Anti-GDF-15 antibodies
Monoclonal antibodies that bind and inhibit the activity of human GDF15 are disclosed. The antibodies can be used to treat body weight loss, including cachexia, associated with the over-expression of human GDF15.
1. An isolated antibody that binds human GDF15 comprising:
an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:234, a CDR H2 comprising the amino acid sequence of SEQ ID NO:238 or SEQ ID NO:241, and a CDR H3 comprising the amino acid sequence of SEQ ID NO:15; and
an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:21, a CDR L2 comprising the amino acid sequence of SEQ ID NO:26, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32.
2. The isolated antibody of claim 1 , wherein the immunoglobulin heavy chain variable region comprises a CDR H1 comprising the amino acid sequence of SEQ ID NO:1, a CDR H2 comprising the amino acid sequence of SEQ ID NO:238, and a CDR H3 comprising the amino acid sequence of SEQ ID NO:15; and
an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:21, a CDR L2 comprising the amino acid sequence of SEQ ID NO:26, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32.
3. The isolated antibody of claim 1 , wherein the immunoglobulin heavy chain variable region comprises a CDR H1 comprising the amino acid sequence of SEQ ID NO:234, a CDR H2 comprising the amino acid sequence of SEQ ID NO:241, and a CDR H3 comprising the amino acid sequence of SEQ ID NO:15; and
an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:21, a CDR L2 comprising the amino acid sequence of SEQ ID NO:26, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32.
4. An isolated nucleic acid comprising a nucleotide sequence encoding the immunoglobulin heavy chain variable region of claim 1 .
5. An isolated nucleic acid comprising a nucleotide sequence encoding the immunoglobulin light chain variable region of claim 1 .
6. An expression vector comprising the nucleic acid of claim 4 .
7. An expression vector comprising the nucleic acid of claim 5 .
8. A host cell comprising the expression vector of claim 6 .
9. A host cell comprising the expression vector of claim 7 .
10. An isolated antibody that binds human GDF15, comprising:
an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO:250, and
an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO:92.
11. An isolated nucleic acid comprising a nucleotide sequence encoding the immunoglobulin heavy chain variable region of claim 10 .
12. An isolated nucleic acid comprising a nucleotide sequence encoding the immunoglobulin light chain variable region of claim 10 .
13. An isolated antibody that binds human GDF15 comprising:
an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO:260, and
an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO:208.
14. An isolated nucleic acid comprising a nucleotide sequence encoding the immunoglobulin heavy chain of claim 13 .
15. An isolated nucleic acid comprising a nucleotide sequence encoding the immunoglobulin light chain of claim 13 .
16. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition comprising the antibody of claim 2 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition comprising the antibody of claim 10 and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition comprising the antibody of claim 13 and a pharmaceutically acceptable carrier.