Granted Patent
B2
US 12,253,525 · App. 17/712,462 · Granted Mar 18, 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 (43)
1. A conjugated polymer having a backbone of x-conjugated repeat units and the structure of the formula:
wherein:
Ar is polycyclic repeat unit substituted with an ethylene glycol oligomer side group;
MU is a polymer modifying unit or band gap modifying unit that is evenly or randomly distributed along the polymer main chain and is optionally substituted with one or more optionally substituted substituents selected from halogen, hydroxyl, C1-C12 alkyl, C2-C12 alkene, C2-C12 alkyne, C3-C12 cycloalkyl, C1-C12 haloalkyl, C1-C12 alkoxy, C2-C18 (hetero)aryloxy, C2-C18 (hetero)arylamino, a C2-C18 (hetero)aryl group and (CH2)x′(OCH2CH2)y′OCH3 where x′ is independently an integer from 0-20 and y′ is independently an integer from 0 to 50;
optional linkers L1 and L2 are each independently an aryl or a heteroaryl group evenly or randomly distributed along the polymer main chain and are 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 molecule or biomolecule; or ii) a conjugated organic dye or biomolecule;
G1 and G2 are each independently selected from hydrogen, halogen, alkyne, optionally substituted aryl, optionally substituted heteroaryl, halogen substituted aryl, boronic acid substituted aryl, boronic ester substituted aryl, boronic ester, boronic acid, optionally substituted fluorene and aryl or heteroaryl, or a conjugated organic dye or biomolecule;
wherein:
the polymer comprises a conjugated biomolecule;
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 from 1 to about 10,000;
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 a mol % from 0 to 90%, and each c and d are mol % from 0 to 25%; and
the polymer has a water solubility in excess of 10 mg/ml.
2. The conjugated polymer according to claim 1 , wherein Ar comprises 1 to 5 aromatic rings.
3. The conjugated polymer according to claim 1 , wherein Ar comprises up to 5 fused and/or bridged rings.
4. The conjugated polymer according to claim 1 , wherein Ar comprises a biphenyl.
5. The conjugated polymer according to claim 4 , wherein the biphenyl is bridged.
6. The conjugated polymer according to claim 1 , wherein the ethylene glycol oligomer side group comprises a polyethylene glycol (PEG).
7. The conjugated polymer according to claim 6 , wherein the PEG comprises mPEG5, mPEG8, mPEG11 or mPEG24.
8. The conjugated polymer according to claim 1 , wherein at least one of G1 and G2 comprises a conjugated biomolecule.
9. The conjugated polymer according to claim 1 , wherein the conjugated biomolecule comprises a sensor protein.
10. The conjugated polymer according to claim 9 , wherein the sensor protein comprises an antibody.
11. The conjugated polymer according to claim 1 , wherein Mu is absent.
12. The conjugated polymer according to claim 1 , wherein Mu is present.
13. A conjugated polymer having the structure of the formula:
wherein:
Ar is polycyclic repeat unit substituted with an ethylene glycol oligomer side group;
MU is a polymer modifying unit or band gap modifying unit that is evenly or randomly distributed along the polymer main chain and is optionally substituted with one or more optionally substituted substituents selected from halogen, hydroxyl, C1-C12 alkyl, C2-C12 alkene, C2-C12 alkyne, C3-C12 cycloalkyl, C1-C12 haloalkyl, C1-C12 alkoxy, C2-C18 (hetero)aryloxy, C2-C18 (hetero)arylamino, a C2-C18 (hetero)aryl group and (CH2)x′(OCH2CH2)y′OCH3 where x′ is independently an integer from 0-20 and y′ is independently an integer from 0 to 50;
optional linkers L1 and L2 are each independently an aryl or a heteroaryl group evenly or randomly distributed along the polymer main chain;
G1 and G2 are each independently selected from hydrogen, halogen, alkyne, optionally substituted aryl, optionally substituted heteroaryl, halogen substituted aryl, boronic acid substituted aryl, boronic ester substituted aryl, boronic ester, boronic acid, optionally substituted fluorene and aryl or heteroaryl substituted with one or more pendant chains, wherein at least one of G1 and G2 comprises a conjugated biomolecule;
n is an integer so that the conjugated polymer has a molecular weight ranging from 5,000 g/mol to 100,000 g/mol from 1 to about 10,000; 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 a mol % from 0 to 90%, and each c and d are mol % from 0 to 25%;
wherein the polymer has a water solubility in excess of 10 mg/ml.
14. The conjugated polymer according to claim 13 , wherein Ar comprises 1 to 5 aromatic rings.
15. The conjugated polymer according to claim 13 , wherein Ar comprises up to 5 fused and/or bridged rings.
16. The conjugated polymer according to claim 13 , wherein Ar comprises a biphenyl.
17. The conjugated polymer according to claim 16 , wherein the biphenyl is bridged.
18. The conjugated polymer according to claim 13 , wherein the ethylene glycol oligomer side group comprises a polyethylene glycol (PEG).
19. The conjugated polymer according to claim 18 , wherein the PEG comprises mPEG5, mPEG8, mPEG11 or mPEG24.
20. The conjugated polymer according to claim 13 , wherein the conjugated biomolecule comprises a sensor protein.
21. The conjugated polymer according to claim 20 , wherein the sensor protein comprises an antibody.
22. The conjugated polymer according to claim 11 , wherein Mu is absent.
23. The conjugated polymer according to claim 11 , wherein Mu is present.
24. The conjugated polymer according to claim 1 , wherein G1 and G2 do not comprise a repeat unit.
25. The conjugated polymer according to claim 13 , wherein G1 and G2 do not comprise a repeat unit.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 26, 2022
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 060625/0501 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 26, 2022
From: SIRIGEN INC.
To: SIRIGEN GROUP LIMITED
Reel/Frame 060625/0540 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 26, 2022
From: SIRIGEN GROUP LIMITED
To: SIRIGEN II LIMITED
Reel/Frame 060625/0591 →
Continuity (9)
Provisional Application
61358406
· Jun 24, 2010
Provisional Application
61296379
· Jan 19, 2010
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