IP Library › Granted Patent US 12692310

Granted Patent B2

US 12692310 · App. 17/628,869 · Granted Jul 28, 2026

ASIC1 channel antagonist antibody

Inventors: Guang Yang (Shanghai, CN); Min Qiang (Shanghai, CN)

Assignee: Shanghaitech University

C07K16/28 A61P9/10 C07K2317/52 C07K2317/565

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Quick Facts

Patent No.: US 12692310
App. No.: 17/628,869
Granted: Jul 28, 2026
Kind: B2

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Abstract

The present technology relates generally to compositions and methods of preventing or treating ischemic stroke. The present technology also relates to administering the anti-ASIC1a antibodies in effective amounts to treat a subject suffering from, or predisposed to, ischemic stroke.

Claims (66)

1 . A method for treating ischemic stroke in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof comprising a heavy chain immunoglobulin variable domain (VH) and a light chain immunoglobulin variable domain (VL),

(a) wherein the V H comprises a V H -CDR1 sequence of SEQ ID NO: 3, a VH-CDR2 sequence of SEQ ID NO: 4, and a VH-CDR3 sequence of SEQ ID NO: 5 and the VL comprises a VL-CDR1 sequence of SEQ ID NO: 8, a VL-CDR2 sequence of SEQ ID NO: 9, and a VH-CDR3 sequence of SEQ ID NO: 10; or

(b) wherein the VH comprises a VH-CDR1 sequence of SEQ ID NO: 13, a VH-CDR2 sequence of SEQ ID NO: 14, and a VH-CDR3 sequence of SEQ ID NO: 15 and the VL comprises a VL-CDR1 sequence of SEQ ID NO: 18, a VL-CDR2 sequence of SEQ ID NO: 19, and a VH-CDR3 sequence of SEQ ID NO: 20; or

(c) wherein the VH comprises a VH-CDR1 sequence of SEQ ID NO: 23, a VH-CDR2 sequence of SEQ ID NO: 24, and a VH-CDR3 sequence of SEQ ID NO: 25 and the VL comprises a VL-CDR1 sequence of SEQ ID NO: 28, a VL-CDR2 sequence of SEQ ID NO: 29, and a VH-CDR3 sequence of SEQ ID NO: 30; or

(d) wherein the VH comprises a VH-CDR1 sequence of SEQ ID NO: 33, a VH-CDR2 sequence of SEQ ID NO: 34, and a VH-CDR3 sequence of SEQ ID NO: 35 and the VL comprises a VL-CDR1 sequence of SEQ ID NO: 38, a VL-CDR2 sequence of SEQ ID NO: 39, and a VH-CDR3 sequence of SEQ ID NO: 40; or

(e) wherein the VH comprises a VH-CDR1 sequence of SEQ ID NO: 43, a VH-CDR2 sequence of SEQ ID NO: 44, and a VH-CDR3 sequence of SEQ ID NO: 45 and the VL comprises a VL-CDR1 sequence of SEQ ID NO: 48, a VL-CDR2 sequence of SEQ ID NO: 49, and a VH-CDR3 sequence of SEQ ID NO: 50,

wherein the antibody or antigen binding fragment thereof binds to the ASIC1a protein.

2 . The method of claim 1 ,

(a) wherein the antibody or antigen binding fragment thereof further comprises a Fc domain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgD, and IgE; or

(b) wherein the antibody or antigen binding fragment thereof is selected from the group consisting of Fab, F(ab′) 2 , Fab′, scF v , and F v ; or

(c) wherein the antibody or antigen binding fragment thereof is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a bispecific antibody.

3 . The method of claim 1 , wherein the antibody or antigen binding fragment thereof

(a) binds an extracellular domain of ASIC1a;

(b) binds an epitope that spans two ASIC1a subunits; and/or

4 . The method of claim 1 , wherein the V H comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 12, 22, 32, and 42, and/or the V L comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 7, 17, 27, 37, and 47.

