Phosphorothioate oligonucleotides that bind to the V3-loop and u

Details Phosphorothioate oligonucleotides that bind to the V3-loop and u Phosphorothioate oligonucleotides that bind to the V3-loop and u

1996-06-05

1998-05-26

Guzo, David

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 231, C07H 7104

Patent

active

057567107

ABSTRACT:
The present invention provides phosphorothioate oligonucleotide moieties comprising a phosphorothioate oligonucleotide comprising the sequence G.sub.m X.sub.n G.sub.p, wherein G is guanosine; X is thymidine, adenosine or cytidine, or a combination thereof; each of m, n and p is independently an integer greater than 2; the phosphorothioate oligonucleotide moiety being capable of binding to a V3 loop of HIV envelope glycoprotein. The invention further provides for a method of inhibiting HIV activity. The invention also provides for a method of inhibiting HIV activity in a subject. The invention further provides for a method of treating an HIV related disorder in a subject. Finally, the invention provides a pharmaceutical composition comprising a phosphorothioate oligonucleotide moiety and a pharmaceutically acceptable carrier.

REFERENCES:
Stull et al., Antigene, ribozyme, and aptamer nucleic acid drugs: progress and prospects, Pharm. Res., vol. 12(4), pp. 465-483., 1995.
Baum, R.M., "Combinatorial Approaches Provide Fresh Leads for Medicinal Chemistry." C & EN (1994) 20-26 (Exhibit B).
Buckheit, R.W., et al. Potent and Specific Inhibition of HIV Envelope-Mediated Cell Fusion and Virus Binding by G Quartet-Forming Oligonucleotide (ISIS 5320). Aids Research and Human Retroviruses (1994) 10(11): 1497-1506 (Exhibit C).
Feng, Y., HIV-1 Entry Cofactor:Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor. Science (1996) 272: 872-877 (Exhibit D).
Ojwang, J.O., et al. T30177, an Oligonucleotide Stabilized by an Intramolecular Guanosine Octet, Is a Potent Inhibitor of Laboratory Strains and Clinical Isolates of Human Immunodeficiency Virus Type 1. Antimicrobial Agents And Chemotherapy (1995) 39:(11) 2426-2435 (Exhibit E).
Ojwang, J.O., et al. Inhibition of Human Immunodeficiency Virus Type 1 Activity In Vitro by Oligonucleotides Composed Entirely of Guanosine and Thymidine. Journal of Acquired Immune Deficiency Syndromes (1994) 7: 560-570 (Exhibit F).
Rusche, J.R., et al. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc. Natl. Acad. Sci. U.S.A. 85: 3198-3202 (1988) (Exhibit G).
Skinner, M.A., et al. Characteristics of a Neutralizing Monoclonal Antibody to the HIV Envelope Glycoprotein. Aids Research and Human Retroviruses 4(3): 187-197 (1988) (Exhibit H).
Stein, C.A., et al. Phosphorothioate Oligodeoxynucleotides Bind to the Third Variable Loop Domain (v3) of Human Immunodeficiency Virus Type 1 gp120. Antisense Research And Development 3: 19-31 (1993) (Exhibit I).

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