Antibody for recognizing rsv pre-f protein and use thereof

Patent metadata

Field	Value
Publication number	US-2024409621-A1
Application number	US-202218702507-A
Country	US
Kind code	A1
Filing date	Aug 15, 2022
Priority date	Dec 6, 2021
Publication date	Dec 12, 2024
Grant date	—

Abstract

The present invention relates to the field of immunology and molecular virology, and in particular relates to the field of the prevention and treatment of RSV. Specifically, provided are a monoclonal antibody capable of specifically binding to a new epitope between an Ø epitope and a V epitope on a pre-F protein or a new epitope between an II epitope and a V epitope, and the use thereof in the detection, prevention and/or treatment of RSV infection and/or diseases caused by the infections.

First claim

What is claimed is:

1 . An antibody or antigen-binding fragment thereof, which specifically binds to an epitope of respiratory syncytial virus (RSV) pre-F protein, wherein the epitope comprises the amino acid residues at positions 294-295 and at least 6 amino acid residues (e.g., non-consecutive amino acid residues) within the amino acid residues at positions 160-182 of the pre-F protein;
preferably, the epitope comprises at least the amino acid residues at positions 161, 165, 166, 169, 180, 182, 294, and 295; preferably, the epitope further comprises the amino acid residue at position 196; preferably, the epitope further comprises the amino acid residues at positions 162 and 184; preferably, the epitope comprises the amino acid residues at positions 161-182 (e.g., the amino acid residues at positions 161-184) and the amino acid residues at positions 294-295; preferably, the epitope is a conformational epitope; preferably, the position of amino acid residue is determined according to SEQ ID NO: 1; preferably, the epitope comprises at least E161, N165, K166, S169, S180, S182, E294 and E295; preferably, the epitope further comprises K196; preferably, the epitope further comprises G162 and G184.

2 . An antibody or antigen-binding fragment thereof, which comprises:
(a) a heavy chain variable region (VH) comprising the following three CDRs: a VH CDR1 comprising the sequence as set forth in SEQ ID NO: 5 or variant thereof, a VH CDR2 comprising the sequence as set forth in SEQ ID NO: 6 or variant thereof, a VH CDR3 comprising the sequence as set forth in SEQ ID NO: 7 or variant thereof; and/or, (b) a light chain variable region (VL) comprising the following three CDRs: a VL CDR1 comprising the sequence as set forth in SEQ ID NO: 8 or variant thereof, a VL CDR2 comprising the sequence as set forth in SEQ ID NO: 9 or variant thereof, a VL CDR3 comprising the sequence as set forth in SEQ ID NO: 10 or variant thereof; wherein, the variant has a sequence identity of at least 70%, 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%, at least 99%, or 100% as compared to the sequence from which it is derived, or the variant has a substitution, deletion or addition of one or several amino acids (e.g., a substitution, deletion or addition of 1, 2 or 3 amino acids) as compared to the sequence from which it is derived; preferably, the substitution is a conservative substitution; preferably, the antibody or antigen-binding fragment thereof is capable of specifically binding to RSV pre-F protein; preferably, the antibody or antigen-binding fragment thereof competes with the antibody or antigen-binding fragment thereof according to claim 1 to bind to RSV pre-F protein; preferably, the antibody or antigen-binding fragment thereof binds to the same epitope of RSV pre-F protein as the antibody or antigen-binding fragment thereof according to claim 1 .

3 . The antibody or antigen-binding fragment thereof according to claim 1 or 2 , wherein:
(i) the antibody or antigen-binding fragment thereof comprises: the following three heavy chain CDRs: a VH CDR1 with the sequence as set forth in SEQ ID NO: 5, a VH CDR2 with the sequence as set forth in SEQ ID NO: 6, and a VH CDR3 with the sequence as set forth in SEQ ID NO: 7; and/or, the following three light chain CDRs: a VL CDR1 with the sequence as set forth in SEQ ID NO: 8, a VL CDR2 with the sequence as set forth in SEQ ID NO: 9, a VL CDR3 with the sequence as set forth in SEQ ID NO: 10; and/or, (ii) the antibody or antigen-binding fragment thereof comprises: three CDRs contained in the heavy chain variable region (VH) as set forth in SEQ ID NO: 3 or 60; and/or, three CDRs contained in the light chain variable region (VL) as set forth in SEQ ID NO: 4 or 61; preferably, the three CDRs contained in the VH and/or the three CDRs contained in the VL are defined by the Kabat, IMGT or Chothia numbering system.

