Oligonucleotide therapies for modulating the effects of herpesviruses

• US 5,658,891 A
• Filed: 10/26/1994
• Issued: 08/19/1997
• Est. Priority Date: 02/26/1990
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Ecker, David J., Crooke, Stanley T., Mirabelli, Christopher K., Draper, Kenneth G.
• Primary Examiner(s): RORIES, CHARLES
• Application Number:
  US08/329,212
• Time in Patent Office: 1,028 Days
• Field of Search: 514/44, 536/24.5, 435/172.3, 435/6, 435/240.2
• 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 31/12 Antivirals
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/1133 against herpetoviridae, e.g. HSV
• CPC Class Codes: C12N 2310/3125 Methylphosphonates
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2710/16622 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Compositions and methods are provided for the treatment and diagnosis of herpesvirus infections. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with RNA or DNA deriving from a gene corresponding to one of the open reading frames UL5, UL8, UL9, UL13, UL29, UL30, UL39, UL40, UL42 AND UL52 of herpes simplex virus type 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 translation initiation site; it is also preferred that they comprise the sequence CAT. Methods of treating animals suspected of being infected with herpesvirus comprising contacting the animal with an oligonucleotide specifically hybridizable with RNA or DNA deriving from one of the foregoing genes of the herpesvirus; are disclosed. Methods for treatment of infections caused by herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, human herpes virus 6, Epstein Barr virus or varicella zoster virus are disclosed.

Claims

1. A method of inhibiting replication of a herpes simplex virus comprising contacting cells of the eye of an animal infected with a herpes simplex virus topically or intralesionally with an antisense oligonucleotide having 10 to 50 nucleic acid subunits and phosphorothioate internucleotide linkages, and comprising having a sequence CAT, said oligonucleotide being complementary to a translation initiation portion of one of the open reading frames UL13, UL39 or UL40 of mRNA of herpes simplex virus type I and inhibitory of the normal function of the mRNA.

2. The method of claim 1 wherein the oligonucleotide is at least 21 nucleotides in length and comprises one of the sequences:

space="preserve" listing-type="tabular">______________________________________3'"'"'-GGA CTC ATC CAT CCT TCG GCC,GCG GCT GGC CAT TTC AAC AGA,CGC GGA ATC CAT GGC AGC AGG,ACC GAG GTC CAT GTC GTA CGC,GGA CTC ATC CAT CCG TCC GCC,GCC GAG GTC CAT GTC GTA CGC,GCG GTT GGC CAT TGG AAC CAA, ANDGGC GGG ATC CAT GGC GAT ATG.______________________________________