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CN-121975005-A - Anti-novel coronavirus antibody or antigen binding fragment thereof, and preparation method and application thereof

CN121975005ACN 121975005 ACN121975005 ACN 121975005ACN-121975005-A

Abstract

The invention belongs to the technical field of biology, and particularly relates to an anti-novel coronavirus antibody or an antigen binding fragment thereof, and a preparation method and application thereof. The antibody or antigen binding fragment thereof can specifically identify and bind to the novel Omicron BA.4/5 coronavirus or RBD protein thereof, has no cross reaction to wild SARS-CoV-2, delta (B.1.617.2), omicron BA.1 or RBD protein thereof, has better neutralization activity to the novel Omicron BA.4/5, omicron XBB.1 and/or Omicron BQ.1.1 coronavirus, and can be used for diagnosing, preventing and/or treating novel coronavirus infection or diseases caused by the novel coronavirus infection, detecting the existence or level of the novel coronavirus or RBD protein in a sample or developing or screening medicaments for preventing and/or treating the novel coronavirus infection or diseases caused by the novel coronavirus infection.

Inventors

  • LI JINGJING
  • LIU XIAOYA
  • HUANG ENQI
  • WU CHANGWEI
  • RONG HUAN

Assignees

  • 安徽智飞龙科马生物制药有限公司
  • 重庆智飞生物制品股份有限公司
  • 北京智飞绿竹生物制药有限公司

Dates

Publication Date
20260505
Application Date
20251219

Claims (12)

