Inhibition of proliferation of cells

• US 6,200,960 B1
• Filed: 04/13/1999
• Issued: 03/13/2001
• Est. Priority Date: 03/07/1996
• Status: Expired due to Fees

• Current Assignee: Unisearch Limited (University Of New South Wales)
• Original Assignee: Unisearch Limited (University Of New South Wales)
• Inventors: Khachigian, Levon Michael
• Primary Examiner(s): Schwartzman, Robert A.
• Assistant Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US09/142,779
• Time in Patent Office: 700 Days
• Field of Search: 435/91.1, 435/6, 435/91.31, 435/440, 435/375, 435/325, 536/23.1, 536/23.2, 536/24.5, 536/24.3, 514/44
• US Class Current: 514/44.00A
• CPC Class Codes: 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
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/121 Hammerhead
• CPC Class Codes: C12N 2310/13 Decoys
• CPC Class Codes: C12N 2310/15 Nucleic acids forming more than 2 strands, e.g. TFOs
• CPC Class Codes: C12N 2310/322 2'-R Modification

Abstract

The present invention provides a method of inhibiting the proliferation of cells. The method comprises inhibiting induction or decreasing expression of Egr-1 or decreasing the nuclear accumulation or activity of the Egr-1 gene product. The present invention also provides a method of reducing the incidence of restenosis in a subject. The method comprises administering to the subject an agent which inhibits induction or decreases expression of Egr-1 or decreases the nuclear accumulation or activity of the Egr-1 gene product.

Claims

1. A method of inhibiting proliferation of cells selected from the group consisting of vascular cells, smooth muscle cells, endothelial cells and neoplasia cells, which method comprises administering locally to the cells an Egr-1 antisense oligonucleotide—

in an amount sufficient to inhibit the proliferation of cells.

2. A method according to claim 1 in which the cells are smooth muscle cells.

3. A method according to claim 1 in which the oligonucleotide decreases expression of Egr-1.

4. A method according to claim 1 in which the antisense oligonucleotide is selected from the group consisting of antisense oligonucleotides having the sequence ACA CTT TTG TCT GCT (SEQ ID NO:

1) and CTT GGC CGC TGC CAT SEQ ID NO;

4).

5. An oligonucleotide for decreasing expression of Egr-1, the oligonucleotide consisting of the sequence ACA CTT TTG TCT GCT (SEQ ID NO:

1).

6. A method of reducing the incidence of restenosis in a subject comprising administering locally to the subject an Egr-1 antisense oligonucleotide.

7. A method according to claim 6 in which the oligonucleotide decreases expression of Egr-1.

8. A method according to claim 6 in which the antisense oligonucleotide has the sequence ACA CTT TTG TCT GCT (SEQ ID NO:

1) or CTT GGC CGC TGC CAT (SEQ ID NO;

4).