(12) United States Patent
`US 9,840,743 B2
`(10) Patent No.:
`Talasaz
`(45) Date of Patent:
`*Dec. 12, 2017
`
`US009840743B2
`
`(54) SYSTEMS AND METHODS TO DETECT
`RARE MUTATIONS AND COPY NUMBER
`VARIATION
`
`(71) Applicant: Guardant Health, Inc., Redwood City,
`CA (US)
`
`(72)
`
`Inventor: AmirAli Talasaz, Menlo Park, CA (US)
`
`(73) Assignee: Guardant Health, Inc., Redwood City,
`CA (US)
`
`*
`
`Notice:
`
`J
`y
`Sub'ect to an disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`This patent is subject to a terminal dis-
`claimer.
`
`(21) Appl. No.: 15/467,570
`
`(22)
`
`Filed:
`
`Mar. 23, 2017
`
`(65)
`
`Prior Publication Data
`
`US 2017/0218459 A1
`
`Aug. 3, 2017
`
`Related US. Application Data
`
`(63) Continuation of application No. 14/425,189, filed as
`application No. PCT/US2013/058061 on Sep. 4,
`2013.
`
`(60) Provisional application No. 61/845,987, filed on Jul.
`13, 2013, provisional application No. 61/793,997,
`filed on Mar. 15, 2013, provisional application No.
`61/704,400,
`filed on Sep. 21, 2012, provisional
`application No. 61/696,734, filed on Sep. 4, 2012.
`
`(51)
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2011.01)
`
`Int. C1.
`0121) 19/34
`C12Q 1/68
`C12N 15/10
`G06F 19/22
`(52) us. Cl.
`CPC ....... C12Q 1/6886 (2013.01); C12N 15/1065
`(2013.01); C12Q 1/6806 (2013.01); CI2Q
`1/6869 (2013.01); C12Q 1/6874 (2013.01);
`G06F 19/22 (2013.01); CIZQ 2600/118
`(2013.01); CIZQ 2600/]56 (2013.01); CIZQ
`2600/]58 (2013.01); CIZQ 2600/16 (2013.01)
`(58) Field of Classification Search
`USPC ................................................ 435/91.1, 91.2
`See application file for complete search history.
`
`(56)
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`(Continued)
`
`Primary Examiner 7 Kenneth Horlick
`(74) Attorney, Agent, or Firm 7 Wilson Sonsini Goodrich
`& Rosati
`
`ABSTRACT
`(57)
`The present disclosure provides a system and method for the
`detection of rare mutations and copy number variations in
`cell free polynucleotides. Generally, the systems and meth-
`ods comprise sample preparation, or the extraction and
`isolation of cell free polynucleotide sequences from a bodily
`fluid; subsequent sequencing of cell free polynucleotides by
`techniques known in the art; and application of bioinfor-
`matics tools to detect rare mutations and copy number
`variations as compared to a reference. The systems and
`methods also may contain a database or collection of dif-
`ferent rare mutations or copy number variation profiles of
`different diseases, to be used as additional references in
`aiding detection of rare mutations, copy number variation
`profiling or general genetic profiling of a disease.
`26 Claims, 16 Drawing Sheets
`
`PGDX EX. 1001
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`PGDX EX. 1001
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`US 9,840,743 B2
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