  1. 1. An anti-novel coronavirus antibody or antigen-binding fragment thereof comprising: a1 HCDR1, HCDR2 and HCDR3 comprised in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID No. 2 and/or LCDR1, LCDR2 and LCDR3 comprised in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID No. 4, or A2 HCDR1, HCDR2, and HCDR3 having one or more amino acid substitutions, deletions, or additions compared to HCDR1, HCDR2, and HCDR3 as indicated in a 1), and/or LCDR1, LCDR2, and LCDR3 having one or more amino acid substitutions, deletions, or additions compared to LCDR1, LCDR2, and LCDR3 as indicated in a 1).
  2. 2. The antibody or antigen-binding fragment thereof according to claim 1, The anti-novel coronavirus antibody or antigen-binding fragment thereof comprises: b1 VH comprising 3 CDRs of HCDR1 having the amino acid sequence shown in SEQ ID NO. 5, HCDR2 having the amino acid sequence shown in SEQ ID NO. 6 and HCDR3 having the amino acid sequence shown in SEQ ID NO. 7, and/or VL comprising 3 CDRs of LCDR1 having the amino acid sequence shown in SEQ ID NO. 8, LCDR2 having the amino acid sequence RAS and LCDR3 having the amino acid sequence shown in SEQ ID NO. 9, or B2 VH comprising 3 CDRs of HCDR1, HCDR2 and HCDR3 having one or more amino acid substitutions, deletions or additions compared to HCDR1, HCDR2 and HCDR3 as shown in b 1), and/or VL comprising 3 CDRs of LCDR1, LCDR2 and LCDR3 having one or more amino acid substitutions, deletions or additions compared to LCDR1, LCDR2 and LCDR3 as shown in b 1); Wherein the CDR is defined according to the IMGT numbering system, or The anti-novel coronavirus antibody or antigen-binding fragment thereof comprises: c1 VH comprising 3 CDRs of HCDR1 having the amino acid sequence shown in SEQ ID NO 10, HCDR2 having the amino acid sequence shown in SEQ ID NO 11 and HCDR3 having the amino acid sequence shown in SEQ ID NO 12, and/or VL comprising 3 CDRs of LCDR1 having the amino acid sequence shown in SEQ ID NO 13, LCDR2 having the amino acid sequence shown in SEQ ID NO 14 and LCDR3 having the amino acid sequence shown in SEQ ID NO 9, or C2 VH comprising 3 CDRs of HCDR1, HCDR2 and HCDR3 having one or more amino acid substitutions, deletions or additions compared to HCDR1, HCDR2 and HCDR3 as indicated in c 1), and/or VL comprising 3 CDRs of LCDR1, LCDR2 and LCDR3 having one or more amino acid substitutions, deletions or additions compared to LCDR1, LCDR2 and LCDR3 as indicated in c 1); Wherein the CDR is defined according to the Kabat numbering system, or The anti-novel coronavirus antibody or antigen-binding fragment thereof comprises: d1 VH comprising 3 CDRs of HCDR1 having the amino acid sequence shown in SEQ ID NO. 15, HCDR2 having the amino acid sequence shown in SEQ ID NO. 16 and HCDR3 having the amino acid sequence shown in SEQ ID NO. 12, and/or VL comprising 3 CDRs of LCDR1 having the amino acid sequence shown in SEQ ID NO. 13, LCDR2 having the amino acid sequence shown in SEQ ID NO. 14 and LCDR3 having the amino acid sequence shown in SEQ ID NO. 9, or D2 VH comprising 3 CDRs of HCDR1, HCDR2 and HCDR3 having one or more amino acid substitutions, deletions or additions compared to HCDR1, HCDR2 and HCDR3 as shown in d 1), and/or VL comprising 3 CDRs of LCDR1, LCDR2 and LCDR3 having one or more amino acid substitutions, deletions or additions compared to LCDR1, LCDR2 and LCDR3 as shown in d 1); Wherein the CDR is defined according to the Chothia numbering system, or The anti-novel coronavirus antibody or antigen-binding fragment thereof comprises: e1 VH comprising 3 CDRs of HCDR1 having the amino acid sequence shown in SEQ ID NO: 17, HCDR2 having the amino acid sequence shown in SEQ ID NO: 18 and HCDR3 having the amino acid sequence shown in SEQ ID NO: 19, and/or VL comprising 3 CDRs of LCDR1 having the amino acid sequence shown in SEQ ID NO:20, LCDR2 having the amino acid sequence shown in SEQ ID NO:21 and LCDR3 having the amino acid sequence shown in SEQ ID NO: 22, or E2 VH comprising 3 CDRs of HCDR1, HCDR2 and HCDR3 having one or more amino acid substitutions, deletions or additions compared to HCDR1, HCDR2 and HCDR3 as indicated by e 1), and/or VL comprising 3 CDRs of LCDR1, LCDR2 and LCDR3 having one or more amino acid substitutions, deletions or additions compared to LCDR1, LCDR2 and LCDR3 as indicated by e 1); wherein the CDR is defined according to the Contact numbering system, or The anti-novel coronavirus antibody or antigen-binding fragment thereof comprises: f1 VH comprising 3 CDRs of HCDR1 having the amino acid sequence shown in SEQ ID NO. 23, HCDR2 having the amino acid sequence shown in SEQ ID NO. 24 and HCDR3 having the amino acid sequence shown in SEQ ID NO. 12, and/or VL comprising 3 CDRs of LCDR1 having the amino acid sequence shown in SEQ ID NO. 13, LCDR2 having the amino acid sequence shown in SEQ ID NO. 14 and LCDR3 having the amino acid sequence shown in SEQ ID NO. 9, or F2 VH comprising 3 CDRs of HCDR1, HCDR2 and HCDR3 having one or more amino acid substitutions, deletions or additions compared to HCDR1, HCDR2 and HCDR3 as indicated by f 1), and/or VL comprising 3 CDRs of LCDR1, LCDR2 and LCDR3 having one or more amino acid substitutions, deletions or additions compared to LCDR1, LCDR2 and LCDR3 as indicated by f 1); Wherein the CDRs are defined according to the AbM numbering system; Preferably, the heavy chain variable region of the anti-novel coronavirus antibody or antigen binding fragment thereof further comprises a framework region of a heavy chain variable region; preferably, the framework region of the heavy chain variable region comprises a framework region of a heavy chain variable region of an immunoglobulin derived from a mouse, primate, cow, horse, pig, sheep, goat, dog, cat, rabbit, camel, donkey, deer, mink, chicken, duck or goose or a mutant thereof; Preferably, the light chain variable region of the anti-novel coronavirus antibody or antigen binding fragment thereof further comprises a framework region of a light chain variable region; Preferably, the framework region of the light chain variable region comprises a framework region of a light chain variable region of an immunoglobulin derived from a mouse, primate, cow, horse, pig, sheep, goat, dog, cat, rabbit, camel, donkey, deer, mink, chicken, duck or goose or a mutant thereof, and more preferably comprises a framework region of a light chain variable region of an immunoglobulin derived from a mouse or a mutant thereof.
