Broad-spectrum monoclonal antibodies against chikungunya virus E1 structural protein
AssigneesOsaka University, Mahidol University
InventorsTatsuo Shioda, Emi Nakayama, Tadahiro Sasaki, Orapim Puiprom, Aekkachai Tuekprakhon, Pornsawan Leaungwutiwong, Natthanej Luplertlop
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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).
Claims6
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).
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.
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 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 comprising a polypeptide consisting of the following amino acid sequence (HC) that is selected from the group consisting of
- amino acid sequences (HC1), (HC2), and (HC3):
- (HC1) an amino acid sequence of SEQ ID NO:
- 19,
- (HC2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO:
- 19, and
- (HC3) 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:
- 19,
- wherein the SEQ ID NO:
- 19 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 comprising a polypeptide consisting of the following amino acid sequence (LA) that is selected from the group consisting of
- amino acid sequences (LA1), (LA2), and (LA3):
- (LA1) an amino acid sequence of SEQ ID NO:
- 20,
- (LA2) an amino acid sequence having 80% or more identity with respect to the amino acid sequence of SEQ ID NO:
- 20, and
- (LA3) an amino acid sequence in which one to forty amino acids are deleted, substituted, inserted and/or added in the amino acid sequence of SEQ ID NO:
- 20,
- wherein SEQ ID NO:
- 20 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.
Dependencies are inferred from the claim text.