Nucleic acids encoding anti-C5 antibodies having improved pharmacokinetics
The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.
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 complement component human C5 comprising the amino acid sequence depicted in SEQ ID NO:12.
2. A nucleic acid encoding complementarity determining regions (CDRs) of heavy and light chain variable regions of an antibody, or antigen-binding fragment thereof, that binds to complement component human C5 comprising the amino acid sequences depicted in SEQ ID NOs: 12 and 8, respectively.
3. A nucleic acid encoding a heavy chain variable region of an antibody, or antigen-binding fragment thereof, that binds to complement component human C5 comprising the amino acid sequence depicted in SEQ ID NO:12.
4. A nucleic acid encoding heavy and light chain variable regions of an antibody, or antigen-binding fragment thereof, that binds to complement component human C5 comprising the amino acid sequences depicted in SEQ ID NOs: 12 and 8, respectively.
5. A nucleic acid encoding a heavy chain polypeptide of an antibody, or antigen-binding fragment thereof, that binds to complement component human C5 comprising the amino acid sequence depicted in SEQ ID NO: 14.
6. A nucleic acid encoding a heavy chain polypeptide and a light chain polypeptide of an antibody, or antigen-binding fragment thereof, that binds to complement component human C5, wherein the heavy chain polypeptide comprises the amino acid sequence depicted in SEQ ID NO: 14 and the light chain polypeptide comprises the amino acid sequence depicted in SEQ ID NO: 11.
7. A vector comprising the nucleic acid according to claim 1 .
8. An expression vector comprising the nucleic acid according to claim 1 .
9. A cell comprising the expression vector according to claim 8 .
10. A method for producing an antibody, or antigen-binding fragment thereof, that binds to complement component human C5, the method comprising culturing the cell of claim 9 under conditions and for a time sufficient to allow expression by the cell of the antibody, or antigen-binding fragment thereof, encoded by the nucleic acid.
11. The method of claim 10 , further comprising isolating the antibody, or antigen-binding fragment thereof.
12. A vector comprising the nucleic acid according to claim 2 .
13. An expression vector comprising the nucleic acid according to claim 2 .
14. A cell comprising the expression vector according to claim 13 .
15. A method for producing an antibody, or antigen-binding fragment thereof, that binds to complement component human C5, the method comprising culturing the cell of claim 14 under conditions and for a time sufficient to allow expression by the cell of the antibody, or antigen-binding fragment thereof, encoded by the nucleic acid.
16. The method of claim 15 , further comprising isolating the antibody, or antigen-binding fragment thereof.
17. A vector comprising the nucleic acid according to claim 3 .
18. An expression vector comprising the nucleic acid according to claim 3 .
19. A cell comprising the expression vector according to claim 18 .
20. A method for producing an antibody, or antigen-binding fragment thereof, that binds to complement component human C5, the method comprising culturing the cell of claim 19 under conditions and for a time sufficient to allow expression by the cell of the antibody, or antigen-binding fragment thereof, encoded by the nucleic acid.
21. The method of claim 20 , further comprising isolating the antibody, or antigen-binding fragment thereof.
22. A vector comprising the nucleic acid according to claim 4 .
23. An expression vector comprising the nucleic acid according to claim 4 .
24. A cell comprising the expression vector according to claim 23 .
25. A method for producing an antibody, or antigen-binding fragment thereof, that binds to complement component human C5, the method comprising culturing the cell of claim 24 under conditions and for a time sufficient to allow expression by the cell of the antibody, or antigen-binding fragment thereof, encoded by the nucleic acid.
26. The method of claim 25 , further comprising isolating the antibody, or antigen-binding fragment thereof.
27. A vector comprising the nucleic acid according to claim 5 .
28. An expression vector comprising the nucleic acid according to claim 5 .
29. A cell comprising the expression vector according to claim 28 .
30. A method for producing an antibody, or antigen-binding fragment thereof, that binds to complement component human C5, the method comprising culturing the cell of claim 29 under conditions and for a time sufficient to allow expression by the cell of the antibody encoded by the nucleic acid.
31. The method of claim 30 , further comprising isolating the antibody, or antigen-binding fragment thereof.
32. A vector comprising the nucleic acid according to claim 6 .
33. An expression vector comprising the nucleic acid according to claim 6 .
34. A cell comprising the expression vector according to claim 33 .
35. A method for producing an antibody, or antigen-binding fragment thereof, that binds to complement component human C5, the method comprising culturing the cell of claim 34 under conditions and for a time sufficient to allow expression by the cell of the antibody encoded by the nucleic acid.
36. The method of claim 35 , further comprising isolating the antibody, or antigen-binding fragment thereof.