  3. 3. The antibody or antigen-binding fragment thereof according to any one of claim 1 to 2, The anti-novel coronavirus antibody or antigen-binding fragment thereof comprises: A heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO. 2 or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity thereto, and/or a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO. 4 or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity thereto; preferably, the anti-novel coronavirus antibody or antigen binding fragment thereof further comprises a heavy chain constant region and/or a light chain constant region; Preferably, the heavy chain constant region comprises at least a portion of an immunoglobulin derived from a mouse, primate, cow, horse, pig, sheep, goat, dog, cat, rabbit, camel, donkey, deer, mink, chicken, duck or goose or a mutant thereof, and more preferably comprises at least a portion of a heavy chain constant region of an immunoglobulin derived from a mouse or a mutant thereof; Preferably, the light chain constant region comprises at least a portion of a light chain constant region derived from an immunoglobulin of murine, primate, bovine, equine, porcine, ovine, caprine, canine, feline, rabbit, camel, donkey, deer, mink, chicken, duck, or goose or a mutant thereof, and further preferably comprises a light chain constant region derived from a murine immunoglobulin or a mutant thereof; Preferably, the heavy chain constant region comprises a heavy chain constant region derived from an IgA1, igA2, igD, igE, igG1, igG2, igG3, igG4 or IgM immunoglobulin, and further preferably comprises a heavy chain constant region derived from an IgG1 immunoglobulin; Preferably, the light chain constant region comprises a light chain constant region derived from kappa and lambda immunoglobulins.
  4. 4. The antibody or antigen-binding fragment thereof according to claim 1 to 3, The anti-novel coronavirus antibody or antigen binding fragment thereof is a murine antibody, a chimeric antibody, a humanized antibody or a fully human antibody; Preferably, the anti-novel coronavirus antibody or antigen-binding fragment thereof comprises a monoclonal antibody, a bispecific antibody, a multispecific antibody, a nanobody, a Fab fragment, a Fab '-SH fragment, a F (ab') 2 fragment, an Fv fragment, a single chain Fv (scFv), a dsFv, or an Fd fragment.
  5. 5. A chimeric antigen receptor comprising an antigen binding domain comprising the antibody or antigen binding fragment thereof of any one of claims 1-4, a transmembrane domain, and an intracellular signaling domain.
  6. 6. A biological material associated with the antibody or antigen binding fragment thereof of any one of claims 1-4 or the chimeric antigen receptor of claim 5, the biological material comprising any one of n 1) -n 9): n 1) a nucleic acid molecule encoding the antibody or antigen-binding fragment thereof of any one of claims 1-4 or the chimeric antigen receptor of claim 5; n 2) an expression cassette comprising n 1) said nucleic acid molecule; n 3) a vector comprising the nucleic acid molecule of n 1); n 4) a vector comprising the expression cassette of n 2); n 5) a cell comprising the nucleic acid molecule of n 1); n 6) a cell comprising the expression cassette of n 2); n 7) cells comprising n 3) said vector; n 8) cells comprising n 4) said vector; n 9) a cell comprising the antibody or antigen-binding fragment thereof of any one of claims 1-4 or the chimeric antigen receptor of claim 5; The cell of any one of n 5) -n 9) does not comprise propagation material.
  7. 7. A method for the preparation of an antibody or antigen binding fragment thereof according to any one of claims 1 to 4 or a chimeric antigen receptor according to claim 5, by culturing the cells according to claim 6.
  8. 8. A conjugate comprising the antibody or antigen-binding fragment thereof of any one of claims 1-4, and a coupling moiety.
  9. 9. The conjugate according to claim 8, wherein the conjugate comprises, The coupling moiety comprises a detectable label or therapeutic agent; preferably, the detectable label comprises an enzyme, a radionuclide, a fluorescent dye, a luminescent substance, a colored substance, and/or biotin.
  10. 10. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1-4, the chimeric antigen receptor of claim 5, the biological material of claim 6, or the conjugate of any one of claims 8-9, and a pharmaceutically acceptable carrier.
  11. 11. A diagnostic or therapeutic kit comprising an antibody or antigen binding fragment thereof according to any one of claims 1 to 4, a chimeric antigen receptor according to claim 5, a biological material according to claim 6, a conjugate according to any one of claims 8 to 9 or a pharmaceutical composition according to claim 10.
  12. 12. Use of the antibody or antigen binding fragment thereof of any one of claims 1-4, the chimeric antigen receptor of claim 5, the biological material of claim 6, the conjugate of any one of claims 8-9, or the pharmaceutical composition of claim 10 in any one of c 1) -c 6): c1 Preparing a product for diagnosing a novel coronavirus infection or a disease caused thereby; c2 Preparing a product for preventing and/or treating a novel coronavirus infection or a disease caused thereby; c3 Preparing a product for detecting the presence or level of a novel coronavirus or RBD protein thereof in a sample; c4 Detecting the presence or level of a novel coronavirus or RBD protein thereof; c5 Preparing a product for drug development or screening for the prevention and/or treatment of a novel coronavirus infection or a disease caused thereby; c6 Drug development or screening for the prevention and/or treatment of novel coronavirus infections or diseases caused thereby.

