG HL Fc Fc IgG KiH CrossMab DVD-ig Orthogonal Fab IgG Fc IgG 1 Fc FcRn Fc Fc 2 Fc A/G 3 Fc IgG bsAb Fc ADCC CDC ADCP 3 FcRn 6 / 19 Nature Reviews Drug Discovery 1 Fc 2 3 Fc T Fc 4 Fc IgG ThermoFisher Fc IgG Fc IgG Fc IgG bsAb BiTE Nanobody Fc IgG 1 2 7 / 19 3 Fc 5 Fc IgG ThermoFisher Fc 1 2 half life PEG Fc PEG PEG Fc pH FcRn ABD XTEN CTP 6 Fc IgG 8 / 19 16 DNA DNA A T G C A C G T G C - 1 2 7 Fc IgG KiH CrossMab DVD-ig Orthogonal Fab IgG YBODY FIT-Ig FIT-Ig 8 Fc IgG 技术平台 公司 Triomab Trion Knob-in-Hole Roche Genentech CrossMab Roche Dutalys ART-IgG Roche Chugai DVD-Ig Abbvie Azymetric Zymeworks EFECT Zymeworks YBODY FIT-Ig CRIB Tetrabody WuxiBody DPL MabPair TEAC GNC 9 / 19 HCAb HBICE Knob-in-Hole KiH KiH CH 3 CH3 366 T W Knob 366 T S 368 L A 407 Y V Hole Hole Knob KiH CH 3 Fc KiH Knob 90% KiH KiH 9 KiH GenScript CrossMab / CrossMab KiH CrossMab Abs Fab VH-VL CH1-CL CrossMab CH1-CL CH1 CL CrossMab VH-VL VH VL 10 / 19 CrossMab Fab CH1-VH CL-VL VH VH CL CL 10 KiH CrossMab YBODY scFv YBODY Knob-in-hole / YBODY Fc N scFv YBODY scFv T CD3 CD3 T T 11 YBODY 11 / 19 DVD-Ig N VL VH DVD-Ig Dual Variable Domain-Ig IgG N VL VH 2 VH VH 2 VL VL 2 Fc DVD-ig 12 DVD-ig GenScript FIT-Ig FIT-Ig Fabs-In-Tandem CEO DVD-Ig FIF-ig Fab N Fab Fab 250kDa 3 DVD-Ig FIT-Ig FIT-Ig 1.FIT-Ig 2.FIT-Ig 13 FIT-ig 12 / 19 HCAb HBICE HCAb nanobody IgG IgG Fc HCAb HCAb HBICE HCAb HBICE CD3 HBICE 14 HBICE 13 / 19 Fc IgG Fc IgG Fc IgG Fc VH VL Fab Fc IgG 150kDa IgG 60kDa IgG FcRn Fc IgG 2 Fc IgG BiTE Nanobody MacroGenics DART 15 Fc IgG 技术平台 公司 BiTE Micromet/ DART MacroGenics Bi-nanobody Ablynx/ TandAbs Affimed Probody CytomX HLE BiTE Fc BiTE Bispecific T-cell Engager T Micromet 2012 Micromet BiTE Blincyto Blinatumomab BiTE 2020 12 16 Blincyto Bispecific Antibodies Design Therapy Perspectives 1 BiTE scFv T CD3 scFv scFv T T 2 55-60kDa 14 / 19 55kD half-life extended(HLE) BiTE BiTE HLE BiTE Fc BiTE Fc IgG Fc FcRn HLE BiTE AMG160 AMG757 17 BiTE 18 BiTE HLE BiTE DART Fc DART Dual affinity re-targeting MacroGenics Linker VL VH VL VH scFv scFv VH VL 1 T 2 DART 3 BiTE DART T 56KD BiTE MacroGenics DART Fc 19 DART 15 / 19 MacroGenics TandAbs TandAbs Affimed scFv TandAbs N C VL1-VH2-VL2-VH1 20 TandAbs Affimed Therapeutics 1 TandAbs 110kDa IgG 23 ; 2 TandAbs 3 TandAbs T /NK 21 TandAbs 16 / 19 Affimed Therapeutics Bi-Nanobody Nanobody VHH CH 2 CH 3 Ablynx 2018 VHH Nanobody Nanobody 22 Nanobody Ablynx Nanobody 1 Nanobody 12-15kDa 2 scFv Nanobody 3 Nanobody VH Nanobody Ablynx Nanobody FcRn 3 23 Nanobody 17 / 19 Ablynx 18 / 19 2016 S0300520100001 10485001 12 300 10% 5%10% -5%5% -5% 12 300 5% -5% 5% 5 19 / 19 60 21-23 6 2 1088 20
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