CN111690059A - Monoclonal antibody 1D7 for resisting SARS-CoV-2 - Google Patents

Monoclonal antibody 1D7 for resisting SARS-CoV-2 Download PDF

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CN111690059A
CN111690059A CN202010570454.8A CN202010570454A CN111690059A CN 111690059 A CN111690059 A CN 111690059A CN 202010570454 A CN202010570454 A CN 202010570454A CN 111690059 A CN111690059 A CN 111690059A
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monoclonal antibody
seq
amino acid
acid sequence
cov
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CN111690059B (en
Inventor
杨晓明
潘勇兵
吴小丽
詹珊珊
王炯
宋刚
桂芳
邓小杰
张囡
敬兆飞
杨溢民
陈莹
杜剑晖
刘建邦
张智
李新国
段凯
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WUHAN INSTITUTE OF BIOLOGICAL PRODUCTS CO LTD
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WUHAN INSTITUTE OF BIOLOGICAL PRODUCTS CO LTD
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The invention relates to a monoclonal antibody 1D7 for resisting SARS-CoV-2, six CDR areas of the antibody are: (1) heavy chain CDR1(VHCDR1) comprises the amino acid sequence shown in SEQ ID No. 1; (2) heavy chain CDR2(VHCDR2) comprises the amino acid sequence shown in SEQ ID No. 2; (3) heavy chain CDR3(VHCDR3) comprises the amino acid sequence shown in SEQ ID No. 3; (4) the light chain CDR1(VLCDR1) comprises the amino acid sequence shown in SEQ ID No. 4; (5) the light chain CDR2(VLCDR2) comprises the amino acid sequence shown in SEQ ID NO. 5; (6) the light chain CDR3(VLCDR3) comprises the amino acid sequence shown in SEQ ID NO. 6.

Description

Monoclonal antibody 1D7 for resisting SARS-CoV-2
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a monoclonal antibody 1D7 for resisting SARS-CoV-2.
Background
Convalescent plasma containing high concentrations of anti-SARS-CoV-2 antibody has shown positive effects in therapy, suggesting that anti-SARS-CoV-2 specific antibodies are effective in blocking virus binding to cells. In addition, a series of monoclonal antibodies having neutralizing activity have been developed during outbreaks of severe infectious diseases such as SARS and MERS, and have been proven to be safe and effective in the prevention and treatment of diseases. These suggest that in response to SARS-CoV-2 virus, it is possible to consider the preparation of monoclonal antibodies against SARS-CoV-2, particularly fully human monoclonal antibodies, which not only protect against virus invasion by blocking the binding of SARS-CoV-2 to the receptor cells, but also have the advantage of less side effects than humanized or human-mouse chimeric antibodies, and will provide a novel means for the specific prevention and treatment of COVID-19.
Disclosure of Invention
The invention firstly relates to a monoclonal antibody 1D7 aiming at SARS-CoV-2 virus, which is characterized in that the six CDR regions of the antibody are:
(1) the heavy chain CDR1(VHCDR1) comprises the amino acid sequence shown in SEQ ID No. 1: GLTVSSNYMS, respectively;
(2) the heavy chain CDR2(VHCDR2) comprises the amino acid sequence shown in SEQ ID NO. 2: VIYSGGSTYYADSVKG, respectively;
(3) the heavy chain CDR3(VHCDR3) comprises the amino acid sequence shown in SEQ ID NO. 3: DLVVYGMDV, respectively;
(4) the light chain CDR1(VLCDR1) comprises the amino acid sequence shown in SEQ ID No. 4: RASQSISSYLN, respectively;
(5) the light chain CDR2(VLCDR2) comprises the amino acid sequence shown in SEQ ID NO. 5: AASSLQS;
(6) the light chain CDR3(VLCDR3) comprises the amino acid sequence shown in SEQ ID NO. 6: QQSYSTLGMYT are provided.
