ST2L antagonists and methods of use

Patent metadata

Field	Value
Publication number	US-10450377-B2
Application number	US-201815922136-A
Country	US
Kind code	B2
Filing date	Mar 15, 2018
Priority date	Apr 30, 2012
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

Abstract

The present invention relates to ST2L antagonists, polynucleotides encoding the antagonists or fragments thereof, and methods of making and using the foregoing.

First claim

We claim:

1. A method of treating IL-33-induced airway inflammation in a patient, comprising administering a therapeutically effective amount of an isolated antibody or fragment thereof that specifically binds Domain I (SEQ ID NO: 9) of human ST2L to a patient in need thereof for a time sufficient to inhibit the IL-33-induced airway inflammation, wherein the antibody comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2, and a HCDR3, and a light chain complementarity determining region (LCDR) 1, a LCDR2, and a LCDR3 of SEQ ID NOs: 97, 114, 84, 130, 90, and 134, respectively.

2. The method of claim 1 , wherein the antibody or fragment thereof blocks IL-33/ST2L interaction.

3. The method of claim 2 , wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
(a) the VH is derived from human IGHV3-23 framework sequence (SEQ ID NO: 158); and
(b) the VL is derived from human IGKV3-11 (L6) framework sequence (SEQ ID NO: 159).

4. The method of claim 3 , wherein the antibody or fragment thereof is of IgG1, IgG2, IgG3, or IgG4 isotype.

5. The method of claim 4 , wherein the antibody or fragment thereof comprises the VH of SEQ ID NO: 191 and the VL of SEQ ID NO: 209.

6. The method of claim 1 , wherein the antibody or fragment thereof is a human or humanized antibody.

7. A method of inhibiting IL-33-induced airway hyper-responsiveness in a patient, comprising administering a therapeutically effective amount of an isolated antibody or fragment thereof that specifically binds Domain I (SEQ ID NO: 9) of human ST2L to a patient in need thereof for a time sufficient to inhibit the IL-33-induced airway hyper-responsiveness, wherein the antibody comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2, and a HCDR3, and a light chain complementarity determining region (LCDR) 1, a LCDR2, and a LCDR3 of SEQ ID NOs: 97, 114, 84, 130, 90, and 134, respectively.

8. The method of claim 7 , wherein the antibody or fragment thereof blocks IL-33/ST2L interaction.

9. The method of claim 8 , wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
(a) the VH is derived from human IGHV3-23 framework sequence (SEQ ID NO: 158); and
(b) the VL is derived from human IGKV3-11 (L6) framework sequence (SEQ ID NO: 159).

10. The method of claim 9 , wherein the antibody or fragment thereof is of IgG1, IgG2, IgG3, or IgG4 isotype.

11. The method of claim 10 , wherein the antibody or fragment thereof comprises the VH of SEQ ID NO: 191 and the VL of SEQ ID NO: 209.

12. The method of claim 7 , wherein the antibody or fragment thereof is a human or humanized antibody.

13. A method of inhibiting human lung mast cell responses in a patient, comprising administering a therapeutically effective amount of an isolated antibody or fragment thereof that specifically binds Domain I (SEQ ID NO: 9) of human ST2L to a patient in need thereof for a time sufficient to inhibit the mast cell responses, wherein the antibody comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2, and a HCDR3, and a light chain complementarity determining region (LCDR) 1, a LCDR2, and a LCDR3 of SEQ ID NOs: 97, 114, 84, 130, 90, and 134, respectively.

14. The method of claim 13 , wherein the antibody or fragment thereof blocks IL-33/ST2L interaction.

15. The method of claim 14 , wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
(a) the VH is derived from human IGHV3-23 framework sequence (SEQ ID NO: 158); and
(b) the VL is derived from human IGKV3-11 (L6) framework sequence (SEQ ID NO: 159).

16. The method of claim 15 , wherein the antibody or fragment thereof is of IgG1, IgG2, IgG3, or IgG4 isotype.

17. The method of claim 16 , wherein the antibody or fragment thereof comprises the VH of SEQ ID NO: 191 and the VL of SEQ ID NO: 209.

18. The method of claim 13 , wherein the antibody or fragment thereof is a human or humanized antibody.

Assignees

• Janssen Biotech Inc

Inventors

• Duffy Karen
• Fursov Natalie
• Hall Leroy
• Healy Catherine
• Lamb Roberta
• Luo Jinquan
• Malaviya Ravi
• Naso Michael
• Pratta Michael
• Tornetta Mark
• Wheeler John
• Wu Sheng-Jiun

Classifications

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K16/44

  against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} · CPC title