Method of down-regulating gene expression

• US 5,591,721 A
• Filed: 10/25/1994
• Issued: 01/07/1997
• Est. Priority Date: 10/25/1994
• Status: Expired due to Term

• Current Assignee: Idera Pharmaceuticals, Inc. (Aceragen Incorporated)
• Original Assignee: Hybridon, Inc. (Aceragen Incorporated)
• Inventors: Agrawal, Sudhir, Zhang, Ruiwen, Diasio, Robert B.
• Primary Examiner(s): RORIES, CHARLES
• Application Number:
  US08/328,520
• Time in Patent Office: 805 Days
• Field of Search: 514/44, 536/24.5, 424/78.15, 424/78.38, 424/601, 424/713
• US Class Current: 514/44.00A
• CPC Class Codes: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Disclosed is a method of down-regulating the expression of a gene in an animal, wherein a pharmalogical formulation comprising an oligonucleotide complementary to the gene is orally administered to an animal. The oligonucleotide administered has non-phosphodiester internucleotide linkages and includes at least one 2'"'"'-substituted ribonucleotide, the oligonucleotide inhibiting the expression of a product of the gene, thereby down-regulating the expression of the gene.

Claims

1. A method for introducing an intact oligonucleotide into a mammal, the method comprising the step of orally administering an oligonucleotide of about 15 to 25 nucleotides, the oligonucleotide comprising phosphorothioate internucleoside linkages between every nucleoside, and further comprising at least two 2'"'"'-O-methyl-ribonucleotides at each end, whereby the oligonucleotide is present in intact form in the systemic plasma and in liver tissue of the mammal at least six hours following oral administration.