Polynucleotide encoding a sclerostin-binding antibody
Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.
1. An isolated polynucleotide comprising a nucleotide sequence encoding a variable region of an antibody or fragment thereof that binds sclerostin of SEQ ID NO: 1, said variable region comprising (a) complementarity determining region (CDR)-H1 of SEQ ID NO:245, CDR-H2 of SEQ ID NO:246, and CDR-H3 of SEQ ID NO:247 or (b) CDR-L1 of SEQ ID NO:78, CDR-L2 of SEQ ID NO:79 and CDR-L3 of SEQ ID NO:80, or both.
2. The polynucleotide of claim 1 comprising a nucleotide sequence encoding a light chain variable region comprising CDR-L1 of SEQ ID NO:78, CDR-L2 of SEQ ID NO:79, and CDR-L3 of SEQ ID NO:80.
3. The polynucleotide of claim 2 , further comprising a nucleotide sequence encoding a light chain constant region.
4. The polynucleotide of claim 1 comprising a nucleotide sequence encoding a heavy chain variable region comprising CDR-H1 of SEQ ID NO:245, CDR-H2 of SEQ ID NO:246, and CDR-H3 of SEQ ID NO:247.
5. The polynucleotide of claim 4 , further comprising a nucleotide sequence encoding an IgG4 or an IgG2 constant region.
6. The polynucleotide of claim 1 , further comprising a nucleotide sequence encoding a light chain and/or heavy chain constant region.
7. The polynucleotide of claim 1 , wherein the antibody or fragment demonstrates a binding affinity (Kd) for sclerostin of SEQ ID NO: 1 of less than or equal to about 10 −7 M.
8. The polynucleotide of claim 1 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.
9. The polynucleotide of claim 1 , wherein the antibody is a monoclonal antibody.
10. The polynucleotide of claim 1 , wherein the antibody comprises an F(ab′)2, Fab, Fab′, Fv, Fc, or Fd fragment.
11. A cloning or expression vector comprising one or more polynucleotide sequences according to claim 1 .
12. The vector of claim 11 , wherein the vector comprises at least one polynucleotide sequence set forth in SEQ ID NO:134, 136, 138, 140, 142, 144, 146, 148, 377, and 379.
13. A host cell comprising one or more cloning or expression vectors according to claim 11 .
14. A host cell comprising one or more cloning or expression vectors according to claim 12 .
15. A polynucleotide comprising a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 378.
16. The polynucleotide of claim 15 , wherein the nucleotide sequence encodes a heavy chain of SEQ ID NO:145 or 392.
17. A cloning or expression vector comprising the polynucleotide of claim 15 .
18. A polynucleotide comprising a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 376.
19. The polynucleotide of claim 18 , wherein the nucleotide sequence encodes a light chain of SEQ ID NO: 141.
20. A cloning or expression vector comprising the polynucleotide of claim 18 .
21. A host cell comprising the polynucleotide of claim 15 and the polynucleotide of claim 18 .
22. A host cell comprising the polynucleotide of claim 16 and the polynucleotide of claim 19 .
23. A process for producing an antibody or fragment thereof, comprising culturing the host cell of claim 13 and isolating the antibody or fragment.
24. A process for producing an antibody or fragment thereof, comprising culturing the host cell of claim 14 and isolating the antibody or fragment.
25. A process for producing of an antibody or fragment thereof, comprising culturing the host cell of claim 21 and isolating the antibody or fragment.
26. A process for producing of an antibody or fragment thereof, comprising culturing the host cell of claim 22 and isolating the antibody or fragment.