# US 11,111,495 B2 · Method for generating aptamers with improved off-rates

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- Number: US 11,111,495 B2
- Document ID: US11111495B2
- Status: Granted
- Kind: B2
- Application number: 16/414,026
- Filed: 2019-05-16
- Published: 2019-10-31
- Granted: 2021-09-07
- Earliest claimed: 2007-01-16
- Assignees: SomaLogic, Inc.
- Applicants: SomaLogic, Inc.
- Inventors: Dominic Zichi; Sheri K. Wilcox; Chris Bock; Daniel J. Schneider; Bruce Eaton; Larry Gold
- Web page: https://patentgrep.com/patent/US11111495B2

## CPC

- 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}
- C12N 9/6429: {Thrombin (3.4.21.5)}
- C12N 15/1048: {SELEX}
- C12Q 1/6811: Selection methods for production or design of target specific oligonucleotides or binding molecules
- C12Q 1/6816: characterised by the detection means (C12Q1/6804 takes precedence)
- C12Q 1/6832: Enhancement of hybridisation reaction
- C12Q 1/6834: Enzymatic or biochemical coupling of nucleic acids to a solid phase
- G01N 33/5308: {for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites}
- G01N 33/58: involving labelled substances (G01N33/53 takes precedence)
- C12N 2310/16: Aptamers
- C12N 2310/314: Phosphoramidates
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/322: 2'-R Modification
- C12N 2310/333: Modified A
- C12N 2310/334: Modified C
- C12N 2310/335: Modified T or U
- C12N 2310/336: Modified G
- C12N 2330/31: Libraries, arrays
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure describes improved SELEX methods for producing aptamers that are capable of binding to target molecules and improved photoSELEX methods for producing photoreactive aptamers that are capable of both binding and covalently crosslinking to target molecules. Specifically, the present disclosure describes methods for producing aptamers and photoaptamers having slower dissociation rate constants than are obtained using prior SELEX and photoSELEX methods. The disclosure further describes aptamers and photoaptamers having slower dissociation rate constants than those obtained using prior methods. In addition, the disclosure describes aptamer constructs that include a variety of functionalities, including a cleavable element, a detection element, and a capture or immobilization element.

## Claims

### Claim 1

A non-covalent complex of an aptamer and a target molecule, wherein the aptamer comprises at least one 5-position modified pyrimidine having a hydrophobic group attached via a linker to the 5-position of the pyrimidine, and wherein the aptamer has binding affinity for the target molecule.

### Claim 2 (depends on 1)

The non-covalent complex of claim 1, wherein the hydrophobic group is selected from the group consisting of a benzyl, iso-butyl, indole and naphthyl.

### Claim 3 (depends on 1)

The non-covalent complex of claim 1, wherein the 5-position modified pyrimidine is a 5-position modified uridine or cytosine.

### Claim 4 (depends on 1)

The non-covalent complex of claim 1, wherein the target molecule is a protein or peptide.

### Claim 5 (depends on 1)

The non-covalent complex of claim 1, wherein the linker is selected from the group of linkers consisting of: