Granted Patent
B2
US 12,235,274 · App. 18/094,122 · Granted Feb 25, 2025
Reagents for directed biomarker signal amplification
Inventors:
Brent S. Gaylord (San Diego, CA); Glenn P. Bartholomew (Escondido, CA); Russell A. Baldocchi (Encinitas, CA); Janice W. Hong (San Diego, CA); William H. Huisman (San Diego, CA); Yongchao Liang (Irvine, CA); Trung Nguyen (San Diego, CA); Lan T. Tran (Oceanside, CA); Jean M. Wheeler (San Diego, CA); Adrian Charles Vernon Palmer (Brighton, GB); Frank Peter Uckert (San Diego, CA)
Assignee:
SIRIGEN II LIMITED
G01N33/58C07K16/2812C07K16/2815C08G61/02C09B57/00C09B68/41C09B69/00C12Q1/6818C12Q1/682G01N33/582H10K85/151C08G2261/1424C08G2261/3142C08G2261/411H10K85/115
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Abstract
Described herein are methods, compositions and articles of manufacture involving neutral conjugated polymers including methods for synthesis of neutral conjugated water-soluble polymers with linkers along the polymer main chain structure and terminal end capping units. Such polymers may serve in the fabrication of novel optoelectronic devices and in the development of highly efficient biosensors. The invention further relates to the application of these polymers in assay methods.
Claims (40)
1. A conjugated polymer comprising n-conjugated repeat units, wherein the π-conjugated repeat units comprise:
a non-ionic Ar polycyclic repeat unit that is evenly or randomly distributed along the polymer main chain;
an MU polymer modifying unit that is evenly or randomly distributed along the polymer main chain; and
a linker L1 that is an aryl or a heteroaryl group evenly or randomly distributed along the polymer main chain; and
G1 and G2 terminating groups, wherein at least one of G1 and G2 is aryl or substituted aryl and G1 and G2 are different from Ar, MU and L1.
2. The conjugated polymer according to claim 1 , wherein Ar comprises fluorene.
3. The conjugated polymer according to claim 2 , wherein L1 comprises an aryl or a heteroaryl group substituted with one or more pendant chains terminated with:
i) a functional group selected from amine, carbamate, carboxylic acid, carboxylate, maleimide, activated ester, N-hydroxysuccinimidyl, hydrazine, hydrazide, hydrazone, azide, alkyne, aldehyde, thiol, and protected groups thereof for conjugation to a biomolecule or organic dye; or
ii) a linked biomolecule or organic dye.
4. The conjugated polymer according to claim 3 , wherein the conjugated polymer further comprises L2 that is an aryl or a heteroaryl group evenly or randomly distributed along the polymer main chain.
5. The conjugated polymer according to claim 3 , wherein L1 comprises a linked biomolecule.
6. The conjugated polymer according to claim 5 , wherein the linked biomolecule comprises an antibody or streptavidin.
7. The conjugated polymer according to claim 6 , wherein the linked biomolecule comprises an antibody.
8. The conjugated polymer according to claim 2 , wherein Ar, MU and L1 are randomly distributed along the polymer main chain.
9. The conjugated polymer according to claim 2 , wherein the polymer modifying unit is aryl or substituted aryl.
10. The conjugated polymer according to claim 9 , wherein the polymer modifying unit is a band gap modifying unit.
11. The conjugated polymer according to claim 2 , wherein L1 comprises an organic dye.
12. The conjugated polymer according to claim 11 , wherein the organic dye is a BODIPY dye.
13. The conjugated polymer according to claim 2 , wherein the conjugated polymer comprises a structure of the formula:
wherein
n is an integer selected so that the conjugated polymer has a molecular weight ranging from 5,000 g/mol to 100,000 g/mol; and
L2 is optional and is an aryl or a heteroaryl group evenly or randomly distributed along the polymer main chain; and
a, b, c and d define the mol % of each unit within the structure which each can be evenly or randomly repeated and where a is a mol % from 10 to 100%, b is present up to 90%, c is present up to mol % 25 and d is a mol % from 0 to 25%.
14. The conjugated polymer according to claim 13 , wherein at L1 comprises a linked biomolecule.
15. The conjugated polymer according to claim 14 , wherein the linked biomolecule comprises an antibody or streptavidin.
16. The conjugated polymer according to claim 14 , wherein the linked biomolecule comprises an antibody.
17. The conjugated polymer according to claim 2 , wherein the fluorene is a substituted fluorene.
18. The conjugated polymer according to claim 1 , wherein Ar comprises fluorene substituted with an alkyl chain.
19. The conjugated polymer according to claim 3 , wherein Ar comprises fluorene substituted with an alkyl chain.
20. The conjugated polymer according to claim 4 , wherein Ar comprises fluorene substituted with an alkyl chain.
21. The conjugated polymer according to claim 6 , wherein Ar comprises fluorene substituted with an alkyl chain.
22. The conjugated polymer according to claim 8 , wherein Ar comprises fluorene substituted with an alkyl chain.
23. The conjugated polymer according to claim 10 , wherein Ar comprises fluorene substituted with an alkyl chain.
24. The conjugated polymer according to claim 12 , wherein Ar comprises fluorene substituted with an alkyl chain.
25. The conjugated polymer according to claim 13 , wherein Ar comprises fluorene substituted with an alkyl chain.
26. The conjugated polymer according to claim 14 , wherein Ar comprises fluorene substituted with an alkyl chain.
27. The conjugated polymer according to claim 18 , wherein G1 and G2 terminating groups are phenyl groups.
28. The conjugated polymer according to claim 19 , wherein G1 and G2 terminating groups are phenyl groups.
29. The conjugated polymer according to claim 24 , wherein G1 and G2 terminating groups are phenyl groups.
30. The conjugated polymer according to claim 26 , wherein G1 and G2 terminating groups are phenyl groups.
Assignments (4)
CORRECTIVE ASSIGNMENT TO CORRECT THE CORRECT THE NAME OF ASSIGNOR TRAN, LAN T. ON THE RECORDATION PREVIOUSLY RECORDED ON REEL 63215 FRAME 669. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT.
Recorded Apr 11, 2024
From: GAYLORD, BRENT S.; BARTHOLOMEW, GLENN P.; BALDOCCHI, RUSSELL A.; HONG, JANICE W.; HUISMAN, WILLIAM H.; LIANG, YONGCHAO; NGUYEN, TRUNG; TRAN, LAN T.; WHEELER, JEAN M.; PALMER, ADRIAN CHARLES VERNON; UCKERT, FRANK PETER
To: SIRIGEN, INC.
Reel/Frame 067097/0395 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 4, 2023
From: GAYLORD, BRENT S.; BARTHOLOMEW, GLENN P.; BALDOCCHI, RUSSELL A.; HONG, JANICE W.; HUISMAN, WILLIAM H.; LIANG, YONGCHAO; NGUYEN, TRUNG; TRAN, LAN P.; WHEELER, JEAN M.; PALMER, ADRIAN CHARLES VERNON; UCKERT, FRANK PETER
To: SIRIGEN, INC.
Reel/Frame 063215/0669 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 4, 2023
From: SIRIGEN INC.
To: SIRIGEN GROUP LIMITED
Reel/Frame 063215/0722 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 4, 2023
From: SIRIGEN GROUP LIMITED
To: SIRIGEN II LIMITED
Reel/Frame 063215/0736 →
Continuity (11)
Provisional Application
61358406
· Jun 24, 2010
Provisional Application
61296379
· Jan 19, 2010
References Cited (298)
US 4486530A
· David et al.
· 1984
[cited by applicant]
US 5143854A
· Pirrung et al.
· 1992
[cited by applicant]
US 5288514A
· Ellman
· 1994
[cited by applicant]
US 5384261A
· Winkler et al.
· 1995
[cited by applicant]
US 5424186A
· Fodor et al.
· 1995
[cited by applicant]
US 5677195A
· Winkler
· 1997
[cited by applicant]
US 5807974A
· Kim
· 1998
[cited by applicant]
US 5990479A
· Weiss et al.
· 1999
[cited by applicant]
US 6263286B1
· Gilmanshin et al.
· 2001
[cited by applicant]
US 6280933B1
· Glazer et al.
· 2001
[cited by applicant]
US 6350431B1
· Snow et al.
· 2002
[cited by applicant]
US 6951682B1
· Zebala
· 2005
[cited by applicant]
US 6998241B2
· Boga
· 2006
[cited by applicant]
US 7141437B2
· Dvornic et al.
· 2006
[cited by applicant]
US 7144950B2
· Bazan et al.
· 2006
[cited by applicant]
US 7208122B2
· Swager et al.
· 2007
[cited by applicant]
US 7214489B2
· Bazan
· 2007
[cited by applicant]
US 7241512B2
· Li et al.
· 2007
[cited by applicant]
US 7270956B2
· Bazan et al.
· 2007
[cited by applicant]
US 7282514B1
· Belfield et al.
· 2007
[cited by applicant]
US 7629448B2
· Bazan et al.
· 2009
[cited by applicant]
US 7666594B2
· Bazan
· 2010
[cited by applicant]
US 7811755B2
· Bazan et al.
· 2010
[cited by applicant]
US 7897684B2
· Bazan et al.
· 2011
[cited by applicant]
US 7914984B2
· Bazan et al.
· 2011
[cited by applicant]
US 8101416B2
· Bazan et al.
· 2012
[cited by applicant]
US 8110673B2
· Bazan et al.
· 2012
[cited by applicant]
US 8158444B2
· Gaylord et al.
· 2012
[cited by applicant]
US 8227187B2
· Bazan et al.
· 2012
[cited by applicant]
US 8309672B2
· Bazan et al.
· 2012
[cited by applicant]
US 8338532B2
· Bazan et al.
· 2012
[cited by applicant]
US 8354239B2
· Gaylord et al.
· 2013
[cited by applicant]
US 8362193B2
· Gaylord et al.
· 2013
[cited by applicant]
US 8455613B2
· Gaylord et al.
· 2013
[cited by applicant]
US 8546081B2
· Bazan et al.
· 2013
[cited by applicant]
US 8575303B2
· Gaylord et al.
· 2013
[cited by applicant]
US 8617814B2
· Bazan et al.
· 2013
[cited by applicant]
US 8669055B2
· Bazan et al.
· 2014
[cited by applicant]
US 8759444B2
· Bazan et al.
· 2014
[cited by applicant]
US 8802450B2
· Gaylord et al.
· 2014
[cited by applicant]
US 8835113B2
· Bazan et al.
· 2014
[cited by applicant]
US 8841072B2
· Bazan et al.
· 2014
[cited by applicant]
US 8969509B2
· Liu et al.
· 2015
[cited by applicant]
US 8993335B2
· Bazan et al.
· 2015
[cited by applicant]
US 9085799B2
· Bazan et al.
· 2015
[cited by applicant]
US 9139869B2
· Gaylord et al.
· 2015
[cited by applicant]
US 9159465B2
· Bazan et al.
· 2015
[cited by applicant]
US 9371559B2
· Bazan et al.
· 2016
[cited by applicant]
US 9383353B2
· Gaylord et al.
· 2016
[cited by applicant]
US 9547008B2
· Gaylord et al.
· 2017
[cited by applicant]
US 20030087311A1
· Wolf
· 2003
[cited by applicant]
US 20040009506A1
· Stephan et al.
· 2004
[cited by applicant]
US 20040023248A1
· O'Malley
· 2004
[cited by applicant]
US 20060160109A1
· MacDonald et al.
· 2006
[cited by applicant]
US 20060175193A1
· Inganas et al.
· 2006
[cited by applicant]
US 20070178470A1
· Bissonnette
· 2007
[cited by applicant]
US 20090230362A1
· Bazan et al.
· 2009
[cited by applicant]
US 20200048469A1
· Bartholomew et al.
· 2020
[cited by applicant]
CA 2365814
· 2003
[cited by applicant]
CN 1594314
· 2005
[cited by applicant]
CN 101553579A
· 2009
[cited by applicant]
EP 1281744
· 2003
[cited by applicant]
EP 708837
· 2006
[cited by applicant]
EP 1279023
· 2007
[cited by applicant]
EP 2117062A1
· 2009
[cited by applicant]
JP 2006510389
· 2006
[cited by applicant]
JP 2008512523A
· 2008
[cited by applicant]
JP 2008280506A
· 2008
[cited by applicant]
JP 2009139214A
· 2009
[cited by applicant]
JP 2013511700A
· 2013
[cited by applicant]
WO WO9015070
· 1990
[cited by applicant]
WO WO9210092
· 1992
[cited by applicant]
WO WO9309668
· 1993
[cited by applicant]
WO WO9310507
· 1993
[cited by applicant]
WO WO9322684
· 1993
[cited by applicant]
WO WO9409169
· 1994
[cited by applicant]
WO WO9926299
· 1999
[cited by applicant]
WO WO0066790
· 2000
[cited by applicant]
WO WO02079268A2
· 2002
[cited by applicant]
WO WO02081735A2
· 2002
[cited by applicant]
WO WO03006468A1
· 2003
[cited by applicant]
WO WO02081735A3
· 2003
[cited by applicant]
WO WO02079268A3
· 2003
[cited by applicant]
WO WO2003096016
· 2003
[cited by applicant]
WO WO2004001379A2
· 2003
[cited by applicant]
WO WO2004037886
· 2004
[cited by applicant]
WO WO2004077014A2
· 2004
[cited by applicant]
WO WO2004092324A2
· 2004
[cited by applicant]
WO WO2005024971A1
· 2005
[cited by applicant]
WO WO2005053056A1
· 2005
[cited by applicant]
WO WO2005086617A2
· 2005
[cited by applicant]
WO WO2006029231A1
· 2006
[cited by applicant]
WO WO2006034081A2
· 2006
[cited by applicant]
WO WO2006040530
· 2006
[cited by applicant]
WO WO2006034081A3
· 2006
[cited by applicant]
WO WO2006074471A2
· 2006
[cited by applicant]
WO WO2006074482A2
· 2006
[cited by applicant]
WO WO2006083932A2
· 2006
[cited by applicant]
WO WO2006092063
· 2006
[cited by applicant]
WO WO2008100344
· 2008
[cited by applicant]
WO WO2009051560
· 2009
[cited by applicant]
WO WO2009123269A1
· 2009
[cited by applicant]
WO WO2010151807
· 2010
[cited by applicant]
WO WO2011057295A2
· 2011
[cited by applicant]
WO WO2011091086
· 2011
[cited by applicant]
WO WO2016144653A1
· 2016
[cited by applicant]
U.S. Appl. No. 13/195,747, filed Aug. 1, 2011, Gaylord.
[cited by applicant]
U.S. Appl. No. 13/195,736, filed Aug. 1, 2011, Gaylord.
[cited by applicant]
U.S. Appl. No. 07/624, 120, filed Dec. 6, 1990, Fodor.
[cited by applicant]
U.S. Appl. No. 60/642,901, filed Jan. 10, 2005, Bazan.
[cited by applicant]
An et al., “A fluorescence ratiometric protein asssay using light-harvesting conjugated polymers,” Macromolecular Rapid Communications, 27(13):993-997 (2006).
[cited by applicant]
Ausebel et al., eds., Current Protocols in Molecular Biology, vols. I, II, and III. 1997.
[cited by applicant]
Ausubel et al., eds., Short Protocols in Molecular Biology: A Compendium of Methods from Current Protocols in Molecular Biology, 5
[cited by applicant]
Bailey et al., “Masked Micheal Acceptors in Poly(phenyleneethynylene)s for Facile Conjugation,” Macromolecules, 39:2815-2818 (2006).
