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Double-antibody composition and application to preparation of COVID-19 (Coronavirus Disease 2019) treatment drugs

A technology of antibody composition and composition, applied in the field of microbiology and immunology

Active Publication Date: 2020-12-15
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is no vaccine and specific drug for the prevention of coronavirus disease 2019 (CoronavirusDisease 2019, COVID-19) caused by SARS-CoV-2

Method used

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  • Double-antibody composition and application to preparation of COVID-19 (Coronavirus Disease 2019) treatment drugs
  • Double-antibody composition and application to preparation of COVID-19 (Coronavirus Disease 2019) treatment drugs
  • Double-antibody composition and application to preparation of COVID-19 (Coronavirus Disease 2019) treatment drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1. Screening and preparation of human-derived anti-SARS-CoV-2 monoclonal antibodies

[0034] The screening and preparation of the human anti-SARS-CoV-2 monoclonal antibody refer to the method disclosed in the Chinese invention patent application CN111303280A, and this application takes the content disclosed by CN111303280A as a part of the specification of this application by reference. In the previous research of this application, CN111303280A screened and obtained a monoclonal antibody 4A8 against novel coronavirus spike protein S. Through the analysis of epitope recognition, it was found that the epitope recognized by monoclonal antibody 4A8 is located in the S1 non-RBD region. The antibody has a very high affinity for the S protein of the new coronavirus, and the equilibrium dissociation constant (KD) is 1.00nM. In the protective effect experiment of SARS-CoV-2 infection, it was shown that its EC50 reached 0.58ug / ml.

[0035] The applicant has screened a gr...

Embodiment 2

[0038] Example 2 Analysis of the binding activity of human-derived anti-SARS-CoV-2 monoclonal antibody 4B7 to S, S1, S2 and RBD

[0039] 2.1 Coating: Dilute the recombinant S antigen, S1 antigen, RBD antigen and S2 antigen with the coating solution to a concentration of 2 μg / mL, coat the microtiter plate, 100 μL per well, and coat overnight at 4 °C.

[0040] 2.2 Blocking: add 300 μL of PBST washing solution to each well, wash 3 times × 3 min each time; tap the liquid in the well, add 2% BSA, 200 μL / well, and block at 37°C for 1 hour.

[0041] 2.3 Sample incubation: add 300 μL PBST washing solution to each well, wash 3 times × 3min / time; clap the liquid in the well, add purified monoclonal antibody diluted in PBS, the first well 9ug / ml, 3-fold serial dilution 100 μL / well, 37 Incubate at ℃ for 1h.

[0042] 2.4 Secondary antibody incubation: wash, same as above; add HRP goat anti-human F C Secondary antibody (diluted 1:20000), 100 μL / well, incubated at 37°C for 1 hour.

[0043...

Embodiment 3

[0048] Embodiment 3.Biacore T200 measures the affinity of monoclonal antibody and S, S1, RBD antigen

[0049] The basic principle of the assay is a biosensing analytical technique based on the physical optical phenomenon of surface plasmon resonance (SPR). Fluorescent and isotopic labels are not necessary, thereby maintaining the natural activity of biomolecules. When the incident light is incident on the interface of two different transparent media at the critical angle, total reflection will occur, and the intensity of the reflected light should be the same at all angles, but if a metal film is coated on the surface of the medium, the incident light can The resonance of the free electrons in the metal is caused, which causes the reflected light to be greatly weakened within a certain angle, and the angle at which the reflected light completely disappears is called the resonance angle. The resonance angle will change with the change of the refractive index of the liquid phas...

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Abstract

The invention relates to an antibody composition containing a monoclonal antibody specifically bound to an S protein receptor binding domain of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and a monoclonal antibody specifically bound to an S protein N-terminal structural domain of the SARS-CoV-2. Compared to the monoclonal antibodies separately used, the antibody composition is significantly improved in the aspect of the neutralizing activity on novel coronavirus infected cells, the neutralizing activity is respectively increased to 6.4 times of that of an anti-S protein receptor binding domain and 3.8 times of that of an anti-S protein N-terminal structural domain, and the antibody composition has a remarkable synergistic effect. The invention further relates to application of the antibody composition to preparation of COVID-19 treatment and / or prevention drugs. The antibody composition can be prepared on a large scale by stable engineered strains and an industrial pharmaceutical method, and has a huge industrial prospect.

Description

technical field [0001] The invention discloses an antibody composition against SARS-CoV-2, belonging to the fields of microbiology and immunology. Background technique [0002] SARS-CoV-2 belongs to the family Coronaviridae (Coro-naviridae) and belongs to the genus Coronavirus. It is a class of enveloped single-stranded positive-sense RNA viruses. Structural protein S can specifically bind to host cell receptors, and is a key protein for viruses to invade host susceptible cells. Different coronaviruses can use different cell receptors to complete the invasion. For example, the receptor of SARS-CoV is angiotensin-converting enzyme 2 (ACE2), while the receptor of MERS-CoV is aminopeptidase 4 (DPP4, also known as CD26 ). Studies have proved that aminopeptidase N is not the receptor of SARS-CoV-2, but ACE2 can be the receptor of SARS-CoV-2. [0003] The S protein can be cleaved by host proteases into two subunits, S1 and S2, in which the S1 subunit is located at the top of th...

Claims

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Application Information

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IPC IPC(8): A61K39/42A61P31/14
CPCC07K16/10A61P31/14C07K2317/565C07K2317/56C07K2317/76A61K2039/507
Inventor 陈薇李建民迟象阳张军付玲于长明徐俊杰侯利华张冠英范鹏飞郝勐董韵竹宋小红陈旖张金龙房婷刘树玲吕鹏于婷
Owner ACADEMY OF MILITARY MEDICAL SCI
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