IP Library › Granted Patent US 12,624,112

Granted Patent B2

US 12,624,112 · App. 17/794,582 · Granted May 12, 2026

Anti-ST2 antibody, encoding nucleic acid molecules thereof and methods of use thereof

Inventors: Xinhui Xiong (Shanghai, CN); Tao Zhang (Shanghai, CN); Kai Zhong (Shanghai, CN); Wei Wu (Shanghai, CN); Qianhui Huang (Shanghai, CN); Xing Li (Shanghai, CN); Hong Pan (Shanghai, CN)

Assignee: MABWELL (SHANGHAI) BIOSCIENCE CO., LTD.

C07K16/2866 A61K2039/505 C07K2317/24 C07K2317/33 C07K2317/565 C07K2317/76 C07K2317/92

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Patent No.: US 12,624,112
App. No.: 17/794,582
Granted: May 12, 2026
Kind: B2

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Abstract

Provided are an anti-ST2 antibody or a fragment thereof. The antibody or the fragment thereof can be specifically bound to human ST2, for inhibiting combination of IL-33 and human ST2, blocking an IL-33/ST2 intracellular signaling pathway, and inhibiting the promoting effect of different forms of IL-33 in cell-derived IL5, IL6 and 118 production. Compared with a known anti-ST2 antibody, this anti-ST2 antibody has higher biological activity, and can be used for preventing, treating or alleviating diseases related to ST2 expression or IL-33/ST2 pathway disorders.

Claims (104)

1 . An antibody or fragment thereof comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region and the light chain variable region comprise heavy chain CDRs and light chain CDRs shown in any one selected from the following combinations:

(1) H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 56, 63, 70 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 85, 93, 97 sequentially;

(II-1): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 57, 64, 71 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 86, 93, 98 sequentially;

(II-2): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 57, 64, 71 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 87, 93, 98 sequentially;

(III): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 58, 65, 72 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 88, 94, 99 sequentially;

(IV-1): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 59, 66, 73 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 89, 95, 100 sequentially;

(IV-2): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 59, 66, 74 sequentially;

and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 89, 95, 100 sequentially;

(IV-3): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 59, 66, 75 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 89, 95, 100 sequentially;

(V-1): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 60, 67, 76 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 90, 95, 101 sequentially;

(V-2): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 60, 67, 76 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 90, 95, 102 sequentially;

(V-3): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 60, 67, 77 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 90, 95, 101 sequentially;

(V-4): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 60, 67, 77 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 90, 95, 102 sequentially;

(V-5): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 60, 67, 78 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 90, 95, 101 sequentially;

(V-6): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 60, 67, 78 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 90, 95, 102 sequentially;

(VI-1): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 61, 68, 79 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 91, 95, 100 sequentially;

(VI-2): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 61, 68, 80 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 91, 95, 100 sequentially;

(VI-3): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 61, 68, 81 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 91, 95, 100 sequentially;

(VII-1): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 62, 69, 82 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 92, 96, 103 sequentially;

(VII-2): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 62, 69, 83 sequentially; and, L-CDR1, L-CDR2, L-CDR3 as shown in SEQ ID NOs. 92, 96, 103 sequentially; and

(VII-3): H-CDR1, H-CDR2, H-CDR3 as shown in SEQ ID NOs. 62, 69, 84 sequentially; and, L-CDR1, L-CDR2, L-CDR3) as shown in SEQ ID NOs. 92, 96, 103 sequentially.

2 . The antibody or fragment thereof according to claim 1 , wherein the heavy chain variable region comprises an amino acid sequence as shown in any one of SEQ ID NO. 1 to SEQ ID NO. 28 or an amino acid sequence having at least 75% identity to the amino acid sequence as shown; and/or, the light chain variable region comprises an amino acid sequence as shown in any one of SEQ ID NO. 29 to SEQ ID NO. 53 or an amino acid sequence having at least 75% identity to the amino acid sequence as shown.

