Claims for Patent: 9,925,260

Summary for Patent: 9,925,260

Title:	Treatment for bone diseases
Abstract:	The invention relates to the treatment of bone disorders. In particular, the invention is directed to the use of a dosing holiday to help overcome the resistance to anti-sclerostin antibodies which develops over time when a plurality of doses of antibody are given to a subject. By giving the subject to be treated such a dosing holiday, the subject may subsequently display an increased response to a subsequent dose of the anti-sclerostin antibody. The subject may be given multiple cycles of a batch of at least two doses of anti-sclerostin antibody and a dosing holiday. In some instances, the subject may be monitored to help determine when to give the dosing holiday. Further, the subject may be given a different treatment for the bone disorder during the dosing holiday from the anti-sclerostin antibody.
Inventor(s):	Robinson; Martyn Kim (Buckinghamshire, GB)
Assignee:	UCB PHARMA S.A. (Slough, GB)
Application Number:	13/934,433
Patent Claims:	1. A method for treating a bone disorder associated with at least one of low bone formation, low bone mineral density, low bone mineral content, low bone mass, low bone quality and low bone strength in a mammalian subject, which method comprises: (a) administering a batch of at least five doses of anti-sclerostin antibody to a subject in need of such treatment, wherein the doses in the batch are administered at about monthly intervals, and monitoring the subject to identify a reduced response to a dose of the anti-sclerostin antibody; (b) then allowing the subject a dosing holiday, which is at least twelve months in length; and (c) administering to the subject a further batch of at least five doses of anti-sclerostin antibody after the dosing holiday of (b), wherein the doses in the further batch are administered at about monthly intervals. 2. The method of claim 1, where the method further comprises: (d) monitoring the subject to identify a reduced response to a dose of the anti-sclerostin antibody, and allowing the subject a further dosing holiday at least twelve months in length; and (e) administering to the subject a further batch of at least five doses of anti-sclerostin antibody after the dosing holiday of step (d). 3. The method of claim 1, wherein: the batch of doses in step (a) comprises from five to twelve doses of anti-sclerostin antibody. 4. The method of claim 3, wherein: the batch of doses in step (a) comprises from five to seven doses of anti-sclerostin antibody. 5. The method of claim 1, wherein the batch of doses in step (a) comprises twelve doses, with the doses given at monthly intervals. 6. The method of claim 1, wherein the subject is administered a batch of from five to twelve doses of anti-sclerostin antibody in step (c). 7. The method of claim 1, where the monitoring is performed using: (a) a marker of bone resorption selected from the group consisting of C-telopeptide, N-telopeptide, deoxypyridinoline, pyridinoline, urinary hydroxyproline, galactosyl hydroxylysine, and tartrate-resistant acid phosphatase; (b) a marker of bone formation and/or mineralization selected from the group consisting of bone-specific alkaline phosphatase, peptides released from N- and C-terminal extension of type I procollagen, and osteocalcin; (c) assessing bone mineral content and/or bone density using a technique selected from the group consisting of single- and dual-energy X-ray absorptiometry, ultrasound, computed tomography, radiography, and magnetic resonance imaging; or (d) any combination of the foregoing. 8. The method of claim 1, wherein step (b) further comprises administering a different treatment for the bone disorder during the dosing holiday. 9. The method of claim 8 where the different treatment is an anti-resorptive. 10. The method of claim 8, wherein the different treatment is bisphosphonate. 11. The method of claim 8 wherein the different treatment is denosumab. 12. The method of claim 8 where the subject is one who has also been administered the different treatment prior to step (a). 13. The method of claim 1, wherein the anti-sclerostin antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-7 M, where said anti-sclerostin antibody binds to the sequence of SEQ ID NO: 6. 14. The method of claim 1, wherein the anti-sclerostin antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-7 M, wherein the anti-sclerostin antibody binds the sequence of at least one of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. 15. The method of claim 14, wherein the anti-sclerostin antibody binds a fragment of sclerostin of SEQ ID NO: 1 consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. 16. The method of claim 1, wherein the anti-sclerostin antibody cross-blocks the binding of at least one of antibodies Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, or Ab-24 to sclerostin and/or is cross-blocked from binding to sclerostin by at least one of antibodies Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, or Ab-24. 