5 . The method of claim 1 , wherein the antibody or antigen binding fragment thereof comprises a HC amino acid sequence and a LC amino acid sequence that comprises the amino acid sequences selected from the group consisting of:

SEQ ID NO: 2 and SEQ ID NO: 7 (ASC01);

SEQ ID NO: 12 and SEQ ID NO: 17 (ASC02);

SEQ ID NO: 22 and SEQ ID NO: 27 (ASC03);

SEQ ID NO: 32 and SEQ ID NO: 37 (ASC04); and

SEQ ID NO: 42 and SEQ ID NO: 47 (ASC05), respectively.

6 . A method for alleviating one or more symptoms of ischemic stroke in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof comprising a heavy chain immunoglobulin variable domain (V H ) and a light chain immunoglobulin variable domain (V L ),

wherein the antibody or antigen binding fragment thereof binds to the ASIC1a protein.

7 . The method of claim 6 , wherein the antibody or antigen binding fragment thereof comprises a HC amino acid sequence and a LC amino acid sequence that comprises the amino acid sequences selected from the group consisting of:

SEQ ID NO: 2 and SEQ ID NO: 7 (ASC01);

SEQ ID NO: 12 and SEQ ID NO: 17 (ASC02);

SEQ ID NO: 22 and SEQ ID NO: 27 (ASC03);

SEQ ID NO: 32 and SEQ ID NO: 37 (ASC04); and

SEQ ID NO: 42 and SEQ ID NO: 47 (ASC05), respectively.

8 . The method of claim 6 ,

(b) wherein the antibody or antigen binding fragment thereof is selected from the group consisting of Fab, F(ab′) 2 , Fab′, scF v , and F v ; or

(c) wherein the antibody or antigen binding fragment thereof is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a bispecific antibody.

9 . The method of claim 6 , wherein the antibody or antigen binding fragment thereof

(a) binds an extracellular domain of ASIC1a;

(b) binds an epitope that spans two ASIC1a subunits; and/or

10 . The method of claim 6 , wherein the one or more symptoms of ischemic stroke is sudden weakness, paralysis or numbness of the face, arms, or legs, drooping of one side of the face, confusion, difficulty with speaking, difficulty with understanding speech, trouble seeing in one or both eyes, blurred vision, blackened vision, double vision, difficulty with breathing, dizziness, difficulty with walking, loss of balance, loss of coordination, unexplained falls, loss of consciousness, sudden headache or severe headache.

11 . The method of claim 6 , wherein the one or more symptoms of ischemic stroke is sudden-onset face weakness, drooping of one side of the face, arm drift or abnormal speech.

12 . An antibody or antigen binding fragment thereof comprising a heavy chain immunoglobulin variable domain (V H ) and a light chain immunoglobulin variable domain (V L ),

wherein the antibody or antigen binding fragment thereof binds to the ASIC1a protein.

13 . The antibody, or antigen binding fragment thereof of claim 12 ,

(b) wherein the antigen binding fragment is selected from the group consisting of Fab, F(ab′) 2 , Fab′, scF v , and F v ; or

(c) wherein antibody, or antigen binding fragment thereof is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a bispecific antibody.

14 . The antibody, or antigen binding fragment thereof of claim 12 , wherein the antibody, or antigen binding fragment thereof

(a) binds an extracellular domain of ASIC1a;

(b) binds an epitope that spans two ASIC1a subunits; and/or

15 . A nucleic acid sequence encoding the antibody or antigen binding fragment of claim 12 , wherein the nucleic acid sequence is selected from the group consisting of SEQ ID NOs: 1, 6, 11, 16, 21, 26, 31, 36, 41, and 46.

16 . A host cell comprising a vector, wherein the vector comprises the nucleic acid of claim 15 .

17 . A kit comprising the antibody, or antigen binding fragment thereof of claim 12 and instructions for use.

18 . The kit of claim 17 , wherein the antibody, or antigen binding fragment is coupled to at least one detectable label selected from the group consisting of a radioactive label, a fluorescent label, and a chromogenic label.

19 . The kit of claim 17 , further comprising a secondary antibody that specifically binds to the antibody, or antigen binding fragment.

20 . A method for detecting ASIC1a protein in a biological sample comprising contacting the biological sample with the antibody, or antigen binding fragment thereof of claim 12 conjugated to a detectable label; and detecting the presence and the level of the detectable label in the biological sample.