Claims
- 1. A RANKL mimic comprising a core, at least one external loop, wherein the sequence of the mimic core comprises the sequence of the core of a non-RANKL TNF superfamily member, and wherein the sequence of at least one external loop is the sequence of the homologous RANKL external loop having essentially the sequence of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 52.
- 2. The RANKL mimic of claim 1, wherein the sequence of each external loop is the sequence of the homologous loop of RANKL.
- 3. A polynucleotide comprising a coding sequence that encodes a RANKL mimic comprising a core, at least one external loops, wherein the sequence of the mimic core comprises the sequence of the core of a non-RANKL TNF superfamily member, wherein the sequence of at least one external loop is the sequence of the homologous RANKL external loop having essentially the sequence of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 52.
- 4. The polynucleotide of claim 3, which further comprises a promoter operably linked to the coding sequence.
- 5. A recombinant cell expressing the polynucleotide of claim 4.
- 6. The recombinant cell of claim 5, wherein the cell is a eukaryotic cell.
- 7. A monomeric RANKL mimic comprising a core and at least one external loop, wherein the sequence of the core comprises the sequence of the core of a non-RANKL TNF superfamily member modified in the trimerizing region, such that it is unable to form trimers, the sequence of at least one external loop is the sequence of the homologous RANKL external loop having essentially the sequence of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 52.
- 8. The monomeric RANKL mimic of claim 7, wherein the sequence of each external loop is the sequence of the homologous loop of RANKL.
- 9. A polynucleotide comprising a coding sequence that encodes a monomeric RANKL mimic comprising a core and at least one external loop, wherein the sequence of the core comprises the sequence of the core of a non-RANKL TNF superfamily member modified in the regions mediating trimerization, such that they no longer homotrimerize, the sequence of at least one external loop is the sequence of the homologous RANKL external loop having essentially the sequence of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 or SEQ ID NO: 46.
- 10. The polynucleotide of claim 9, which further comprises a promoter operably linked to the coding sequence.
- 11. A recombinant cell expressing the polynucleotide of claim 10.
- 12. The recombinant cell of claim 11, wherein the cell is a eukaryotic cell.
- 13. The recombinant RANKL mimic of claim 1, wherein the TNF superfamily member is selected from the group consisting of TRAIL, CD40L, TNF-alpha, TNF-beta, and ACRP30.
- 14. The recombinant RANKL mimic of claim 7, wherein the TNF superfamily member is selected from the group consisting of TRAIL, CD40L, TNF-alpha, TNF-beta, and ACRP30.
- 15. The polynucleotide sequence of claim 3, wherein the TNF superfamily member is selected from the group consisting of TRAIL, CD40L, TNF-alpha, TNF-beta, and ACRP30.
- 16. The polynucleotide sequence of claim 9, wherein the TNF superfamily member is selected from the group consisting of TRAIL, CD40L, TNF-alpha, TNF-beta, and ACRP30.
- 17. A recombinant RANKL mimic in which the TNF superfamily member is RANKL or other TNF superfamily member wherein the oligomerizing DE loop is that of TALL-1, and at least one of the remaining external loops are the AA″, EF, and CD loops of RANKL.
- 18. A polynucleotide encoding the RANKL mimic of claim 17.
- 19. An oligomeric RANKL mimic comprising a core, at least one external loop and an oligomerizing domain, wherein the sequence of the mimic core comprises the sequence of the core of a non-RANKL TNF superfamily member, and wherein the sequence of at least one external loop is the sequence of the homologous RANKL external loop having essentially the sequence of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 52.
- 20. The oligomeric RANKL mimic of claim 19, wherein the sequence of each external loop is the sequence of the homologous loop of RANKL.
- 21. A polynucleotide; comprising a coding sequence that encodes an oligomeric RANKL mimic comprising a core, at least one external loop and an oligomerizing domain, wherein the sequence of the mimic core comprises the sequence of the core of a non-RANKL TNF superfamily member, and wherein the sequence of at least one external loop is the sequence of the homologous RANKL external loop having essentially the sequence of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 52.
- 22. The polynucleotide of claim 21, further comprising a promoter operably linked to the coding sequence.
- 23. A recombinant cell expressing the polynucleotide of claim 22.
- 24. The recombinant cell of claim 23, wherein the cell is a eukaryotic cell.
- 25. The recombinant RANKL mimic of claim 19, wherein the TNF superfamily member is selected from the group consisting of TRAIL, CD40L, TNF-alpha, TNF-beta, and ACRP30.
- 26. The polynucleotide sequence of claim 21, wherein the TNF superfamily member is selected from the group consisting of TRAIL, CD40L, TNF-alpha, TNF-beta, and ACRP30.
- 27. A recombinant RANKL mimic in which the TNF superfamily member is RANKL or other TNF superfamily member wherein the oligomerizing DE loop is that of TALL-1, and at least one of the remaining external loops are the AA″, EF, or CD loops of RANKL.
- 28. A polynucleotide encoding the oligomerizing RANKL mimic of claim 27.
- 29. The RANKL mimic of claim 19, wherein the oligomerizing domain is operably linked to the amino terminus.
- 30. The RANKL mimic of claim 29, wherein the oligomerizing domain is glutathione S-transferase.
- 31. The RANKL mimic of claim 19, wherein the oligomerizing domain is operably linked to the carboxy terminus.
- 32. The RANKL mimic of claim 19,-wherein the oligomerizing domain is internally linked.
- 33. The RANKL mimic of claim 29, wherein the oligomerizing domain is glutathione S-transferase.
- 34. A polynucleotide encoding the RANKL mimic of claim 29.
- 35. A polynucleotide encoding the RANKL mimic of claim 30.
- 36. A polynucleotide encoding the RANKL mimic of claim 31.
- 37. A polynucleotide encoding the RANKL mimic of claim 32.
Parent Case Info
[0001] This application is related to and claims the benefit of the following U.S. applications, which are incorporated herein by reference as if restated here in full: Ser. No. 60/277,855 filed Mar. 22, 2001; Ser. No. 10/105,057 filed Mar. 22, 2002; Ser. No. 60/311,163 filed Aug. 9, 2001; Ser. No. 10/215,446 filed Aug. 9, 2002; Ser. No. 60/329,231 filed Oct. 12, 2001; Ser. No. 60/329,393 filed Oct. 15, 2001; Ser. No. 60/329,360 filed Oct. 15, 2001; Ser. No. 60/328,876 filed Oct. 12, 2001; U.S. non-provisional application entitled Methods for Screening Osteogenic Compounds, Lam, et al., filed Oct. 15, 2002; and U.S. non-provisional application entitled Bone Anti-Resorptive Compounds, Lam, et al., filed Oct. 15, 2002.
Government Interests
[0002] This invention was made in part with U.S. Government support under National Institutes of Health Grants AR32788, AR46123 and DE05413. The Government has certain rights in the invention.
Provisional Applications (4)
|
Number |
Date |
Country |
|
60329393 |
Oct 2001 |
US |
|
60329231 |
Oct 2001 |
US |
|
60329360 |
Oct 2001 |
US |
|
60328876 |
Oct 2001 |
US |