17. The method of claim 1, wherein the anti-sclerostin antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-7 M and comprises a CDR-H1 of SEQ ID NO:245, a CDR-H2 of SEQ ID NO:246, a CDR-H3 of SEQ ID NO:247, a CDR-L1 of SEQ ID NO:78, a CDR-L2 of SEQ ID NO:79 and a CDR-L3 of SEQ ID NO:80. 18. The method of claim 17, wherein the anti-sclerostin antibody comprises heavy chains comprising SEQ ID NO: 378 and light chains comprising SEQ ID NO 376. 19. The method of claim 17, wherein the anti-sclerostin antibody comprises heavy chains of SEQ ID NO: 145 or SEQ ID NO: 392 and light chains of SEQ ID NO: 141. 20. The method of claim 8, wherein the anti-sclerostin antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-7 M and comprises a CDR-H1 of SEQ ID NO:245, a CDR-H2 of SEQ ID NO:246, a CDR-H3 of SEQ ID NO:247, a CDR-L1 of SEQ ID NO:78, a CDR-L2 of SEQ ID NO:79 and a CDR-L3 of SEQ ID NO:80. 21. The method of claim 20, wherein the anti-sclerostin antibody comprises heavy chains comprising SEQ ID NO: 378 and light chains comprising SEQ ID NO 376. 22. The method of claim 20, wherein the anti-sclerostin antibody comprises heavy chains of SEQ ID NO: 145 or SEQ ID NO: 392 and light chains of SEQ ID NO: 141. 23. The method of claim 1, wherein the amount of anti-sclerostin antibody administered for each dose is from about 50 to 250 mg. 24. The method of claim 1, wherein the amount of anti-sclerostin antibody administered for each dose is about 70 mg. 25. The method of claim 1, wherein the amount of anti-sclerostin antibody administered for each dose is about 140 mg. 26. The method of claim 25, wherein the amount of anti-sclerostin antibody administered for each dose is about 210 mg. 27. The method of claim 1, wherein the subject has osteoporosis or osteopenia. 28. The method of claim 17, wherein the subject is a postmenopausal woman. 29. The method of claim 20, wherein the subject is a postmenopausal woman. 30. A method for treating a bone disorder associated with at least one of low bone formation, low bone mineral density, low bone mineral content, low bone mass, low bone quality and low bone strength in a mammalian subject, which method comprises: (a) administering a batch of at least five doses of anti-sclerostin antibody to a subject in need of such treatment, and monitoring the subject to identify whether the subject shows a reduced response to a dose of the anti-sclerostin antibody; (b) if such a reduced response is identified, allowing the subject a dosing holiday which is at least twelve months in length; and (c) if a dosing holiday is given in (b), administering to the subject a further batch of at least five dose of anti-sclerostin antibody after the dosing holiday of (b). 31. The method of claim 30, wherein: (i) the subject is known to have been administered at least two doses of anti-sclerostin antibody prior to step (a); (ii) the subject is one considered to be likely to display reduced responsiveness to the anti-sclerostin antibody due to previous administration of the antibody; or (iii) a combination of the foregoing. 32. The method of claim 30, wherein the monitoring is performed using: (a) a marker of bone resorption selected from the group consisting of C-telopeptide, N-telopeptide, deoxypyridinoline, pyridinoline, urinary hydroxyproline, galactosyl hydroxylysine, and tartrate-resistant acid phosphatase; (b) a marker of bone formation and/or mineralization selected from the group consisting of bone-specific alkaline phosphatase, peptides released from N- and C-terminal extension of type I procollagen, and osteocalcin; (c) assessing bone mineral content and/or bone density using a technique selected from the group consisting of single- and dual-energy X-ray absorptiometry, ultrasound, computed tomography, radiography, and magnetic resonance imaging; or (d) any combination of the foregoing. 33. A method for treating osteoporosis in a postmenopausal woman, which method comprises: (a) administering a batch of at least five doses of an anti-sclerostin antibody to the woman at about monthly intervals, and monitoring the woman to identify a reduced response to a dose of the anti-sclerostin antibody; (b) then allowing the woman a dosing holiday of at least twelve months; and (c) administering to the woman a further batch of at least five doses of anti-sclerostin antibody after the dosing holiday of (b). 34. The method of claim 33, wherein step (a) comprises twelve doses given at about monthly intervals. 35. The method of claim 33, wherein step (c) comprises twelve doses given at about monthly intervals. 36. The method of claim 33, wherein during the dosing holiday, the woman is administered a different treatment for osteoporosis. 37. The method of claim 36, wherein the different treatment is bisphosphonate. 38. The method of claim 36, wherein the different treatment is denosumab. 39. The method of claim 33, wherein each dose of the anti-sclerostin antibody is 210 mg.

Details for Patent 9,925,260

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	PROLIA	denosumab	Injection	125320	06/01/2010		2025-05-03
Amgen, Inc.	XGEVA	denosumab	Injection	125320	11/18/2010		2025-05-03