Granted Patent
B2
US 12,312,377 · App. 16/510,794 · Granted May 27, 2025
Biconjugatable labels and methods of use
Inventors:
Jonathan M. Rothberg (Guilford, CT); Jeremy Lackey (Guilford, CT); Roger Nani (Madison, CT); David Dodd (Guilford, CT)
Assignee:
Quantum-Si Incorporated
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Aspects of the disclosure provide biconjugatable labels, labeled biomolecules, and methods of using and making the same.
Claims (20)
1. A labeled biomolecule of the formula:
wherein:
Q 1 and Q 2 are independently monomeric or oligomeric biomolecules;
L 1 and L 2 are independently optionally substituted alkylene; and
X − is a counterion or is absent.
2. The labeled biomolecule of claim 1 , wherein Q 1 and Q 2 are independently nucleosides, nucleotides, oligonucleotides, nucleic acids, or derivatives or fragments thereof.
3. The labeled biomolecule of claim 2 , wherein Q 1 and/or Q 2 form a first oligonucleotide strand.
4. The labeled biomolecule of claim 3 , further comprising a second oligonucleotide strand hybridized to the first oligonucleotide strand.
5. The labeled biomolecule of claim 1 , wherein a nucleoside polyphosphate is attached through a terminal phosphate to Q 1 and/or Q 2 .
6. The labeled biomolecule of claim 1 , wherein the labeled biomolecule is of the formula:
wherein n is independently an integer from 1-20, inclusive.
7. The labeled biomolecule of claim 6 , wherein the labeled biomolecule is of the formula:
8. The labeled biomolecule of claim 7 , wherein the labeled biomolecule is of the formula:
9. The labeled biomolecule of claim 1 , wherein L 1 and L 2 are independently optionally substituted C 1-20 alkylene.
10. The labeled biomolecule of claim 9 , wherein L 1 and L 2 are independently optionally substituted C 1-10 alkylene.
11. The labeled biomolecule of claim 3 , wherein the first oligonucleotide strand comprises at least 10 and fewer than 200 nucleotides.
12. The labeled biomolecule of claim 11 , wherein the first oligonucleotide strand comprises at least 10 and fewer than 100 nucleotides.
13. The labeled biomolecule of claim 12 , wherein the first oligonucleotide strand comprises at least 10 and fewer than 50 nucleotides.
14. The labeled biomolecule of claim 1 , wherein Q 1 and Q 2 are independently oligonucleotides, nucleic acids, or derivatives or fragments thereof, and wherein Q 1 and Q 2 form a first oligonucleotide strand.
15. The labeled biomolecule of claim 14 , further comprising a second oligonucleotide strand hybridized to the first oligonucleotide strand.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 22, 2019
From: ROTHBERG, JONATHAN M.; LACKEY, JEREMY; NANI, ROGER; DODD, DAVID
To: QUANTUM-SI INCORPORATED
Reel/Frame 050128/0089 →
Continuity (2)
Provisional Application
62698006
· Jul 13, 2018
References Cited (229)
US 5210015A
· Gelfand et al.
· 1993
[cited by applicant]
US 5487972A
· Gelfand et al.
· 1996
[cited by applicant]
US 5594117A
· Urdea et al.
· 1997
[cited by applicant]
US 5707804A
· Mathies et al.
· 1998
[cited by applicant]
US 5851840A
· Sluka et al.
· 1998
[cited by applicant]
US 6133445A
· Waggoner et al.
· 2000
[cited by applicant]
US 6153442A
· Pirio et al.
· 2000
[cited by applicant]
US 6248518B1
· Parkhurst et al.
· 2001
[cited by applicant]
US 6255083B1
· Williams
· 2001
[cited by applicant]
US 6399335B1
· Kao et al.
· 2002
[cited by applicant]
US 6444682B1
· Simmonds et al.
