Inhibitors of human immunodeficiency virus

• US 5,523,389 A
• Filed: 09/28/1993
• Issued: 06/04/1996
• Est. Priority Date: 09/29/1992
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Imbach, Jean L., Ecker, David J., Wyatt, Jacqueline R.
• Primary Examiner(s): LeGuyader, John L.
• Application Number:
  US08/128,011
• Time in Patent Office: 980 Days
• Field of Search: 435/6, 435/91.1, 435/172.1, 536/23.1, 514/44
• US Class Current: 536/23.1
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• 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 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 15/1133 against herpetoviridae, e.g. HSV
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 15/117 Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• CPC Class Codes: C12N 2310/151 more than 3 strands, e.g. tetrads, H-DNA
• CPC Class Codes: C12N 2310/18 acting by a non-sequence specific mechanism other than C12N2310/16 or C12N2310/17
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• 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 2310/3521 Methyl
• CPC Class Codes: C12Q 1/701 Specific hybridization probes
• CPC Class Codes: C12Y 207/07049 : RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
• CPC Class Codes: C12Y 301/01004 : Phospholipase A2 (3.1.1.4)

Abstract

The phosphorothioate oligonucleotide T₂ G4T2 was identified as an inhibitor of HIV infection in vitro by combinatorial screening of a library of phosphorothioate oligonucleotides that contained all possible 8-nucleotide sequences. The oligonucleotide forms a parallel-stranded tetrameric guanosinequartet (G-quartet) structure. Tetramer formation and the phosphorothioate backbone are essential for antiviral activity. The G-quartet structure binds to the HIV envelope protein gp120 at the V3 loop and inhibits both cell-to-cell and virus-to-cell infection.

Claims

1. An oligonucleotide TTGGGGTT wherein at least one linkage is a phosphorothioate.