Claims
- 1. A method of treating a patient in need thereof comprising administering to said patient a RANK antagonist in an amount and at a frequency sufficient to stimulate an increase in the rate of formation of new bone, wherein:
(a) said RANK antagonist is capable of inhibiting the ability of RANK to induce NF-κB, wherein RANK is a proteinconsisting of amino acids 1-616 of SEQ ID NO:4; (b) said patient is selected from the group consisting of patients who have acute septic arthritis, osteomalacia, hyperparathyroidism, Cushing's syndrome, monoostotic fibrous dysplasia, polyostotic fibrous dysplasia, Gaucher's disease, Langerhans' cell histiocytosis, spinal cord injury, patients requiring periodontal reconstruction and patients who have completed a course of radiation therapy for cancer; and (c) said RANK antagonist is selected from the group consisting of an antibody capable of specifically binding a RANK polypeptide comprising amino acids 33-196 of SEQ ID NO:4; an antisense oligonucleotide that blocks transcription or translation of RANK or RANKL mRNA; a ribozyme that cleaves RANK or RANKL mRNA; an antibody capable of specifically binding a RANKL polypeptide comprising amino acids 69-317 of SEQ ID NO:10; and an OPG polypeptide that comprises amino acids 22-185 of SEQ ID NO:8 and is capable of binding a RANKL polypeptide consisting of amino acids 1-317 of SEQ ID NO:10.
- 2. A method according to claim 1, wherein the patient has not experienced loss of bone density for at least one month preceding the initiation of treatment.
- 3. A method according to claim 1, wherein the sufficiency of treatment is monitored by repeatedly measuring bone density during the time the treatment is being administered.
- 4. A method according to claim 1, wherein the RANK antagonist is an antibody capable of specifically binding a RANKL polypeptide comprising amino acids 69-317 of SEQ ID NO:10.
- 5. A method according to claim 1, wherein the RANK antagonist is an OPG polypeptide that comprises amino acids 22-185 of SEQ ID NO:8 and is capable of binding a RANKL polypeptide consisting of amino acids 1-317 of SEQ ID NO:10.
- 6. A method of treating a patient in need thereof comprising administering to said patient a RANK antagonist in an amount and at a frequency sufficient to stimulate an increase in the rate of formation of new bone, wherein:
(a) said RANK antagonist is capable of inhibiting the ability of RANK to induce NF-κB, wherein RANK is a protein consisting of amino acids 1-616 of SEQ ID NO:4; (b) the RANK antagonist is a soluble RANK polypeptide that is capable of binding a RANKL polypeptide comprising amino acids 69-317 of SEQ ID NO:10, wherein said soluble RANK polypeptide has an at least 90% identity to a RANK polypeptide comprising amino acids 33-196 of SEQ ID NO:4; and (c) said patient is selected from the group consisting of patients who have acute septic arthritis, osteomalacia, hyperparathyroidism, Cushing's syndrome, monoostotic fibrous dysplasia, polyostotic fibrous dysplasia, Gaucher's disease, Langerhans' cell histiocytosis, spinal cord injury, patients requiring periodontal reconstruction and patients who have completed a course of radiation therapy for cancer.
- 7. A method according to claim 6, wherein said soluble RANK polypeptide is encoded by a nucleic acid molecule that is capable of hybridizing under stringent conditions with a nucleic acid molecule consisting of the nucleotide sequence shown in SEQ ID NO:3 or its complement, wherein said stringent conditions comprise hybridizing in 6×SSC at 63° C., and washing in 3×SSC at 55° C.
- 8. A method according to claim 6, wherein the soluble RANK polypeptide comprises amino acids 33-196 of SEQ ID NO:10.
- 9. A method according to claim 6, wherein the soluble RANK polypeptide further comprises a moiety selected from the group consisting of an immunoglobulin Fc domain, a FLAG™ tag, a peptide comprising at least about 6 His residues, a leucine zipper, polyethylene glycol and combinations thereof.
- 10. A method according to claim 9, wherein the further moiety comprises an immunoglobulin Fc domain.
- 11. A method according to claim 10, wherein the soluble RANK polypeptide consists of amino acids 30-433 of SEQ ID NO:5.
- 12. A method according to claim 10, wherein the soluble RANK polypeptide consists of amino acids 30-433 of SEQ ID NO:5 except that glutamic acid is substituted for aspartic acid at residue 352 and methionine is substituted for leucine at residue 354.
- 13. A method according to claim 6, wherein the patient has not experienced loss of bone density for at least one month preceding the initiation of treatment.
- 14. A method according to claim 6, wherein the sufficiency of treatment is monitored by repeatedly measuring bone density during the time the treatment is being administered.
- 15. A method of treating a human patient in need thereof comprising administering to said patient a RANK antagonist in an amount and at a frequency sufficient to stimulate an increase in the rate of formation of new bone, wherein:
(a) the RANK antagonist is selected from the group consisting of a soluble RANK polypeptide that is capable of binding a RANKL polypeptide comprising amino acids 69-317 of SEQ ID NO:10, said soluble RANK polypeptide having an at least 90% identity to a RANK polypeptide comprising amino acids 33-196 of SEQ ID NO:4; an antibody capable of specifically binding a RANK polypeptide comprising amino acids 33-196 of SEQ ID NO:4; an antisense oligonucleotide that blocks transcription or translation of RANK or RANKL mRNA; a ribozyme that cleaves RANK or RANKL mRNA; an antibody capable of specifically binding a RANKL polypeptide comprising amino acids 69-317 of SEQ ID NO:10; and an OPG polypeptide that comprises amino acids 22-185 of SEQ ID NO:8 and is capable of binding a RANKL polypeptide consisting of amino acids 1-317 of SEQ ID NO:10; (b) said patient is selected from the group consisting of prosthetic joint recipients, bone graft recipients and ligament graft recipients; and (c) the first dose of the antagonist is administered within one month of surgical implantation of the prosthetic joint, bone graft or ligament graft.
- 16. A method according to claim 15, wherein the sufficiency of treatment is monitored by repeatedly measuring bone density during the time the treatment is being administered.
- 17. A method according to claim 15, wherein the RANK antagonist is an antibody capable of specifically binding a RANKL polypeptide comprising amino acids 69-317 of SEQ ID NO:10.
- 18. A method according to claim 15, wherein the RANK antagonist is an OPG polypeptide that comprises amino acids 22-185 of SEQ ID NO:8 and is capable of binding a RANKL polypeptide consisting of amino acids 1-317 of SEQ ID NO:10.
- 19. A method according to claim 15, wherein the RANK antagonist is a soluble RANK polypeptide comprising amino acids 33-196 of SEQ ID NO:4.
- 20. A method according to claim 19, wherein the soluble RANK polypeptide further comprises a moiety selected from the group consisting of an immunoglobulin Fc domain, a FLAG™ tag, a peptide comprising at least about 6 His residues, a leucine zipper, polyethylene glycol and combinations thereof.
- 21. A method according to claim 20, wherein the soluble RANK polypeptide consists of the amino acid sequence shown in SEQ ID NO:5.
- 22. A method according to claim 20, wherein the soluble RANK polypeptide consists of amino acids 30-433 of SEQ ID NO:5 except that glutamic acid is substituted for asparatic acid at residue 352 and methionine is substituted for leucine at residue 354.
Parent Case Info
[0001] This patent application claims the benefit of priority under 35 U.S.C. §119 to U.S. Provisional Application Serial No. 60/291,919, the disclosure of which is incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60291919 |
May 2001 |
US |