Further, in the above-mentioned case,
the full length of the heavy chain variable region of the monoclonal antibody 1D7 comprises an amino acid sequence shown as SEQ ID NO. 7: EVQLVESGGGWIQPGGSLRLSCAASGLTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSL RAEDTAVYYCARDLVVYGMDVWGQGTTVTVSS；
The full length of the variable region of the light chain of the monoclonal antibody 1D7 comprises an amino acid sequence shown as SEQ ID NO. 8: AIRMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLGMYTFGQGTKLEIK。
Further, the monoclonal antibody 1D7 is a human IgG type antibody.
Furthermore, the antigen bound by the monoclonal antibody 1D7 is spike protein S1 of SARS-CoV-2 virus, and specifically, the antigenic structural region bound by the monoclonal antibody 1D7 is RBD structural region in spike protein S1 of SARS-CoV-2 virus.
Most preferably, the light chain variable region and the heavy chain variable region of monoclonal antibody 1D7 are the amino acid sequences shown in SEQ ID NO.8 and SEQ ID NO.7, respectively.
The invention also relates to a nucleic acid fragment encoding the monoclonal antibody 1D 7.
The invention also relates to an antibody, wherein the light chain of the antibody is:
(1) the amino acid sequence shown in SEQ ID NO.8 is replaced, deleted or added with one or more amino acids to form a sequence with the same function;
or (2) an amino acid sequence with homology of more than 95 percent with the amino acid sequence shown in SEQ ID NO. 8;
the heavy chain of the antibody is:
(1) the amino acid sequence shown in SEQ ID NO.7 is replaced, deleted or added with one or more amino acids to form a sequence with the same function;
or (2) an amino acid sequence with homology of more than 95 percent with the amino acid sequence shown in SEQ ID NO. 7.
The invention also includes the application of the monoclonal antibody 1D7 in the preparation of a reagent for detecting SARS-CoV-2 virus.
The invention also includes the application of the monoclonal antibody 1D7 in the preparation of a reagent for inhibiting SARS-CoV-2 virus.
The invention also includes the application of the monoclonal antibody 1D7 in preparing medicaments for preventing and/or treating diseases caused by SARS-CoV-2 virus infection.
The invention has the beneficial effects that: because there are no vaccines and specific drugs on the market for the diseases caused by SARS-CoV-2 virus, although the convalescent plasma treatment has been proved to be a promising treatment method, the large-scale preparation is limited, and the method mainly aims at patients with severe and critical illness, while the monoclonal antibody has the advantages of high purity, strong targeting property, small side effect, large-scale preparation and the like. The experimental result of the 1D7 antibody shows that the neutralizing activity and the blocking activity of the monoclonal antibody 1D7 are both high. Therefore, the human monoclonal antibody 1D7 obtained by the invention provides a new candidate drug for specific prevention and treatment of COVID-19.
Drawings
FIG. 1, SDS-PAGE electrophoresis detection of monoclonal antibody 1D 7: lane 1 is a non-reducing SDS-PAGE electrophoresis, and lane 2 is a reducing SDS-PAGE electrophoresis.
FIG. 2 SEC-HPLC detection of monoclonal antibody 1D 7.
FIG. 3, results of the detection of the binding activity of monoclonal antibody 1D 7. A is the binding activity against SARS-CoV-2 spike protein S1; b is the binding activity against the RBD domain of the SARS-CoV-2 spike protein S1.
FIG. 4 shows the results of the detection of the blocking activity of monoclonal antibody 1D 7. A is the blocking activity against SARS-CoV-2 spike protein S1; b is blocking activity against the RBD domain of SARS-CoV-2 spike protein S1.
FIG. 5 shows the result of affinity detection of monoclonal antibody 1D 7.
FIG. 6, results of the live virus neutralization assay of monoclonal antibody 1D 7.
Detailed Description
Unless otherwise specified, the technical means used in the following examples are conventional means well known to those skilled in the art, and all reagent consumables are commercially available.
Example 1 construction, expression and purification of monoclonal antibody 1D7 expression vector
The coding gene segments containing the heavy chain and light chain variable regions of the 1D7 antibody are respectively integrated into pcDNA3.4 expression vectors containing the heavy chain and light chain constant region sequences of the human IgG1 antibody to obtain recombinant expression vectors capable of respectively expressing the heavy chain and the light chain of the target antibody.