Description

Anti-novel coronavirus antibody or antigen binding fragment thereof, and preparation method and application thereof Technical Field The invention belongs to the technical field of biology, and particularly relates to an anti-novel coronavirus antibody or an antigen binding fragment thereof, and a preparation method and application thereof. Background The novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) is an RNA virus, which is susceptible to mutation during replication, most of which have no significant effect on viral function, but occasionally produce mutants with survival advantages, such as mutants with greater transmissibility, greater immune escape capacity or altered pathogenicity. When a variant accumulates a series of specific, dominant mutations and exhibits a significant spread advantage or immune escape ability in the population, it is identified as a "variant of interest", such as Delta, omicron and numerous subtypes thereof (BA.1, BA.2, BA.4, BA.5, XBB, JN.1, KP.2, KP.3, etc.). Since Omicron appeared, the variation exhibited significant immune escape, and had a strong escape capacity for past infection and vaccination-induced immunity, resulting in increased repeat infection and breakthrough infection. Omicron has evolved internally a large number of subtypes with different combinations of mutations, competition between them is intense, dominant subtype changes are rapid (e.g. from ba.1 to ba.4/5, to XBB, jn.1, kp.2/kp.3, etc.), and rapid subtype/branch changes also present challenges for vaccine development. For research and development of novel coronavirus variant vaccines, quantification of a target antigen is one of indexes for evaluating effectiveness of the novel coronavirus variant vaccine, and a common method for quantitatively detecting the target antigen is an enzyme-linked immunosorbent assay (ELISA), which has high requirements on specificity of the antigen and can specifically identify the target antigen. Thus, there is an urgent need to develop anti-novel coronavirus antibodies or antigen-binding fragments thereof. Disclosure of Invention It is an object of the first aspect of the present invention to provide anti-novel coronavirus antibodies or antigen binding fragments thereof. It is an object of the second aspect of the present invention to provide chimeric antigen receptors. The object of a third aspect of the present invention is to provide a biomaterial. The object of the fourth aspect of the present invention is to provide a method for producing an antibody or antigen-binding fragment thereof according to the first aspect of the present invention or a chimeric antigen receptor according to the second aspect. It is an object of a fifth aspect of the present invention to provide conjugates. The object of the sixth aspect of the present invention is to provide a pharmaceutical composition. The object of the seventh aspect of the present invention is to provide a diagnostic or therapeutic kit. An object of an eighth aspect of the invention is to provide the use of an antibody or antigen binding fragment thereof of the first aspect of the invention, a chimeric antigen receptor of the second aspect, a biomaterial of the third aspect, a conjugate of the fifth aspect or a pharmaceutical composition of the sixth aspect. The object of the ninth aspect of the present invention is to provide a method for preventing and/or treating a novel coronavirus infection or a disease caused thereby. A tenth aspect of the invention aims to provide a method. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: In a first aspect of the invention, there is provided an anti-novel coronavirus antibody or antigen-binding fragment thereof comprising: a1 HCDR1, HCDR2 and HCDR3 comprised in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID No. 2 and/or LCDR1, LCDR2 and LCDR3 comprised in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID No. 4, or A2 HCDR1, HCDR2, and HCDR3 having one or more amino acid substitutions, deletions, or additions compared to HCDR1, HCDR2, and HCDR3 as indicated in a 1), and/or LCDR1, LCDR2, and LCDR3 having one or more amino acid substitutions, deletions, or additions compared to LCDR1, LCDR2, and LCDR3 as indicated in a 1). In some embodiments, the CDRs are defined according to Kabat, chothia, IMGT, contact or AbM numbering system. In some embodiments, the anti-novel coronavirus antibody or antigen binding fragment thereof comprises: b1 VH comprising 3 CDRs of HCDR1 having the amino acid sequence shown in SEQ ID NO. 5, HCDR2 having the amino acid sequence shown in SEQ ID NO. 6 and HCDR3 having the amino acid sequence shown in SEQ ID NO. 7, and/or VL comprising 3 CDRs of LCDR1 having the amino acid sequence shown in SEQ ID NO. 8, LCDR2 having the amino acid sequence RAS and LCDR3 having the amino acid sequence shown in SEQ ID NO. 9,