Aptamers and diagnostic methods for detecting the EGF receptor

Patent metadata

Field	Value
Publication number	US-9316647-B2
Application number	US-201214365332-A
Country	US
Kind code	B2
Filing date	Dec 28, 2012
Priority date	Dec 30, 2011
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

The present invention provides aptamers that specifically bind to the EGF receptor in a sample, and diagnostic and analytical methods using those aptamers.

First claim

That which is claimed is:

1. An aptamer comprising the nucleotide sequence:
XGANNGNNYGANNCNN (SEQ ID NO: 55);

wherein
X is a G, C or A;
Y is a G or A; and
N is, independently a 5-position modified 2′-deoxyuridine selected from the group consisting of 5-(N-benzylcarboxyamide)-2′-deoxyuracilyl, 5-(N-isobutylcarboxyamide)-2′-deoxyuridine, 5-(N-tryptaminocarboxyamide)-2′-deoxyuridine, 5-(N-[1-(3-trimethylamonium) propyl]carboxyamide)-2′-deoxyuridine chloride, 5-(N-naphthylmethylcarboxamide)-2′-deoxyuridine, and 5-(N-[1-(2,3-dihydroxypropyl)]carboxyamide)-2′-deoxyuridine.

2. The aptamer of claim 1 , wherein said 5-position modified 2′-deoxyuridine is a 5-(N-benzylcarboxyamide)-2′-deoxyuridine (BndU).

3. The aptamer of claim 1 , wherein the aptamer is capable of binding to Epidermal Growth Factor receptor (EGFR).

4. The aptamer of claim 3 , wherein the binding of the aptamer to EGFR is reduced in a dose-dependent manner based on the presence of an EGFR antagonist.

5. The aptamer of claim 4 , wherein the EGFR antagonist is selected from the group consisting of cetuximab and panitumumab.

6. The aptamer of claim 4 , wherein the K d of the aptamer to EGFR is at least 10-fold greater based on the presence of the EGFR antagonist relative to the K d of the aptamer to free EGFR.

7. The aptamer of claim 4 , wherein the K d of the aptamer to EGFR is at least 10 2 -fold greater based on the presence of the EGFR antagonist relative to the K d of the aptamer to free EGFR.

8. The aptamer of claim 1 , wherein the aptamer binds to the extracellular domain of EGFR.

9. An aptamer that binds to EGFR comprising a nucleotide sequence selected from the group consisting of SEQ. ID. NOS: 1-54.

10. An aptamer that binds EGFR comprising a nucleotide sequence having at least 90% identity to anyone of the nucleotide sequences of SEQ ID NOs: 1-54.

Assignees

• Somalogic Inc

Inventors

• Nikrad Malti P
• Gawande Bharat Nathu

Classifications

• G01N33/5759 Primary

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C12N2310/317

  with an inverted bond, e.g. a cap structure · CPC title

• C12N2310/3517

  Marker; Tag · CPC title

• C12N2320/10

  in screening processes · CPC title

• G01N2333/71

  for growth factors; for growth regulators · CPC title