[cited by applicant]
Bruchez et al., “Semiconductor nanocrystals as fluorescent biological labels,” Science, 281:2013-2016 (1998).
[cited by applicant]
Chen et al., “Highly sensitive biological and chemical sensors based on reversible fluorescence quenching in a conjugated polymer,” PNAS USA, 96(220):12287-12292 (1999).
[cited by applicant]
Delagrave et al., “Isolated mutants of cloned Aequorea victoria GFP that had red-shifted excitation spectra,” Bio/Tech 13:151-154 (1995).
[cited by applicant]
Fodor et al., “Light-directed, spatially addressable parallel chemical synthesis,” Science 251(4995):767-773 (1991).
[cited by applicant]
Gaylord et al., “DNA detection using water-soluble conjugated polymers and peptide nucleic acid probes,” PNAS USA, 99(17):10954-10957 (2002).
[cited by applicant]
Gaylord et al., “DNA hybridization detection with water-soluble conjugated polymers and chromophore-labeled single-stranded DNA,” J Am Chem Soc, 124(4):896-900 (2003).
[cited by applicant]
Gaylord et al., “SNP detection using peptide nucleic acid probes and conjugated polymers: application in neurodegenerative disease identification,” PNAS USA, 102(1):34-39 (2005).
[cited by applicant]
Geierstanger and Wemmer, “Complexes of the minor groove of DNA,” Annu Rev Biophys Biomol Struct, 24:463-493 (1995).
[cited by applicant]
Glumoff and Goldman, Nucleic Acids in Chemistry and Biology, 2
[cited by applicant]
Heeger et al., “Making sense of polymer-based biosensors,” PNAS USA, 96(22):12219-12221 (1999).
[cited by applicant]
Heim et al., “Improved green fluorescence,” Nature, 373:663-664 (1995).
[cited by applicant]
Heim et al., “Wavelength mutations and post-translational autoxidation of green fluorescent protein,” PNAS USA, 91:12501-12504 (1994).
[cited by applicant]
Ho et al., “Colorimetric and fluorometric detection of nucleic acids using cationic polythiophene derivatives,” Angewandte Chemie International Edition, 41(9):1548-1551 (2002).
[cited by applicant]
Ho et al., “Direct molecular detection of nucleic acids by fluorescence signal amplification,” J Am Chem Soc, 127(36):12673-12676 (2005).
[cited by applicant]
Innis et al., eds., PCR Protocols: A Guide to Methods and Applications, Elsevier Science & Technology Books 1990.
[cited by applicant]
Invitrogen—Molecular Probes, available at www.probes.com, accessed Dec. 19, 2007.
[cited by applicant]
Invitrogen—available at www.invitrogen.com, accessed Dec. 19, 2007.
[cited by applicant]
Kanehisa, “Use of statistical criteria for screening potential homologies in nucleic acid sequences,” Nucleic Acids Research, 12(1 Pt 1):203-213 (1984).
[cited by applicant]
Kreuzer et al., “LightCycler technology fo rthe quantitation of bcr/abl fusion transcripts,” Cancer Research, 59(13):3171-3174 (1999).
[cited by applicant]
Kreyenschmidt et al., “A New Soluble poly(p-phenylene) with Tetrahydropryrene Repeating Units,” Macromolecules, 28:4577-4582 (1995).
[cited by applicant]
Larson and Verdine, Bioorganic Chemistry: Nucleic Acids, Hecht ed., Oxford University Press: New York 1996 pp. 324-346.
[cited by applicant]
Laurendeau et al., “Quantitation of MYC gene expression in sporadic breast tumors with a real-time reverse transcription PCR assay,” Cancer Res, 59(12):2759-2765 (1999).
[cited by applicant]
Laurendeau et al., “TaqMan PCR-based gene dosage assay for predictive testing in individuals from a cancer family with INK4 locus haploinsufficiency,” Clin Chem, 45(7):982-986 (1999).
[cited by applicant]
Leclerc, “Polyfluorenes: Twenty Years of Progress,” Polym Sci Part A: Polym Chem, 39:2867-2873 (2001).
[cited by applicant]
Lee, “Functionalized Conjugated Polymers for Signal Amplifying Biosensors and Sensor Arrays,” Dissertation, The University of Michigan, 2008.
[cited by applicant]
Lee et al., “Synthesis and Characterization of Oligo(9,9-dihyexyl-2,7-fluorene ethynylene)s: For Application as Blue Light-Emitting Diode,” Org Lett, 3:2005-2007 (2001).
[cited by applicant]
Liu et al., “Characterization of tectoRNA assembly with cationic conjugated polymers,” J Am Chem Soc, 126(13):4076-4077 (2004).
[cited by applicant]
Liu et al., “Interpolyelectrolyte complexes of conjugated copolymers and DNA: platforms for multicolor biosensors,” J Am Chem Soc, 126(7):1942-1943 (2004).
[cited by applicant]
Liu et al., “Methods for strand-specific DNA detection with cationic conjugated polymers suitable for incorporation into DNA chips and microarrays,” PNAS USA, 102(3):589-593 (2005).
