Case 1:20-cv-01580-LPS Document 1-4 Filed 11/23/20 Page 1 of 61 PageID #: 209
`Case 1:20-cv-01580-LPS Document 1-4 Filed 11/23/20 Page 1 of 61 PageID #: 209
`
`
`
`
`
`EXHIBIT 4
`
`EXHIBIT 4
`
`

`

`USO10793916B2
`
`( 12 ) United States Patent
`Talasaz
`
`US 10,793,916 B2
`( 10 ) Patent No .:
`( 45 ) Date of Patent :
`* Oct . 6 , 2020
`
`( * ) Notice :
`
`( 54 ) SYSTEMS AND METHODS TO DETECT
`RARE MUTATIONS AND COPY NUMBER
`VARIATION
`( 71 ) Applicant : GUARDANT HEALTH , INC . ,
`Redwood City , CA ( US )
`( 72 ) Inventor : Amir Ali Talasaz , Atherton , CA ( US )
`( 73 ) Assignee : GUARDANT HEALTH , INC . ,
`Redwood City , CA ( US )
`Subject to any 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 .: 16 / 575,128
`Sep. 18 , 2019
`( 22 ) Filed :
`( 65 )
`Prior Publication Data
`Mar. 19 , 2020
`US 2020/0087735 A1
`
`( 63 )
`
`Related U.S. Application Data
`Continuation of application No. 16 / 283,635 , filed on
`Feb. 22 , 2019 , now Pat . No. 10,494,678 , which is a
`continuation of application No. 15 / 872,831 , filed on
`Jan. 16 , 2018 , now Pat . No. 10,457,995 , which is a
`continuation of application No. 15 / 828,099 , filed on
`Nov. 30 , 2017 , which is a continuation of application
`No. 15 / 467,570 , filed on Mar. 23 , 2017 , now Pat . No.
`9,840,743 , which is a continuation of application No.
`application
`No.
`14 / 425,189 ,
`filed
`as
`PCT / US2013 / 058061 on Sep. 4 , 2013 , now Pat . No.
`10,041,127 .
`( 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 ) Int . Ci .
`( 2006.01 )
`C12P 19/34
`( 2018.01 )
`C12Q 1/6886
`( 2019.01 )
`G16B 30/00
`( 2018.01 )
`C12Q 1/6869
`C12N 15/10
`( 2006.01 )
`( 2018.01 )
`C12Q 1/6806
`( 2018.01 )
`C12Q 1/6874
`( 52 ) U.S. CI .
`???
`C12Q 1/6886 ( 2013.01 ) ; C12N 15/1065
`( 2013.01 ) ; C12Q 1/6806 ( 2013.01 ) ; C12Q
`1/6869 ( 2013.01 ) ; C12Q 1/6874 ( 2013.01 ) ;
`G16B 30/00 ( 2019.02 ) ; C12Q 2600/118
`( 2013.01 ) ; C120 2600/156 ( 2013.01 ) ; C120
`2600/158 ( 2013.01 ) ; C12Q 2600/16 ( 2013.01 )
`( 58 ) Field of Classification Search
`None
`See application file for complete search history .
`
`( 56 )
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`Primary Examiner Kenneth R Horlick
`( 74 ) Attorney , Agent , or Firm — Timothy Hott
`( 57 )
`ABSTRACT
`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 .
`30 Claims , 16 Drawing Sheets
`
`Case 1:20-cv-01580-LPS Document 1-4 Filed 11/23/20 Page 2 of 61 PageID #: 210
`
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