Cyanine derivatives and related uses

Patent metadata

Field	Value
Publication number	US-12516374-B2
Application number	US-202418424417-A
Country	US
Kind code	B2
Filing date	Jan 26, 2024
Priority date	Dec 7, 2022
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

Abstract

The present disclosure provides a compound of Formula (I), (II), or (III): an ionic derivative thereof, an isomer thereof, or a salt thereof. The present disclosure also provides conjugates of the compounds, and methods of using the compounds and the conjugates. The disclosure also provides the use of the compounds and conjugates in methods of sequencing nucleic acids.

First claim

The invention claimed is:

1 . A compound, wherein the compound is

or an ionic derivative thereof, or a salt thereof.

2 . A compound, wherein the compound is:

or an ionic derivative thereof, or a salt thereof.

3 . A method of sequencing comprising:
(a) contacting (i) a plurality of polymerases, (ii) a plurality of nucleic acid template molecules and (iii) a plurality of nucleic acid sequencing primers under conditions suitable to form a plurality of complexes comprising a polymerase bound to a nucleic acid duplex, wherein the nucleic acid duplex comprises a nucleic acid template molecule hybridized to a primer; (b) contacting the plurality of complexes with a plurality of nucleotides under conditions suitable for binding at least one nucleotide to one of the polymerases bound to a nucleic acid duplex; and (c) incorporating at least one nucleotide into the 3′ end of an extendible primer of at least one of the complexes, wherein at least one nucleotide in the plurality of nucleotides is labeled with the compound of claim 1 .

4 . A method of sequencing comprising:
(a) contacting (i) a plurality of sequencing polymerases, (ii) a first plurality of nucleic acid template molecules and (iii) a plurality of nucleic acid sequencing primers under conditions suitable to form a plurality of complexes comprising a first polymerase bound to a nucleic acid duplex, wherein the nucleic acid duplex comprises a nucleic acid template molecule hybridized to a nucleic acid sequencing primer; (b) contacting the plurality of complexes with a plurality of multivalent molecules to form a plurality of complexes, each complex comprising one or more polymerases, nucleic acid templates and sequencing primers,
wherein the nucleic acid templates and the sequencing primers are associated in a duplex,
wherein individual multivalent molecules comprise a core attached to multiple nucleotide arms and each nucleotide arm is attached to a nucleotide unit; and
wherein individual multivalent molecules in the plurality comprise the compound of claim 1 ; and
(c) detecting the plurality of multivalent-complexed polymerases.

5 . A method of sequencing comprising:
(a) contacting (i) a plurality of polymerases, (ii) a plurality of nucleic acid template molecules and (iii) a plurality of nucleic acid sequencing primers under conditions suitable to form a plurality of complexes comprising a polymerase bound to a nucleic acid duplex, wherein the nucleic acid duplex comprises a nucleic acid template molecule hybridized to a primer; (b) contacting the plurality of complexes with a plurality of nucleotides under conditions suitable for binding at least one nucleotide to one of the polymerases bound to a nucleic acid duplex; and (c) incorporating at least one nucleotide into the 3′ end of an extendible primer of at least one of the complexes, wherein at least one nucleotide in the plurality of nucleotides is labeled with the compound of claim 2 .

6 . A method of sequencing comprising:
(a) contacting (i) a plurality of sequencing polymerases, (ii) a first plurality of nucleic acid template molecules and (iii) a plurality of nucleic acid sequencing primers under conditions suitable to form a plurality of complexes comprising a first polymerase bound to a nucleic acid duplex, wherein the nucleic acid duplex comprises a nucleic acid template molecule hybridized to a nucleic acid sequencing primer; (b) contacting the plurality of complexes with a plurality of multivalent molecules to form a plurality of complexes, each complex comprising one or more polymerases, nucleic acid templates and sequencing primers,
wherein the nucleic acid templates and the sequencing primers are associated in a duplex,
wherein individual multivalent molecules comprise a core attached to multiple nucleotide arms and each nucleotide arm is attached to a nucleotide unit; and
wherein individual multivalent molecules in the plurality comprise the compound of claim 2 ; and
(c) detecting the plurality of multivalent-complexed polymerases.

7 . A compound, wherein the compound is

or an ionic derivative thereof, or a salt thereof.

8 . The compound of claim 7 , wherein the compound is:

or an ionic derivative thereof, or a salt thereof.

9 . A method of sequencing comprising:
(a) contacting (i) a plurality of polymerases, (ii) a plurality of nucleic acid template molecules and (iii) a plurality of nucleic acid sequencing primers under conditions suitable to form a plurality of complexes comprising a polymerase bound to a nucleic acid duplex, wherein the nucleic acid duplex comprises a nucleic acid template molecule hybridized to a primer; (b) contacting the plurality of complex

Assignees

• Element Biosciences Inc

Inventors

• Zheng Genhua
• Wibawa Njoo Audrey
• Zhang Xi
• Yang Zhimin
• Jellen Marcus James
• Shen Gene

Classifications

• G01N2333/91245

  Nucleotidyltransferases (2.7.7) · CPC title

• C12Q1/485

  involving kinase · CPC title

• C09B23/105

  two >CH- groups · CPC title

• C09B23/06

  three >CH- groups, e.g. carbocyanines · CPC title

• C12Q2563/107

  fluorescence · CPC title