IP Library › Granted Patent US 12,516,374
Granted Patent B2
US 12,516,374 · App. 18/424,417 · Granted Jan 6, 2026

Cyanine derivatives and related uses

Inventors: Genhua Zheng (San Diego, CA); Njoo Audrey Wibawa (San Diego, CA); Xi Zhang (San Diego, CA); Zhimin Yang (San Diego, CA); Marcus James Jellen (San Diego, CA); Gene Shen (San Diego, CA)
Assignee: Element Biosciences, Inc.
C12Q1/6874C09B23/06C09B23/105C12Q1/485G01N2333/91245
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,516,374
App. No.
18/424,417
Granted
Jan 6, 2026
Kind
B2
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.

Claims (79)

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 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 7 .

10 . 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 7 ; and

(c) detecting the plurality of multivalent-complexed polymerases.

11 . A compound, wherein the compound is

or an ionic derivative thereof, or a salt thereof.

12 . 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 11 .

13 . 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 11 ; and

(c) detecting the plurality of multivalent-complexed polymerases.

14 . The compound of claim 1 , wherein the compound is

or a salt thereof.

15 . The compound of claim 1 , wherein the compound is

or an ionic derivative thereof.

16 . The compound of claim 1 , wherein the compound is

17 . The compound of claim 2 , wherein the compound is:

or a salt thereof.

18 . The compound of claim 2 , wherein the compound is

or an ionic derivative thereof.

19 . The compound of claim 2 , wherein the compound is

20 . The compound of claim 7 , wherein the compound is

or a salt thereof.

21 . The compound of claim 7 , wherein the compound is

or an ionic derivative thereof.

22 . The compound of claim 7 , wherein the compound is

23 . The compound of claim 8 , wherein the compound is

or a salt thereof.

24 . The compound of claim 8 , wherein the compound is

or an ionic derivative thereof.

25 . The compound of claim 8 , wherein the compound is

26 . The compound of claim 11 , wherein the compound is

or a salt thereof.

27 . The compound of claim 11 , wherein the compound is

or an ionic derivative thereof.