· 2002
[cited by applicant]
US 6762048B2
· Williams
· 2004
[cited by applicant]
US 6787308B2
· Balasubramanian et al.
· 2004
[cited by applicant]
US 6846638B2
· Shipwash
· 2005
[cited by applicant]
US 6869764B2
· Williams et al.
· 2005
[cited by applicant]
US 6936702B2
· Williams et al.
· 2005
[cited by applicant]
US 7041812B2
· Kumar et al.
· 2006
[cited by applicant]
US 7052847B2
· Korlach et al.
· 2006
[cited by applicant]
US 7056661B2
· Korlach et al.
· 2006
[cited by applicant]
US 7057026B2
· Barnes et al.
· 2006
[cited by applicant]
US 7229799B2
· Williams
· 2007
[cited by applicant]
US 7361466B2
· Korlach et al.
· 2008
[cited by applicant]
US 7405281B2
· Xu et al.
· 2008
[cited by applicant]
US 7625701B2
· Williams et al.
· 2009
[cited by applicant]
US 7968702B2
· Wegener et al.
· 2011
[cited by applicant]
US 7973146B2
· Shen et al.
· 2011
[cited by applicant]
US 8034623B2
· Oh et al.
· 2011
[cited by applicant]
US 8084734B2
· Vertes et al.
· 2011
[cited by applicant]
US 8133702B2
· Shen et al.
· 2012
[cited by applicant]
US 8148516B2
· Williams et al.
· 2012
[cited by applicant]
US 8153375B2
· Travers et al.
· 2012
[cited by applicant]
US 8192961B2
· Williams
· 2012
[cited by applicant]
US 8252910B2
· Korlach et al.
· 2012
[cited by applicant]
US 8257954B2
· Clark et al.
· 2012
[cited by applicant]
US 8309330B2
· Travers et al.
· 2012
[cited by applicant]
US 8354252B2
· Wegener et al.
· 2013
[cited by applicant]
US 8383791B1
· McDowell et al.
· 2013
[cited by applicant]
US 8420366B2
· Clark et al.
· 2013
[cited by applicant]
US 8455193B2
· Travers et al.
· 2013
[cited by applicant]
US 8530154B2
· Williams
· 2013
[cited by applicant]
US 8581179B2
· Franzen
· 2013
[cited by applicant]
US 8846881B2
· Korlach et al.
· 2014
[cited by applicant]
US 8906614B2
· Wegener et al.
· 2014
[cited by applicant]
US 8927212B2
· Kong et al.
· 2015
[cited by applicant]
US 8980584B2
· Williams
· 2015
[cited by applicant]
US 9062091B2
· Bjornson et al.
· 2015
[cited by applicant]
US 9404146B2
· Travers et al.
· 2016
[cited by applicant]
US 9435810B2
· Havranek et al.
· 2016
[cited by applicant]
US 9464107B2
· Wegener et al.
· 2016
[cited by applicant]
US 9542527B2
· Travers et al.
· 2017
[cited by applicant]
US 9551031B2
· Korlach et al.
· 2017
[cited by applicant]
US 9551660B2
· Kong et al.
· 2017
[cited by applicant]
US 9566335B1
· Emili et al.
· 2017
[cited by applicant]
US 9582640B2
· Travers et al.
· 2017
[cited by applicant]
US 9600626B2
· Travers et al.
· 2017
[cited by applicant]
US 9678080B2
· Bjornson et al.
· 2017
[cited by applicant]
US 9719073B2
· Emig et al.
· 2017
[cited by applicant]
US 9845501B2
· Williams
· 2017
[cited by applicant]
US 9879319B2
· Korlach et al.
· 2018
[cited by applicant]
US 9910956B2
· Travers et al.
· 2018
[cited by applicant]
US 9957291B2
· Sebo et al.
· 2018
[cited by applicant]
US 20050014154A1
· Weizenegger
· 2005
[cited by applicant]
US 20070219367A1
· Shchepinov et al.
