EFFECTIVE AND EFFICIENT CONTROL OF SERUM PHOSPHATE FOR OPTIMAL BONE FORMATION

• US 20150353633A1
• Filed: 05/29/2015
• Published: 12/10/2015
• Est. Priority Date: 06/09/2014
• Status: Active Grant

• Current Assignee: Kyowa Kirin Co., Ltd. (Kirin Holdings Company Limited), Ultragenyx Pharmaceutical Inc.
• Original Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited), Ultragenyx Pharmaceutical Inc.
• Inventors: SUDO, Tomohiro, KAKKIS, Emil D., SAN MARTIN, Javier
• Granted Patent: US 10,639,360 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/001132 Fibroblast growth factors [FGF]
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/90 characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin

Abstract

The present invention provides compositions and methods for treating a hypophosphatemic disorder, such as X-linked hypophosphatemia (XLH). The method entails administering to a subject a pharmaceutical composition containing an anti-FGF23 ligand, wherein the dosing regimen of the pharmaceutical is designed to reach effective and efficient control of FGF23 activity.

Claims

1. A method of using an anti-FGF23 ligand comprising administering to a subject in need of such treatment an effective amount of an anti-FGF23 ligand, wherein the dosing regimen of the anti-FGF23 ligand is determined based on one or more PD parameters of the anti-FGF23 ligand in the subject.

2. The method of claim 1, wherein the PD parameter of the anti-FGF23 ligand is selected from the group consisting AUC serum phosphorus within a dose interval, peak and trough serum phosphorus, Tmp/GFR, serum 1,25-dihydroxy vitamin D, and serum 25-hydroxy vitamin D.

3. The method of claim 1, wherein the anti-FGF23 ligand is selected from the group consisting of anti-FGF23 antibodies, FGF23 antisense oligonucleotides, small molecule inhibitors of FGF23, and FGF23 antagonists.

4. The method of claim 1, wherein the anti-FGF23 ligand is an anti-FGF23 antibody.

5. The method of claim 1, wherein the anti-FGF23 ligand comprises one or more CDR sequences selected from SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO. 3, SEQ ID NO;

4, SEQ ID NO;

5, and SEQ ID NO. 6.

6. The method of claim 1, wherein the dosing regimen of the anti-FGF23 ligand provides a predetermined level of serum phosphorus over a dosing cycle.

7. The method of claim 1, wherein the dosing regimen comprises a dosing frequency that provides a sustained effect on NaPi transporter without a decline of NaPi transporter activity during a dosing cycle.

8. The method of claim 1, wherein the dosing regimen comprises administering anti-FGF23 ligand every two weeks.

9. The method of claim 1, wherein the dosing regimen provides an increase in bone remodeling.

10. A method of treating a condition related to FGF23 comprising administering to a subject in need of such treatment an effective amount of an anti-FGF23 ligand, wherein the anti-FGF23 ligand is administered on a dosing regimen determined based on one or more PD parameters of the anti-FGF23 ligand in the subject.

11. The method of claim 10, wherein the anti-FGF23 ligand is an anti-FGF23 antibody.

12. The method of claim 10, wherein the subject has XLH.

13. The method of claim 10, wherein the anti-FGF23 ligand is an antibody and the dosing regimen comprises administering the anti-FGF23 antibody every two weeks.

14. The method of claim 10, wherein the dosing regimen of anti-FGF23 ligand provides a predetermined level of serum phosphorus over a dosing cycle.

15. A method of increasing bone remodeling comprising administering to a subject in need of such treatment an effective amount of an anti-FGF23 ligand, wherein the anti-FGF23 ligand causes an increase of a marker selected from the group consisting of Serum Type 1 Pro-collagen/N-terminal (P1NP) and carboxy-terminal collagen crosslink (CTX)

16. The method of claim 15, wherein the subject has XLH.

17. A method treating a condition related to FGF23 comprising administering to a subject in need of such treatment an effective amount of an anti-FGF23 ligand, wherein the anti-FGF23 ligand is administered every two weeks or every four weeks.

18. The method of claim 17, wherein the anti-FGF23 ligand is an anti-FGF23 antibody.

19. The method of claim 17, wherein the subject has XLH.

20. The method of claim 17, wherein the anti-FGF23 ligand is an antibody and the dosing regimen comprises administering the anti-FGF23 antibody every two weeks.