Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2

• US 5,789,573 A
• Filed: 05/24/1996
• Issued: 08/04/1998
• Est. Priority Date: 08/14/1990
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Bennett, C. Frank, Anderson, Kevin P., Baker, Brenda
• Primary Examiner(s): LeGuyader, John L.
• Assistant Examiner(s): WANG, ANDREW J
• Application Number:
  US08/653,653
• Time in Patent Office: 802 Days
• Field of Search: 514/44, 536/23.1, 536/24.5, 536/25.3, 435/6, 435/91.1, 435/325
• US Class Current: 536/24.5
• CPC Class Codes: A61K 31/711 Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
• 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: 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 31/22 for herpes viruses
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• 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 15/113 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 15/1133 against herpetoviridae, e.g. HSV
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/318 where the PO2 is completely replaced, e.g. MMI or formacetal
• CPC Class Codes: C12N 2310/3181 Peptide nucleic acid, PNA
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 : 2'-R Modification
• CPC Class Codes: C12N 2310/346 : having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/352 : linked to the nucleic acid via a carbon atom
• CPC Class Codes: C12N 2310/3521 : Methyl
• CPC Class Codes: C12N 2310/3525 : MOE, methoxyethoxy
• CPC Class Codes: C12N 2310/3527 : Other alkyl chain
• CPC Class Codes: C12N 2310/3531 : Hydrogen
• CPC Class Codes: C12N 2310/3533 : Halogen
• CPC Class Codes: C12N 2710/16122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 9/1252 : DNA-directed DNA polymerase (2.7.7.7), i.e. DNA replicase
• CPC Class Codes: C12Q 1/705 : for herpetoviridae, e.g. herpes simplex, varicella zoster

Abstract

Compositions and methods are provided for inhibiting the translation of a capped target mRNA. Antisense oligomers of the invention are targeted to the 5'"'"' cap region of the target mRNA and include oligonucleosides, PNAs, or oligonucleotides modified at the 2'"'"' position of the sugar. Preferably said oligomers inhibit protein translation directly via interference with ribosome assembly.

Claims

1. A composition for inhibiting the translation of a capped target mRNA encoding ICAM-1, E-selectin or CMV IE1/IE2 comprising an oligomer which is 8-25 bases in length and is selected from the group consisting of:

an oligonucleotide comprising a modified 2'"'"'-position;

an oligonucleoside;

or a peptide-nucleic acid oligomer;

said oligomer being specifically hybridizable with a 5'"'"' cap region of a capped target mRNA which includes at least one of the first 20 nucleotides at the 5'"'"' terminus of said target mRNA, and being capable of interfering with ribosome assembly on the mRNA wherein said target mRNA encodes ICAM-1, E-selectin or CMV IE1/IE2.

2. The composition of claim 1 wherein said oligonucleoside comprises at least one morpholino, amide-3, amide-4 or methylene(methylimino) internucleoside linkage.

3. The composition of claim 1 wherein the oligomer has a 2'"'"'-OCH₂ CH₂ OCH₃ modification on each 3'"'"'-deoxy sugar moiety.

4. A composition for inhibiting the translation of a capped target mRNA encoding ICAM-1, E-selectin or CMV IE1/IE2 comprising an oligonucleotide having SEQ ID NO:

1 or 2, SEQ ID NO;

3, or SEQ ID NO;

5, 6, 7 or 8, respectively, wherein said oligonucleotide has a 2'"'"'-OCH₂ CH₂ OCH₃ modification on each 3'"'"'-deoxy sugar moiety.