IP Library › Granted Patent US 9,011,852
Granted Patent B2
US 9,011,852 · App. 13/695,277 · Granted Apr 21, 2015

Anti-C5a antibodies

Inventors: Russell P. Rother (Oklahoma City, OK); Douglas L. Sheridan (Branford, CT); Paul P. Tamburini (Kensington, CT); Yuchun Zhang (Cheshire, CT)
Assignee: Alexion Pharmaceuticals, Inc.
C07K16/461A61K2039/505C07K16/18C07K2317/24C07K2317/33C07K2317/34C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 9,011,852
App. No.
13/695,277
Granted
Apr 21, 2015
Kind
B2
Abstract

The present disclosure relates to, inter alia, antibodies, or antigen-binding fragments thereof, that bind to C5a and to use of the antibodies in methods for treating or preventing complement-associated disorders such as, but not limited to, atypical hemolytic uremic syndrome, age-related macular degeneration, rheumatoid arthritis, sepsis, severe burn, antiphospho lipid syndrome, asthma, lupus nephritis, Goodpasture's syndrome, and chronic obstructive pulmonary disease.

Claims (47)

1. An isolated antibody, or antigen-binding fragment thereof, that binds C5a, wherein the antibody, or antigen-binding fragment thereof, comprises:

(a) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:140; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:96; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:142; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:115; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:144; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:117;

(b) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:21; and a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:22; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:28; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:67; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:30;

(c) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:156; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:157; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:158; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:160; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:161; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:162;

(d) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:164; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:165; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:166; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:168; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:169; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:170;

(e) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:172; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:173; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:174; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:176; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:177; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:178;

(f) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:84; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:85; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:86; a heavy chain CDR1comprising the amino acid sequence depicted in SEQ ID NO:115; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:116; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:117;

(g) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:88; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:89; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:90; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:119; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:120; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:121;

(h) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:99; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:100; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:101; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:119; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:126; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:127;

(i) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:21; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:113; a heavy chain CDR1comprising the amino acid sequence depicted in SEQ ID NO:28; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:46; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:47;

(j) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:110; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:111; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:136; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:137; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:138;

(k) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:105; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:106; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:107; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:115; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:124; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:117;

(l) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:21; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:22; a heavy chain CDR1comprising the amino acid sequence depicted in SEQ ID NO:28; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:29; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:30;

(m) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:38; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:22; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:28; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:29; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:30;

(n) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:21; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:22; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:28; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:46; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:47; or

(o) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:38; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:22; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:28; a heavy chain CDR2comprising the amino acid sequence depicted in SEQ ID NO:46; and a heavy chain CDR3comprising the amino acid sequence depicted in SEQ ID NO:47.

2. An isolated antibody, or antigen-binding fragment thereof, that binds C5a, wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chains, wherein the light chain comprises the amino acid sequence depicted in SEQ ID NO: 17, 36, or 40.

3. An isolated antibody, or antigen-binding fragment thereof, that binds C5a, wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chains, wherein the heavy chain comprises the amino acid sequence depicted in SEQ ID NO: 25, 33, 44, or 49.

4. An isolated antibody, or antigen-binding fragment thereof, that binds C5a, wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chain variable regions, wherein the light chain variable region comprises the amino acid sequence depicted in SEQ ID NO: 19, 37, or 42.

5. An isolated antibody, or antigen-binding fragment thereof, that binds C5a, wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chain variable regions, wherein the heavy chain variable region comprises the amino acid sequence depicted in SEQ ID NO: 27 or 45.

6. An isolated antibody, or antigen-binding fragment thereof, that binds C5a, wherein the isolated antibody, or antigen-binding fragment thereof, comprises:

(a) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:19 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:27;

(b) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:17 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:25;

(c) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:17 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:33;

(d) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:37 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:27;

(e) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:36 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:33;

(f) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:42 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:27;

(g) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:40 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:33;

(h) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:19 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:45;

(i) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:17 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:44;

(j) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:17 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:49;

(k) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:37 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:45;

(l) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:36 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:49;

(m) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:42 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:45; or

(n) a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:40 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:49.

7. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, comprises a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:20; a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:21; a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:22; a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:28; a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:46; and a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:47.

8. The isolated antibody, or antigen-binding fragment thereof, of claim 2 , wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chains, wherein the light chain comprises the amino acid sequence depicted in SEQ ID NO: 40.

9. The isolated antibody, or antigen-binding fragment thereof, of claim 3 , wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chains, wherein the heavy chain comprises the amino acid sequence depicted in SEQ ID NO: 49.

10. The isolated antibody, or antigen-binding fragment thereof, of claim 4 , wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chain variable regions, wherein the light chain variable region comprises the amino acid sequence depicted in SEQ ID NO: 42.

11. The isolated antibody, or antigen-binding fragment thereof, of claim 5 , wherein the isolated antibody, or antigen-binding fragment thereof, comprises heavy and light chain variable regions, wherein the heavy chain variable region comprises the amino acid sequence depicted in SEQ ID NO: 45.

12. The isolated antibody, or antigen-binding fragment thereof, of claim 6 , wherein the isolated antibody, or antigen-binding fragment thereof, comprises: a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:42 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:45.

13. The isolated antibody, or antigen-binding fragment thereof, of claim 6 , wherein the isolated antibody, or antigen-binding fragment thereof, comprises: a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:40 and a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:49.

14. The isolated antibody or antigen-binding fragment thereof of any one of claims 1 - 6 , wherein the antibody or antigen-binding fragment thereof binds to hC5a with a K D that is less than 8.0×10 −11 M.

15. The isolated antibody or antigen-binding fragment thereof of any one of claims 1 - 6 , wherein the antibody inhibits by at least 90% human C5a-dependent human neutrophil activation at a molar ratio of 1:1 (antigen-binding site: C5a).

16. The isolated antibody, or antigen-binding fragment thereof, of any one of claims 1 - 6 , wherein the antibody or antigen-binding fragment thereof inhibits the interaction between C5a and a C5a receptor.

17. The isolated antibody, or antigen-binding fragment, of any one of claims 1 - 6 , wherein the antibody, or antigen-binding fragment, is selected from the group consisting of a monoclonal antibody, a humanized antibody, a fully human antibody, a recombinant antibody, a bispecific antibody, a single chain antibody, a diabody, an intrabody, a chimerized or chimeric antibody, a deimmunized human antibody, an Fv fragment, an Fd fragment, an Fab fragment, an Fab′ fragment, and an F(ab′) 2 fragment.

18. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of any one of claims 1 - 3 and a pharmaceutically-acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2013
From: SHERIDAN, DOUGLAS L.; TAMBURINI, PAUL P.; ZHANG, YUCHUN
To: ALEXION PHARMACEUTICALS, INC.
Reel/Frame 030484/0690 →
Continuity (3)
Provisional Application 61330260 · Apr 30, 2010
Provisional Application 61471465 · Apr 4, 2011
Related Publication 20130224187A1 · Aug 29, 2013