IP Library › Granted Patent US 9,309,310
Granted Patent B2
US 9,309,310 · App. 14/933,368 · Granted Apr 12, 2016

Nucleic acids encoding 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.
C07K16/18A61K2039/505C07K2317/24C07K2317/33C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 9,309,310
App. No.
14/933,368
Granted
Apr 12, 2016
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, antiphospholipid syndrome, asthma, lupus nephritis, Goodpasture's syndrome, and chronic obstructive pulmonary disease.

Claims (35)

1. An isolated nucleic acid comprising a nucleotide sequence encoding an antibody, or antigen binding fragment thereof, 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:144; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:67; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:161; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:169; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:177; and a heavy chain CDR3 comprising 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 CDR1 comprising the amino acid sequence depicted in SEQ ID NO:115; a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:116; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:120; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:126; and a heavy chain CDR3 comprising 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 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;

(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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:137; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:124; and a heavy chain CDR3 comprising 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 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:29; and a heavy chain CDR3 comprising 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 CDR2 comprising the amino acid sequence depicted in SEQ ID NO:29; and a heavy chain CDR3 comprising 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 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; 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 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.

2. The isolated nucleic acid 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.

3. An isolated nucleic acid comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises the amino acid sequence depicted in SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 36, SEQ ID NO: 40, SEQ ID NO: 44, or SEQ ID NO: 49.

4. The isolated nucleic acid of claim 3 , wherein the polypeptide comprises the amino acid sequence depicted in SEQ ID NO: 40.

5. The isolated nucleic acid of claim 3 , wherein the polypeptide comprises the amino acid sequence depicted in SEQ ID NO: 49.

6. An isolated nucleic acid comprising a nucleotide sequence encoding an antibody variable region, wherein the antibody variable region is at least 90% identical to the amino acid sequence depicted in SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 42, or SEQ ID NO: 45.

7. The isolated nucleic acid of claim 6 , wherein the antibody variable region is at least 90% identical the amino acid sequence depicted in SEQ ID NO: 42.

8. The isolated nucleic acid of claim 6 , wherein the antibody variable region is at least 90% identical the amino acid sequence depicted in SEQ ID NO: 45.

9. An isolated nucleic acid comprising a nucleotide sequence encoding an antibody variable region, wherein the antibody variable region comprises the amino acid sequence depicted in SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 42, or SEQ ID NO: 45.

10. The isolated nucleic acid of claim 9 , wherein the antibody variable region comprises the amino acid sequence depicted in SEQ ID NO: 42.

11. The isolated nucleic acid of claim 9 , wherein the antibody variable region comprises the amino acid sequence depicted in SEQ ID NO: 45.

12. An isolated nucleic acid comprising a nucleotide sequence encoding an antibody, or antigen binding fragment thereof, wherein the antibody, or antigen binding fragment thereof, comprises a light chain variable region comprising the amino acid sequence depicted in SEQ ID NO:42 and a heavy chain variable region comprising the amino acid sequence depicted in SEQ ID NO:45.

13. An expression vector comprising the nucleic acid of claim 1 .

14. A host cell comprising the nucleic acid of claim 13 .

15. An expression vector comprising the nucleic acid of claim 3 .

16. A host cell comprising the nucleic acid of claim 15 .

17. An expression vector comprising the nucleic acid of claim 6 .

18. A host cell comprising the nucleic acid of claim 17 .

19. An expression vector comprising the nucleic acid of claim 9 .

20. A host cell comprising the nucleic acid of claim 19 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2015
From: SHERIDAN, DOUGLAS L.; TAMBURINI, PAUL P.; ZHANG, YUCHUN
To: ALEXION PHARMACEUTICALS, INC.
Reel/Frame 037099/0276 →
Continuity (5)
Division 14657176 · Mar 13, 2015
Division 13695277
Provisional Application 61471465 · Apr 4, 2011
Provisional Application 61330260 · Apr 30, 2010
Related Publication 20160053004A1 · Feb 25, 2016