[cited by applicant]
Liu et al., “Optimization of the molecular orbital energies of conjugated polymers for optical amplification of fluorescent sensors,” J Am Chem Soc, 128:1188-1196 (2006).
[cited by applicant]
Liu et al., “Shape-adaptable water-soluble conjugated polymers,” J Am Chem Soc, 124(44):13306-13307 (2003).
[cited by applicant]
Mikroyannidis et al., “Alternating copolyfluorenevinyles with polynuclear aromatic moieties: Synthesis, photophysics, and electroluminescence,” J Polym Sci Part A:Polym Chem, 45:4661-4670 (2007).
[cited by applicant]
Pei et al., “Efficient Photoluminescence and Electroluminescence from a Soluble Polyfluorene,” J Am Chem Soc, 118:7416-7417 (1996).
[cited by applicant]
Pierce, Biotechnology, available at www.piercenet.com, accessed Dec. 19, 2007.
[cited by applicant]
Sambrook et al., Molecular Cloning: A Laboratory Manual, 3
[cited by applicant]
Sekar et al., “Phycobiliproteins as a commodity: trends in applied research, patents and commercialization,” J Appl Phycol, 20:113-136 (2008).
[cited by applicant]
Sonogashira et al., “A convenient synthesis of acetylenes: catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes and bromopyridines,” Tetra Lett, 16:4467-4470 (1975).
[cited by applicant]
Wang et al., “Biosensors from conjugated polyelectrolyte complexes,” PNAS USA, 99(1):49-53 (2002).
[cited by applicant]
Wang et al., “Collective optical behavior of cationic water-soluble dendrimers,” Advanced Materials, 16(23-24):2127-2132 (2004).
[cited by applicant]
Wang et al., “Fluorescein provides a resonance gate for FRET from conjugated polymers to DNA intercalated dyes,” J Am Chem Soc, 126(17):5446-5451 (2004).
[cited by applicant]
Wang, “From DNA biosensors to gene chips,” Nucl Acids Res, 28(16):3011-3016 (2000).
[cited by applicant]
Wang et al., “Optimally amplified RNA-protein detection methods using light-harvesting conjugated polymers,” Advanced Materials, 15(17):1425-1428 (2003).
[cited by applicant]
Wosnick et al., “Synthesis and application of poly(phenylen ethynylene)s for bioconjugation: a conjugated polymer-based fluorogenic proble for proteases,” J Am Chm Soc, 127:3400-3405 (2005).
[cited by applicant]
Xu et al., “Magnetically assisted DNA assays: high selectivity using conjugated polymers for amplified fluorescent transduction,” Nucl Acids Res, 33(9):e83 (2005).
[cited by applicant]
Yamamoto et al., “Preparation of π-Conjugated Poly(thiophene-2,5-diyl), Poly(p-phenylene), and Related Polymers Using Zerovalent Nickel Complexes. Linear Structure and Properties of the π-Conjugated Polymers,” Macromole…
[cited by applicant]
Zhou et al., “Polyfluorenes with phosphonate groups in the side chains as chemosensors and electroluminescent materials,” Macromolecules, 38:5416-5424 (2005).
[cited by applicant]
EP 07873316 Supplemental Search Report dated Aug. 3, 2010.
[cited by applicant]
JP 2009-531642 Office Action mailed Mar. 22, 2012.
[cited by applicant]
PCT/US2010/40051 International Search Report dated Sep. 30, 2010.
[cited by applicant]
PCT/US11/21775 Search Report and Written Opinion dated May 19, 2011.
[cited by applicant]
Xue, et al. “Highly water-soluble, fluorescent, conjugated fluorene-based glycopolymers with poly(ethylene glycol)-tethered spacers for sensitive detection of
[cited by applicant]
USPTO Petitioner's Reply Inter Partes Review IPR2022-01207 U.S. Pat. No. 10,288,620, Jul. 14, 2023, 32 pages.
[cited by applicant]
USPTO Petitioner's Reply Inter Partes Review IPR2022-01206 U.S. Pat. No. 10,302,648, Jul. 14, 2023, 32 pages.
[cited by applicant]
USPTO Petitioner's Reply Inter Partes Review IPR2022-01205 U.S. Pat. No. 10,955,417, Jul. 14, 2023, 19 pages.
[cited by applicant]
USPTO Petitioner's Reply Inter Partes Review IPR2022-01204 U.S. Pat. No. 10,365,285, Jul. 14, 2023, 32 pages.
[cited by applicant]
USPTO Petitioner's Reply Inter Partes Review IPR2022-01203 U.S. Pat. No. 10,458,989, Jul. 14, 2023, 32 pages.
[cited by applicant]
Wang, et al. “A Water-Soluble TT-Conjugated Polymer with up to 100 mg mL-1 Solubility”, Macro Molecular Rapid Communications, vol. 28, Issue16, Aug. 14, 2007, pp. 1645-1650.
[cited by applicant]
Abbel, et al. “Fluorene-based materials and their supramolecular properties”, J. Polym. Sci. Part A, 47:4215-4223, 2009.
[cited by applicant]
Becker, et al. “Optimisation of polyfluorenes for light emitting applications”, Synthetic Metals, 125:73-80, 2002.
