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申请号:201811309856.1 公开号:CN111138526A 主分类号:C07K16/10
摘要:【中文】本发明公开了一种抗埃博拉病毒糖蛋白GP2亚基的单克隆抗体2G1,所述抗体具有独特的CDR区,在抗原结合能力上显示了优异的广谱性,与EBOVGP、BDBV GP、SUDV GP和RESTV GP具有良好的结合活性,并且结合稳定,不受次级内体低pH环境的影响,为其发挥中和作用提供了基础。与对照抗体相比,2G1在体外可有效地中和EBOV、BDBV和SUDV假病毒;而且本发明提供抗体的中和活性随着抗体浓度的升高而增强,在1μg/mL的浓度下即可对EBOV、BDBV和SUDV三种埃博拉假病毒实现近100%的保护。本发明提供的抗体还具有独特的作用位点,不同于现有技术中的抗埃博拉病毒包膜糖蛋白单克隆抗体的作用位点,提示其具有与其他中和抗体组成鸡尾酒组合疗法的潜力。 【EN】The invention discloses a monoclonal antibody 2G1 of an anti-Ebola virus glycoprotein GP2 subunit, which has a unique CDR region, shows excellent broad spectrum on the antigen binding capacity, has good binding activity with EBOVGP, BDBVGP, SUDV GP and RESTV GP, is stable in binding, is not influenced by the low pH environment of a secondary endosome, and provides a basis for the neutralization effect. 2G1 was effective in neutralizing EBOV, BDBV, and SUDV pseudoviruses in vitro, compared to control antibodies; the neutralizing activity of the antibody is enhanced along with the increase of the concentration of the antibody, and nearly 100 percent of protection can be realized on three Ebola pseudoviruses of EBOV, BDBV and SUDV under the concentration of 1 mu g/mL. The antibody provided by the invention also has a unique action site, which is different from the action site of the anti-Ebola virus envelope glycoprotein monoclonal antibody in the prior art, and the potential of the antibody in combination therapy with other neutralizing antibodies in cocktail composition is suggested.
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申请号:201811310292.3 公开号:CN111138527A 主分类号:C07K16/10
摘要:【中文】本发明公开了一种抗埃博拉病毒糖蛋白GP1亚基的单克隆抗体4F1,所述抗体具有独特的CDR区,与EBOV GP1亚基具有特异性的结合活性,并且结合稳定,不受次级内体低pH环境的影响,为其发挥中和作用提供了基础。与对照抗体相比,4F1在体外可有效地中和EBOV假病毒。4F1中和活性随着抗体浓度的升高而增强,在1μg/mL的浓度下即可对EBOV实现100%的保护。本发明提供的单克隆抗体4F1与MIL77‑3等对照抗体都结合于GP1亚基,且竞争结合,但4F1具有体外中和活性,而其他抗体则不具有中和活性,提示4F1具有与其他结合于GP2亚基的中和抗体组成鸡尾酒组合疗法的潜力。 【EN】The invention discloses a monoclonal antibody 4F1 of an anti-Ebola virus glycoprotein GP1 subunit, which has a unique CDR region, has specific binding activity with an EBOV GP1 subunit, is stably bound, is not influenced by the low pH environment of a secondary endosome, and provides a foundation for the neutralization effect of the secondary endosome. 4F1 was effective in neutralizing EBOV pseudoviruses in vitro, as compared to control antibodies. The neutralizing activity of 4F1 increased with increasing antibody concentration, and 100% protection was achieved for EBOV at a concentration of 1. mu.g/mL. The monoclonal antibody 4F1 provided by the invention and a control antibody such as MIL77-3 and the like are bound to GP1 subunit and compete for binding, but 4F1 has in vitro neutralizing activity, and other antibodies do not have neutralizing activity, which suggests that 4F1 has the potential of composing cocktail combination therapy with other neutralizing antibodies bound to GP2 subunit.
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申请号:201811310604.0 公开号:CN111138528A 主分类号:C07K16/10
摘要:【中文】本发明公开了一种特异性结合于埃博拉病毒糖蛋白聚糖帽的单克隆抗体5A8,所述抗体具有独特的CDR区,与EBOV GP1亚基的聚糖帽区域具有特异性的结合活性。5A8单抗与EBOV GP具有良好的结合活性,EC50值为0.014μg/mL。与对照抗体相比,5A8在体外可有效地中和EBOV假病毒,中和活性随着抗体浓度的升高而增强,在3μg/mL的浓度下即可对EBOV假病毒感染细胞实现100%的保护。5A8与MIL77‑3等对照抗体都结合于GP1亚基,且竞争结合,但5A8具有体外中和活性,而其他抗体则不具有中和活性,提示5A8具有与其他结合于GP2亚基的中和抗体组成鸡尾酒组合疗法的潜力。 【EN】The invention discloses a monoclonal antibody 5A8 specifically binding to an Ebola virus glycoprotein glycan cap, wherein the antibody has a unique CDR region and has specific binding activity with a glycan cap region of an EBOV GP1 subunit. The 5A8 monoclonal antibody and EBOV GP have good combination activity, EC50The value was 0.014. mu.g/mL. Compared with a control antibody, the 5A8 can effectively neutralize the EBOV pseudovirus in vitro, the neutralizing activity is enhanced along with the increase of the concentration of the antibody, and 100 percent of protection can be realized on EBOV pseudovirus infected cells at the concentration of 3 mu g/mL. 5A8 was bound to control antibodies such as MIL77-3In GP1 subunit and competes for binding, but 5a8 had neutralizing activity in vitro, whereas the other antibodies did not, suggesting that 5a8 has the potential to constitute cocktail combination therapy with other neutralizing antibodies bound to GP2 subunit.
