Antibody Binding to Human IL-33, Preparation Method Therefor, and Use Thereof
AssigneeSunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
InventorsWei Guo, Xuesai Zhang, Huiting Xu, Qingrou Li, Le Zhao, Jianhe Chen, Haomin Huang, Zhenping Zhu
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Abstract
The present invention relates to an antibody binding to human IL-33 or an antigen-binding fragment thereof, which can bind to the human IL-33 with a high affinity and block the binding of ST2 to IL-33, can be used in the preparation of a drug for treating diseases with a high IL-33 expression (such as asthma, atopic/allergic dermatitis, chronic rhino sinusitis and chronic obstructive pulmonary diseases (COPD)), and has good clinical application prospects.
Claims24
An antibody binding to human IL-33 or antigen-binding fragment thereof comprising a light chain complementary determining region L-CDR2 having the amino acid sequence of SEQ ID NO:
- 22, wherein the affinity EC50 of the antibody or antigen-binding fragment thereof binding to human IL-33 is less than 1 nM;
- and
- wherein the antibody or antigen-binding fragment thereof has the following characteristics:
- (t1) blocking the binding of IL-33 to receptor ST2;
- (t2) inhibiting IL-6 secretion of HUVEC cells induced by IL-33;
- (t3) inhibiting IFNγ secretion of human PBMCs induced by IL-33 protein;
- (t4) inhibiting IFNγ secretion of NK cells induced by IL-33;
- and
- (t5) inhibiting IL-5 and IL13 secretion of KU812 cells induced by IL-33.
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8-9. (canceled)
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A mutant of IL-33 protein, wherein corresponding to the amino acid sequence of a wild-type human IL-33 protein, the mutant comprises one or more mutations corresponding to SEQ ID NO:
- 55 at one or more sites selected from the group consisting of:
- (Z1) lysine at position 45 (K45);
- (Z2) valine at position 49 (V49);
- (Z3) aspartic acid at position 65 (D65);
- (Z4) leucine at position 50 (L50);
- (Z5) serine at position 60 (S60);
- (Z6) serine at position 52 (S52);
- (Z7) lysine at position 48 (K48);
- (Z8) leucine at position 51 (L51);
- (Z9) tyrosine at position 53 (Y53);
- and
- (Z10) glutamic acid at position 55 (E55).
Dependencies are inferred from the claim text.