Regulated aptamer therapeutics

• US 20040110235A1
• Filed: 07/25/2003
• Published: 06/10/2004
• Est. Priority Date: 07/25/2002
• Status: Abandoned Application

• Current Assignee: Archemix Corp. (Baxter International Inc.)
• Original Assignee: Archemix Corp. (Baxter International Inc.)
• Inventors: Epstein, David, Wilson, Charles, Diener, John L.
• Application Number:
  US10/627,543
• Publication Number:
  US 20040110235A1
• Time in Patent Office: Days
• US Class Current: 435/7.2
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12N 15/1048 SELEX
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/16 Aptamers
• CPC Class Codes: C12N 2310/3519 Fusion with another nucleic acid
• CPC Class Codes: C12N 2320/50 Methods for regulating/modulating their activity
• CPC Class Codes: C12Q 1/6811 Selection methods for production or design of target specific oligonucleotides or binding molecules
• CPC Class Codes: C12Q 2541/101 Selex
• CPC Class Codes: C12Q 2563/131 the label being a member of a cognate binding pair, i.e. extends to antibodies, haptens, avidin
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

Materials and methods of use thereof are presented for the treatment of diabetes and other diseases. Therapeutic compositions including regulated aptamer therapeutic compositions with specificity to components of diabetes disease are presented with methods of administering these therapeutic compositions.

Claims

1. An aptamer comprising a first binding domain which recognizes a first ligand coupled to a second binding domain which recognizes a second ligand wherein binding of the second ligand by the second binding domain is regulated by binding of the first ligand by the first binding domain.

2. The aptamer of claim 1, wherein the first ligand binding domain specifically interacts with an allosteric effector molecule and the second ligand binding domain specifically interacts with a drug target of the allosteric effector molecule.

3. The aptamer of claim 2, wherein the allosteric effector molecule is glucose and the drug target is the insulin receptor.

4. The aptamer of claim 1, wherein binding of the second ligand by the second binding domain is activated by binding of the first ligand by the first binding domain.

5. The aptamer of claim 2, wherein binding of the second ligand by the second binding domain is activated by binding of the first ligand by the first binding domain.

6. The aptamer of claim 1, wherein binding of the second ligand by the second binding domain is suppressed by binding of the first ligand by the first binding domain.

7. The aptamer of claim 2, wherein binding of the second ligand by the second binding domain is suppressed by binding of the first ligand by the first binding domain.

8. A method of selecting regulated aptamers comprising the steps of isolating first and second aptamers which bind first and second ligands, respectively, using SELEX, engineering a diverse sequence pool of molecules that contain the binding domains of the first and second aptamers, and selecting for regulated aptamers from that pool wherein binding of the second ligand by the second binding domain is regulated by binding of the first ligand by the first binding domain.

9. A method of treating diabetes in a subject comprising the steps of administering a therapeutically effective amount of an insulin receptor aptamer, wherein said insulin receptor aptamer binds to a glucose effector and is activated by the glucose effector to bind to said insulin receptor, and triggering glucose uptake by cells.