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申请号:201811311943.0 公开号:CN111138529A 主分类号:C07K16/10
摘要:【中文】本发明公开了抗埃博拉病毒糖蛋白GP2亚基的单克隆抗体5E1,所述抗体具有独特的CDR区,与EBOV GP1亚基的聚糖帽区域具有特异性的结合活性。5E1单抗与EBOV GP具有良好的结合活性,EC50值为0.027μg/mL。与对照抗体相比,5E1在体外可有效地中和EBOV和BDBV假病毒。5E1中和活性随着抗体浓度的升高而增强,在1μg/mL的浓度下即可对EBOV和BDBV假病毒感染的细胞实现50%的保护。5E1与结合于GP2亚基的中和抗体MIL77‑1和MIL77‑2也不存在竞争,说明5E1与这些抗体的结合表位不同。5E1对EBOV和BDBV具有良好的体外中和活性,可作为埃博拉病毒病候选治疗药物,其结合表位不同于其他中和抗体,具有与其他中和抗体组成鸡尾酒组合疗法的潜力。 【EN】The invention discloses a monoclonal antibody 5E1 of an anti-Ebola virus glycoprotein GP2 subunit, which has a unique CDR region and specific binding activity with a glycan cap region of an EBOV GP1 subunit. The 5E1 monoclonal antibody and EBOV GP have good combination activity, EC50The value was 0.027. mu.g/mL. 5E1 was effective in neutralizing EBOV and BDBV pseudoviruses in vitro, as compared to control antibodies. The neutralizing activity of 5E1 increased with the increase of antibody concentration, and 50% protection was achieved on EBOV and BDBV pseudovirus infected cells at a concentration of 1. mu.g/mL. 5E1 with neutralizing antibody MIL77 bound to GP2 subunit1 and MIL77-2 also did not compete, indicating that 5E1 does not bind to the same epitope as these antibodies. 5E1 has good in vitro neutralizing activity on EBOV and BDBV, can be used as candidate therapeutic drugs for Ebola virus, has different binding epitopes from other neutralizing antibodies, and has the potential of composing cocktail combination therapy with other neutralizing antibodies.
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申请号:201811313136.2 公开号:CN111138530A 主分类号:C07K16/10
摘要:【中文】本发明公开了抗埃博拉病毒糖蛋白GP1亚基的单克隆抗体5E9,所述抗体具有独特的CDR区,与EBOV GP具有良好的结合活性,EC50值为0.006μg/mL。与对照抗体相比,5E9在体外可有效地中和EBOV假病毒,其中和活性随着抗体浓度的升高而增强,在1μg/mL的浓度下即可对EBOV假病毒感染到的细胞实现100%的保护。5E9还对EBOV具有良好的体外中和活性,可作为埃博拉病毒病候选治疗药物,5E9的结合表位位于GP抗原的第95‑190位氨基酸,不同于现有技术中的中和抗体,具有与其他中和抗体组成鸡尾酒组合疗法的潜力。 【EN】The invention discloses a monoclonal antibody 5E9 of an anti-Ebola virus glycoprotein GP1 subunit, which has a unique CDR region, good binding activity with EBOV GP and EC50The value was 0.006. mu.g/mL. Compared with a control antibody, the 5E9 can effectively neutralize the EBOV pseudovirus in vitro, wherein the neutralizing activity is enhanced along with the increase of the concentration of the antibody, and 100 percent of protection can be realized on cells infected by the EBOV pseudovirus at the concentration of 1 mu g/mL. 5E9 also has good in vitro efficacy against EBOVThe neutralizing activity can be used as a candidate therapeutic drug for Ebola virus diseases, the binding epitope of 5E9 is positioned at amino acids 95-190 of GP antigen, and the neutralizing antibody has the potential of composing cocktail combination therapy with other neutralizing antibodies, different from the neutralizing antibodies in the prior art.
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申请号:201811315415.2 公开号:CN111138531A 主分类号:C07K16/10
摘要:【中文】本发明公开了抗埃博拉病毒糖蛋白GP1亚基的单克隆抗体8F9,所述抗体具有独特的CDR区,与EBOV GP具有良好的结合活性,EC50值为0.015μg/mL。与对照抗体相比,8F9在体外可有效地中和EBOV假病毒。8F9中和活性随着抗体浓度的升高而增强,在1μg/mL的浓度下即可对EBOV假病毒感染的细胞实现90%的保护。8F9还对EBOV具有良好的体外中和活性,可作为埃博拉病毒病候选治疗药物,8F9的结合表位位于GP抗原的第227‑295位氨基酸,不同于现有技术中的中和抗体,具有与其他中和抗体组成鸡尾酒组合疗法的潜力。 【EN】The invention discloses a monoclonal antibody 8F9 of an anti-Ebola virus glycoprotein GP1 subunit, which has a unique CDR region, good binding activity with EBOV GP and EC50The value was 0.015. mu.g/mL. 8F9 was effective in neutralizing EBOV pseudoviruses in vitro, as compared to control antibodies. The neutralizing activity of 8F9 is enhanced with the increase of the antibody concentration, and 90% of protection can be realized on EBOV pseudovirus infected cells at the concentration of 1 mu g/mL. 8F9 also has good in vitro neutralizing activity on EBOV, and can be used as candidate therapeutic drug for Ebola virus, and the binding epitope of 8F9 is located at 227-29 th of GP antigenAmino acid 5, unlike prior art neutralizing antibodies, has the potential to constitute a cocktail of combination therapies with other neutralizing antibodies.
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