[cited by applicant]
Bernius, et al.“Progress with light-emitting polymers”, Adv. Mater., 12(23):1737-1750, 2000.
[cited by applicant]
Brinkley, et al. “A Brief Survey of Methods for Preparing Protein Conjugates with Dyes, Haptens, and Cross-Linking Reagents”, Bioconjugate Chem., 3:2-13, 2002.
[cited by applicant]
Canalle, et al. “Polypeptide-polymer bioconjugates”, Chem. Soc. Rev., 39:329-353, 2010.
[cited by applicant]
Disney, et a;. “Detection of Bacteria with Carbohydrate-Functionalized Fluorescent Polymers”, J. Am. Chem. Soc., 126:13343-13346, 2004.
[cited by applicant]
Ebewele, et al. “Polymer Science and Technology”, CRC Press, 2000, 544 pp. 2000.
[cited by applicant]
Eckelt, et al. “Solubility of Polymers”, Encylopedia of Polymer Science & Technology, 4th Edition, 2009, Macromolecular Chemistry and Physics, 210, 1433-1439 (2009).
[cited by applicant]
Ego, et al. “Attaching Perylene Dyes to Polyfluorene: Three Simple Efficient Methods for Facile Color Tuning of Light-Emitting Polymers”, J. Am. Chem. Soc., 125:437-443, 2003.
[cited by applicant]
Francke, et al. Synthesis of α,ω-Difunctionalized Oligo- and Poly(p-phenyleneethynylene) s, Macromol. 31:2447-2453, 1998.
[cited by applicant]
Garti, et al. “Graft Copolymers as Emulsifiers: Part I: Grafted Polyethyleneglycol on Polymethylmetacrylate”, J. Disperson Sci. & Tech., 14:47-70, 1993.
[cited by applicant]
Gauthier, et al. “Peptide/protein-polymer conjugates:synthetic strategies and design concepts”, Chem. Commun., 2591-2611, 2008.
[cited by applicant]
Gordon, et al. “Synthesis of end-labeled multivalent ligands for exploring cell-surfacereceptor-ligand interactions”, Chemistry & Biology, 7:9-16, 2000.
[cited by applicant]
Stork, et al. “Energy Transfer in Mixtures of Water-Soluble Oligomers: Effect of Charge, Aggregation”, and Surfactant Complexation, Adv. Mater., 14(5):361-366, 2002.
[cited by applicant]
Grayson, et a;. “Convergent Dendrons and Dendrimers: from Synthesis to Applications”, Chem. Rev., 101:3819-3867, 2001.
[cited by applicant]
Hashida, et al. “More Useful Maleimide Compounds for the Conjugation of Fab' to Horseradish Perodise through Thiol Groups in the Hinge”, J. Appl. Biochem., 6:56-63, 1984.
[cited by applicant]
Haugland, et al. “Antibody Conjugates in Cell Biology”, Current Protocols in Cell Biology, 16.5.1-16.5.22, 2000.
[cited by applicant]
Haugland, et al. “Coupling of Monoclonal Antibodies with Fluorophores”, Methods in Molecular Biology, 45:205-221, 1995.
[cited by applicant]
Heeger, et al. “Making sense of polymer-based biosensors”, PNAS, 96(22): 12219-12221, 1999.
[cited by applicant]
Heredia, et al. “Synthesis of protein-polymer conjugates”, Org. Biomol. Chem., 5:45-53, 2007.
[cited by applicant]
Hermanson, et al. “Bioconjugate Techniques, Second Edition”, 2008, 1233 pages, Elsevier Inc.
[cited by applicant]
Hoffman, et a;. “Conjugates of stimuli-responsive polymers and proteins”, Prog. Polym. Sci., 32:922-932, 2007.
[cited by applicant]
Hou, et al. “Novel red-emitting fluorene-based copolymers”, J. Mat. Chem. 12:2887-92, 2002.
[cited by applicant]
Inbasekaran, et al. “Fluorene homopolymers and copolymers”, Synthetic Metals 111-112:397-401, 2000.
[cited by applicant]
Jones, et al. “Compendium of Polymer Terminology and Nomenclature”, IUPAC Recommendations 2009.
[cited by applicant]
Jenkins, et al “Glossary of Basic Terms in Polymer Science (IUPAC Recommendations 1996)”, Pure & Appl. Chem., 68(12):2287-231, 1996.
[cited by applicant]
Johnson, et al. “Fluorophores for optical imaging”, Optical Imaging of Cancer 59-77, 2009.
[cited by applicant]
Khan, et al. “Practical synthesis of an amphiphilic, non-ionic poly(paraphenyleneethynylene) derivative with a remarkable quantum yield in water”, Chem. Commun.2005, 584-586, 2005.
[cited by applicant]
Kikuchi, et al. “Recent advances in the design of smallmolecule-based FRET sensors for cell biology”, Trends in Analytical Chemistry, 23:407-415, 2004.
[cited by applicant]
Kim, et al. “Nonspecific Interactions of a Carboxylate-Substituted PPE with Proteins. A Cautionary Tale for Biosensor Applications”, Langmuir,21:7985-7989, 2005.
[cited by applicant]
Kristensen, et al. “Behold Cytometrists: One Block Is Not Enough!”, Cytometry, 99:265-268, 2020.
