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US 2022/0064282 A1Published application
Antibody binding to human il-1 beta, preparation method therefor and use thereof
AssigneeZeda Biopharmaceuticals, Inc.
InventorsYu XIA, Zhongmin WANG, Peng ZHANG, Baiyong LI
Life of this patent
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Abstract
Disclosed is an antibody of an entirely new structure that can bind to human IL-1β, or an antigen binding fragment thereof, which has a good biological function of blocking the binding of IL-1β to receptors thereof and thereby down regulate the activity of IL-1β, and can be used to prepare drugs for the treatment of immune diseases (such as arthritis, osteoporosis, and tumor necrosis factor receptor-associated periodic syndrome) mediated by IL-1β overexpression, and so has good prospects for clinical application.
Claims16
1:
- An antibody or antigen-binding fragment thereof that binds to human IL-1β, characterized in that, the antibody or antigen-binding fragment thereof comprises:
- (1) heavy chain complementarity determining regions H-CDR1, H-CDR2, H-CDR3, wherein the H-CDR1 having the amino acid sequence as shown in SEQ ID NO:
- 1, the H-CDR2 having the amino acid sequence as shown in SEQ ID NO:
- 2, and the H-CDR3 having the amino acid sequence as shown in SEQ ID NO:
- 3, and
- (2) light chain complementarity determining regions L-CDR1, L-CDR2, L-CDR3, wherein the L-CDR1 having the amino acid sequence as shown in SEQ ID NO:
- 4, the L-CDR2 having the amino acid sequence as shown in SEQ ID NO:
- 5, and the L-CDR3 having the amino acid sequence as shown in SEQ ID NO:
- 6.
6 more elements
2:
- The antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 1, characterized in that, the antibody is a murine antibody or a humanized antibody.
3:
- The antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 2, characterized in that, the antibody is a murine antibody, comprising a heavy chain variable region having the amino acid sequence as shown in SEQ ID NO:
- 7, and a light chain variable region having the amino acid sequence as shown in SEQ ID NO:
- 8.
4:
- The antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 2, characterized in that, the antibody is a humanized antibody, comprising a heavy chain variable region having the amino acid sequence as shown in one of SEQ ID NO:
- 9, SEQ ID NO:
- 11 or SEQ ID NO:
- 13, and a light chain variable region having the amino acid sequence as shown in one of SEQ ID NO:
- 10, SEQ ID NO:
- 12 or SEQ ID NO:
- 14.
4 more elements
5:
- The antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 1, characterized in that, the antigen-binding fragment comprises a Fab fragment, a F(ab)′2 fragment, a Fv fragment, a single chain antibody or a single domain antibody.
6:
- The antibody or antigen-binding fragment thereof that binds to human IL-1β of claim 1, characterized in that, the heavy chain complementarity determining region H-CDR2 of the antibody or antigen-binding fragment thereof comprises a C53A mutation site, and the H-CDR2 has the amino acid sequence as shown in SEQ ID NO:38.
7:
- A nucleic acid molecule, characterized in that, the nucleic acid molecule encodes the antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 1.
8:
- The nucleic acid molecule according to claim 7, characterized in that, the nucleic acid molecule has the nucleotide sequence encoding the heavy chain variable region as shown in one of SEQ ID NO:
- 15, SEQ ID NO:
- 17, SEQ ID NO:
- 19 or SEQ ID NO:
- 21, and the nucleotide sequence encoding the light chain variable region as shown in one of SEQ ID NO:
- 16, SEQ ID NO:
- 18, SEQ ID NO:
- 20 or SEQ ID NO:
- 22.
6 more elements
9:
- An expression vector, characterized in that, the expression vector comprises the nucleic acid molecule according to claim 1.
10:
- A host cell, characterized in that, the host cell comprises the expression vector according to claim 9.
11:
- A method for preparing an antibody or antigen-binding fragment thereof that binds to human IL-1β, characterized in that, the method comprises the following steps of:
- a) under expression conditions, culturing the host cell according to claim 10, to express the antibody or antigen-binding fragment thereof that binds to human IL-1β;
- b) isolating and purifying the antibody or antigen-binding fragment thereof that binds to human IL-1β of step a).
12:
- A pharmaceutical composition, characterized in that, the pharmaceutical composition comprises the antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 1, and a pharmaceutically acceptable carrier.
13:
- A method for treating an immune disease caused by IL-1β overexpression comprising:
- administering to an individual in need thereof an antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 1.
14:
- The method according to claim 13, characterized in that, the immune disease caused by IL-1β overexpression is arthritis, osteoporosis or psoriasis.
15:
- An antibody or antigen-binding fragment thereof that binds to human IL-1β, characterized in that, the main binding epitopes between the antibody or antigen-binding fragment thereof and human IL-1β comprise:
- a tryptophan at position 120 and an isoleucine at position 122 of SEQ ID NO:
- 23.
16:
- The antibody or antigen-binding fragment thereof that binds to human IL-1β according to claim 15, characterized in that, the binding epitopes further comprise a phenylalanine at position 112, a serine at position 123, and a threonine at position 124 of SEQ ID NO:23.