Nucleic acids encodng anti-C5A antibodies

• US 9,434,784 B1
• Filed: 05/23/2016
• Issued: 09/06/2016
• Est. Priority Date: 04/30/2010
• Status: Active Grant

• Current Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Original Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Inventors: Rother, Russell P., Sheridan, Douglas L., Tamburini, Paul P., Zhang, Yuchun
• Primary Examiner(s): Gambel, Phillip
• Application Number:
  US15/161,893
• Publication Number:
  US 20160264654A1
• Time in Patent Office: 106 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• 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 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 3/06 Antihyperlipidemics
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: C07K 14/472 : Complement proteins, e.g. anaphylatoxin, C3a, C5a
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/28 : against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/461 : Igs containing Ig-regions, -domains or -residues form different species
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• 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 2317/41 : Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/51 : Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 : Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• 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 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/71 : Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance

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

1. A nucleic acid encoding complementarity determining regions (CDRs) of a heavy chain variable region of an antibody, or antigen-binding fragment thereof, that binds to human C5a, wherein the heavy chain variable region comprises the amino acid sequence depicted in SEQ ID NO:

45.

10. An expression vector comprising the nucleic acid according to claim 1.

11. A cell comprising the expression vector according to claim 10.

2. A nucleic acid encoding complementarity determining regions (CDRs) of a light chain variable region of an antibody, or antigen-binding fragment thereof, that binds to human C5a, wherein the light chain variable region comprises the amino acid sequence depicted in SEQ ID NO:

42.

12. An expression vector comprising the nucleic acid according to claim 2.

13. A cell comprising the expression vector according to claim 12.

3. A nucleic acid encoding complementarity determining regions (CDRs) of heavy and light chain variable regions of an antibody, or antigen-binding fragments thereof, that bind to human C5a, wherein the heavy and light chain variable regions comprise the amino acid sequences depicted in SEQ ID NOs:

45 and 42, respectively.

14. An expression vector comprising the nucleic acid according to claim 3.

15. A cell comprising the expression vector according to claim 14.

4. A nucleic acid encoding a heavy chain variable region of an antibody, or antigen-binding fragment thereof, that binds to human C5a, wherein the heavy chain variable region comprises the amino acid sequence depicted in SEQ ID NO:

45.

16. An expression vector comprising the nucleic acid according to claim 4.

17. A cell comprising the expression vector according to claim 16.

5. A nucleic acid encoding a light chain variable region of an antibody, or antigen-binding fragment thereof, that binds to human C5a, wherein the light chain variable region comprising the amino acid sequence depicted in SEQ ID NO:

42.

18. An expression vector comprising the nucleic acid according to claim 5.

19. A cell comprising the expression vector according to claim 18.

6. A nucleic acid encoding heavy and light chain variable regions of an antibody, or antigen-binding fragments thereof, that bind to human C5a, wherein the heavy and light chain variable regions comprise the amino acid sequences depicted in SEQ ID NOs:

45 and 42, respectively.

20. An expression vector comprising the nucleic acid according to claim 6.

21. A cell comprising the expression vector according to claim 20.

7. A nucleic acid encoding a heavy chain of an antibody, or antigen-binding fragment thereof, that binds to C5a, wherein the heavy chain comprises the amino acid sequence depicted in SEQ ID NO:

49.

22. An expression vector comprising the nucleic acid according to claim 7.

23. A cell comprising the expression vector according to claim 22.

8. A nucleic acid encoding a light chain of an antibody, or antigen-binding fragment thereof, that binds to C5a, wherein the light chain comprises the amino acid sequence depicted in SEQ ID NO:

40.

24. An expression vector comprising the nucleic acid according to claim 8.

25. A cell comprising the expression vector according to claim 24.

9. A nucleic acid encoding a heavy chain and a light chain of an antibody, or antigen-binding fragment thereof, that binds to human C5a, wherein the heavy chain comprises the amino acid sequence depicted in SEQ ID NO:

49 and the light chain comprises the amino acid sequence depicted in SEQ ID NO;

40.

26. An expression vector comprising the nucleic acid according to claim 9.

27. A cell comprising the expression vector according to claim 26.