VHH antibody for PCSK9 and application thereof
Disclosed is an antibody capable of specifically recognizing PCSK9 or an antigen-binding fragment thereof. The antibody comprises heavy chain variable region CDR1, CDR2, and CDR3 sequences shown in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 or shown in amino acid sequences having at least 95% identity to SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. The antibody can specifically bind to PCSK9 and inhibit the activity of PCSK9.
1 . An antibody capable of specifically recognizing PCSK9 or an antigen-binding fragment thereof, wherein the antibody comprises a heavy chain variable region having amino sequence SEQ ID NO: 20.
2 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody further comprises a heavy chain constant region, at least a part of the heavy chain constant region is derived from at least one of a murine antibody, a human antibody, a primate antibody, or a mutant thereof.
3 . The antibody or the antigen-binding fragment thereof according to claim 2 , wherein the heavy chain constant region of the antibody is derived from a human IgG antibody or a mutant thereof.
4 . The antibody or the antigen-binding fragment thereof according to claim 2 , wherein the heavy chain constant region of the antibody is derived from a human IgG4.
5 . The antibody or the antigen-binding fragment thereof according to claim 4 , wherein a constant region of the antibody constant region has a full-length sequence shown in SEQ ID NO: 26.
6 . The antibody or the antigen-binding fragment thereof according to claim 5 , wherein the antibody has a heavy chain having amino acid sequence SEQ ID NO: 31.
7 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody is a small molecule antibody, wherein the small molecule antibody comprises at least one of a VHH antibody, an Fab antibody, an Fv antibody, or a minimal recognition unit.
8 . A nucleic acid molecule, encoding the antibody or the antigen-binding fragment thereof according to claim 1 .
9 . The nucleic acid molecule according to claim 8 , wherein the nucleic acid molecule is DNA having nucleotide in SEQ ID NO: 41.
10 . An expression vector, carrying the nucleic acid molecule according to claim 9 .
11 . The expression vector according to claim 10 , wherein the expression vector is a prokaryotic expression vector.
12 . A recombinant cell, expressing the antibody or the antigen-binding fragment thereof according to claim 1 .
13 . The recombinant cell according to claim 12 , wherein the recombinant cell is a prokaryotic cell.
14 . A pharmaceutical composition, comprising the antibody according to claim 1 .
15 . A pharmaceutical composition, comprising the nucleic acid molecule according to claim 8 .
16 . A pharmaceutical composition, comprising the expression vector according to claim 10 .
17 . A pharmaceutical composition, comprising the recombinant cell according to claim 12 .
18 . A method for preventing or treating PCSK9-related diseases, comprising administering the antibody according to claim 1 to a subject in need thereof.
19 . The method according to claim 18 , wherein the PCSK9-related diseases comprise hyperlipidemia, hypercholesterolemia, and conditions caused by atherosclerosis.
20 . A kit for detecting PCSK9, the kit comprising the antibody according to claim 1 .