Broad-spectrum monoclonal antibodies against chikungunya virus E1 structural protein

Patent metadata

Field	Value
Publication number	US-11560421-B2
Application number	US-201916968470-A
Country	US
Kind code	B2
Filing date	Feb 8, 2019
Priority date	Feb 9, 2018
Publication date	Jan 24, 2023
Grant date	Jan 24, 2023

Abstract

The present invention provides a new antibody against ECSA type Chikungunya virus, WA type Chikungunya virus, and Asian type Chikungunya virus or an antigen-binding fragment of the antibody. The antibody against Chikungunya virus or the antigen-binding fragment of the antibody of the present invention includes a heavy chain variable region or a heavy chain (1), (2), or (3) and a light chain variable region or a light chain (4).

First claim

The invention claimed is:

1. An antibody against Chikungunya virus or an antigen-binding fragment of the antibody, comprising the following heavy chain variable region (1), (2), or (3) and the following light chain variable region (4):
(1) a heavy chain variable region comprising heavy chain complementarity determining regions (CDRHA)-1, CDRHA-2, and CDRHA-3:
CDRHA-1 is a polypeptide comprising the following amino acid sequence (H1-A1),
CDRHA-2 is a polypeptide comprising the following amino acid sequence (H2-A1), and
CDRHA-3 is a polypeptide comprising the following amino acid sequence (H3-A1):
(H1-A1) an amino acid sequence of SEQ ID NO: 1 (GYTFTSYW),
(H2-A1) an amino acid sequence of SEQ ID NO: 2 (IYPGDGDTRYT), and
(H3-A1) an amino acid sequence of SEQ ID NO: 3 (SYDPFDY),

(2) a heavy chain variable region comprising CDRHB-1, CDRHB-2, and CDRHB-3:
CDRHB-1 is a polypeptide comprising the following amino acid sequence (H1-B1),
CDRHB-2 is a polypeptide comprising the following amino acid sequence (H2-B1), and
CDRHB-3 is a polypeptide comprising the following amino acid sequence (H3-B1):
(H1-B1) an amino acid sequence of SEQ ID NO: 4 (GYAFSTSW),
(H2-B1) an amino acid sequence of SEQ ID NO: 5 (IYPGDGDT), and
(H3-B1) an amino acid sequence of SEQ ID NO: 6 (SNDGYYVGY),

(3) a heavy chain variable region comprising CDRHC-1, CDRHC-2, and CDRHC-3:
CDRHC-1 is a polypeptide comprising the following amino acid sequence (H1-C1),
CDRHC-2 is a polypeptide comprising the following amino acid sequence (H2-C1), and
CDRHC-3 is a polypeptide comprising the following amino acid sequence (H3-C1):
(H1-C1) an amino acid sequence of SEQ ID NO: 7 (GYTFTSYY),
(H2-C1) an amino acid sequence of SEQ ID NO: 8 (INPSNGGT), and
(H3-C1) an amino acid sequence of SEQ ID NO: 9 (GYYGNPFFAY),

(4) a light chain variable region comprising light chain complementarity determining regions (CDRL)-1, CDRL-2, and CDRL-3:
CDRL-1 is a polypeptide comprising the following amino acid sequence (L1-A1),
CDRL-2 is a polypeptide comprising the following amino acid sequence (L2-A1), and
CDRL-3 is a polypeptide comprising the following amino acid sequence (L3-A1):
(L1-A1) an amino acid sequence of SEQ ID NO: 10 (ENVVTY),
(L2-A1) an amino acid sequence of SEQ ID NO: 11 (GAS), and
(L3-A1) an amino acid sequence of SEQ ID NO: 12 (GQGYSYPYT).

2. An antibody against Chikungunya virus or an antigen-binding fragment of the antibody, comprising the following heavy chain variable region (1), (2), or (3) and the following light chain variable region (4):
(1) a heavy chain variable region comprising a polypeptide consisting of the following amino acid sequence (H-A) that is selected from the group consisting of amino acid sequences (H-A1), (H-A2), and (H-A3):
(H-A1) an amino acid sequence of SEQ ID NO: 13,
(H-A2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO: 13, and
(H-A3) an amino acid sequence in which one to twenty amino acids are deleted, substituted, inserted and/or added in the amino acid sequence of SEQ ID NO: 13,

wherein each of (H-A1), (H-A2), and (H-A3) comprises sequences of heavy chain complementarity determining regions (CDRHA)-1 comprising an amino acid sequence of SEQ ID NO: 1, CDRHA-2 comprising an amino acid sequence of SEQ ID NO: 2, and CDRHA-3 comprising an amino acid sequence of SEQ ID NO: 3,
wherein the CDRHA-1, the CDRHA-2, and the CDRHA-3 sequences are invariant, (2) a heavy chain variable region comprising a polypeptide consisting of the following amino acid sequence (H-B) that is selected from the group consisting of amino acid sequences (H-B1), (H-B2), and (H-B3):
(H-B1) an amino acid sequence of SEQ ID NO: 14,
(H-B2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO: 14, and
(H-B3) an amino acid sequence in which one to twenty amino acids are deleted, substituted, inserted and/or added in the amino acid sequence of SEQ ID NO: 14,

