Oligonucleotide modulation of cell adhesion

• US 6,849,612 B2
• Filed: 10/18/2001
• Issued: 02/01/2005
• Est. Priority Date: 01/21/1993
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Mirabelli, Christopher, Bennett, C. Frank
• Primary Examiner(s): Shukla, Ram R.
• Assistant Examiner(s): ZARA, JANE J
• Application Number:
  US09/982,262
• Publication Number:
  US 20030077565A1
• Time in Patent Office: 1,202 Days
• Field of Search: 435/6, 435/91.1, 435/91.31, 435/455, 435/458, 514/44, 536/23.1, 536/24.5
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• 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: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy

Abstract

Compositions and methods for the treatment of ophthalmic disorders, particularly preservation of corneal explants and prevention of corneal allograft rejection. These compositions comprise oligonucleotides which are specifically hybridizable with nucleic acids encoding the cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1).

Claims

1. A method for preserving a corneal explant ex vivo, comprising incubating a corneal explant in a solution comprising a corneal storage medium and an antisense oligonucleotide between 8 and 50 nucleotides in length that is targeted to intercellular adhesion molecule-1 (ICAM-1), and wherein said antisense oligonucleotide inhibits the expression of intercellular adhesion molecule-1 (ICAM-1), and wherein inhibition of ICAM-1 expression results in preserving a corneal, explant ex vivo.

2. The method of claim 1, wherein said antisense oligonucleotide is SEQ ID NO:

22.

3. The method of claim 1, wherein said explant is a human explant.

4. A method of inhibiting corneal allograft rejection, comprising contacting a corneal allograft with a topical formulation comprising an antisense oligonucleotide between 8 and 50 nucleotides in length that is targeted to intercellular adhesion molecule-1 (ICAM-1), and wherein said antisense oligonucleotide inhibits the expression of intercellular adhesion molecule-1 (ICAM-1), and wherein inhibition of ICAM-1 expression results in corneal allograft rejection inhibition.

5. The method of claim 4, wherein said antisense oligonucleotide is SEQ ID NO:

22.

6. The method of claim 4, wherein the allograft is a human allograft.

7. The method of claim 4, wherein the topical formulation is a solution.

8. A method for preserving a corneal explant ex vivo, comprising incubating a corneal, explant in a solution comprising a corneal storage medium and an antisense oligonucleotide between 8 and 50 nucleotides in length that is targeted to extracellular adhesion molecule-1 (ELAM-1) or vascular cell adhesion molecule-1 (VCAM-1), and wherein said antisense oligonucleotide inhibits the expression of extracellular adhesion molecule-1 (ELAM-1) or vascular cell adhesion molecule-1 (VCAM-1), and wherein inhibition of ELAM-1 and VCAM-1 expression results in preserving a corneal explant ex vivo.

9. The method of claim 8, wherein the explant is a human explant.