Polynucleotides encoding anti-C5 antibodies
The present invention provides monoclonal antibodies that bind to the complement factor 5 (C5) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to C5 protein. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing C5 activity, thus providing a means of treating or preventing a C5-related disease or disorder in humans. In some embodiments, the invention provides for an anti-C5 antibody that has improved pharmacokinetic and pharmacodynamic properties, e.g., a half-life of more than 10 days.
1. An isolated polynucleotide molecule comprising a nucleotide sequence that encodes a heavy chain variable region of an antibody or antigen-binding fragment thereof that binds specifically to C5 comprising
a HCDR1 that comprises the amino acid sequence set forth in SEQ ID NO: 100;
a HCDR2 that comprises the amino acid sequence set forth in SEQ ID NO: 102; and
a HCDR3 that comprises the amino acid sequence set forth in SEQ ID NO: 104.
2. An isolated polynucleotide molecule comprising a nucleotide sequence that encodes a light chain variable region of an antibody or antigen-binding fragment thereof that binds specifically to C5 comprising
a LCDR1 that comprises the amino acid sequence set forth in SEQ ID NO: 108;
a LCDR2 that comprises the amino acid sequence set forth in SEQ ID NO: 110; and
a LCDR3 that comprises the amino acid sequence set forth in SEQ ID NO: 112.
3. A vector comprising the polynucleotide of claim 1 .
4. A cell comprising the vector of claim 3 .
5. An isolated polynucleotide molecule comprising a nucleotide sequence that encodes a heavy chain variable region of an antibody or antigen-binding fragment thereof that binds specifically to C5 comprising
a HCDR1 that comprises the amino acid sequence set forth in SEQ ID NO: 100,
a HCDR2 that comprises the amino acid sequence set forth in SEQ ID NO: 102, and
a HCDR3 that comprises the amino acid sequence set forth in SEQ ID NO: 104;
and a light chain variable region of an antibody or antigen-binding fragment thereof that binds specifically to C5 comprising
a LCDR1 that comprises the amino acid sequence set forth in SEQ ID NO: 108,
a LCDR2 that comprises the amino acid sequence set forth in SEQ ID NO: 110, and
a LCDR3 that comprises the amino acid sequence set forth in SEQ ID NO: 112.
6. The isolated polynucleotide molecule of claim 5 , wherein:
the HCDR1 is encoded by a nucleotide sequence as set forth in SEQ ID NO: 99,
the HCDR2 is encoded by a nucleotide sequence as set forth in SEQ ID NO: 101,
the HCDR3 is encoded by a nucleotide sequence as set forth in SEQ ID NO: 103,
the LCDR1 is encoded by a nucleotide sequence as set forth in SEQ ID NO: 107,
the LCDR2 is encoded by a nucleotide sequence as set forth in SEQ ID NO: 109, and
the LCDR3 is encoded by a nucleotide sequence as set forth in SEQ ID NO: 111.
7. The isolated polynucleotide molecule of claim 5 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 98.
8. The isolated polynucleotide molecule of claim 7 , wherein the heavy chain variable region is encoded by a nucleotide sequence as set forth in SEQ ID NO: 97.
9. The isolated polynucleotide molecule of claim 5 , wherein the antibody or antigen-binding fragment comprises a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 106.
10. The isolated polynucleotide molecule of claim 9 , wherein the light chain variable region is encoded by a nucleotide sequence set forth in SEQ ID NO: 105.
11. The isolated polynucleotide molecule of claim 5 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 98; and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 106.
12. The isolated polynucleotide molecule of claim 11 , wherein the heavy chain variable region is encoded by the nucleotide sequence as set forth in SEQ ID NO: 97; and the light chain variable region is encoded by a nucleotide sequence as set forth in SEQ ID NO: 105.
13. The isolated polynucleotide molecule of claim 11 , wherein the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO: 353.
14. The isolated polynucleotide molecule of claim 11 , wherein the antibody or antigen-binding fragment comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 354.
15. The isolated polynucleotide molecule of claim 11 , wherein the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO: 353; and a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 354.
16. A vector comprising the polynucleotide molecule of claim 7 .
17. A vector comprising the polynucleotide molecule of claim 9 .
18. A vector comprising the polynucleotide molecule of claim 11 .
19. A vector comprising the polynucleotide molecule of claim 15 .
20. A cell comprising the vector of claim 16 .
21. A cell comprising the vector of claim 17 .
22. A cell comprising the vector of claim 18 .
23. A cell comprising the vector of claim 19 .