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

• US 10,639,369 B2
• Filed: 07/31/2017
• Issued: 05/05/2020
• Est. Priority Date: 08/01/2016
• Status: Active Grant

• Current Assignee: Omeros Corporation, University of Leicester
• Original Assignee: Omeros Corporation
• Inventors: Cummings, W. Jason, Demopulos, Gregory A., Dudler, Thomas, Tjoelker, Larry W., Wood, Christi L., Yabuki, Munehisa
• Primary Examiner(s): Wen, Sharon X
• Application Number:
  US15/665,030
• Publication Number:
  US 20180140697A1
• Time in Patent Office: 1,009 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/02 : Antidotes
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 7/08 : Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B82Y 25/00 : Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
• CPC Class Codes: C01F 17/206 : oxide or hydroxide being the only anion
• CPC Class Codes: C01P 2002/54 : one element only
• CPC Class Codes: C01P 2002/84 : by UV- or VIS- data
• CPC Class Codes: C01P 2004/64 : Nanometer sized, i.e. from 1-100 nanometer
• CPC Class Codes: C07K 16/40 : against enzymes
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/90 : characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C09K 11/77 : containing rare earth metals
• CPC Class Codes: C09K 11/7728 : containing europium
• CPC Class Codes: C12N 9/6424 : Serine endopeptidases (3.4.21)
• CPC Class Codes: C12Y 304/21104 : Mannan-binding lectin-associated serine protease-2 (3.4.21.104)
• CPC Class Codes: H01F 1/0054 : Coated nanoparticles, e.g. nanoparticles coated with organic surfactant

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.

Claims

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.

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.

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

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

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.