3 . The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region and a light chain variable region as shown in any one selected from the following combinations:

(I-1): the heavy chain variable region as shown in SEQ ID NO. 1 and the light chain variable region as shown in SEQ ID NO. 29;

(I-2): the heavy chain variable region as shown in SEQ ID NO. 2 and the light chain variable region as shown in SEQ ID NO. 30;

(I-3): the heavy chain variable region as shown in SEQ ID NO. 2 and the light chain variable region as shown in SEQ ID NO. 31;

(I-4): the heavy chain variable region as shown in SEQ ID NO. 3 and the light chain variable region as shown in SEQ ID NO. 30;

(I-5): the heavy chain variable region as shown in SEQ ID NO. 3 and the light chain variable region as shown in SEQ ID NO. 31;

(II-1): the heavy chain variable region as shown in SEQ ID NO. 4 and the light chain variable region as shown in SEQ ID NO. 32;

(II-2): the heavy chain variable region as shown in SEQ ID NO. 5 and the light chain variable region as shown in SEQ ID NO. 33;

(II-3): the heavy chain variable region as shown in SEQ ID NO. 5 and the light chain variable region as shown in SEQ ID NO. 34;

(II-4): the heavy chain variable region as shown in SEQ ID NO. 5 and the light chain variable region as shown in SEQ ID NO. 35;

(II-5): the heavy chain variable region as shown in SEQ ID NO. 6 and the light chain variable region as shown in SEQ ID NO. 33;

(II-6): the heavy chain variable region as shown in SEQ ID NO. 6 and the light chain variable region as shown in SEQ ID NO. 34;

(II-7): the heavy chain variable region as shown in SEQ ID NO. 6 and the light chain variable region as shown in SEQ ID NO. 35;

(III-1): the heavy chain variable region as shown in SEQ ID NO. 7 and the light chain variable region as shown in SEQ ID NO. 36;

(III-2): the heavy chain variable region as shown in SEQ ID NO. 8 and the light chain variable region as shown in SEQ ID NO. 37;

(III-3): the heavy chain variable region as shown in SEQ ID NO. 8 and the light chain variable region as shown in SEQ ID NO. 38;

(III-4): the heavy chain variable region as shown in SEQ ID NO. 9 and the light chain variable region as shown in SEQ ID NO. 37;

(III-5): the heavy chain variable region as shown in SEQ ID NO. 9 and the light chain variable region as shown in SEQ ID NO. 38;

(IV-1): the heavy chain variable region as shown in SEQ ID NO. 10 and the light chain variable region as shown in SEQ ID NO. 39;

(IV-2): the heavy chain variable region as shown in SEQ ID NO. 11 and the light chain variable region as shown in SEQ ID NO. 40;

(IV-3): the heavy chain variable region as shown in SEQ ID NO. 11 and the light chain variable region as shown in SEQ ID NO. 41;

(IV-4): the heavy chain variable region as shown in SEQ ID NO. 12 and the light chain variable region as shown in SEQ ID NO. 40;

(IV-5): the heavy chain variable region as shown in SEQ ID NO. 12 and the light chain variable region as shown in SEQ ID NO. 41;

(IV-6): the heavy chain variable region as shown in SEQ ID NO. 13 and the light chain variable region as shown in SEQ ID NO. 40;

(IV-7): the heavy chain variable region as shown in SEQ ID NO. 13 and the light chain variable region as shown in SEQ ID NO. 41;

(IV-8): the heavy chain variable region as shown in SEQ ID NO. 14 and the light chain variable region as shown in SEQ ID NO. 40;

(IV-9): the heavy chain variable region as shown in SEQ ID NO. 14 and the light chain variable region as shown in SEQ ID NO. 41;

(V-1): the heavy chain variable region as shown in SEQ ID NO. 15 and the light chain variable region as shown in SEQ ID NO. 42;

(V-2): the heavy chain variable region as shown in SEQ ID NO. 16 and the light chain variable region as shown in SEQ ID NO. 43;

(V-3): the heavy chain variable region as shown in SEQ ID NO. 16 and the light chain variable region as shown in SEQ ID NO. 44;

(V-4): the heavy chain variable region as shown in SEQ ID NO. 16 and the light chain variable region as shown in SEQ ID NO. 45;

(V-5): the heavy chain variable region as shown in SEQ ID NO. 17 and the light chain variable region as shown in SEQ ID NO. 43;

(V-6): the heavy chain variable region as shown in SEQ ID NO. 17 and the light chain variable region as shown in SEQ ID NO. 44;

(V-7): the heavy chain variable region as shown in SEQ ID NO. 17 and the light chain variable region as shown in SEQ ID NO. 45;

