Aptamers to β-NGF and their use in treating β-NGF mediated diseases and disorders

• US 8,598,140 B2
• Filed: 04/12/2011
• Issued: 12/03/2013
• Est. Priority Date: 04/12/2010
• Status: Active Grant

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited), SomaLogic Operating Co., Inc. (Somalogic Incorporated)
• Original Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited), Somalogic Incorporated
• Inventors: Schneider, Daniel J., Hisaminato, Akihiko, Waugh, Sheela, Resnicow, Daniel, Nagabukuro, Akira, Ono, Toshihide
• Primary Examiner(s): Vivlemore, Tracy
• Assistant Examiner(s): POLIAKOVA-GEORGA, EKATERINA
• Application Number:
  US13/634,618
• Publication Number:
  US 20130012693A1
• Time in Patent Office: 966 Days
• Field of Search: None
• US Class Current: 514/44.R
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• 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 2310/335 Modified T or U

Abstract

The present disclosure relates generally to the field of nucleic acids and, more particularly, to aptamers capable of binding to β-NGF; pharmaceutical compositions comprising such β-NGF aptamers; and methods of making and using the same.

Claims

1. An aptamer comprised of the sequence

2. The aptamer of claim 1, wherein the aptamer binds to β

-NGF.

3. The aptamer of claim 2, wherein the aptamer inhibits the function of β

-NGF.

4. The aptamer of claim 2, wherein said aptamer has the ability to modulate the binding of β

-NGF to its one or more of its cellular receptors.

5. The aptamer of claim 4 wherein said cellular receptor is selected from p75 or TrkA.

6. The aptamer of claim 2, wherein the aptamer comprises a K_d for β

-NGF of 30 nM or less.

7. The aptamer of claim 1, wherein said modified pyrimidine is a C-5 modified pyrimidine.

8. The aptamer of claim 7, wherein the C-5 modified pyrimidine is selected from the group consisting of the following compounds:

9. The aptamer of claim 7, wherein the C-5 modified pyrimidine is selected from the group consisting of 5-(N-benzylcarboxyamide)-2′

-deoxyuridine (BndU), 5-(N-isobutylcarboxyamide)-2′

-deoxyuridine (iBudU), 5-(N-tryptaminocarboxyamide)-2′

-deoxyuridine (TrpdU) and 5-(N-naphthylmethylcarboxyamide)-2′

-deoxyuridine (NapdU).

10. The aptamer of claim 7, wherein the C-5 modified pyrimidine is 5-(N-benzylcarboxyamide)-2′

-deoxyuridine (BndU).

11. The aptamer of claim 1, wherein said aptamer has the following sequence:

12. An aptamer comprised of the sequence

13. An aptamer that binds to β

-NGF comprising a sequence selected from the group consisting of SEQ. ID. NOS;

1, 2, 9-44 and 149.

14. The aptamer of claim 13, wherein the aptamer inhibits the function of β

-NGF.

15. The aptamer of claim 13, wherein said aptamer has the ability to modulate the binding of β

-NGF to its one or more of its cellular receptors.

16. The aptamer of claim 15, wherein said cellular receptor is selected from p75 or TrkA.

17. The aptamer of claim 16, wherein the sequence has at least about 90% identity, at least about 91% identity, at least about 92% identity, at least about 93% identity, at least about 94% identity, or at least about 95% identity.