[cited by applicant]
Kuroda, et al. “Synthesis of a nonionic water soluble semiconductive polymer”, Chem.Commun., 2002, 2003:26-27.
[cited by applicant]
Li, et al. “Generic strategy of preparing fluorescent conjugated-polymer-loaded poly(DL-lactide-co-glycolide) nanoparticles for targeted cell imaging”, Adv. Funct. Mater., 19:3535-42, 2009.
[cited by applicant]
Liu, et al. “Synthesis of a novel cationic watersoluble efficient blue photoluminescent conjugated polymer”, Chem. Commun., 551-552, 2000.
[cited by applicant]
Li, et al. “Water-soluble conjugated polymers as the platform for protein sensors”, Polym. Chem., 1:252-259, 2010.
[cited by applicant]
Shi, et al. “Synthesis and characterization of water-soluble conjugated glycopolymer for fluorescent sensing of concanavalin A”, Chem. Asian J., 5:301-08, 2010.
[cited by applicant]
Lou, et al. “Polymer-Based Elemental Tags for Sensitive Bioassays,” Angew. Chem. Int. Ed., 46:6111-6114, 2007.
[cited by applicant]
Lutz, et al. “Polymer Modifiers and Additives”, 2000, CRC Press, 533 pages.
[cited by applicant]
Maecker, et al. “Selecting fluorochrome conjugates for maximum sensitivity, Cytometry”, 62A:169-173, 2004.
[cited by applicant]
Meister, et al. “A review of polymer dissolution”, Prog. Polym. Sci., 28:1223-1270, 2000.
[cited by applicant]
Miller-Chou, et al. “review of polymer dissolution” , Prog.Polym. Sci., 28:1223-1270, 2003.
[cited by applicant]
Minato, et al. “Polymerization of naphthalene and reactions of polynaphthalene”, Chem. Soc'y of Japan, 42:779-81, 1969.
[cited by applicant]
Morales, et al. “Amine-Reactive Fluorene Probes:Synthesis, Optical Characterization, Bioconjugation, and Two-Photon Fluorescence Imaging”, Bioconjugate Chem., 19:2559-2567, 2008.
[cited by applicant]
Odian, et al. “Principles of Polymerization”, Fourth Edition, A John Wiley & Sons, Inc. 2004, 839 pages.
[cited by applicant]
Panchuk-Voloshina, et al. “Alexa Dyes, a Series of New Fluorescent Dyes that Yield Exception Bright”, Photostable Conjugates, J. Histochem. Cytochem., 47:1179-1188, 1996.
[cited by applicant]
Phillips, et al. “Sugar-Substituted Poly(pphenyleneethynylene)s: Sensitivity Enhancement toward Lectins and Bacteria”, Macromol., 41:7316-7320, 2008.
[cited by applicant]
Prechtl, et al. “Precision and Purity of Conjugated Polymers—To be Ensured Before Processing”, Solution-Processable Components for Organic Electronic Devices, pp. 1-55, 2019.
[cited by applicant]
Sakamoto, et al. “Suzuki Polycondensation: Polyarylenes ála Carte”, Macromol. Rapid Commun., 30:653-687, 2003.
[cited by applicant]
Shapiro, et al. “Practical Flow Cytometry”, Fourth Edition, John Wiley & Sons Inc, 2003.
[cited by applicant]
Stockton, et al. “Hydrolysis of 3-carboxy-6,8-difluoro-7-hydroxycoumarin (Pacific BlueTM) succinimidyl ester under acidic and basic conditions”, Dyes & Pigments, 97:148-151, 2012.
[cited by applicant]
Grimsdale, et al. “Synthesis of Light-Emitting Conjugated Polymers for Applications in Electroluminescent Devices”, Chemical Reviews, American Chemical Society, US, vol. 109, Feb. 1, 2009 (Feb. 1, 2009), pp. 897-1091.
[cited by applicant]
Sumranjit, et al. “Conjugated Organic Molecules as Models for Potential Sensors”, Univ. of Mass, Dept. of Chemistry, 2008, 137 pages.
[cited by applicant]
Thomas, et al. “Chemical Based on Amplifying Fluorescent Conjugated Polymers”, Chem. Rev., 107:1339-1386, 2007.
[cited by applicant]
Thompson, et al. Synthesis and applications of heterobifunctional poly(ethylene oxide) oligomers, Polymer, 49:345-373, 2007.
[cited by applicant]
Wang, et al. “Size-Specific Interactions Between Single- and Double-Stranded Oligonucleotides and Cationic Water-Soluble Oligofluorenes”, Adv. Func. Mater., 13(6):463-467, 2002.
[cited by applicant]
Wang, et al. “Synthesis, characterization and selfassembly behavior in water as fluorescent sensors of cationic watersoluble conjugated polyfluorene-b-poly (N-isopropylacrylamide) diblock copolymers”, Polymer, 50:1236-4…
[cited by applicant]
Wang, et al. Conjugated polymer as a signal amplifier for novel silica nanoparticlebased fluoroimmunoassay, Biosens. Bioelectron., 24:3293-3298, 2009.