(V-8): the heavy chain variable region as shown in SEQ ID NO. 18 and the light chain variable region as shown in SEQ ID NO. 43;

(V-9): the heavy chain variable region as shown in SEQ ID NO. 18 and the light chain variable region as shown in SEQ ID NO. 44;

(V-10): the heavy chain variable region as shown in SEQ ID NO. 18 and the light chain variable region as shown in SEQ ID NO. 45;

(V-11): the heavy chain variable region as shown in SEQ ID NO. 19 and the light chain variable region as shown in SEQ ID NO. 43;

(V-12): the heavy chain variable region as shown in SEQ ID NO. 19 and the light chain variable region as shown in SEQ ID NO. 44;

(V-13): the heavy chain variable region as shown in SEQ ID NO. 19 and the light chain variable region as shown in SEQ ID NO. 45;

(VI-1): the heavy chain variable region as shown in SEQ ID NO. 20 and the light chain variable region as shown in SEQ ID NO. 46;

(VI-2): the heavy chain variable region shown as SEQ ID NO. 21 and the light chain variable region shown as SEQ ID NO. 47;

(VI-3): the heavy chain variable region as shown in SEQ ID NO. 21 and the light chain variable region as shown in SEQ ID NO. 48;

(VI-4): the heavy chain variable region as shown in SEQ ID NO. 22 and the light chain variable region as shown in SEQ ID NO. 47;

(VI-5): the heavy chain variable region as shown in SEQ ID NO. 22 and the light chain variable region as shown in SEQ ID NO. 48;

(VI-6): the heavy chain variable region as shown in SEQ ID NO. 23 and the light chain variable region as shown in SEQ ID NO. 47;

(VI-7): the heavy chain variable region as shown in SEQ ID NO. 23 and the light chain variable region as shown in SEQ ID NO. 48;

(VI-8): the heavy chain variable region as shown in SEQ ID NO. 24 and the light chain variable region as shown in SEQ ID NO. 47;

(VI-9): the heavy chain variable region as shown in SEQ ID NO. 24 and the light chain variable region as shown in SEQ ID NO. 48;

(VII-1): the heavy chain variable region as shown in SEQ ID NO. 25 and the light chain variable region as shown in SEQ ID NO. 49;

(VII-2): the heavy chain variable region as shown in SEQ ID NO. 26 and the light chain variable region as shown in SEQ ID NO. 52;

(VII-3): the heavy chain variable region shown as SEQ ID NO. 26 and the light chain variable region shown as SEQ ID NO. 53;

(VII-4): the heavy chain variable region as shown in SEQ ID NO. 26 and the light chain variable region as shown in SEQ ID NO. 50;

(VII-5): the heavy chain variable region shown as SEQ ID NO. 26 and the light chain variable region shown as SEQ ID NO. 51;

(VII-6): the heavy chain variable region shown as SEQ ID NO. 27 and the light chain variable region shown as SEQ ID NO. 52;

(VII-7): the heavy chain variable region shown as SEQ ID NO. 27 and the light chain variable region shown as SEQ ID NO. 53;

(VII-8): the heavy chain variable region shown as SEQ ID NO. 27 and the light chain variable region shown as SEQ ID NO. 50;

(VII-9): the heavy chain variable region shown as SEQ ID NO. 27 and the light chain variable region shown as SEQ ID NO. 51;

(VII-10): the heavy chain variable region as shown in SEQ ID NO. 28 and the light chain variable region as shown in SEQ ID NO. 52;

(VII-11): the heavy chain variable region as shown in SEQ ID NO. 28 and the light chain variable region as shown in SEQ ID NO. 53;

(VII-12): the heavy chain variable region as shown in SEQ ID NO. 28 and the light chain variable region as shown in SEQ ID NO. 50; and

(VII-13): the heavy chain variable region as shown in SEQ ID NO. 28 and the light chain variable region as shown in SEQ ID NO. 51.

4 . The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof binds to human ST2.

5 . The antibody or fragment thereof according to claim 1 , wherein the antibody is a monoclonal antibody, a single chain antibody, a diabody, a single domain antibody, a nanobody, a fully or partially humanized antibody, or a chimeric antibody; and

the fragment is a functionally active fragment of the antibody which is capable of specifically binding to ST2 or any portion thereof.

