Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.
대표청구항▼
1. An isolated polynucleotide encoding a monoclonal antibody that binds to amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 2. The polynucleotide of claim 1, wherein the antibody is a humanized antibody or a chimeric antibody. 3. The polynucleotide o
1. An isolated polynucleotide encoding a monoclonal antibody that binds to amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 2. The polynucleotide of claim 1, wherein the antibody is a humanized antibody or a chimeric antibody. 3. The polynucleotide of claim 1, wherein the antibody is a human antibody. 4. The polynucleotide of claim 1, wherein the antibody is an immunoglobulin comprising heavy chains and light chains. 5. The polynucleotide of claim 1, wherein the antibody comprises a non-native constant region. 6. The polynucleotide of claim 1, wherein the antibody is an IgG. 7. The polynucleotide of claim 1, wherein the antibody is an F(ab′)2, Fab, Fab′, Fv, Fc, or Fd fragment. 8. An isolated polynucleotide encoding a monoclonal antibody that binds to a fragment of a human sclerostin polypeptide of SEQ ID NO: 1, wherein the fragment consists of the amino acid sequences set forth in SEQ ID NOs: 70-73, wherein SEQ ID NO: 70 and 71 are joined by a disulfide bond, and SEQ ID NO: 72 and SEQ ID NO: 73 are joined by a disulfide bond. 9. An isolated polynucleotide encoding a monoclonal antibody that binds to a fragment of a human sclerostin polypeptide of SEQ ID NO: 1, produced by proteolytic digestion of SEQ ID NO: 1, and consisting of the amino acid sequences set forth in SEQ ID NOs: 2-5, wherein SEQ ID NO: 2 and 4 are joined by a disulfide bond at amino acid positions 57 and 111 with reference to SEQ ID NO: 1, and SEQ ID NO: 3 and 5 are joined by at least one of (a) a disulfide bond at amino acid positions 82 and 142 with reference to SEQ ID NO: 1, and (b) a disulfide bond at amino acid positions 86 and 144 with reference to SEQ ID NO: 1. 10. The polynucleotide of claim 9, wherein the fragment of said human sclerostin polypeptide retains the tertiary structure of the corresponding polypeptide region of human sclerostin of SEQ ID NO:1. 11. The polynucleotide thereof of claim 9, wherein the antibody is a humanized antibody or a chimeric antibody. 12. The polynucleotide thereof of claim 9, wherein the antibody is a human antibody. 13. The polynucleotide of claim 9, wherein the antibody is an immunoglobulin comprising heavy chains and light chains. 14. The polynucleotide of claim 9, wherein the antibody is an IgG. 15. The polynucleotide of claim 9, wherein the antibody is an F(ab′)2, Fab, Fab′, Fv, Fc, or Fd fragment. 16. The polynucleotide of claim 9, wherein the antibody binds to human sclerostin with a binding affinity (Kd) of less than or equal to 1×10−6 M. 17. The polynucleotide of claim 9, wherein the antibody binds to human sclerostin with a binding affinity (Kd) of less than or equal to 1×10−7M. 18. An isolated polynucleotide encoding a heavy chain of a monoclonal antibody that binds to an epitope of amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 19. An isolated polynucleotide encoding a light chain of a monoclonal antibody that binds to an epitope of amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 20. An isolated polynucleotide encoding a heavy chain of a monoclonal antibody that binds to a peptide consisting of amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 21. An isolated polynucleotide encoding a light chain of a monoclonal antibody that binds to a peptide consisting of amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 22. An isolated polynucleotide encoding a heavy chain of a monoclonal antibody that binds to a fragment of a human sclerostin polypeptide of SEQ ID NO: 1, wherein the fragment consists of the amino acid sequences set forth in SEQ ID NOs: 70-73, wherein SEQ ID NO: 70 and 71 are joined by a disulfide bond, and SEQ ID NO: 72 and SEQ ID NO: 73 are joined by a disulfide bond. 23. An isolated polynucleotide encoding a light chain of a monoclonal antibody that binds to a fragment of a human sclerostin polypeptide of SEQ ID NO: 1, wherein the fragment consists of the amino acid sequences set forth in SEQ ID NOs: 70-73, wherein SEQ ID NO: 70 and 71 are joined by a disulfide bond, and SEQ ID NO: 72 and SEQ ID NO: 73 are joined by a disulfide bond. 24. A vector comprising the polynucleotide of claim 1. 25. A vector comprising the polynucleotide of claim 9. 26. An isolated host cell comprising a polynucleotide encoding a heavy chain of a monoclonal antibody that binds to an epitope of amino acids 138-149 of SEQ ID NO: 1 with a binding affinity (Kd) of less than or equal to 1×10−6 M and a polynucleotide encoding a light chain of a monoclonal antibody that binds to an epitope of amino acids 138-149 of SEQ ID NO: 1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 27. An isolated host cell comprising a polynucleotide encoding a heavy chain of a monoclonal antibody that binds to a peptide consisting of amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M and a polynucleotide encoding a light chain of a monoclonal antibody that binds to a peptide consisting of amino acids 138-149 of SEQ ID NO:1 with a binding affinity (Kd) of less than or equal to 1×10−6 M. 28. An isolated host cell comprising a polynucleotide encoding a heavy chain of a monoclonal antibody that binds to a fragment of a human sclerostin polypeptide of SEQ ID NO: 1 and a light chain of a monoclonal antibody that binds to a fragment of a human sclerostin polypeptide of SEQ ID NO: 1, wherein the fragment consists of the amino acid sequences set forth in SEQ ID NOs: 70-73, wherein SEQ ID NO: 70 and 71 are joined by a disulfide bond, and SEQ ID NO: 72 and SEQ ID NO: 73 are joined by a disulfide bond. 29. A method of producing an antibody comprising the step of culturing the host cell of claim 26 and isolating the antibody produced therefrom. 30. A method of producing an antibody comprising the step of culturing the host cell of claim 27 and isolating the antibody produced therefrom. 31. A method of producing an antibody comprising the step of culturing the host cell of claim 28 and isolating the antibody produced therefrom.
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