Targeted oligonucleotide conjugates

• US 6,660,720 B2
• Filed: 10/31/2002
• Issued: 12/09/2003
• Est. Priority Date: 06/16/1998
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Manoharan, Muthiah
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US10/284,834
• Publication Number:
  US 20030130220A1
• Time in Patent Office: 404 Days
• Field of Search: 514/1, 514/44, 435/6, 536/23.1
• US Class Current: 514/44.00A
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

The present invention provides improved ingress of therapeutic and other moieties into cellular targets. In accordance with preferred embodiments, complexes are provided which carry primary moieties, chiefly therapeutic moieties, to such target cells. Such complexes preferably feature cell surface receptor ligands to provide specificity. Such ligands are preferably bound to primary moieties through polyfunctional manifold compounds.

Claims

1. A complex having the structure:

wherein;

Q_a is a nucleoside, nucleotide, an oligonucleoside, an oligonucleotide or a pro-drug form of said nucleoside, nucleotide, oligonucleoside or oligonucleotide, or a peptide, protein, a molecule that can bind RNA, an antibiotic or an antibacterial compound; and

each R_a, R_b, and R_c independently, is a cell surface receptor ligand.

2. The complex of claim 1 wherein Q_a is a nucleoside, nucleotide, oligonucleoside or an oligonucleotide.

3. The complex of claim 2 wherein Q_a is an oligonucleotide.

4. The complex of claim 3 wherein said oligonucleotide is a modified oligonucleotide.

5. The complex of claim 4 wherein said modified oligonucleotide comprises one or more modified pyrimidine or purine base, substitution at a 2′

position, alteration of an inter-nucleoside linkage, carbohydrate ring substitutions or a positional variation.

6. The complex of claim 1 wherein each of said cell surface receptor ligands is the same.

7. The complex of claim 1 wherein each of said cell surface receptor ligands is a carbohydrate.

8. The complex of claim 7 wherein each of said carbohydrates is a monosaccharide or a polysaccharide.

9. The complex of claim 8 wherein each of said monosaccharide or polysaccharide is selected from the group consisting of galactose, lactose, N-acetylgalactosamine, mannose and mannose 6-phosphate.

10. The complex of claim 9 wherein each of said monosaccharide or polysaccharide is galactose or lactose.