6 . A conjugate or fusion protein comprising the antibody or fragment thereof according to claim 1 .

7 . A composition comprising the antibody or fragment thereof according to claim 1 , a conjugate or fusion protein comprising the antibody or fragment thereof, a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain CDR, a light chain CDR, a heavy chain variable region, a light chain variable region, a heavy chain or a light chain comprised in the antibody or fragment thereof, a vector comprising the nucleic acid molecule, and/or a host cell comprising the nucleic acid molecule and/or the vector, or transformed or transfected with the nucleic acid molecule and/or the vector.

8 . The composition according to claim 7 manufactured to be a medicament for reducing the likelihood of treating, or ameliorating a disease associated with expression of ST2 or dysregulation of IL-33/ST2 pathway.

9 . The composition according to claim 7 wherein the composition is a pharmaceutical composition.

10 . The composition according to claim 8 , wherein the disease is an inflammatory disease or an autoimmune disease.

11 . The composition according to claim 8 , wherein the disease is heart failure, allergic rhinitis, nasal polyps, atopic dermatitis, chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, sepsis, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, wegener's granulomatosis, or chemotherapy-associated diarrhea.

12 . A pharmaceutical combination comprising the antibody or fragment thereof according to claim 1 , a conjugate or fusion protein comprising the antibody or fragment thereof, and/or a composition comprising the antibody or fragment thereof or the conjugate or fusion protein, and optionally an additional drug.

13 . A kit comprising the antibody or fragment thereof according to claim 1 , a conjugate or fusion protein comprising the antibody or fragment thereof, a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain CDR, a light chain CDR, a heavy chain variable region, a light chain variable region, a heavy chain or a light chain comprised in the antibody or fragment thereof, a vector comprising the nucleic acid molecule, and/or a host cell comprising the nucleic acid molecule and/or the vector, or transformed or transfected with the nucleic acid molecule and/or the vector, and/or a composition comprising the antibody or fragment thereof, the conjugate or fusion protein, the nucleic acid molecule, the vector, and/or the host cell.

14 . A nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain CDR, a light chain CDR, a heavy chain variable region, a light chain variable region, a heavy chain or a light chain comprised in the antibody or fragment thereof according to claim 1 .

15 . A vector comprising the nucleic acid molecule according to claim 14 .

16 . An isolated host cell comprising the nucleic acid molecule according to claim 14 and/or a vector comprising the nucleic acid molecule, or transformed or transfected with the nucleic acid molecule and/or the vector.

17 . A method for detecting a disease associated with expression of ST2 or dysregulation of IL-33/ST2 pathway, including contacting the antibody or fragment thereof according to claim 1 , a conjugate or fusion protein comprising the antibody or fragment thereof, and/or a composition comprising the antibody or fragment thereof or the conjugate or fusion protein with a sample from a subject.

18 . The method according to claim 17 , wherein the disease is an inflammatory disease or an autoimmune disease.

19 . The method according to claim 17 , wherein the disease is heart failure, allergic rhinitis, nasal polyps, atopic dermatitis, chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, sepsis, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, wegener's granulomatosis, or chemotherapy-associated diarrhea.

20 . A method for reducing the likelihood of, treating or ameliorating a disease associated with expression of ST2 or dysregulation of IL-33/ST2 pathway, including administering to a subject in need thereof the antibody or fragment thereof according to claim 1 , a conjugate or fusion protein comprising the antibody or fragment thereof, and/or a composition comprising the antibody or fragment thereof or the conjugate or fusion protein, and optionally an additional drug.

21 . The method according to claim 20 , wherein the disease is an inflammatory disease or an autoimmune disease.

22 . The method according to claim 20 , wherein the disease is heart failure, allergic rhinitis, nasal polyps, atopic dermatitis, chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, sepsis, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, wegener's granulomatosis, or chemotherapy-associated diarrhea.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 6, 2022

From: XIONG, XINHUI; ZHANG, TAO; ZHONG, KAI; WU, EI; HUANG, QIANHUI; LI, XING; PAN, HONG

To: MABWELL (SHANGHAI) BIOSCIENCE CO., LTD.

Reel/Frame 060738/0885 →

Priority Claims (1)

CN 202010072085.X · Jan 21, 2020 · national

Continuity (1)

Related Publication 20230220086A1 · Jul 13, 2023

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