28 . The compound of claim 11 , wherein the compound is

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 24, 2025
From: ZHENG, GENHUA; WIBAWA, NJOO AUDREY; ZHANG, XI; YANG, ZHIMIN; JELLEN, MARCUS JAMES
To: ELEMENT BIOSCIENCES, INC.
Reel/Frame 072363/0813 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 24, 2025
From: SHEN, GENE G.
To: ELEMENT BIOSCIENCES, INC.
Reel/Frame 073766/0979 →
Continuity (3)
Continuation PCTUS2023082907 · Dec 7, 2023
Provisional Application 63430993 · Dec 7, 2022
Related Publication 20240240249A1 · Jul 18, 2024
References Cited (72)
US 5558991A · Trainor · 1996 [cited by applicant]
US 6974873B2 · Leung et al. · 2005 [cited by applicant]
US 7170050B2 · Turner et al. · 2007 [cited by applicant]
US 7302146B2 · Turner et al. · 2007 [cited by applicant]
US 7405281B2 · Xu et al. · 2008 [cited by applicant]
US 7968702B2 · Wegener et al. · 2011 [cited by applicant]
US 8252910B2 · Korlach et al. · 2012 [cited by applicant]
US 8388982B2 · Kong et al. · 2013 [cited by applicant]
US 8637650B2 · Cherkasov et al. · 2014 [cited by applicant]
US 8889886B2 · Yue · 2014 [cited by examiner]
US 8906612B2 · Shen et al. · 2014 [cited by applicant]
US 8927212B2 · Kong et al. · 2015 [cited by applicant]
US 9062091B2 · Bjornson et al. · 2015 [cited by applicant]
US 9200311B2 · Otto et al. · 2015 [cited by applicant]
US 9441270B2 · Yue · 2016 [cited by examiner]
US 9637782B2 · Shen et al. · 2017 [cited by applicant]
US 9957291B2 · Sebo et al. · 2018 [cited by applicant]
US 10233490B2 · Stapleton et al. · 2019 [cited by applicant]
US 10246744B2 · Vijayan et al. · 2019 [cited by applicant]
US 10669299B2 · Sebo et al. · 2020 [cited by applicant]
US 10731141B2 · Iyidogan · 2020 [cited by applicant]
US 10768173B1 · Arslan et al. · 2020 [cited by applicant]
US 10781483B2 · Sebo et al. · 2020 [cited by applicant]
US 10800805B2 · Sebo et al. · 2020 [cited by applicant]
US 11427855B1 · Arslan et al. · 2022 [cited by applicant]
US 11530439B2 · Francais et al. · 2022 [cited by applicant]
US 11624089B2 · Yue et al. · 2023 [cited by applicant]
US 11787947B2 · Knowlton et al. · 2023 [cited by applicant]
US 11859171B2 · Quake et al. · 2024 [cited by applicant]
US 20020077487A1 · Leung · 2002 [cited by examiner]
US 20090186343A1 · Wang et al. · 2009 [cited by applicant]
US 20120052506A1 · Yue · 2012 [cited by examiner]
US 20170145496A1 · Sebo · 2017 [cited by examiner]
US 20170313883A1 · Park · 2017 [cited by examiner]
US 20200231964A1 · Ben-Yehezkel et al. · 2020 [cited by applicant]
US 20200255668A1 · Shin et al. · 2020 [cited by applicant]
US 20220228063A1 · Chappellet · 2022 [cited by examiner]
US 20220315614A1 · Graham et al. · 2022 [cited by applicant]
WO WO0226891A1 · 2002 [cited by applicant]
WO WO2005111240A2 · 2005 [cited by applicant]
WO WO2008040994A2 · 2008 [cited by applicant]
WO WO2009105077A2 · 2009 [cited by applicant]
WO WO2010096720A2 · 2010 [cited by applicant]
WO WO2010121163A2 · 2010 [cited by applicant]
WO WO2013109859A1 · 2013 [cited by applicant]
WO WO2018045109A1 · 2018 [cited by applicant]
WO WO2019231568A1 · 2019 [cited by applicant]
WO WO2021146443A1 · 2021 [cited by applicant]
WO WO2021168155A1 · 2021 [cited by applicant]
WO WO2022129439A1 · 2022 [cited by applicant]
WO WO2022136402A1 · 2022 [cited by applicant]
WO WO2022155331A1 · 2022 [cited by applicant]
WO WO2022212280A1 · 2022 [cited by applicant]
WO WO2022243480A1 · 2022 [cited by applicant]
WO WO2024124008A2 · 2024 [cited by applicant]
Lin et al. Guangpuxue Yu Guangpu Fenxi (2007), 27(9), 1775-1779.(abstract only) (Year: 2007). [cited by examiner]
Eschenmoser, A., “Chemical Etiology of Nucleic Acid Structure,” Science, Jun. 25, 1999, 284:2118-2124. [cited by applicant]
Ferraro, M. & Gotor, V., “Biocatalytic Selective Modifications of Conventional Nucleosides, Carbocyclic Nucleosides, and C-Nucleosides,” Chem. Rev., 2000, 100:4319-4347. [cited by applicant]
Jeong, L.S. et al., “Structure-Activity Relationships of B-D-(2S,5R)- and α-D-(2S,5S)-1,3-Oxathiolanyl Nucleosides as Potential Anti-HIV Agents,” J. Med. Chem., 1993, 36: 2627-2638. [cited by applicant]
Kim, H. O. et al., “1,3-Dioxolanylpurine Nucleosides (2R,4R) and (2R,4S) with Selective Anti-HIV-1 Activity in Human Lymphocytes,” J. Med. Chem., 1993, 36:30-37. [cited by applicant]
Martinez, C. I. et al., “Acyclic Nucleoside Triphosphate Analogs as Terminators in Biocatalytic DNA Replication,” Bioorganic & Medicinal Chemistry Letters, 1997, 7(23):3013-3016. [cited by applicant]
Martinez, C. I. et al., “An allylic/acyclic adenosine nucleoside triphosphate for termination of DNA synthesis by DNA template-dependent polymerases,” Nucleic Acids Research, 1999, 27(5):1271-1274. [cited by applicant]
Wang, F. et al., “TEQUILA-seq: a versatile and low-cost method for targeted long-read RNA sequencing,” Nat Commun., (2023); 14(1):4760, pp. 1-15. [cited by applicant]
Anderson, J.P. et al.; Fluorescent Structural DNA Nanoballs Functionalized with Phosphate-Linked Nucleotide Triphosphates. Nano Letters 10(3):788-792 (2010). [cited by applicant]
Chen, X., et al.; “Efficient in situ barcode sequencing using padlock probe-based BaristaSeq,” Nucleic Acids Research; 46(4):e22 pp. 1-10 (2018). [cited by applicant]
Mignardi, M., et al.; “Fourth-generation sequencing in the cell and the clinic,” Genome Med.; 6(4):31; pp. 1-4 (2014). [cited by applicant]
Altman, R. B. et al. “Cyanine Fluorophore Derivatives with Enhanced Photostability.” Nature Methods, vol. 9, No. 1, Jan. 2012, pp. 68-73. [cited by applicant]
Altman, R. B. et al. “Enhanced Photostability of Cyanine Fluorophores Across the Visible Spectrum.” Nature Methods, vol. 9, No. 5, May 2012, pp. 428-429. [cited by applicant]
Asher, W. B. et al. “Single-Molecule FRET Imaging of GPCR Dimers in Living Cells.” Nature Methods, vol. 18, Apr. 2021, pp. 1-26. [cited by applicant]
Juette, M. F. et al. “The Bright Future of Single-Molecule Fluorescence Imaging.” Current Opinion in Chemical Biology, vol. 20, Jun. 2014, pp. 103-111. [cited by applicant]
Martin, M. I. et al. “Leveraging Baird Aromaticity for Advancement of Bioimaging Applications.” Journal of Physical Organic Chemistry, vol. 36, No. 1, Jan. 2023, pp. 1-7. [cited by applicant]
Zheng, Q. et al. “Ulta-Stable Organic Fluorophores for Single-Molecule Research.” Chemical Society Reviews, vol. 43, No. 4, Feb. 2014, pp. 1044-1056. [cited by applicant]