Composition and method for the diagnosis and treatment of iron-related disorders

Patent metadata

Field	Value
Publication number	US-12098189-B2
Application number	US-202017034454-A
Country	US
Kind code	B2
Filing date	Sep 28, 2020
Priority date	Dec 14, 2011
Publication date	Sep 24, 2024
Grant date	Sep 24, 2024

Abstract

Provided herein are methods of using the antibodies that bind to RGMc to treat and diagnose iron-related disorders.

First claim

We claim:

1. A method comprising administering to a subject an anti-RGMc antibody that comprises a variable heavy chain region comprising a complementary determining region (CDR)1 with an amino acid sequence set forth in SEQ ID NO: 17, a CDR2 with an amino acid sequence set forth in SEQ ID NO: 18; a CDR3 with an amino acid sequence set forth in SEQ ID NO: 19; and a variable light chain region comprising a CDR1 with an amino acid sequence set forth in SEQ ID NO: 20, a CDR2 with an amino acid sequence set forth in SEQ ID NO: 21, and a CDR3 with an amino acid sequence set forth in SEQ ID NO: 22, wherein the subject has anemia of chronic disease (ACD) or anemia of chronic kidney disease.

2. The method of claim 1 , wherein the variable light chain region of the antibody comprises the amino acid sequence set forth in SEQ ID NO: 6.

3. The method of claim 2 , wherein the variable heavy chain region of the antibody comprises the amino acid sequence set forth in SEQ ID NO: 5 with up to one amino acid difference in a framework region.

4. The method of claim 3 , wherein the antibody comprises a heavy chain immunoglobulin constant domain, which is a human IgG 1 constant domain.

5. The method of claim 1 , wherein the administration results in inhibition of RGMc activity in the subject and wherein the inhibition of RGMc activity affects iron metabolism in the subject.

6. The method of claim 5 , wherein the inhibition of RGMc activity results in decreased hepcidin expression in the subject.

7. The method of claim 6 , wherein the subject has a serum hepcidin level higher than that of a normal control.

8. The method of claim 7 , wherein the subject has a serum hepcidin level higher than 300 mg/l prior to administration of the antibody.

9. The method of claim 1 , wherein the subject has a hemoglobin level of lower than 15.5 g/dl prior to administration of the antibody.

10. The method of claim 1 , wherein the subject has a transferrin saturation of less than 25% prior to administration of the antibody.

11. The method of claim 1 , wherein the subject has a total iron binding capacity of lower than 50% prior to administration of the antibody.

12. The method of claim 1 , wherein the subject has a serum iron level of less than 60 μg/dl prior to administration of the antibody.

13. The method of claim 3 , wherein the administration results in inhibition of RGMc activity in the subject and wherein the inhibition of RGMc activity affects iron metabolism in the subject.

14. The method of claim 13 , wherein the inhibition of RGMc activity results in decreased hepcidin expression in the subject.

15. The method of claim 14 , wherein the subject has a serum hepcidin level higher than that of a normal control.

16. The method of claim 15 , wherein the subject has a serum hepcidin level higher than 300 mg/l prior to administration of the antibody.

17. The method of claim 3 , wherein the subject has a hemoglobin level of lower than 15.5 g/dl prior to administration of the antibody.

18. The method of claim 3 , wherein the subject has a transferrin saturation of less than 25% prior to administration of the antibody.

19. The method of claim 3 , wherein the subject has a total iron binding capacity of lower than 50% prior to administration of the antibody.

20. The method of claim 3 , wherein the subject has a serum iron level of less than 60 μg/dl prior to administration of the antibody.

21. The method of claim 1 , wherein the subject has anemia of chronic disease (ACD).

22. The method of claim 1 , wherein the subject has anemia of chronic kidney disease.

23. The method of claim 3 , wherein the subject has anemia of chronic disease (ACD).

24. The method of claim 3 , wherein the subject has anemia of chronic kidney disease.

Assignees

• Abbvie Deutschland
• Abbvie Inc

Inventors

• Mueller Bernhard
• Popp Andreas
• Perez Jennifer M

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/28 Primary

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title