· 2007
[cited by applicant]
US 20090068645A1
· Sibson
· 2009
[cited by applicant]
US 20090104614A1
· Tsourkas et al.
· 2009
[cited by applicant]
US 20090214436A1
· Achilefu et al.
· 2009
[cited by applicant]
US 20090263327A1
· Achilefu
· 2009
[cited by examiner]
US 20100035254A1
· Williams
· 2010
[cited by applicant]
US 20100317005A1
· Hardin et al.
· 2010
[cited by applicant]
US 20110165652A1
· Hardin et al.
· 2011
[cited by applicant]
US 20120016128A1
· Diwu
· 2012
[cited by examiner]
US 20170362651A1
· Rothberg et al.
· 2017
[cited by applicant]
US 20230221330A1
· Reed et al.
· 2023
[cited by applicant]
US 20240035081A1
· Rothberg et al.
· 2024
[cited by applicant]
US 20240068027A1
· Rothberg et al.
· 2024
[cited by applicant]
CA 2373385C
· 2000
[cited by applicant]
CA 2457513A1
· 2003
[cited by applicant]
CN 1373813A
· 2002
[cited by applicant]
CN 1771336A
· 2006
[cited by applicant]
CN 1938328A
· 2007
[cited by applicant]
CN 101076537A
· 2007
[cited by applicant]
CN 101268200A
· 2008
[cited by applicant]
CN 101346472A
· 2009
[cited by applicant]
CN 101434988A
· 2009
[cited by applicant]
CN 101636406A
· 2010
[cited by applicant]
CN 102124128A
· 2011
[cited by applicant]
CN 102329884A
· 2012
[cited by applicant]
CN 102782159A
· 2012
[cited by applicant]
CN 103866010A
· 2014
[cited by applicant]
CN 105001292A
· 2015
[cited by applicant]
EP 1681356A1
· 2006
[cited by applicant]
EP 1421213B1
· 2010
[cited by applicant]
EP 1179085B1
· 2010
[cited by applicant]
EP 2226330A1
· 2010
[cited by applicant]
EP 2263087A1
· 2010
[cited by applicant]
EP 2814953
· 2014
[cited by applicant]
GB 2398383A
· 2004
[cited by applicant]
JP H07502992A
· 1995
[cited by applicant]
JP 2002508428
· 2002
[cited by applicant]
JP 2002543847
· 2002
[cited by applicant]
JP 2005507674A
· 2005
[cited by applicant]
JP 2009518009A
· 2009
[cited by applicant]
JP 2015073523A
· 2015
[cited by applicant]
JP 2016011429A
· 2016
[cited by applicant]
WO WO199309128A1
· 1993
[cited by applicant]
WO WO0070073A1
· 2000
[cited by applicant]
WO WO200109389A2
· 2001
[cited by applicant]
WO WO03089670A2
· 2003
[cited by applicant]
WO WO2003102239A2
· 2003
[cited by applicant]
WO WO2004096997A2
· 2004
[cited by applicant]
WO WO2005044836A2
· 2005
[cited by applicant]
WO WO2007015168A2
· 2007
[cited by applicant]
WO WO2007041342A2
· 2007
[cited by applicant]
WO WO2007064905A2
· 2007
[cited by applicant]
WO WO2007070572A2
· 2007
[cited by applicant]
WO WO2009114182A1
· 2009
[cited by applicant]
WO WO2010065322A1
· 2010
[cited by applicant]
WO WO2010115016A2
· 2010
[cited by applicant]
WO WO2010117420A2
· 2010
[cited by applicant]
WO WO2011150852A1
· 2011
[cited by applicant]
WO WO2012027625A2
· 2012
[cited by applicant]
WO WO2016187580A1
· 2016
[cited by applicant]
WO WO2017201514A1
· 2017
[cited by applicant]
WO WO2019023257A1
· 2019
[cited by applicant]
WO WO2019040825A1
· 2019
[cited by applicant]
Demeter et al. (Bioconj. Chem. 2017, 28, 1552-1559).
