Antibodies specifically binding to MASP-3 for the treatment of various diseases and disorders

Patent metadata

Field	Value
Publication number	US-10639369-B2
Application number	US-201715665030-A
Country	US
Kind code	B2
Filing date	Jul 31, 2017
Priority date	Aug 1, 2016
Publication date	May 5, 2020
Grant date	May 5, 2020

Abstract

The present invention relates to MASP-3 inhibitory antibodies and compositions comprising such antibodies for use in inhibiting the adverse effects of MASP-3 dependent complement activation.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. An isolated antibody, or antigen-binding fragment thereof, that binds to MASP-3 comprising: a heavy chain variable region comprising a HC-CDR1 set forth as SEQ Id NO:84 (GKWIE); a HC-CDR2 set forth as SEQ ID NO:86 (EILPGTGSTNYNEKFKG) or SEQ ID NO:275 (EILPGTGSTNYAQKFQG); and a HC-CDR3 set forth as SEQ ID NO:88 (SEDV); and a light chain variable region comprising a LC-CDR1 set forth as SEQ ID NO: 142 (KSSQSLLNSRTRKNYLA), SEQ lD NO:257 (KSSQSLLQSRTRKNYLA); SEQ ID NO:258 (KSSQSLLASRTRKNYLA); or SEQ lD NO:259 (KSSQSLLNTRTRKNYLA), a LC-CDR2 set forth as SEQ ID NO: 144 (WASTRES); and a LC-CDR3 set forth as SEQ ID NO:161 (KQSYNIPT).

2. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises SEQ ID NO:258.

3. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment is selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a murine antibody, and an antigen-binding fragment of any of the foregoing.

4. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof is selected from the group consisting of a single chain antibody, an ScFv, a Fab fragment, an Fab′ fragment, an F(ab′)2 fragment, a univalent antibody lacking a hinge region and a whole antibody.

5. The antibody or antigen-binding fragment thereof of claim 1 , further comprising an immunoglobulin constant region.

6. The antibody or antigen binding fragment thereof of claim 3 , wherein the antibody or antigen-binding fragment is humanized.

7. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody binds to the serine protease domain of human MASP-3 with an affinity of less than 500 pM.

8. The antibody or antigen-binding fragment thereof of 1 , wherein said antibody inhibits alternative pathway activation in mammalian blood.

9. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the HC-CDR2 comprises SEQ ID NO:86.

10. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the HC-CDR2 comprises SEQ ID NO:275.

11. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises SEQ ID NO:142.

12. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises SEQ ID NO:257.

13. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises SEQ ID NO:259.

14. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the HC-CDR1 comprises SEQ ID NO:84, the HC-CDR2 comprises SEQ ID NO:86, the HC-CDR3 comprises SEQ ID NO:88, the LC-CDR1 comprises SEQ ID NO:258, the LC-CDR2 comprises SEQ ID NO:144 and the LC-CDR3 comprises SEQ ID NO:161.

15. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the HC-CDR1 comprises SEQ ID NO:84, the HC-CDR2 comprises SEQ ID NO:275, the HC-CDR3 comprises SEQ ID NO:88; the LC-CDR1 comprises SEQ ID NO:258, the LC-CDR2 comprises SEQ ID NO:144 and the LC-CDR3 comprises SEQ ID NO:161.

16. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:30.

17. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:45.

18. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:30 and the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:45.

19. The isolated antibody or antigen-binding fragment thereof of claim 6 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:254.

20. The isolated antibody or antigen-binding fragment thereof of claim 6 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:255.

21. The isolated antibody or antigen-binding fragment thereof of claim 6 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:256.

22. The isolated antibody or antigen-binding fragment thereof of claim 6 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:280.

23. An isolated antibody or antigen-binding fragment thereof that binds to human MASP-3, comprising a heavy chain variable region comprising SEQ ID NO:254 or SEQ ID NO:255 and a light chain variable region comprising SEQ ID NO:256 or SEQ ID NO:280.

24. The isolated antibody or antigen-binding fragment thereof of claim 23 , wherein the heavy chain variable region comprises SEQ ID NO:254 and the light chain variable region comprises SEQ ID NO:256.

25. The isolated antibody or antigen-binding fragment thereof of claim 23 , wherein the heavy chain variable region comprises SEQ ID NO:255 and the light chain variable region comprises SEQ ID NO:256.

26. The isolated antibody or antigen-binding fragment thereof of claim 23 , wherein the heavy chain variable region comprises SEQ 1D NO:254 and the light chain variable region comprises SEQ ID NO: 280.

27. The isolated antibody or antigen-binding fragment thereof of claim 23 , wherein the heavy chain variable region comprises SEQ ID NO:255 and the light chain variable region comprises SEQ ID NO: 280.

28. The isolated antibody of claim 23 , wherein the antibody is selected from the group consisting of a single chain antibody, an ScFv, a Fab fragment, an Fab′ fragment, an F(ab′)2 fragment, a univalent antibody lacking a hinge region and a whole antibody.

29. The isolated antibody of claim 23 , further comprising an immunoglobulin constant region.

30. A composition comprising the antibody or antigen-binding fragment of any of claims 1 , 6 or 22 and a pharmaceutically acceptable excipient.

Assignees

• Omeros Corp

Inventors

• Cummings W Jason
• Demopulos Gregory A
• Dudler Thomas
• Tjoelker Larry W
• Wood Christi L
• Yabuki Munehisa

Classifications

• A61P11/16

  Central respiratory analeptics · CPC title

• C07K2317/76

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

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title