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

Patent metadata

Field	Value
Publication number	US-10118958-B2
Application number	US-201213714238-A
Country	US
Kind code	B2
Filing date	Dec 13, 2012
Priority date	Dec 14, 2011
Publication date	Nov 6, 2018
Grant date	Nov 6, 2018

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. An isolated anti-human Repulsive Guidance Molecule c (“RGMc”) antibody comprising (a) a variable heavy chain region comprising a complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:11, a CDR2 comprising the amino acid sequence of SEQ ID NO:12, and a CDR3 comprising the amino acid sequence of SEQ ID NO:13 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:14, a CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a CDR3 comprising the amino acid sequence of SEQ ID NO:16, (b) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:17, a CDR2 comprising the amino acid sequence of SEQ ID NO:18, and a CDR3 comprising the amino acid sequence of SEQ ID NO:19 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:20, a CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a CDR3 comprising the amino acid sequence of SEQ ID NO:22, (c) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:23, a CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a CDR3 comprising the amino acid sequence of SEQ ID NO:25 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:26, a CDR2 comprising the amino acid sequence of SEQ ID NO:27, and a CDR3 comprising the amino acid sequence of SEQ ID NO:28, or (d) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:29, a CDR2 comprising the amino acid sequence of SEQ ID NO:30, and a CDR3 comprising the amino acid sequence of SEQ ID NO:31 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:32, a CDR2 comprising the amino acid sequence of SEQ ID NO:33, and a CDR3 comprising the amino acid sequence of SEQ ID NO:34.

2. The isolated anti-human RGMc antibody of claim 1 , wherein the anti-human RGMc antibody is selected from the group consisting of an affinity matured antibody, a monoclonal antibody, and a humanized antibody.

3. The isolated anti-human RGMc antibody of claim 1 , wherein the antibody further comprises an agent selected from the group consisting of an immunoadhesion molecule, an imaging agent, and a therapeutic agent, wherein the imaging agent is selected from the group consisting of a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and biotin, and wherein the radiolabel is selected from the group consisting of 3H, 14C, 35S, 90Y, 99Tc, 111In, 125I, 131I, 177Lu, 166Ho, and 153Sm.

4. An isolated nucleic acid encoding the anti-human RGMc antibody of claim 1 .

5. A pharmaceutical composition comprising the anti-human RGMc antibody of claim 1 and a pharmaceutically acceptable carrier.

6. A method of treating Anemia of Chronic Disease (ACD), iron-refractory iron-deficiency anemia or anemia of chronic kidney disease, comprising administering to a subject in need thereof a therapeutically effective amount of the anti-human RGMc antibody of claim 1 .

7. The method of claim 6 , wherein the anti-human RGMc antibody is selected from the group consisting of a monoclonal antibody, an affinity matured antibody, and a humanized antibody.

8. A kit for assaying a test sample for human Repulsive Guidance Molecule c (“RGMc”), which kit comprises at least one component for assaying the test sample for RGMc and instructions for assaying the test sample for RGMc, wherein the at least one component includes at least one composition comprising an isolated anti-human RGMc antibody comprising (a) a variable heavy chain region comprising a complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:11, a CDR2 comprising the amino acid sequence of SEQ ID NO:12, and a CDR3 comprising the amino acid sequence of SEQ ID NO:13 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:14, a CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a CDR3 comprising the amino acid sequence of SEQ ID NO:16, (b) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:17, a CDR2 comprising the amino acid sequence of SEQ ID NO:18, and a CDR3 comprising the amino acid sequence of SEQ ID NO:19 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:20, a CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a CDR3 comprising the amino acid sequence of SEQ ID NO:22, (c) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:23, a CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a CDR3 comprising the amino acid sequence of SEQ NO:25 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:26, a CDR2 comprising the amino acid sequence of SEQ ID NO:27, and a CDR3 comprising the amino acid sequence of SEQ ID NO:28, or (d) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:29, a CDR2 comprising the amino acid sequence of SEQ ID NO:30, and a CDR3 comprising the amino acid sequence of SEQ ID NO:31 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:32, a CDR2 comprising the amino acid sequence of SEQ ID NO:33, and a CDR3 comprising the amino acid sequence of SEQ ID NO:34, wherein the anti-human RGMc antibody is optionally detectably labeled.

9. The kit of claim 8 , wherein the human RGMc is membrane-associated RGMc or soluble RGMc.

10. The kit of claim 8 , wherein the kit further comprises at least one component for assaying a test sample for hepcidin and instructions for assaying the test sample for hepcidin.

11. A kit for assaying a test sample for human Repulsive Guidance Molecule c (“RGMc”), which kit comprises at least one component for assaying the test sample for RGMc and instructions for assaying the test sample for RGMc, wherein the at least one component includes at least one composition comprising an isolated anti-human RGMc antibody comprising (a) a variable heavy chain region comprising a complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:95, a CDR2 comprising the amino acid sequence of SEQ ID NO:96, and a CDR3 comprising the amino acid sequence of SEQ ID NO:97 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:98, a CDR2 comprising the amino acid sequence of SEQ ID NO:99, and a CDR3 comprising the amino acid sequence of SEQ ID NO:100, (b) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:119, a CDR2 comprising the amino acid sequence of SEQ ID NO:120, and a CDR3 comprising the amino acid sequence of SEQ ID NO:121 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:122, a CDR2 comprising the amino acid sequence of SEQ ID NO:123, and a CDR3 comprising the amino acid sequence of SEQ ID NO:124, (c) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:125, a CDR2 comprising the amino acid sequence of SEQ ID NO:126, and a CDR3 comprising the amino acid sequence of SEQ ID NO:127 and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:128, a CDR2 comprising the amino acid sequence of SEQ ID NO:129, and a CDR3 comprising the amino acid sequence of SEQ ID NO:130, (d) a variable heavy chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:137, a CDR2 comprising the amino acid seque

Assignees

• Abbvie Deutschland
• Abbvie Inc

Inventors

• Mueller Bernhard
• Popp Andreas
• Perez Jennifer M

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P7/06

  Antianaemics · CPC title

• C07K16/28 Primary

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

• C07K2317/24

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

• C07K2317/565

  Complementarity determining region [CDR] · CPC title