IP Library Granted Patent US 11,274,146
Granted Patent B2
US 11,274,146 · App. 16/495,979 · Granted Mar 15, 2022

Anti-C5a antibodies and uses thereof

Inventors: Wenchao Song (Bryn Mawr, PA); Sayaka Sato (Philadelphia, PA); Takashi Miwa (Bala Cynwyd, PA); Damodar Gullipalli (Philadelphia, PA)
Assignee: The Trustees of the University of Pennsylvania
C07K16/18C12N15/85C07K2317/24C07K2317/54C07K2317/565C07K2317/622C07K2317/76C12N2015/8518
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Quick Facts
Patent No.
US 11,274,146
App. No.
16/495,979
Granted
Mar 15, 2022
Kind
B2
Abstract

This invention relates to inhibition of the complement signaling using an anti-C5a antibody. Specifically, the invention relates to methods of treating a complement-mediated disease or complement-mediated disorder in an individual by contacting the individual with an anti-C5a antibody.

Claims (27)

1. An antibody that specifically binds to human C5a,

wherein the antibody comprises a heavy chain variable (VH) region and a light chain variable (VL) region,

wherein the VH region comprises

i) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 3;

ii) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 4; and

iii) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 5; and

wherein the VL region comprises

i) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 8;

ii) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 9; and

iii) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 10.

2. The antibody of claim 1 , wherein the antibody is a chimeric antibody.

3. The antibody of claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:2, or a variant thereof.

4. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:7, or a variant thereof.

5. The antibody of claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:2, or a variant thereof, and a light chain comprising the amino acid sequence of SEQ ID NO:7, or a variant thereof.

6. A method of treating a complement pathway-mediated disease or disorder in an individual, comprising the step of administering to said individual the anti-C5a antibody of claim 1 .

7. The method of claim 6 , wherein the disease or disorder is at least one selected from the group consisting of: macular degeneration (MD), age-related macular degeneration (AMD), ischemia reperfusion injury, arthritis, rheumatoid arthritis, lupus, ulcerative colitis, stroke, post-surgery systemic inflammatory syndrome, asthma, allergic asthma, chronic obstructive pulmonary disease (COPD), paroxysmal nocturnal hemoglobinuria (PNH) syndrome, autoimmune hemolytic anemia (AIHA), Gaucher disease, myasthenia gravis, neuromyelitis optica, (NMO), multiple sclerosis, delayed graft function, antibody-mediated rejection, atypical hemolytic uremic syndrome (aHUS), central retinal vein occlusion (CRVO), central retinal artery occlusion (CRAO), epidermolysis bullosa, sepsis, septic shock, organ transplantation, inflammation, inflammation associated with cardiopulmonary bypass surgery and kidney dialysis, C3 glomerulopathy, membranous nephropathy, IgA nephropathy, glomerulonephritis, anti-neutrophil cytoplasmic antibody (ANCA)-mediated glomerulonephritis, lupus nephritis, ANCA-mediated vasculitis, Shiga toxin induced HUS, antiphospholipid antibody-induced pregnancy loss, graft versus host disease (GVHD), and any combinations thereof.

8. The antibody of claim 1 , wherein the antibody has a heavy chain variable (VH) region that has an amino acid sequence that is more than 90% identical to SEQ ID NO: 2.

9. The antibody of claim 8 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab)2, F(ab′)2, scFv, and combinations thereof.

10. The antibody of claim 1 , wherein the antibody has a light chain variable (VL) region that has an amino acid sequence that is more than 90% identical to SEQ ID NO: 7.

11. The antibody of claim 10 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab)2, F(ab′)2, scFv, and combinations thereof.

12. A cell comprising the antibody of claim 1 .

13. The cell of claim 12 , wherein the cell produces the antibody of claim 1 .

14. The cell of claim 12 , wherein the cell is a hybridoma.

15. A method of reducing the activity of a complement system of an individual, wherein the method comprises administering an antibody to the individual via a route of administration selected from the group consisting of enteral administration, parenteral administration, and a combination thereof, and wherein the antibody comprises six complementarity determining regions having the following amino acid sequences: SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO: 8; SEQ ID NO: 9; and SEQ ID NO: 10.

16. The method of claim 15 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab)2, F(ab′)2, scFv, and combinations thereof.

17. An antibody that specifically binds to human C5a, wherein the antibody has a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH region has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the VL region has an amino acid sequence set forth in SEQ ID NO: 7.

18. The antibody of claim 17 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab)2, F(ab′)2, scFv, and combinations thereof.

Assignments (2)
CONFIRMATORY LICENSE Recorded Aug 11, 2023
From: UNIVERSITY OF PENNSYLVANIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064572/0285 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2023
From: SONG, WENCHAO; MIWA, TAKASHI; SATO, SAYAKA; GULLIPALLI, DAMODAR
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 063042/0165 →
Continuity (2)
Provisional Application 62475573 · Mar 23, 2017
Related Publication 20200148754A1 · May 14, 2020