[cited by examiner]
Demeter et al. (Chem. Eur. J. 2016, 22, 6382-6388).
[cited by examiner]
Gutsche et al. (Chem. Eur. J. 2016, 22, 13953-19364).
[cited by examiner]
Linck et al. (Photochem. Photobiol. 2012, 88, 867-875).
[cited by examiner]
Lakshmi et al. (Reports Org. Chem. 2016, 6, 1-24 ).
[cited by examiner]
Kowada et al. (Chem. Soc. Rev. 2015, 44, 4953-4972).
[cited by examiner]
Gerowska, M. (2012). Synthesis and Properties of New Fluorescent Dyes and Dye-Labelled Oligonucleotides, Thesis for the degree of Doctor of Philosophy, University of Southampton).
[cited by examiner]
Ryabinin et al. (Russian J. Bioorg. Chem. 2016, 42, 111-114).
[cited by examiner]
Algar et al. (Analyt. Chim. Acta 2007, 581, 193-201).
[cited by examiner]
Inoyama et al. (J. Biomol. Screen. 2012, 17, 435-447).
[cited by examiner]
Extended European Search Report mailed May 6, 2021 for Application No. EP 18837972.1.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/US2018/043526 mailed Feb. 6, 2020.
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2019/041717 mailed Nov. 13, 2019.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/US2019/041717 mailed Jan. 28, 2021.
[cited by applicant]
Invitation to Pay Additional Fees for International Application No. PCT/US2020/014856 mailed May 8, 2020.
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2020/014856 mailed Jun. 30, 2020.
[cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2020/014856 mailed Aug. 5, 2021.
[cited by applicant]
Bunt et al., FRET from single to multiplexed signaling events. Biophys Rev. 2017;9:119-29. Epub Mar. 23, 2017.
[cited by applicant]
Koushik et al., Cerulean, Venus, and VenusY67C FRET reference standards. Biophys J. Dec. 15, 2006;91(12):L99-L101. doi: 10.1529/biophysj.106.096206. Epub Oct. 13, 2006. PMID: 17040988; PMCID: PMC1779932.
[cited by applicant]
Saito et al., Dual-labeled oligonucleotide probe for sensing adenosine via FRET: a novel alternative to SNPs genotyping. Chem Commun (Camb). Jun. 7, 2007;(21):2133-5. doi: 10.1039/b618465k. Epub Feb. 28, 2007. PMID: 175…
[cited by applicant]
Sato et al., Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin. J Am Chem Soc. Jan. 31, 2007;129(4):873-80. doi: 10.1021/ja0655643. PMID: 17243…
[cited by applicant]
Stryer et al., Energy transfer: a spectroscopic ruler. Proc Natl Acad Sci U S A. Aug. 1967;58(2):719-26. doi: 10.1073/pnas.58.2.719. PMID: 5233469; PMCID: PMC335693.
[cited by applicant]
Williams et al., An artificial processivity clamp made with streptavidin facilitates oriented attachment of polymerase—DNA complexes to surfaces. Nucleic Acids Res. Oct. 2008;36(18):e121. doi: 10.1093/nar/gkn531. Epub A…
[cited by applicant]
U.S. Appl. No. 61/069,247, filed Mar. 13, 2008, Korlach et al.
[cited by applicant]
U.S. Appl. No. 61/979,724, filed Apr. 14, 2014.
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2017/033706 dated Sep. 12, 2017.
[cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2017/033706 dated Nov. 29, 2018.
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2018/043526 dated Oct. 3, 2018.
[cited by applicant]
Invitation to Pay Additional Fees for Application No. PCT/US2019/041717 mailed Sep. 20, 2019.
