Claims
- 1. An essentially purified and isolated noggin polypeptide having an amino acid sequence as set forth in FIG. 1 (Sequence l.D. No. 2) or a functionally equivalent amino acid sequence.
- 2. The human noggin polypeptide as claimed in claim 1, encoded by the DNA of hnogλ-9 (deposited with the American Type Culture Collection under Accession No. 75310) or hnogλ-10 (deposited with the American Type Culture Collection under Accession No. 75308) and fragments and derivatives thereof exhibiting noggin activity.
- 3. An isolated nucleic acid selected from a nucleic acid encoding a noggin polypeptide as claimed in claim 1, and substantially similar nucleotide sequences.
- 4. A nucleic acid as claimed in claim 3, which hybridizes to at least one nucleotide probe selected from the sequence of nucleotides 2 to 262 of Sequence I.D. No. 10 and the sequence:
5′GARGGIATGGTITGYAARCC (SEQ ID NO. 22).
- 5. A nucleic acid as claimed in claim 3, wherein said nucleic acid is isolated from a λ human placental genomic library.
- 6. A nucleic acid as claimed in claim 5, wherein said nucleic acid is isolated from a phage selected from hnogλ-9 (ATCC No. 75310) or hnogλ-10 (ATCC No. 75308).
- 7. A substantially purified nucleic acid as claimed in claim 3, encoding the human noggin polypeptide corresponding to Sequence I.D. No. 2.
- 8. A mutated variant of a nucleic acid as claimed in claim 3, which encodes a noggin agonist or antagonist.
- 9. A mutant noggin polypeptide which is a noggin agonist or antagonist obtainable by expression of a nucleic acid as claimed in claim 8.
- 10. An isolated nucleic acid which contains a nucleotide coding sequence for a noggin polypeptide as claimed in claim 1, in the anti-sense direction.
- 11. A phage selected from the group consisting of hnogλ-9 as deposited with the American Type Culture Collection and assigned Accession Number 75310 and hnogλ-10 as deposited with the American Type Culture Collection and assigned Accession Number 75308.
- 12. An expression vector comprising expression regulatory sequences operably linked to a nucleotide sequence which encodes noggin, wherein said nucleotide sequence is selected from the group consisting of:
a) a nucleotide sequence which encodes the amino acid sequence set forth in FIG. 1 (SEQ I.D. NO. 2), and b) sequences which hybridize to the sequence of (a) and encode a protein which promotes the induction of neural tissue.
- 13. An expression vector as claimed in claim 12, capable of directing expression of a functional noggin polypeptide in a eukaryotic host cell.
- 14. An expression vector as claimed in claim 13, wherein said host cell is selected from the group consisting of COS cells and CHO cells.
- 15. An expression vector as claimed in claim 12, capable of directing the expression of a functional noggin polypeptide in a prokaryotic host.
- 16. The expression vector as claimed in claim 15, wherein said host is E. coli.
- 17. An expression vector as claimed in claim 12, capable of directing the expression of a functional noggin polypeptide in a baculovirus host.
- 18. Host cells transformed by an expression vector as claimed in claim 12.
- 19. A method of producing a noggin polypeptide which comprises culturing transformed host cells as claimed in claim 18, under conditions suitable for expression of said polypeptide.
- 20. A method as claimed in claim 19, wherein human noggin is produced in a form substantially free of proteins of non-human origin.
- 21. A pharmaceutical composition comprising a therapeutically effective amount of a polypeptide as claimed in claim 1, together with a pharmaceutically acceptable carrier.
- 22. A culture medium suitable for use in culturing nerve cells containing a noggin polypeptide as claimed in claim 1.
- 23. An isolated receptor which in vivo binds a noggin polypeptide as claimed in claim 1, or a fragment thereof retaining the binding site for said polypeptide.
- 24. An antibody which binds one or more noggin polypeptides as claimed in claim 1, but not other growth factors.
- 25. A hybridoma capable of producing a monoclonal antibody as claimed in claim 24.
- 26. The monoclonal antibody obtainable from hybridoma RP57-16.
- 27. Hybridoma RP57-16.
- 28. A hybridization probe suitable for detecting a nucleic acid as claimed in claim 3, having the sequence:
5′GARGGIATGGTITGYAARCC (SEQ I.D. NO. 22).
- 29. A noggin polypeptide as claimed in claim 1, for use in a method of treatment of a human or animal.
- 30. A method of treatment of a human or animal comprising administering a therapeutic dosage of a noggin polypeptide as claimed in claim 1, wherein said treatment is selected from the group consisting of regulation of cartilage and bone growth, therapy of a congenital condition or degenerative disorder of the nervous system, and treatment of damaged nerve cells.
Parent Case Info
[0001] This application is a continuation of copending U.S. patent application Ser. No. 08/392,935 filed on Mar. 3, 1995, which is the U.S. National Stage of PCT/US93/08326 filed Sep. 2, 1993, which is a continuation-in-part of U.S. Ser. No. 07/957,401 filed on Oct. 6, 1992, which is a continuation-in-part of U.S. patent application Ser. No. 07/950,410 filed on Sep. 23, 1992, which is a continuation-in-part of U.S. patent application Ser. No. 07/939,954 filed on Sep. 3, 1992.
Government Interests
[0002] This invention was made, in part, with government support under Grant Contract No. ROI-GM-42341, awarded by the National Institutes of Health. The government has certain rights in this invention.
Continuations (4)
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