# US 2010/0168010 A1 · Compositions and methods of modulating cell growth and motility

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- Number: US 2010/0168010 A1
- Document ID: US20100168010A1
- Status: Published application
- Kind: A1
- Application number: 12/516,000
- Filed: 2007-11-21
- Published: 2010-07-01
- Earliest claimed: 2006-11-22
- Inventors: Alfred Malouf; Scott W. Young
- Web page: https://patentgrep.com/patent/US20100168010A1

## CPC

- C07K 14/4702: {Regulators; Modulating activity}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)

## Abstract

A method of modulating cell growth and motility in subject includes administering to a cell expressing GTPase an amount of an ARHGAP4 regulating agent effective to regulate the growth and motility of the cell.

## Claims

### Claim 1

A method of modulating cell growth and motility in a subject, the method including:
administering to a cell expressing a GTPase an amount of an ARHGAP4 regulating agent effective to regulate the growth and motility of the cell.

### Claim 2 (depends on 1)

The method of claim 1, the cell expressing a GTPase comprising a nerve cell.

### Claim 3 (depends on 2)

The method of claim 2, the nerve cell being located at a central nervous system or peripheral nervous system injury site.

### Claim 4 (depends on 3)

The method of claim 3, the central nervous system injury comprising a spinal cord injury and the ARHGAP4 being administered directly to nerve cell at site of injury.

### Claim 5 (depends on 1)

The method of claim 1, the ARHGAP4 regulating agent comprising a polypeptide or nucleic that inhibits the bioactivity or expression of ARHGAP4 in a cell.

### Claim 6 (depends on 5)

The method of claim 5, the ARHGAP4 regulating agent comprising a competitive inhibitor of ARHGAP4.

### Claim 7 (depends on 6)

The method of claim 6, the competitive inhibitor of ARHGAP4 including a GAP loss of function mutation.

### Claim 8 (depends on 7)

The method of claim 7, the competitive inhibitor of claim 7 including the amino acid sequence of SEQ ID NO: 1.

### Claim 9 (depends on 1)

The method of claim 1, the ARHGAP4 regulating agent comprising ARHGAP4, an ARHGAP4 mimetic, or a vector, which can be used to express ARHGAP4 in a nerve cell.

### Claim at position 10

10-13. (canceled)

### Claim 14

A method of promoting axonal growth in a nerve cell comprising;
administering to the nerve cell an ARHGAP4 regulating agent such that axonal growth occurs, wherein said agent regulates the expression or bioactivity of ARHGAP4 in the cell.

### Claim 15 (depends on 14)

The method of claim 14, wherein regulation of the expression or bioactivity of ARHGAP4 in the cell comprises decreasing expression or bioactivity of ARHGAP4 in the cell.

### Claim 16 (depends on 15)

The method of claim 15, the ARHGAP4 regulating agent comprising a competitive inhibitor of ARHGAP4.

### Claim 17 (depends on 16)

The method of claim 16, the competitive inhibitor including a GAP loss of function mutation.

### Claim 18 (depends on 17)

The method of claim 17, the competitive inhibitor having an amino acid sequence of SEQ ID NO:1.

### Claim 19 (depends on 14)

The method of claim 14 further comprising administering to the cell an additional agent that reduces inhibition of axon outgrowth.

### Claim 20 (depends on 14)

The method of claim 14, the ARHGAP4 regulating agent comprising an interfering RNA that inhibits expression of ARGAP 4 in the cell.

### Claim at position 18

21-26. (canceled)

### Claim 27

A method of regulating cell motility, comprising:
administering to the cell a therapeutically effective amount of an ARHGAP4 regulating agent, wherein said agent regulates the bioactivity or expression of ARHGAP4 in the cell.

### Claim 28 (depends on 27)

The method of claim 27, wherein the ARHGAP4 regulating agent decreases cell motility.

### Claim 29 (depends on 28)

The method of claim 28, the cell comprising a metastatic neoplastic cell and the ARHGAP4 regulating agent decreasing neoplastic cell motility.

### Claim 30 (depends on 27)

The method of claim 27, wherein the cell is a fibroblast cell and the ARHGAP4 regulating agent increases cell motility of the fibroblast cell.

### Claim 31 (depends on 30)

The method of claim 30, the ARHGAP4 being administered to a fibroblast cell at the site of a wound to promote fibroblast motility at the wound.