Transfection, antibody expression and purification of cells
1. Transfection: transfection was performed using the transfection kit from Gibco, Inc. according to the instructions, and the procedure is briefly described as follows:
mixing the two recombinant expression vector total DNAs with a transfection reagent to form a DNA Expifeactine (TM) 293 complex;
then 40mL of 2.94X10 was added6one/mL in Expi293 cell culture;
finally, the mixture was placed at 37 ℃ and 125rpm in 8% CO2And (5) culturing.
2. And (3) purification:
after 5 days of incubation, the supernatant was collected by centrifugation at 4000rpm for 10 minutes at 25 ℃ and then purified by a MabSelect Sure affinity column. The purification steps are briefly described as follows:
equilibrating with 0.1M Tris buffer, pH 7.0;
after loading, eluting with 0.1M Tris buffer solution with pH7.0;
elution was then carried out with 1.0M Tris buffer, pH 8.0.
The eluate was collected and further dialyzed against PBS buffer. The purified antibody was subjected to SDS-PAGE and HPLC-SEC detection.
3. And (4) analyzing results: the results of SDS-PAGE are shown in FIG. 1, which shows that the human SARS-CoV-2 antibody exhibits a band with a molecular weight of about 150kDa under non-reducing conditions; two bands with molecular weights of approximately 50kDa and 25kDa are present under reducing conditions, corresponding to the heavy and light chains of the antibody, respectively. The SEC-HPLC results are shown in FIG. 2, which shows that the purity of the purified monoclonal antibody reaches more than 98%. The amino acid sequence of the purified monoclonal antibody obtained by peptide map analysis is consistent with the expected amino acid sequence. Specifically, the sequences of the light chain variable region and the heavy chain variable region are respectively the same as SEQ ID NO.8 and SEQ ID NO. 7.
Example 2 functional analysis of antibodies
1. Detection of binding Activity of human anti-SARS-CoV-2 antibody 1D7 with antigen
The binding ability of the antibody to the spike protein S1 of SARS-CoV-2 virus and its RBD domain was determined by ELISA. The steps are briefly described as follows:
(1) SARS-CoV-2 spike S1-His recombinant protein (Sino company, goods number: 40591-V08H) or RBD structure domain recombinant protein (Sino company, goods number 40592-V05H) is used as coating antigen, 1.0 mu g/mL antigen is coated on an enzyme label plate by bicarbonate buffer solution, and the temperature is kept at 4 ℃ overnight;
(2) blocking with casein buffer at 37 ℃ for 1 h; adding the serially diluted antibodies to be detected, and keeping the temperature at 37 ℃ for 1 h;
(3) adding 1: 10000 diluted goat anti-human IgG-HRP (Bethyl company, cat # A80-304P), 37 ℃ for 1 h;
(4) after developing with developing solution, terminating the reaction by 2M HCl; and detecting absorbance A450 and A540 values by a microplate reader.
As a result:
the results of the detection of the binding activity of the 1D7 antibody to the antigen are shown in fig. 3, and it can be seen that the binding activity of the monoclonal antibody 1D7 against S1 protein (a in fig. 3) is EC50 ═ 0.092 nM; the binding activity against the RBD domain (B in fig. 3) was EC50 ═ 0.055 nM.
2. Detection of blocking Activity of human anti-SARS-CoV-2 antibody 1D7
ELISA assay was used to test the ability of the antibody to block the binding of ACE2 recombinant protein (His-tagged) to the spike protein S1 and RBD domain of SARS-CoV-2(2019-nCoV) virus. The steps are briefly described as follows:
(1) SARS-CoV-2 spike S1 subunit protein (Sino company, goods number: 40591-V02H) or recombinant protein of RBD structure domain (Sino company, goods number 40592-V05H) is used as coating antigen, 1.0 mu g/mL antigen is coated on an enzyme label plate by bicarbonate buffer solution, and the temperature is kept at 4 ℃ overnight;
(2) blocking with casein buffer at 37 ℃ for 1 h; adding the antibody to be detected after serial dilution and ACE recombinant protein with the concentration of 0.5 mu g/mL or 0.02 mu g/mL for co-incubation at 37 ℃ for 1 h;
(3) adding 1: 3000 diluted biotin-labeled mouse anti-His tag antibody (GenScript, Cat: A00613), 1h at 37 ℃;
(4) adding 1: 20000 diluted streptavidin-HRP (Thermofeisher Co., Ltd., cat # SNN1004), 37 ℃ for 1 h; after developing with developing solution, terminating the reaction by 2M HCl; and detecting absorbance A450 and A540 values by a microplate reader.