[cited by applicant]
Brown et al., Synthesis of a modified thymidine monomer for site-specific incorporation of reporter groups into oligonucleotides. Tetrahedron Letters. 2001;42:2587-2591.
[cited by applicant]
Cheng-Yao, DNA polymerases drive DNA sequencing-by-synthesis technologies: both past and present. Frontiers in Microbiology. 2014. 10 pages.
[cited by applicant]
Kretschy et al., Comparison of the sequence-dependent fluorescence of the cyanine dyes Cy3, Cy5, DyLight DY547 and DyLight DY647 on single-stranded DNA. PLoS One. Jan. 15, 2014;9(1):e85605. doi: 10.1371/journal.pone.008…
[cited by applicant]
Kumar et al., Terminal phosphate labeled nucleotides: synthesis, applications, and linker effect on incorporation by DNA polymerases. Nucleosides Nucleotides Nucleic Acids. Nov. 2005; 24(5-7):401-8.
[cited by applicant]
Takkellapati et al., Synthesis of aminomethyl- and bis-aminomethyl-fluorescein energy transfer terminators. Nucleosides Nucleotides Nucleic Acids. Dec. 2007; 26(10-12):1467-70.
[cited by applicant]
U.S. Appl. No. 15/600,979, filed May 22, 2017, Rothberg et al.
[cited by applicant]
U.S. Appl. No. 15/161,125, filed May 20, 2016, Rothberg et al.
[cited by applicant]
U.S. Appl. No. 16/043,547, filed Jul. 24, 2018, Rothberg et al.
[cited by applicant]
PCT/US2017/033706, Sep. 12, 2017, International Search Report and Written Opinion.
[cited by applicant]
PCT/US2017/033706, Nov. 29, 2018, International Preliminary Report on Patentability.
[cited by applicant]
PCT/US2018/043526, Oct. 3, 2018, International Search Report and Written Opinion.
[cited by applicant]
PCT/US2019/041717, Sep. 20, 2019, Invitation to Pay Additional Fee.
[cited by applicant]
Antonio et al., Boronic acids as building blocks for the construction of therapeutically useful bioconjugates. Chem Soc Rev. Jul. 1, 2019;48(13):3513-3536. doi: 10.1039/c9cs00184k.
[cited by applicant]
Lee et al., Bodipy-diacrylate imaging probes for targeted proteins inside live cells. Chem Commun (Camb). Apr. 21, 2011;47(15):4508-10. doi: 10.1039/c1cc10362h. Epub Mar. 8, 2011.
[cited by applicant]
Scheck et al., Surveying protein structure and function using bis-arsenical small molecules. Acc Chem Res. Sep. 20, 2011;44(9):654-65. doi: 10.1021/ar2001028. Epub Jul. 18, 2011.
[cited by applicant]
Sun et al., Boronic acids for fluorescence imaging of carbohydrates. Chem Commun (Camb). Feb. 28, 2016;52(17):3456-69. doi: 10.1039/c5cc08633g. Epub Jan. 5, 2016.
[cited by applicant]
Vives et al., Facile functionalization of a fully fluorescent perfluorophenyl BODIPY: photostable thiol and amine conjugates. Chem Commun (Camb). Oct. 7, 2011;47(37):10425-7. doi: 10.1039/c1cc13778f. Epub Aug. 19, 2011.
[cited by applicant]
Li et al., A photocleavable fluorescent nucleotide for DNA sequencing and analysis. Proceedings of the National Academy of Sciences. Jan. 21, 2003;100(2):414-9.
[cited by applicant]
Hall et al., A highly fluorescent DNA toolkit: synthesis and properties of oligonucleotides containing new Cy3, Cy5 and Cy3B monomers. Nucleic acids research. Aug. 1, 2012;40(14):e108-. 10 pages.
[cited by applicant]
U.S. Appl. No. 18/153,093, filed Jan. 11, 2023, Reed et al.
[cited by applicant]