US 12,000,000 B2
Labeled nucleotide analogs, reaction mixtures, and methods and systems for sequencing
Lubomir Sebo, Redwood City, CA (US); Gene Shen, Santa Clara, CA (US); Stephen Yue, Eugene, OR (US); Honey Osuna, San Francisco, CA (US); Yuri Lapin, Newark, CA (US); Louis Brogley, Santa Cruz, CA (US); and Andrei Fedorov, San Bruno, CA (US)
Assigned to Pacific Biosciences of California, Inc., Menlo Park, CA (US)
Filed by Pacific Biosciences of California, Inc., Menlo Park, CA (US)
Filed on Oct. 10, 2022, as Appl. No. 18/045,436.
Application 18/045,436 is a continuation of application No. 17/006,669, filed on Aug. 28, 2020, granted, now 11,466,319.
Application 17/006,669 is a continuation of application No. 15/357,966, filed on Nov. 21, 2016, granted, now 10,781,483, issued on Sep. 22, 2020.
Claims priority of provisional application 62/258,416, filed on Nov. 20, 2015.
Prior Publication US 2023/0366018 A1, Nov. 16, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12Q 1/68 (2018.01); C07H 19/10 (2006.01); C07H 19/207 (2006.01); C07K 19/00 (2006.01); C09B 69/10 (2006.01); C12Q 1/6869 (2018.01)
CPC C12Q 1/6869 (2013.01) [C07H 19/10 (2013.01); C07H 19/207 (2013.01); C07K 19/00 (2013.01); C09B 69/105 (2013.01)] 43 Claims
 
1. A labeled nucleotide analog comprising:
a first avidin protein having four subunits, each subunit comprising one biotin binding site;
a first nucleotide compound, bound to the first avidin protein, the first nucleotide compound comprising a polyphosphate element, a nucleoside element, an optional multivalent central core element, a terminal coupling element, and a nucleotide linker element; and
a first dye-labeled compound, bound to the first avidin protein;
wherein the first dye-labeled compound is a compound of structural formula (IIIG):

OG Complex Work Unit Chemistry
 wherein
each L′ is independently a dye compound linker element;
each S is independently a shield element;
each Dye is independently either an acceptor dye or a donor dye;
each B″ is independently a terminal coupling element;
each p is independently 0 or 1; and
each r″ is independently an integer from 0 to 8;
s is an integer from 1 to 6; and
t is 0 or 1;
wherein the compound of structural formula (IIIG) comprises at least one shield element,
at least one acceptor dye, and at least one donor dye; and
wherein the at least one shield element does not comprise a protein.