I 1111111111111111 1111111111 11111 11111 11111 11111 1111111111 111111111111111111
`USO 11118221B2
`
`c12) United States Patent
`Talasaz et al.
`
`US 11,118,221 B2
`(IO) Patent No.:
`*Sep.14,2021
`(45) Date of Patent:
`
`(54) METHODS AND SYSTEMS FOR DETECTING
`GENETIC VARIANTS
`
`(71) Applicant: GUARDANT HEALTH, INC.,
`Redwood City, CA (US)
`
`(72)
`
`Inventors: Amir Ali Talasaz, Atherton, CA (US);
`Stefanie Ann Ward Mortimer, Morgan
`Hill, CA (US); Helmy Eltoukhy,
`Atherton, CA (US)
`
`(73) Assignee: GUARDANT HEALTH, INC.,
`Redwood City, CA (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by O days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 16/672,267
`
`(22) Filed:
`
`Jan. 7, 2020
`
`5,445,934 A
`5,604,097 A
`5,635,352 A
`5,635,400 A
`5,648,245 A
`5,654,413 A
`5,656,731 A
`5,658,737 A
`5,714,330 A
`5,744,305 A
`5,759,778 A
`5,763,175 A
`5,800,992 A
`5,846,719 A
`5,854,033 A
`5,871,928 A
`5,925,525 A
`5,935,793 A
`5,952,170 A
`5,968,740 A
`5,981,176 A
`5,981,179 A
`6,013,445 A
`6,020,124 A
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`(Continued)
`
`FOREIGN PATENT DOCUMENTS
`
`(65)
`
`Prior Publication Data
`
`US 2020/0115746 Al
`
`Apr. 16, 2020
`
`CN
`EP
`
`2/2013
`102933721 A
`0799897 Bl
`6/2006
`(Continued)
`
`Related U.S. Application Data
`
`OTHER PUBLICATIONS
`
`(63) Continuation of application No. 16/601,168, filed on
`Oct. 14, 2019, now Pat. No. 10,801,063, which is a
`continuation of application No. 15/892,178, filed on
`Feb. 8, 2018, which is a continuation of application
`No. 14/861,989, filed on Sep. 22, 2015, now Pat. No.
`9,920,366, which is a continuation of application No.
`PCT/US2014/072383, filed on Dec. 24, 2014.
`
`(60) Provisional application No. 61/948,509, filed on Mar.
`5, 2014, provisional application No. 61/921,456, filed
`on Dec. 28, 2013.
`
`(51)
`
`(52)
`
`(58)
`
`(56)
`
`(2006.01)
`(2018.01)
`(2018.01)
`(2019.01)
`
`Int. Cl.
`C12P 19134
`C12Q 116869
`C12Q 116886
`Gl6B 15/00
`U.S. Cl.
`CPC ......... C12Q 116869 (2013.01); C12Q 116886
`(2013.01); Cl2Q 2535/122 (2013.01); Cl2Q
`2600/158 (2013.01); Gl6B 15/00 (2019.02)
`Field of Classification Search
`CPC .................................................... C12Q 1/6869
`See application file for complete search history.
`
`References Cited
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`(Continued)
`
`Primary Examiner - Kenneth R Horlick
`(74) Attorney, Agent, or Firm - Timothy A. Hott
`
`(57)
`
`ABSTRACT
`
`Disclosed herein in are methods and systems for determin(cid:173)
`ing genetic variants (e.g., copy number variation) in a
`polynucleotide sample. A method for determining copy
`number variations includes tagging double-stranded poly(cid:173)
`nucleotides with duplex tags, sequencing polynucleotides
`from the sample and estimating total number of polynucle(cid:173)
`otides mapping to selected genetic loci. The estimate of total
`number of polynucleotides can involve estimating the num(cid:173)
`ber of double-stranded polynucleotides in the original
`sample for which no sequence reads are generated. This
`number can be generated using the number of polynucle(cid:173)
`otides for which reads for both complementary strands are
`detected and reads for which only one of the two comple(cid:173)
`mentary strands is detected.
`
`30 Claims, 11 Drawing Sheets
`
`00001
`
`EX1001
`
`

`

`(56)
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