Treatment for bone diseases

1 . A method for treating osteogenesis imperfecta (OI) in a mammalian subject, which method comprises:

(a) administering a batch of at least five doses of an anti-sclerostin antibody to a subject in need of such treatment, wherein the doses in the batch are administered at intervals of three to six weeks;

(b) then allowing the subject a dosing holiday that is at least 12 months in length; and

(c) administering to the subject at least one further dose of the anti-sclerostin antibody after the dosing holiday of (b).

2 . The method of claim 1 , wherein:

(i) the batch of doses in (a) comprises from five to twelve doses of the anti-sclerostin antibody; and/or

(ii) in (c) the subject is administered a batch of from five to twelve doses of the anti-sclerostin antibody.

3 . The method of claim 1 , wherein:

(i) the batch of doses in (a) comprises from five to seven doses of the anti-sclerostin antibody; or

(ii) the batch of doses in (a) comprises twelve doses, with the doses given at intervals of about monthly or four weeks.

4 . The method of claim 1 , wherein the method further comprises:

(d) allowing the subject a further dosing holiday that is at least 12 months in length; and

(e) administering to the subject at least two further doses of the anti-sclerostin antibody; and

(f) optionally repeating steps (d) and (e) one or more further times.

5 . The method of claim 1 , wherein the amount of the anti-sclerostin antibody administered for each dose is: (i) from about 50 to 250 mg; (ii) about 70 mg; (iii) about 140 mg; or (iv) about 210 mg.

6 . The method of claim 1 , wherein the anti-sclerostin antibody:

(i) is administered subcutaneously;

(ii) demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1×10 −7 M;

iii) neutralizes human sclerostin in a MC3T3 cell-based mineralization assay; iv) has an IC 50 of 100 nM or less, 50 nM or less, or 25 nM or less for neutralizing human sclerostin in a cell-based assay;

(v) has an IC 50 of 100 nM or less for neutralizing human sclerostin in a cell-based Wnt signalling assay in HEK293 cells; and/or

(vi) has an IC 50 of 500 nM or less for neutralizing human sclerostin in a BMP2-induced mineralization assay in MC3T3 cells.

7 . The method of claim 1 , wherein the anti-sclerostin antibody binds to a sclerostin polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1, where said anti-sclerostin antibody binds to:

(i) the sequence of SEQ ID NO: 6,

(ii) the sequence of at least one of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5; or

(iii) the sequence of at least one of SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, or SEQ ID NO: 73.

8 . The method of claim 1 , wherein the anti-sclerostin antibody:

(i) 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, and 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, and Ab-24;

(ii) 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;

(iii) comprises heavy chains comprising SEQ ID NO: 378 and light chains comprising SEQ ID NO 376; or

(iv) has heavy chains of SEQ ID NO: 145 or SEQ ID NO: 392 and light chains of SEQ ID NO: 141.

9 . A method for treating osteogenesis imperfecta (OI) in a mammalian subject, which method comprises:

(a) administering at least five doses of an anti-sclerostin antibody to a subject in need of such treatment, and monitoring the subject to identify when the subject shows a reduced response to a dose of the anti-sclerostin antibody;

(b) when such a reduced response is identified, allowing the subject a dosing holiday that is at least 12 months in length; and

(c) administering to the subject at least one further dose of the anti-sclerostin antibody after the dosing holiday of (b).

10 . The method of claim 9 , wherein:

(i) the subject is known to have been administered at least two doses of the anti-sclerostin antibody prior to step (a); and/or

(ii) the subject is one considered to be likely to display reduced responsiveness to the anti-sclerostin antibody due to previous administration of the anti-sclerostin antibody.

11 . The method of claim 9 , 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; and/or

(c) assessing bone mineral content and/or bone density using a technique selected from the group consisting of single- and dual-energy X-ray absorptometry, ultrasound, computed tomography, radiography, and magnetic resonance imaging.

12 . A method for treating osteogenesis imperfecta (OI) in a mammalian subject, which method comprises:

(a) administering to a subject in need of such treatment a batch of at least five doses of an anti-sclerostin antibody, wherein the doses in the batch are administered at intervals of three to six weeks;

(b) then allowing the subject a dosing holiday that is at least 12 months in length; wherein during the dosing holiday, the subject is administered a different treatment for OI; and

(c) administering to the subject at least one further dose of the anti-sclerostin antibody after the dosing holiday of (b).

13 . The method of claim 12 , wherein:

(i) the different treatment is an anti-resorptive, optionally a bisphosphonate; and/or

(ii) the subject is one who has been administered the different treatment prior to step (a).