US 11,970,731 B2
Enhancement of nucleic acid polymerization by aromatic compounds
Mark Stamatios Kokoris, Bothell, WA (US); John Tabone, Kirkland, WA (US); Melud Nabavi, Seattle, WA (US); Aaron Jacobs, Seattle, WA (US); Dylan O'Connell, Seattle, WA (US); Drew Goodman, Seattle, WA (US); Lacey Merrill, Seattle, WA (US); Jagadeeswaran Chandrasekar, Seattle, WA (US); Kendall Berg, Seattle, WA (US); Samantha Vellucci, Seattle, WA (US); and Jessica Vellucci, Bremerton, WA (US)
Assigned to Roche Sequencing Solutions, Inc., Pleasanton, CA (US)
Appl. No. 16/959,985
Filed by Roche Sequencing Solutions, Inc., Pleasanton, CA (US)
PCT Filed Dec. 27, 2018, PCT No. PCT/US2018/067763
§ 371(c)(1), (2) Date Jul. 2, 2020,
PCT Pub. No. WO2019/135975, PCT Pub. Date Jul. 11, 2019.
Claims priority of provisional application 62/717,549, filed on Aug. 10, 2018.
Claims priority of provisional application 62/656,696, filed on Apr. 12, 2018.
Claims priority of provisional application 62/614,120, filed on Jan. 5, 2018.
Prior Publication US 2021/0062251 A1, Mar. 4, 2021
Int. Cl. C12Q 1/6848 (2018.01); C07D 249/06 (2006.01); C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 471/04 (2006.01); C12Q 1/6869 (2018.01)
CPC C12Q 1/6848 (2013.01) [C07D 249/06 (2013.01); C07D 401/14 (2013.01); C07D 403/14 (2013.01); C07D 471/04 (2013.01); C12Q 1/6869 (2013.01)] 40 Claims
 
1. A method of enhancing a nucleic acid polymerase reaction, the method comprising:
a. forming a nucleic acid polymerase reaction composition comprising:
i. a template nucleic acid,
ii. a nucleic acid polymerase,
iii. a mixture of nucleotides or nucleotide analogs, and
iv. at least one compound of formula (I); and
b. incubating the nucleic acid polymerase reaction composition under conditions allowing a nucleic acid polymerization reaction, wherein the at least one compound of formula (I) increases the processivity, rate, or fidelity of the nucleic acid polymerase reaction; wherein the compound of formula (I) is represented by:

OG Complex Work Unit Chemistry
wherein, independently at each occurrence:
m is 1, 2 or 3;
n is 0, 1 or 2;
p is 0, 1 or 2;
Ar1 is optionally substituted aryl;
Ar2 is selected from 5- and 6-membered monocyclic aromatic rings and 9- and 10-membered fused bicyclic rings comprising two 5- and/or 6-membered monocyclic rings fused together, where at least one of the two monocyclic rings is an aromatic ring, where
Ar2 is optionally substituted with one or more substituents selected from halide, C1-C6alkyl, C1-C6haloalkyl, E-CO2R0, E-CONH2, E-CHO, E-C(O)NH(OH), E-N(R0)2, and E-OR0, where
E is selected from a direct bond and C1-C6alkylene; and
R0 is selected from H, C1-C6alkyl and C1-C6haloalkyl,
M is selected from hydrogen, halogen and C1-C4alkyl; and
L is a linking group;
or a solvate, hydrate, tautomer, chelate or salt thereof.