# US 7,745,407 B2 · Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin

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- Number: US 7,745,407 B2
- Document ID: US7745407B2
- Status: Granted
- Kind: B2
- Application number: 12/397,589
- Filed: 2009-03-04
- Published: 2009-09-17
- Granted: 2010-06-29
- Earliest claimed: 2005-06-29
- Assignees: The Regents of the University of California; Xenon Pharmaceuticals Inc.
- Inventors: Tomas Ganz; Lan Lin; Yigal P. Goldberg
- Web page: https://patentgrep.com/patent/US7745407B2

## CPC

- A61K 38/1709: {from mammals}
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/02: Nutrients, e.g. vitamins, minerals
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are hemojuvelin-specific siRNAs that vary hemojuvelin mRNA concentration. Also disclosed herein, GPI-hemojuvelin positively regulated hepcidin mRNA expression, independently of the IL-6 pathway, whereas soluble hemojuvelin (s-hemojuvelin) suppressed hepcidin mRNA expression in primary human hepatocytes in a log-linear dosedependent manner. Disclosed are compositions and methods for modulating diseases of iron metabolism and hepcidin expression or hepcidin levels.

## Claims

### Claim 1

A method of decreasing hepcidin production or suppressing hepcidin mRNA levels in a mammalian subject which comprises administering to the mammalian subject at least one soluble mammalian hemojuvelin protein.

### Claim 2 (depends on 1)

The method of claim 1, and further comprising assaying the amount of the membrane-associated GPI-linked hemojuvelin, the amount of the soluble mammalian hemojuvelin protein, or both in the mammalian subject and determining whether the amount is normal or abnormal.

### Claim 3 (depends on 1)

The method of claim 1, and further comprising assaying the amount of hepcidin production, hepcidin mRNA levels, or both in the mammalian subject and determining whether the amount is normal or abnormal.

### Claim 4 (depends on 1)

The method of claim 1, wherein the soluble mammalian hemojuvelin protein lacks its glycophosphatidylinositol anchor.

### Claim 5 (depends on 1)

The method of claim 1, wherein the soluble mammalian hemojuvelin protein comprises at least 335 consecutive amino acid residues of SEQ ID NO:1.

### Claim 6 (depends on 1)

The method of claim 1, wherein the soluble mammalian hemojuvelin protein consists of SEQ ID NO:1.

### Claim 7 (depends on 1)

The method of claim 1, wherein the soluble mammalian hemojuvelin protein is administered in the form of a pharmaceutical composition.
