Oligonucleotide inhibition of cell adhesion

• US 6,300,491 B1
• Filed: 01/20/1998
• Issued: 10/09/2001
• Est. Priority Date: 08/14/1990
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Bennett, C. Frank, Mirabelli, Christopher K.
• Primary Examiner(s): McGarry, Sean
• Assistant Examiner(s): Lacourciere, Karen A.
• Application Number:
  US09/009,490
• Time in Patent Office: 1,358 Days
• Field of Search: 514/44, 536/23.1, 536/23.2, 536/24.5, 536/24.3, 536/24.31, 536/24.33
• US Class Current: 536/24.5
• 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: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/70525 ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C07K 14/70542 CD106
• CPC Class Codes: C07K 14/70564 Selectins, e.g. CD62
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/352 linked to the nucleic acid via a carbon atom
• CPC Class Codes: C12N 2310/3533 Halogen

Abstract

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of the synthesis or metabolism of intercellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5′-untranslated sequences, 3′-untranslated sequences, and intervening sequences. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating cell adhesion proteins with an oligonucleotide specifically hybridizable with RNA or DNA corresponding to one of the foregoing proteins are disclosed. Methods for treatment of diseases responding to modulation cell adhesion molecules are disclosed.

Claims

1. An antisense oligonucleotide having from about 12 to about 22 nucleotide subunits comprising a sequence specifically hybridizable via Watson-Crick base-pairing with a sequence which is contained within SEQ ID NO:

92, which represents bases 92 to 122 of the nucleic acid encoding human vascular cell adhesion molecule-1 (SEQ ID NO;

90), wherein said antisense oligonucleotide inhibits the production of said vascular cell adhesion molecule-1.

2. The antisense oligonucleotide of claim 1, said antisense oligonucleotide comprising the sequence

3. The antisense oligonucleotide of claim 1 wherein said antisense oligonucleotide is a phosphorothioate oligonucleotide.

4. An antisense oligonucleotide having from about 12 to about 22 nucleotide subunits comprising a sequence specifically hybridizable via Watson-Crick base-pairing with a sequence which is contained within SEQ ID NO:

0.94, which represents bases 1 to 49 of the nucleic acid encoding human vascular cell adhesion molecule-1 (SEQ ID NO;

90), wherein said antisense oligonucleotide inhibits the production of said vascular cell adhesion molecule-1.

5. The antisense oligonucleotide of claim 4, said antisense oligonucleotide comprising the sequence

6. The oligonucleotide of claim 4 wherein said oligonucleotide is a phosphorothioate oligonucleotide.