Method of treating asthma

Patent metadata

Field	Value
Publication number	US-12281160-B2
Application number	US-201916982762-A
Country	US
Kind code	B2
Filing date	Mar 22, 2019
Priority date	Mar 23, 2018
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

The present disclosure relates to methods of treating asthma, such as allergic asthma, neutrophilic asthma, mixed granulocytic asthma, and severe asthma. The present disclosure also relates to compounds for use in the treatment of asthma, as well as the use of such compounds in the manufacture of medicaments for the treatment of asthma.

First claim

The invention claimed is:

1. A method for treating asthma in a subject, the method comprising administering an antibody that binds to granulocyte colony stimulating factor receptor (G-CSFR) and inhibits granulocyte colony stimulating factor (G-CSF) signaling, wherein the antibody comprises:
(a) a heavy chain variable region (VH) comprising three CDRs of a VH comprising an amino acid sequence set forth in SEQ ID NO: 4 and a light chain variable region (VL) comprising three CDRs of a VL comprising an amino acid sequence set forth in SEQ ID NO: 5; or
(b) a VH comprising three CDRs of a VH comprising an amino acid sequence set forth in SEQ ID NO: 2 and a VL comprising three CDRs of a VL comprising an amino acid sequence set forth in SEQ ID NO: 3.

2. The method of claim 1 , wherein the asthma is allergic asthma.

3. The method of claim 1 , wherein the asthma is neutrophilic asthma.

4. The method of claim 1 , wherein the asthma is severe asthma.

5. The method of claim 1 , wherein the subject has airway bacterial colonisation and/or a respiratory viral infection.

6. The method of claim 1 , wherein the antibody is administered in an amount sufficient to prevent or reduce the severity of an asthma exacerbation.

7. The method of claim 1 , wherein the antibody is administered in an amount sufficient to reduce or prevent neutrophilic lung inflammation.

8. The method of claim 1 , wherein the antibody is administered in an amount sufficient to reduce or prevent airway hyper-responsiveness (AHR).

9. The method of claim 1 , wherein the compound that inhibits G-CSF signaling is administered in an amount sufficient to reduce or prevent an increase in mucus production.

10. The method of claim 1 , wherein the antibody is administered in an amount sufficient to have one or more of the following effects in the subject's lung:
(i) Reduce or prevent an increase in neutrophil levels;
(ii) reduce or prevent an increase in neutrophil elastase levels;
(iii) reduce or prevent an increase in extracellular double stranded DNA levels;
(iv) reduce or prevent an increase in eosinophil levels; and
(v) reduce or prevent an increase in T H 2 cell levels.

11. The method of claim 1 , wherein the antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO: 4 and a VL comprising an amino acid sequence set forth in SEQ ID NO: 5.

12. The method of claim 1 , wherein the antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO: 2 and a VL comprising an amino acid sequence set forth in SEQ ID NO: 3.

13. The method of claim 1 , wherein the antibody comprises:
(i) a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 14 or 18 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 15; or
(ii) one heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 14 and one heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 18 and two light chains comprising an amino acid sequence set forth in SEQ ID NO: 15.

14. A method for treating asthma in a subject, the method comprising administering an antibody which comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 14 or 18 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 15.

15. The method of claim 14 , wherein the subject is human.

16. The method of claim 15 , wherein the asthma is severe.

Assignees

• Csl Ltd

Inventors

• Wilson Nicholas
• Bozinovski Steven

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K16/2866

  against receptors for cytokines, lymphokines, interferons · CPC title