4 . The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3 , wherein the antibody or antigen-binding fragment thereof comprises:
a VH comprising the sequence as set forth in SEQ ID NO: 3 or variant thereof, and/or, a VL comprising the sequence as set forth in SEQ ID NO: 4 or variant thereof; wherein, the variant has a sequence identity of at least 70%, 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%, at least 99%, or 100% as compared to the sequence from which it is derived, or the variant has a substitution, deletion or addition of one or more amino acids (e.g., a substitution, deletion or addition of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids) as compared to the sequence from which it is derived; preferably, the substitution is a conservative substitution; preferably, the antibody or antigen-binding fragment thereof comprises: a VH as set forth in SEQ ID NO: 3, and/or a VL as set forth in SEQ ID NO: 4.

5 . An antibody or antigen-binding fragment thereof, which specifically binds to an epitope of respiratory syncytial virus (RSV) pre-F protein, wherein the epitope comprises at least 5 amino acid residues (e.g., non-consecutive amino acid residues) within the amino acid residues at positions 160-185 and 290-295 of the pre-F protein;
preferably, the epitope comprises at least the amino acid residues at positions 161, 162, 184, 293 and 294; preferably, the epitope comprises the amino acid residues at positions 161-184 and the amino acid residues at positions 293-294; preferably, the epitope is a conformational epitope; preferably, the position of amino acid residue is determined according to SEQ ID NO: 1; preferably, the epitope comprises at least E161, G162, G184, K293 and E294.

6 . An antibody or antigen-binding fragment thereof, which comprises:
(a) a heavy chain variable region (VH) comprising the following three CDRs: a VH CDR1 comprising the sequence as set forth in SEQ ID NO: 13 or variant thereof, a VH CDR2 comprising the sequence as set forth in SEQ ID NO: 14 or variant thereof, a VH CDR3 comprising the sequence as set forth in SEQ ID NO: 15 or variant thereof; and/or, (b) a light chain variable region (VL) comprising the following three CDRs: a VL CDR1 comprising the sequence as set forth in SEQ ID NO: 16 or variant thereof, a VL CDR2 comprising the sequence as set forth in SEQ ID NO: 17 or variant thereof, a VL CDR3 comprising the sequence as set forth in SEQ ID NO: 18 or variant thereof; wherein, the variant has a sequence identity of at least 70%, 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%, at least 99%, or 100% as compared to the sequence from which it is derive, or the variant has a substitution, deletion or addition of one or several amino acids (e.g., a substitution, deletion or addition of 1, 2 or 3 amino acids) as compared to the sequence from which it is derive; preferably, the substitution is a conservative substitution; preferably, the antibody or antigen-binding fragment thereof is capable of specifically binding to RSV pre-F protein; preferably, the antibody or antigen-binding fragment thereof competes with the antibody or antigen-binding fragment thereof according to claim 5 to bind to RSV pre-F protein; preferably, the antibody or antigen-binding fragment thereof binds to the same epitope of RSV pre-F protein as the antibody or antigen-binding fragment thereof according to claim 5 .

7 . The antibody or antigen-binding fragment thereof according to claim 5 or 6 , wherein:
(i) the antibody or antigen-binding fragment thereof comprises: the foll

Assignees

• Univ Xiamen

Inventors

• Zheng Zizheng
• Sun Yongpeng
• Lei Siyu
• Qiang Hongsheng
• Chen Li
• Xia Ningshao

Classifications

• C07K16/11 Primary

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• C07K16/104 Primary

  Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] · CPC title

• C12P21/02

  having a known sequence of two or more amino acids, e.g. glutathione · CPC title

• G01N2469/10

  Detection of antigens from microorganism in sample from host · CPC title

• G01N2333/135

  Respiratory syncytial virus · CPC title