Monoclonal antibodies specific for IL20-Rb, encoding nucleic acids thereof and methods of use thereof to treat bacterial-induced exacerbation of chronic obstructive pulmonary disease

Patent metadata

Field	Value
Publication number	US-12460009-B2
Application number	US-202017638464-A
Country	US
Kind code	B2
Filing date	Sep 3, 2020
Priority date	Sep 4, 2019
Publication date	Nov 4, 2025
Grant date	Nov 4, 2025

Abstract

Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality worldwide. Acute exacerbation of COPD (AE-COPD) in patients are mostly due to respiratory infection and are associated with an inexorable decline in lung function, enhanced oedema as well as airway and systemic inflammation. Previous results show that treatment with anti-IL-20Rb blocking antibodies increased the bacterial clearance in control mice infected by S. pneumoniae and protected CS-exposed mice from bacterial infection, by decreasing the bacterial burden and the inflammatory infiltrate. Therefore there is an interest for generating monoclonal antibodies specific for IL-20Rb with a neutralizing activity for their use in the treatment of AE-COPD. The present invention fulfills this need by providing antibodies having specificity for IL-20Rb.

First claim

The invention claimed is:

1 . A monoclonal antibody which cross-competes for binding to IL-20Rb with the monoclonal antibody comprising a heavy chain comprising the following CDRs i) the VH-CDR1 as set forth in SEQ ID NO:2 (NY-X3-MN wherein X3 is S or A), ii) the VH-CDR2 as set forth in SEQ ID NO:3 (YISGSSRYISYADFVKG) and iii) the VH-CDR3 as set forth in SEQ ID NO:4 (SYYGMDV) and a light chain comprising the following CDRs: i) the VL-CDR1 as set forth in SEQ ID NO:5 (AGTSSDVGGNYYVS), ii) the VL-CDR2 as set forth in SEQ ID NO:6 (GDSYRPS) and iii) the VL-CDR3 as set forth in SEQ ID NO:7 (SSYTYYSTRV).

2 . The monoclonal antibody of claim 1 which cross-competes for binding to IL-20Rb with the monoclonal antibody comprising a heavy chain comprising the following CDRs i) the VH-CDR1 as set forth in SEQ ID NO:8 (NYSMN), ii) the VH-CDR2 as set forth in SEQ ID NO:3 (YISGSSRYISYADFVKG) and iii) the VH-CDR3 as set forth in SEQ ID NO:4 (SYYGMDV) and a light chain comprising the following CDRs: i) the VL-CDR1 as set forth in SEQ ID NO:5 (AGTSSDVGGNYYVS), ii) the VL-CDR2 as set forth in SEQ ID NO:6 (GDSYRPS) and iii) the VL-CDR3 as set forth in SEQ ID NO:7 (SSYTYYSTRV).

3 . The monoclonal antibody of claim 1 which cross-competes for binding to IL-20Rb with the monoclonal antibody comprising a heavy chain comprising the following CDRs i) the VH-CDR1 as set forth in SEQ ID NO:9 (NYAMN), ii) the VH-CDR2 as set forth in SEQ ID NO:3 (YISGSSRYISYADFVKG) and iii) the VH-CDR3 as set forth in SEQ ID NO:4 (SYYGMDV) and a light chain comprising the following CDRs: i) the VL-CDR1 as set forth in SEQ ID NO:5 (AGTSSDVGGNYYVS), ii) the VL-CDR2 as set forth in SEQ ID NO:6 (GDSYRPS) and iii) the VL-CDR3 as set forth in SEQ ID NO:7 (SSYTYYSTRV).

4 . The monoclonal antibody of claim 1 which is chimeric, a humanized or a human antibody.

