USE OF ANTI-SCLEROSTIN ANTIBODIES IN THE TREATMENT OF OSTEOGENESIS IMPERFECTA

• US 20190330322A1
• Filed: 12/21/2017
• Published: 10/31/2019
• Est. Priority Date: 12/21/2016
• Status: Active Grant

• Current Assignee: Mereo Biopharma 3 Limited (Mereo BioPharma Group Plc)
• Original Assignee: Mereo Biopharma 3 Limited (Mereo BioPharma Group Plc)
• Inventors: JUNKER, Uwe, KNEISSEL, Michaela, HALL, Anthony Kent, EUDY, Rena Joy, RIGGS, Matthew Manning
• Granted Patent: US 10,961,305 B2
• Time in Patent Office: Days
• 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 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• 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 2317/56 variable (Fv) region, i.e. VH and/or VL
• 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

Abstract

Disclosed are methods for treating a patient suffering from osteogenesis imperfecta comprising administering to the patient a therapeutically effective amount of an anti-sclerostin antibody. Methods for increasing bone formation and reducing bone resorption in an osteogenesis imperfecta patient by administering to the patient a therapeutically effective amount of an anti-sclerostin antibody are also disclosed. Further disclosed are compositions for increasing bone formation and reducing bone resorption in an osteogenesis imperfecta patient. The compositions comprise a therapeutically effective amount of an anti-sclerostin antibody. The invention also provides an anti-sclerostin antibody for use in the treatment of osteogenesis imperfecta.

Claims

1. A method for treating osteogenesis imperfecta (OI) in a human patient comprising administering to the human patient a therapeutically effective amount of an anti-sclerostin antibody, wherein the anti-sclerostin antibody comprises:

(a) a heavy chain variable region CDR1 comprising an amino acid sequence set forth in SEQ ID NO;

4;

(b) a heavy chain variable region CDR2 comprising an amino acid sequence set forth in SEQ ID NO;

15;

(c) a heavy chain variable region CDR3 comprising an amino acid sequence set forth in SEQ ID NO;

26;

(d) a light chain variable region CDR1 comprising an amino acid sequence set forth in SEQ ID NO;

37;

(e) a light chain variable region CDR2 comprising an amino acid sequence set forth in SEQ ID NO;

48; and

(f) a light chain variable region CDR3 comprising an amino acid sequence set forth in SEQ ID NO;

59;

and wherein the anti-sclerostin antibody is administered intravenously at a dose of 1-50 mg per kg body weight of the human patient.

2. The method according to claim 1, wherein the OI is type I OI, type III OI or type IV OI.

3. The method according to claim 1 or claim 2, wherein the human patient has one or more mutations in the COL1A1 and/or COL1A2 genes.

4. The method according to any one of claims 1-3, wherein the anti-sclerostin antibody comprises:

a) a VH polypeptide sequence having at least 90 percent sequence identity to the amino acid sequences set forth as SEQ ID NO;

70; and

/or

b) a VL polypeptide sequence having at least 90 percent sequence identity to the amino acid sequences set forth as SEQ ID NO;

81.

5. The method according to claims 1-4, wherein the anti-sclerostin antibody comprises a VL polypeptide sequence comprising the amino acid sequence set forth as SEQ ID NO:

81 and a VH polypeptide sequence comprising the amino acid sequence set forth as SEQ ID NO;

70.

6. The method according to any one of claims 1-5, wherein the anti-sclerostin antibody comprises:

a) a full length heavy chain amino acid sequence having at least 90 percent sequence identity to the amino acid sequence set forth as SEQ ID NO;

172; and

/or

b) a full length light chain amino acid sequence having at least 90 percent sequence identity to the amino acid sequence set forth as SEQ ID NO;

173.

7. The method according to any one of claims 1-6, wherein the anti-sclerostin antibody comprises a full length light chain amino acid sequence comprising the amino acid sequence set forth as SEQ ID NO:

173 and a full length heavy chain amino acid sequence comprising the amino acid sequence set forth as SEQ ID NO;

172.

8. The method according to any preceding claim, wherein the anti-sclerostin antibody is administered at a dose of 10-30 mg per kg body weight of the human patient.

9. The method according to any preceding claim, wherein the anti-sclerostin antibody is administered to the human patient on a daily, weekly, bi-weekly, monthly, bi-monthly or quarterly basis.

10. The method according to any preceding claim, wherein the anti-sclerostin antibody is administered to the human patient on a monthly basis.

11. The method according to any preceding claim, wherein the anti-sclerostin antibody is administered to the human patient on a bi-monthly or quarterly basis.

12. The method according to any preceding claim, wherein the treatment regimen comprises a first dosing regimen optionally followed by a second dosing regimen.

13. The method according to claim 12 wherein the first dosing regimen is 1-50 mg per kg body weight of a patient administered on a monthly basis.

14. The method according to claim 12, wherein the first dosing regimen is 20 mg per kg body weight of a patient administered on a monthly basis.

15. The method according to any one of claims 12-14, wherein the second dosing regimen is 1-50 mg per kg body weight of a patient administered on a bi-monthly or quarterly basis.

16. The method according to any one of claims 12-15, wherein the second dosing regimen is 20 mg per kg body weight of a patient administered on a bi-monthly or quarterly basis.

17. The method according to any one of claims 12-16, wherein the first dosing regimen is 20 mg per kg body weight of a patient administered on a monthly basis and the second dosing regimen is 20 mg per kg body weight of a patient administered on a bi-monthly or quarterly basis.

18. The method according to claim 17, wherein the first dosing regimen is 20 mg per kg body weight of a patient administered on a monthly basis for a period of 1 year, and the second dosing regimen is 20 mg per kg body weight of a patient administered on a bi-monthly or quarterly basis for a period of at least 1 year.

19. The method according to any preceding claim, comprising administering a further therapeutic agent, such as bisphosphonate, parathyroid hormone, calcilytics, calcimimetics (e.g., cinacalcet), statins, anabolic steroids, lanthanum and strontium salts, and/or sodium fluoride.

20. A lyophilizate comprising an anti-sclerostin antibody as defined in any one of claims 1-7.

21. The lyophilizate according to claim 20, further comprising sucrose, arginine hydrochloride, L-histidine, polysorbate 80, and hydrochloric acid.

22. A kit comprising an anti-sclerostin antibody as defined in any one of claims 1-7, or a lyophilizate according to claim 20 or claim 21

23. The kit according to claim 22 comprising a further therapeutic agent, such as a combination therapy agent e.g bisphosphonate, parathyroid hormone, calcilytics, calcimimetics (e.g., cinacalcet), statins, anabolic steroids, lanthanum and strontium salts, and/or sodium fluoride.

24. The anti-sclerostin antibody as defined in any one of claims 1-7, the lyophilizate according to claim 20 or claim 21, or the kit according to claim 22 or claim 23, for use in a method according to any one of claims 1-19.

25. The method, anti-sclerostin antibody, lyophilizate, kit, and/or use substantially as described herein with reference to the drawings.