Anti-c5a antibodies

Patent metadata

Field	Value
Publication number	US-2016376357-A1
Application number	US-201615262697-A
Country	US
Kind code	A1
Filing date	Sep 12, 2016
Priority date	Apr 30, 2010
Publication date	Dec 29, 2016
Grant date	—

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.

First claim

What is claimed is:

1 . An isolated antibody or antigen-binding fragment thereof that binds to a free C5a polypeptide, wherein the free C5a is a human polypeptide (hC5a) having the amino acid sequence depicted in SEQ ID NO:1, and wherein the antibody or antigen-binding fragment thereof binds to the free hC5a polypeptide in vitro with a K D that is less than 1.25×10 −9 M in the presence of a molar excess of uncleaved, native human C5.

2 . The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the concentration of uncleaved, native human C5 is between 2-fold and 20-fold greater than the concentration of free hC5a.

3 . The isolated antibody or antigen-binding fragment thereof of claim 1 or 2 , wherein the concentration of uncleaved human C5 is between 2-fold and 15-fold greater than the concentration of free hC5a.

4 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 3 , wherein the uncleaved, native human C5 is from human plasma.

5 . An isolated antibody or antigen-binding fragment thereof that binds to a free C5a polypeptide, wherein the free C5a polypeptide is a human polypeptide (hC5a) having the amino acid sequence depicted in SEQ ID NO:1, wherein the antibody or antigen-binding fragment thereof binds to the human C5a polypeptide with a K D that is less than 1.25×10 −9 M, wherein the antibody or antigen-binding fragment thereof binds to free hC5a polypeptide with an affinity that is at least 100-fold greater than its corresponding affinity for uncleaved human C5.

6 . An isolated antibody or antigen-binding fragment thereof that binds to a free C5a polypeptide, wherein the free C5a polypeptide is a human polypeptide (hC5a) having the amino acid sequence depicted in SEQ ID NO:1, wherein the antibody inhibits by at least 50% hC5a-dependent human neutrophil activation in vitro at a molar ratio of 1:1 (antigen-binding site: hC5a).

7 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 6 , wherein the antibody or antigen-binding fragment thereof binds to free C5a from a non-human mammalian species.

8 . An isolated antibody or antigen-binding fragment thereof that binds to a free C5a polypeptide, wherein the free C5a polypeptide is a human polypeptide (hC5a) or a non-human mammalian species C5a polypeptide, and wherein the antibody or antigen-binding fragment thereof binds to the free hC5a polypeptide with a K D that is less than 1.25×10 −9 M.

9 . The isolated antibody or antigen-binding fragment thereof of claim 7 or 8 , wherein the non-human mammalian species is a non-human primate.

10 . The isolated antibody or antigen-binding fragment thereof of claim 9 , wherein the non-human primate is a cynomolgus macaque, rhesus macaque, or baboon.

11 . The isolated antibody or antigen-binding fragment thereof of any one of claims 7 to 10 , wherein the antibody or antigen-binding fragment thereof binds to free hC5a with an affinity no greater than 100-fold its corresponding affinity for free C5a from the non-human mammalian species.

12 . The isolated antibody or antigen-binding fragment thereof of any one of claims 7 to 11 , wherein the antibody or antigen-binding fragment thereof binds to human C5a with an affinity no greater than 50-fold its corresponding affinity for C5a from the non-human mammalian species.

13 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 5 or 8 to 12 , wherein the antibody inhibits by at least 50% hC5a-dependent human neutrophil activation at a molar ratio of 1:1 (antigen-binding site: hC5a).

14 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 13 , wherein the antibody or antigen-binding fragment thereof binds to a free hC5a polypeptide having the amino acid sequence depicted in SEQ ID NO:2.

15 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 14 , wherein the antibody or antigen-binding fragment thereof comprises a light chain polypeptide comprising: 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.

16 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 14 , wherein the antibody or antigen-binding fragment thereof comprises a light chain polypeptide comprising: 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; and a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:22.

17 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 16 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain polypeptide comprising: 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.

18 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 16 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain polypeptide comprising: 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.

19 . The isolated antibody or antigen-binding fragment thereof of any one of claim 1 to 5 , 14 , or 16 , wherein the isolated antibody or antigen-binding fragment thereof comprises a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:37 or SEQ ID NO:36.

20 . The isolated antibody or antigen-binding fragment thereof of any one of claim 1 to 5 , 14 , 16 , or 19 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:27 or SEQ ID NO:33.

21 . The isolated antibody or antigen-binding fragment thereof of claim 19 or 20 , wherein the isolated antibody or antigen-binding fragment thereof comprises 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.

22 . The isolated antibody or antigen-binding fragment thereof of claim 19 or 20 , wherein the isolated antibody or antigen-binding fragment thereof comprises 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.

23 . The isolated antibody or antigen-binding fragment thereof of any one of claims 1 to 15 , wherein the isolated antibody or antigen-binding fragment thereof comprises a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:19 or SEQ ID NO:17.

24 . The isolated antibody or antigen-binding fragment thereof of any one of claim 1 to 15 or 23 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:27 or

Assignees

• Alexion Pharma Inc

Inventors

• Rother Russell P
• Sheridan Douglas L
• Tamburini Paul P
• Zhang Yuchun

Classifications

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title