JPWO2020221910A5

JPWO2020221910A5 -

Info

Publication number: JPWO2020221910A5
Application number: JP2021561902A
Authority: JP
Publication date: 2023-04-24

Claims

(i) heavy chain CDR1, CDR2, and CDR3 sequences represented by SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 12, respectively, and SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively; a light chain CDR1, CDR2, and CDR3 sequence, or (ii) a heavy chain CDR1, CDR2, and CDR3 sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and SEQ ID NO: 4; (iii) the heavy chain CDR1 sequences represented by SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 12, respectively; , CDR2 and CDR3 sequences, and light chain CDR1, CDR2 and CDR3 sequences represented by SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 14, respectively. binding fragment.

The antibody or antigen-binding fragment thereof has (i) an amino acid sequence represented by SEQ ID NO: 13, or at least 70 %, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% SEQ ID NO: 13 A heavy chain variable region comprising an amino acid sequence having % identity with an amino acid sequence represented by SEQ ID NO:8 or at least 70% , at least 75%, at least 80%, at least 85%, at least 90% with SEQ ID NO:8 or a light chain variable region comprising an amino acid sequence having at least 95% identity, wherein said CDR sequence of claim 1 is maintained, or (ii) an amino acid sequence represented by SEQ ID NO:7, or a heavy chain variable region comprising an amino acid sequence having at least 70 %, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity to SEQ ID NO:7; or a light chain variable region comprising an amino acid sequence having at least 70 %, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity to SEQ ID NO: 15; The CDR sequence of claim 1 is maintained, or (iii) the amino acid sequence represented by SEQ ID NO: 16 or at least 70% , at least 75%, at least 80%, at least 85%, at least SEQ ID NO: 16 A heavy chain variable region comprising an amino acid sequence having 90% or at least 95% identity with an amino acid sequence represented by SEQ ID NO:8, or at least 70% , at least 75%, at least 80%, at least a light chain variable region comprising an amino acid sequence having 85%, at least 90%, or at least 95% identity, wherein said CDR sequence of claim 1 is maintained, or (iv) with SEQ ID NO: 11 a heavy chain variable region comprising an amino acid sequence represented or having at least 70 %, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity to SEQ ID NO: 11; A light chain comprising an amino acid sequence represented by SEQ ID NO: 15 or an amino acid sequence having at least 70% , at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity to SEQ ID NO: 15 wherein the CDR sequences of claim 1 are maintained, or (v) the amino acid sequence represented by SEQ ID NO: 13, or at least 70% , at least 75%, at least 80% with SEQ ID NO: 13 , a heavy chain variable region comprising an amino acid sequence having at least 85%, at least 90%, or at least 95% identity with an amino acid sequence represented by SEQ ID NO: 15, or at least 70% , at least 75% with SEQ ID NO: 15 , a light chain variable region comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity, wherein the CDR sequences of claim 1 are maintained, or ( vi) comprises an amino acid sequence represented by SEQ ID NO: 16 or an amino acid sequence having at least 70 %, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity with SEQ ID NO: 16 heavy chain variable region with the amino acid sequence represented by SEQ ID NO: 15, or with at least 70% , at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity with SEQ ID NO: 15 wherein the CDR sequence of claim 1 is maintained, or (vii) the amino acid sequence represented by SEQ ID NO: 104, or at least 70% of SEQ ID NO: 104 A heavy chain variable region comprising an amino acid sequence having 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity with an amino acid sequence represented by SEQ ID NO:8, or at least with SEQ ID NO:8 and a light chain variable region comprising an amino acid sequence having 70 %, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity, wherein the CDR sequence of claim 1 is maintained or (viii) the amino acid sequence represented by SEQ ID NO: 104 or at least 70% , at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 104 and an amino acid sequence represented by SEQ ID NO: 15, or at least 70% , at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% SEQ ID NO: 15 and a light chain variable region comprising an amino acid sequence with % identity, wherein the CDR sequences of claim 1 are maintained.

An antibody or an antigen-binding fragment thereof comprising a heavy chain variable region comprising the amino acid sequence represented by SEQ ID NO: 11 and a light chain variable region comprising the amino acid sequence represented by SEQ ID NO: 8 an antigen-binding fragment thereof.

4. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein said antibody or antigen-binding fragment thereof is a human antibody and/or a monoclonal antibody.

5. The antibody or antigen-binding fragment thereof of any of claims 1-4, wherein said antibody comprises an Fc portion.

6. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, wherein said antibody or antigen-binding fragment thereof comprises mutations M428L and/or N434S in the heavy chain constant region.

7. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 6, wherein said antibody is of the IgG type, preferably of the IgG1 type.

8. Any of claims 1-7, wherein the antibody or antigen-binding fragment thereof is purified, is a single chain antibody, or is selected from Fab, Fab', F(ab')2, Fv, or scFv. The antibody or antigen-binding fragment thereof according to .

9. The antibody or antigen-binding thereof according to any one of claims 2 to 8, wherein said heavy chain variable region of said antibody or antigen-binding fragment thereof is encoded by a nucleic acid comprising a gene of the VH3 gene family, such as gene VH3-30. piece.

10. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 9 for use as a medicament, preferably for use in the prevention or treatment of malaria.

10. A nucleic acid molecule comprising a polynucleotide encoding the antibody or antigen-binding fragment thereof of any one of claims 1-9.

A combination of a first nucleic acid molecule and a second nucleic acid molecule, wherein the first nucleic acid molecule is a polynucleotide encoding the heavy chain of the antibody or antigen-binding fragment thereof of any one of claims 1-9. wherein said second nucleic acid molecule comprises a polynucleotide encoding the corresponding light chain of the same antibody or antigen-binding fragment thereof.

A vector, characterized in that it comprises a nucleic acid molecule according to claim 11 or a combination of nucleic acid molecules according to claim 12.

A combination of a first vector and a second vector,
A vector, characterized in that said first vector comprises a first nucleic acid molecule according to claim 12 and said second vector comprises a corresponding second nucleic acid molecule according to claim 12. combination.

A cell characterized in that it expresses an antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, or comprises a vector according to claim 13 or a combination of vectors according to claim 14. .

The antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, the nucleic acid molecule according to claim 11, the combination of the nucleic acid molecule according to claim 12, the vector according to claim 13, and the vector according to claim 14. 16. A pharmaceutical composition, characterized in that it comprises a combination of vectors according to claim 15 or cells according to claim 15 and optionally a pharmaceutically acceptable diluent or carrier.

An antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, a nucleic acid molecule according to claim 11, a nucleic acid molecule combination according to claim 12, for use in the prevention or treatment of malaria. A vector according to claim 13, a combination of vectors according to claim 14, a cell according to claim 15, or a pharmaceutical composition according to claim 16.