Claims
- 1. An isolated DNA selected from the group consisting of:
(a) a DNA encoding a protein having an amino acid sequence as set forth in SEQ ID NO:6, wherein the protein has an amino terminus selected from the group consisting of an amino acid between amino acid 1 and amino acid 33, inclusive, of SEQ ID NO:6, and a carboxy terminus selected from the group consisting an amino acid between amino acid 196 and amino acid 616, inclusive; (b) a DNA encoding a protein having an amino acid sequence as set forth in SEQ ID NO:15, wherein the protein has an amino terminus selected from the group consisting of an amino acid between amino acid 1 and amino acid 30, inclusive, of SEQ ID NO:15, and a carboxy terminus selected from the group consisting an amino acid between amino acid 197 and amino acid 625, inclusive; (c) DNA molecules capable of hybridization to the DNA of (a) or (b) under stringent conditions, and which encode biologically active RANK; and (d) DNA molecules encoding fragments of proteins encoded by the DNA of (a), (b) or (c).
- 2. The isolated DNA of claim 1, which encods a RANK polypeptide that is at least about 80% identical in amino acid sequence to the native form of RANK
- 3. The isolated DNA of claim 1, which encodes a soluble RANK polypeptide.
- 4. The isolated DNA of claim 2, which encodes a soluble RANK polypeptide.
- 5. The isolated DNA of claim 3, which further comprises a DNA encoding a polypeptide selected from the group consisting of an immunoglobulin Fc domain, an immnunoglobulin Fc mutein, a FLAG™ tag, a peptide comprising at least about 6 His residues, a leucine zipper, and combinations thereof.
- 6. The isolated DNA of claim 4, which further comprises a DNA encoding a polypeptide selected from the group consisting of an immunoglobulin Fc domain, an immunoglobulin Fc mutein, a FLAG™ tag, a peptide comprising at least about 6 His residues, a leucine zipper, and combinations thereof.
- 7. A recombinant expression vector comprising a DNA sequence according to claim 1.
- 8. A recombinant expression vector comprising a DNA sequence according to claim 2.
- 9. A recombinant expression vector comprising a DNA sequence according to claim 3.
- 10. A recombinant expression vector comprising a DNA sequence according to claim 4.
- 11. A recombinant expression vector comprising a DNA sequence according to claim 5.
- 12. A recombinant expression vector comprising a DNA sequence according to claim 6 .
- 13. A host cell transformed or transfected with an expression vector according to claim 7.
- 14. A host cell transformed or transfected with an expression vector according to claim 8.
- 15. A host cell transformed or transfected with an expression vector according to claim 9.
- 16. A host cell transformed or transfected with an expression vector according to claim 10.
- 17. A host cell transformed or transfected with an expression vector according to claim 11.
- 18. A host cell transformed or transfected with an expression vector according to claim 12.
- 19. A process for preparing a RANK protein, comprising culturing a host cell according to claim 13 under conditions promoting expression and recovering the RANK.
- 20. A process for preparing a RANK protein, comprising culturing a host cell according to claim 14 under conditions promoting expression and recovering the RANK.
- 21. A process for preparing a RANK protein, comprising culturing a host cell according to claim 15 under conditions promoting expression and recovering the RANK.
- 22. A process for preparing a RANK protein, comprising culturing a host cell according to claim 16 under conditions promoting expression and recovering the RANK.
- 23. A process for preparing a RANK protein, comprising culturing a host cell according to claim 17 under conditions promoting expression and recovering the RANK.
- 24. A process for preparing a RANK protein, comprising culturing a host cell according to claim 18 under conditions promoting expression and recovering the RANK.
- 25. An isolated DNA selected from the group consisting of oligonucleotides of at least about 17 nucleotides in length, oligonucleotides of at least about 25 nucleotides in length, and oligonucleotides of at least about 30 nucleotides in length, which is a fragment of the DNA of SEQ ID NO:5 or SEQ ID NO:14.
- 26. An isolated RANK polypeptide selected from the group consisting of:
(a) a polypeptide having an amino acid sequence of amino acids 33 through 196 of SEQ ID NO: 6; (b) a polypeptide having an amino acid sequence of amino acids 30 through 197 of SEQ ID NO: 15; (c) a RANK polypeptide encoded by a DNA capable of hybridization to a DNA encoding the protein of (a) or (b) under stringent conditions, and which is biologically active; and (d) fragments of the polypeptides of (a), (b) or (c) which are biologically active.
- 27. The protein according to claim 26, having an amino acid sequence at least about 80% identical to SEQ ID NO:6 or SEQ ID NO:15.
- 28. The protein according to claim 27, which is a soluble RANK.
- 29. The protein according to claim 26, which is a soluble RANK.
- 30. A soluble RANK protein which further comprises a peptide selected from the group consisting of an immunoglobulin Fc domain, an immunoglobulin Fc mutein, a FLAG™ tag, a peptide comprising at least about 6 His residues, a leucine zipper, and combinations thereof.
- 31. An antibody immunoreactive with RANK polypeptide according to claim 26.
- 32. The antibody according to claim 31, which is a monoclonal antibody.
- 33. A method of inhibiting activation of NFκB, comprising contacting a cell that expresses membrane-associated RANK with a soluble RANK and allowing the soluble RANK to bind RANKL and inhibit binding thereof to the cell.
- 34. A method of regulating an immune or inflammatory response, comprising administering a soluble RANK polypeptide composition to an individual at risk for an immune or inflammatory response, and allowing the soluble RANK to bind RANKL and inhibit binding thereof to cells expressing RANK.
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 60/064,671, filed Oct. 14, 1997, and a continuation in part of U.S. Ser. No. 08/813,509, filed Mar. 7, 1997, and a continuation-in part of U.S. Ser. No. 60/059,978, filed Dec. 23, 1996.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60064671 |
Oct 1997 |
US |
|
60077181 |
Mar 1997 |
US |
|
60059978 |
Dec 1996 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09466496 |
Dec 1999 |
US |
Child |
09871856 |
May 2001 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
08996139 |
Dec 1997 |
US |
Child |
09466496 |
Dec 1999 |
US |