wherein each of (H-B1), (H-B2), and (H-B3) comprises sequences of CDRHB-1 comprising an amino acid sequence of SEQ ID NO: 4, CDRHB-2 comprising an amino acid sequence of SEQ ID NO: 5, and CDRHB-3 comprising an amino acid sequence of SEQ ID NO: 6,
wherein the CDRHB-1, the CDRHB-2, and the CDRHB-3 sequences are invariant, (3) a heavy chain variable region comprising a polypeptide consisting of the following amino acid sequence (H-C) that is selected from the group consisting of
amino acid sequences (H-C1), (H-C2), and (H-C3):
(H-C1) an amino acid sequence of SEQ ID NO: 15,
(H-C2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO: 15, and
(H-C3) an amino acid sequence in which one to twenty amino acids are deleted, substituted, inserted and/or added in the amino acid sequence of SEQ ID NO: 15,

wherein each of (H-C1), (H-C2), and (H-C3) comprises sequences of CDRHC-1 comprising an amino acid sequence of SEQ ID NO: 7, CDRHC-2 comprising an amino acid sequence of SEQ ID NO: 8, and CDRHC-3 comprising an amino acid sequence of SEQ ID NO: 9,
wherein the CDRHC-1, the CDRHC-2, and the CDRHC-3 sequences are invariant, (4) a light chain variable region comprising a polypeptide consisting of the following amino acid sequence (L-A) that is selected from the group consisting of
amino acid sequences (L-A1), (L-A2), and (L-A3):
(L-A1) an amino acid sequence of SEQ ID NO: 16,
(L-A2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO: 16, and
(L-A3) an amino acid sequence in which one to twenty amino acids are deleted, substituted, inserted and/or added in the amino acid sequence of SEQ ID NO: 16,

wherein each of (L-A1), (L-A2), and (L-A3) comprises sequences of light chain complementarity determining regions (CDRL)-1 comprising an amino acid sequence of SEQ ID NO: 10, CDRL-2 comprising an amino acid sequence of SEQ ID NO: 11, and CDRL-3 comprising an amino acid sequence of SEQ ID NO: 12,
wherein the CDRL-1, the CDRL-2, and the CDRL-3 sequences are invariant.

3. An antibody against Chikungunya virus or an antigen-binding fragment of the antibody, comprising the following heavy chain (1), (2), or (3) and the following light chain (4):
(1) a heavy chain comprising a polypeptide consisting of the following amino acid sequence (HA) that is selected from the group consisting of
amino acid sequences (HA1), (HA2), and (HA3):
(HA1) an amino acid sequence of SEQ ID NO: 17,
(HA2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO: 17, and
(HA3) an amino acid sequence in which one to eighty amino acids are deleted, substituted, inserted and/or added in the amino acid sequence of SEQ ID NO: 17,

wherein the SEQ ID NO: 17 comprises sequences of heavy chain complementarity determining regions (CDRHA)-1 comprising an amino acid sequence of SEQ ID NO: 1, CDRHA-2 comprising an amino acid sequence of SEQ ID NO: 2, and CDRHA-3 comprising an amino acid sequence of SEQ ID NO: 3,
wherein the CDRHA-1, the CDRHA-2, and the CDRHA-3 sequences are invariant, (2) a heavy chain comprising a polypeptide consisting of the following amino acid sequence (HB) that is selected from the group consisting of
amino acid sequences (HB1), (HB2), and (HB3):
(HB1) an amino acid sequence of SEQ ID NO: 18,
(HB2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO: 18, and
(HB3) an amino acid sequence in which one to eighty amino acids are deleted, substituted, inserted and/or added in the amino acid sequence of SEQ ID NO: 18,

wherein the SEQ ID NO: 18 comprises sequences of CDRHB-1 comprising an amino acid sequence of SEQ ID NO: 4, CDRHB-2 comprising an amino acid sequence of SEQ ID NO: 5, and CDRHB-3 comprising an ami

Assignees

• Univ Osaka
• Mahidol Univ

Inventors

• Shioda Tatsuo
• Nakayama Emi
• Sasaki Tadahiro
• PUIPROM Orapim
• TUEKPRAKHON Aekkachai
• LEAUNGWUTIWONG Pornsawan
• Luplertlop Natthanej

Classifications

• C12N2770/36111

  Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki · CPC title

• C07K16/1081 Primary

  Chemistry & Metallurgy · mapped topic

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• G01N33/56983

  Viruses · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title