5 . A monoclonal antibody having specificity for IL-20Rb which comprises a heavy chain comprising the following CDRs i) the VH-CDR1 as set forth in SEQ ID NO: 2 (NY-X3-MN wherein X3 is S or A), ii) the VH-CDR2 as set forth in SEQ ID NO: 3 (YISGSSRYISYADFVKG) and iii) the VH-CDR3 as set forth in SEQ ID NO:4 (SYYGMDV) and a light chain comprising the following CDRs: i) the VL-CDR1 as set forth in SEQ ID NO:5 (AGTSSDVGGNYYVS), ii) the VL-CDR2 as set forth in SEQ ID NO:6 (GDSYRPS) and iii) the VL-CDR3 as set forth in SEQ ID NO:7 (SSYTYYSTRV).

6 . The monoclonal of claim 5 which comprises a heavy chain comprising the following CDRs i) the VH-CDR1 as set forth in SEQ ID NO:8 (NYSMN), ii) the VH-CDR2 as set forth in SEQ ID NO:3 (YISGSSRYISYADFVKG) and iii) the VH-CDR3 as set forth in SEQ ID NO:4 (SYYGMDV) and a light chain comprising the following CDRs: i) the VL-CDR1 as set forth in SEQ ID NO:5 (AGTSSDVGGNYYVS), ii) the VL-CDR2 as set forth in SEQ ID NO:6 (GDSYRPS) and iii) the VL-CDR3 as set forth in SEQ ID NO:7 (SSYTYYSTRV).

7 . The monoclonal of claim 5 which comprises a heavy chain comprising the following CDRs i) the VH-CDR1 as set forth in SEQ ID NO:9 (NYAMN), ii) the VH-CDR2 as set forth in SEQ ID NO:3 (YISGSSRYISYADFVKG) and iii) the VH-CDR3 as set forth in SEQ ID NO:4 (SYYGMDV) and a light chain comprising the following CDRs: i) the VL-CDR1 as set forth in SEQ ID NO:5 (AGTSSDVGGNYYVS), ii) the VL-CDR2 as set forth in SEQ ID NO:6 (GDSYRPS) and iii) the VL-CDR3 as set forth in SEQ ID NO:7 (SSYTYYSTRV).

8 . The monoclonal antibody of claim 5 which comprises a heavy chain having 70% of identity with SEQ ID NO:10 or SEQ ID NO: 11 and/or a light chain having 70% of identity with SEQ ID NO:12.

9 . The antibody of claim 4 which comprises the heavy chain as set forth in SEQ ID NO: 10 or SEQ ID NO:11 and the light chain as set forth in SEQ ID NO:12.

10 . The antibody of claim 1 which does not comprise a Fc region that mediates antibody-dependent cell-mediated cytotoxicity and thus does not comprise an Fc portion that induces antibody dependent cellular cytotoxicity (ADCC).

11 . The antibody of claim 5 which does not comprise a Fc region that mediates antibody-dependent cell-mediated cytotoxicity and thus does not comprise an Fc portion that induces antibody dependent cellular cytotoxicity (ADCC).

12 . A pharmaceutical composition comprising the monoclonal antibody of claim 1 .

13 . A pharmaceutical composition comprising the monoclonal antibody of claim 5 .

14 . A nucleic acid molecule encoding for a heavy chain and/or a light chain of the antibody of claim 1 .

15 . An isolated host cell which has been transfected, infected or transformed by the nucleic acid of claim 14 .

16 . A nucleic acid molecule encoding for a heavy chain and/or a light chain of the antibody of claim 5 .

17 . An isolated host cell which has been transfected, infected or transformed by the nucleic acid of claim 16 .

18 . A method of treating bacterial-induced exacerbations of chronic obstructive pulmonary disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the monoclonal antibody of claim 1 .

19 . A method of treating bacterial-induced exacerbations of chronic obstructive pulmonary disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the monoclonal antibody of claim 5 .

Assignees

• Inst Nat Sante Rech Med
• Centre Nat Rech Scient
• Univ Lille
• Pasteur Institut
• Univ Montpellier
• Inst Regional Cancer Montpellier

Inventors

• Gosset Philippe
• Pichavant Muriel
• Martineau Pierre
• Chentouf Myriam
• Robert Bruno
• Le Roux Mélina

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K2039/505

  comprising antibodies · CPC title