As a result:
the detection result of the blocking activity of the 1D7 antibody is shown in fig. 4, and it can be seen that the blocking activity of the monoclonal antibody 1D7 against the binding of ACE2 and S1 (a in fig. 4) is that IC50 is 7.80nM, and the maximum blocking rate is 91%; the blocking activity against ACE2 binding to RBD was (B in fig. 4) 4.10nM with an IC50, with a maximum blocking rate of 92%.
3. Affinity detection of human anti-SARS-CoV-2 antibody 1D7
A Biacore 8K instrument of GE company is used for carrying out a surface plasma resonance experiment to detect the affinity of the antibody.
The results of the affinity assay for monoclonal antibody 1D7 are shown in FIG. 5, which shows that 1D7 has a binding constant ka of 3.57E + 041/Ms, a dissociation constant KD of 8.63E-041/s, and an affinity constant KD of 2.42E-08M.
4. Living virus neutralization assay for human anti-SARS-CoV-2 antibodies
The virus plaque reduction neutralization test was carried out using the SARS-CoV-2 virus BetacoV/Wuhan/IVDC-HB-envF13/2020 strain. The steps are briefly described as follows: a quantitative amount of SARS-CoV-2 virus and a dilution series of the monoclonal antibody were mixed and incubated, and then added to a previously prepared assay plate containing Vero cells, and after incubation, the number of viral plaques was observed and the virus-neutralizing activity (expressed as IC 50) was calculated.
As a result:
the result of the detection of the antibody 1D7 in the live virus neutralization experiment is shown in FIG. 6, and it can be seen that the monoclonal antibody can well neutralize SARS-CoV-2 virus (IC50<24 ng/mL).
Finally, it should be noted that the above embodiments are only used to help those skilled in the art understand the essence of the present invention, and are not intended to limit the protection scope of the present invention.
SEQUENCE LISTING
<110> Wuhan Biometrics institute of Biotechnology, Inc
<120> monoclonal antibody 1D7 for anti-SARS-CoV-2
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<211>10
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<213> Artificial sequence
<400>1
Gly Leu Thr Val Ser Ser Asn Tyr Met Ser
1 5 10
<210>2
<211>16
<212>PRT
<213> Artificial sequence
<400>2
Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210>3
<211>9
<212>PRT
<213> Artificial sequence
<400>3
Asp Leu Val Val Tyr Gly Met Asp Val
1 5
<210>4
<211>11
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<213> Artificial sequence
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Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn
1 5 10
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Ala Ala Ser Ser Leu Gln Ser
1 5
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Gln Gln Ser Tyr Ser Thr Leu Gly Met Tyr Thr
1 5 10
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Glu Val Gln Leu Val Glu Ser Gly Gly Gly Trp Ile Gln Pro Gly Gly
15 10 15
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20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
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85 90 95
Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr
100 105 110
Val Thr Val Ser Ser
115
<210>8
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<213> Artificial sequence
<400>8
Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
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20 25 30
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35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Leu Gly
85 90 95
Met Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105

Claims (8)

1. Monoclonal antibody 1D7 directed against SARS-CoV-2 virus, comprising the six CDR regions:
(1) the heavy chain CDR1(VHCDR1) comprises the amino acid sequence shown in SEQ ID No. 1: GLTVSSNYMS, respectively;
(2) the heavy chain CDR2(VHCDR2) comprises the amino acid sequence shown in SEQ ID NO. 2: VIYSGGSTYYADSVKG, respectively;
(3) the heavy chain CDR3(VHCDR3) comprises the amino acid sequence shown in SEQ ID NO. 3: DLVVYGMDV, respectively;
(4) the light chain CDR1(VLCDR1) comprises the amino acid sequence shown in SEQ ID No. 4: RASQSISSYLN, respectively;
(5) the light chain CDR2(VLCDR2) comprises the amino acid sequence shown in SEQ ID NO. 5: AASSLQS;
(6) the light chain CDR3(VLCDR3) comprises the amino acid sequence shown in SEQ ID NO. 6: QQSYSTLGMYT are provided.