[cited by applicant]
Xue, et al. “Synthesis of Highly Water-Soluble Fluorescent Conjugated Glycopoly(pphenylene) s for Lectin and
[cited by applicant]
Xue, et al. Facile, Versatile Prepolymerization and PostpolymerizationFunctionalization Approaches for Well-Defined Fluorescent Conjugated Fluorene-Based Glycopolymers, Macromol., 39:5747-5752, 2006.
[cited by applicant]
Xue, et al. Post-Polymerization Functionalization Approach for Highly Water-Soluble Dell-Defined Regioregular Head-to-Tail Glycopolythiophenes, Macromol., 40:6863-6870, 2007.
[cited by applicant]
Xue, et al.“Highly water-soluble, fluorescent, conjugated fluorene-based glycopolymers with poly(ethyleneglycol)-tethered spacers for sensitive detection of
[cited by applicant]
Yeates, et al. “Ethylene glycol oligomers”, Makromol. Chem., 185:1559-1563, 1984.
[cited by applicant]
Yu, et al. “Synthesis of water-soluble dendritic conjugated polymers for fluorescent DNA assays”, Macromol. Rapid Commun., 27:1739-45, 2006.
[cited by applicant]
Zalipsky, et al. “Functionalized Poly(ethylene glycols) for Preparation of Biologically Relevant Conjugates”, Bioconjugate Chem., 6:150-165, 1995.
[cited by applicant]
Zheng, et al. “Biotinylated poly(p-phenylene ethynylene): unexpected energy transfer results in the detection of biological analytes”, Chem. Commun. 2798-2799, 2004.
[cited by applicant]
Zhou, et a;. “Methodology for Enhancing the Sensitivity of Fluorescent Chemosensors: Energy Migration in Conjugated Polymers”, J. Am. Chem. Soc., 117:7017-7018.
[cited by applicant]
Zhou, et a;. “Fluorescent Chemosensors Based on Energy Migration in Conjugated Polymers: The Molecular Wire Approach to Increased Sensitivity”, J. Am. Chem. Soc., 117:12593-12602, 1995.
[cited by applicant]
Barendt et al., “Supramolecular Assemblies for Electronic Materials”, Chem. Eur. J., vol. 26, No. 17, pp. 3744-3748 (2020).
[cited by applicant]
McQuade, et al., “Conjugated Polymer-Based Chemical Sensors”, Chem. Rev., vol. 100, pp. 2537-2574 (2000).
[cited by applicant]
Nobel Prize 2000 The Nobel Prize in Chemistry 2000, https://www.nobelprize.org/prizes/chemistry/2000/summary/ (last accessed Aug. 17, 2022).
[cited by applicant]
USPTO Decision Granting Institution of Inter Partes Review 35 U.S.C. § 314, IPR2022-01204 U.S. Pat. No. 10,365,285 B2, Jan. 6, 2023, 48 pages.
[cited by applicant]
USPTO Decision Denying Institution of Inter Partes Review 35 U.S.C. § 314, IPR2022-01208 U.S. Pat. No. 8,575,303 B2, Jan. 6, 2023, 28 pages.
[cited by applicant]
USPTO Decision Granting Institution of Inter Partes Review 35 U.S.C. § 314, IPR2022-01205 U.S. Pat. No. 10,955,417 B2, Jan. 6, 2023, 45 pages.
[cited by applicant]
USPTO Decision Granting Institution of Inter Partes Review 35 U.S.C. § 314, IPR2022-01207 U.S. Pat. No. 10,288,620 B2, Jan. 6, 2023, 40 pages.
[cited by applicant]
USPTO Decision Granting Institution of Inter Partes Review 35 U.S.C. § 314, IPR2022-01206 U.S. Pat. No. 10,302,648 B2, Jan. 6, 2023, 48 pages.
[cited by applicant]
USPTO Decision Granting Institution of Inter Partes Review 35 U.S.C. § 314, IPR2022-01203 U.S. Pat. No. 10,458,989 B2, Jan. 6, 2023, 51 pages.
[cited by applicant]
USPTO Judgment—Final Written Decision Determining All Claims Unpatentable Granting Motions to Seal 35 U.S.C. § 318(a), Inter Partes Review IPR2022-01203 U.S. Pat. No. 10,458,989, Dec. 21, 2023, 79 pages.
[cited by applicant]
USPTO Judgment—Final Written Decision Determining All Claims Unpatentable Granting Motions to Seal 35 U.S.C. § 318(a), Inter Partes Review IPR2022-01204 U.S. Pat. No. 10,365,285, Dec. 21, 2023, 82 pages.
[cited by applicant]
USPTO Judgment—Final Written Decision Determining All Claims Unpatentable Granting Motions to Seal 35 U.S.C. § 318(a), Inter Partes Review IPR2022-01205 U.S. Pat. No. 10,955,417, Dec. 21, 2023, 68 pages.
[cited by applicant]
USPTO Judgment—Final Written Decision Determining All Claims Unpatentable Granting Motions to Seal 35 U.S.C. § 318(a), Inter Partes Review IPR2022-01206 U.S. Pat. No. 10,302,648, Dec. 21, 2023, 77 pages.
[cited by applicant]
USPTO Judgment—Final Written Decision Determining All Claims Unpatentable Granting Motions to Seal 35 U.S.C. § 318(a), Inter Partes Review IPR2022-01206 U.S. Pat. No. 10,288,620, Dec. 21, 2023, 87 pages.
[cited by applicant]