2. The antibody of claim 1,
the full length of the heavy chain variable region of the monoclonal antibody 1D7 comprises an amino acid sequence shown as SEQ ID NO. 7:
the full length of the variable region of the light chain of the monoclonal antibody 1D7 comprises an amino acid sequence shown in SEQ ID NO. 8.
3. The antibody of claim 1 or 2, wherein monoclonal antibody 1D7 is a human IgG-type antibody.
4. The antibody of claim 1 or 2, wherein the antigen bound by monoclonal antibody 1D7 is spike protein S1 of SARS-CoV-2 virus, and specifically, the antigenic domain bound by monoclonal antibody 1D7 is RBD domain of spike protein S1 of SARS-CoV-2 virus.
5. A nucleic acid fragment encoding the antibody of any one of claims 1-4.
6. Use of the monoclonal antibody 1D7 of any one of claims 1-4 in the preparation of a reagent for detecting SARS-CoV-2 virus.
7. Use of the monoclonal antibody 1D7 of any one of claims 1-4 in the preparation of a reagent for inhibiting SARS-CoV-2 virus.
8. Use of the monoclonal antibody 1D7 of any one of claims 1-4 in the manufacture of a medicament for the prevention and/or treatment of a disease caused by SARS-CoV-2 viral infection.
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WO2022053054A1 (en) * 2020-09-14 2022-03-17 Vazyme Biotech Co., Ltd. Neutralizing antibodies against sars-cov-2
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WO2022065445A1 (en) * 2020-09-25 2022-03-31 学校法人慶應義塾 SARS-CoV-2 NEUTRALIZING ANTIBODY OR FRAGMENT THEREOF
WO2022068895A1 (en) * 2020-09-30 2022-04-07 南京金斯瑞生物科技有限公司 Monoclonal antibody of anti-sars-cov-2 spike protein extracellular domain and application thereof
WO2022095996A1 (en) * 2020-11-09 2022-05-12 上海济煜医药科技有限公司 Anti-sars-cov-2 antibody and application thereof
WO2022101839A1 (en) * 2020-11-12 2022-05-19 Cadila Healthcare Limited Anti-sars-cov-2 monoclonal antibodies and cocktail thereof
CN114573690A (en) * 2020-12-02 2022-06-03 深圳先进技术研究院 anti-SAR-COV-2 fully human monoclonal antibody and preparation method and application thereof
CN114656556A (en) * 2022-05-24 2022-06-24 易康生物(苏州)有限公司 Fully human monoclonal antibody for resisting novel coronavirus and application thereof
WO2022143815A1 (en) * 2020-12-31 2022-07-07 中国科学院分子细胞科学卓越创新中心 Neutralizing antibody against epitopes of receptor binding domain of novel coronavirus and use thereof
WO2022182662A1 (en) 2021-02-23 2022-09-01 10X Genomics, Inc. Compositions and methods for mapping antigen-binding molecule affinity to antigen regions of interest
WO2022179561A1 (en) * 2021-02-24 2022-09-01 The University Of Hong Kong Neutralizing antibodies against covid-19 and methods of use thereof
WO2022228827A1 (en) * 2021-04-26 2022-11-03 Institut Pasteur Human neutralizing monoclonal antibodies against sars-cov-2 and uses thereof
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WO2023130770A1 (en) * 2022-01-10 2023-07-13 中国人民解放军军事科学院军事医学研究院 Fully human broadly neutralizing antibody zw2g10 against novel coronavirus and application thereof
CN114231497A (en) * 2022-02-24 2022-03-25 广州伯尼兹生物科技有限公司 Monoclonal antibody hybridoma cell line for expressing novel coronavirus S1 protein and neutralizing active antibody
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