Case 1:20-cv-01580-LPS Document 22-1 Filed 01/14/21 Page 1 of 786 PageID #: 2889
`Case 1:20-cv-01580-LPS Document 22-1 Filed 01/14/21 Page 1 of 786 PageID #: 2889
`
`EXHIBIT 1
`EXHIBIT 1
`
`
`
`

`

`Case 1:20-cv-01580-LPS Document 22-1 Filed 01/14/21 Page 2 of 786 PageID #: 2890
`I IIIII IIIIIIII Ill lllll lllll lllll lllll lllll lllll lllll lllll 111111111111111111
`US009902992B2
`
`c12) United States Patent
`Talasaz et al.
`
`(IO) Patent No.:
`(45) Date of Patent:
`
`US 9,902,992 B2
`*Feb.27,2018
`
`(54) SYSTEMS AND METHODS TO DETECT
`RARE MUTATIONS AND COPY NUMBER
`VARIATION
`
`USPC ......................................................... 435/91.2
`See application file for complete search history.
`
`(71) Applicant: Guardant Health, Inc., Redwood City,
`CA (US)
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`(72)
`
`Inventors: AmirAli Talasaz, Menlo Park, CA
`(US); Helmy Eltoukhy, Atherton, CA
`(US)
`
`(73) Assignee: Guardant Helath, 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.: 15/076,565
`
`(22) Filed:
`
`Mar. 21, 2016
`
`(65)
`
`Prior Publication Data
`
`US 2016/0251704 Al
`
`Sep. 1, 2016
`
`(63)
`
`(60)
`
`Related U.S. Application Data
`
`Continuation of application No. 14/855,301, filed on
`Sep. 15, 2015, which is a continuation of application
`No. PCT/US2014/000048, filed on Mar. 15, 2014,
`which is a continuation-in-part of application No.
`PCT/US2013/058061, filed on Sep. 4, 2013, said
`application No.
`PCT/US2014/000048
`is
`a
`continuation-in-part of application No. 13/969,260,
`filed on Aug. 16, 2013, now abandoned.
`
`Provisional application No. 61/793,997, filed on Mar.
`15, 2013, provisional application No. 61/845,987,
`filed on Jul. 13, 2013, provisional application No.
`61/948,530, filed on Mar. 5, 2014, provisional
`application No. 61/696,734, filed on Sep. 4, 2012,
`provisional application No. 61/704,400, filed on Sep.
`21, 2012, provisional application No. 61/793,997,
`filed on Mar. 15, 2013, provisional application No.
`61/845,987, filed on Jul. 13, 2013, provisional
`application No. 61/696,734, filed on Sep. 4, 2012,
`provisional application No. 61/704,400, filed on Sep.
`21, 2012, provisional application No. 61/793,997,
`filed on Mar. 15, 2013.
`
`(51)
`
`(52)
`
`(58)
`
`(2006.01)
`(2018.01)
`(2011.01)
`
`Int. Cl.
`C12P 19/34
`C12Q 1/68
`G06F 19/22
`U.S. Cl.
`CPC ......... C12Q 1/6827 (2013.01); C12Q 1/6806
`(2013.01); G06F 19/22 (2013.01); C12Q
`1/6869 (2013.01)
`
`Field of Classification Search
`CPC ............ C12Q 1/6806; C12Q 2521/501; C12Q
`2525/191; C12Q 2565/514; C12Q 1/6827;
`C12Q 1/6869; G06F 19/22
`
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`OTHER PUBLICATIONS
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`Alkan, et al. Personalized copy number and segmental duplication
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`(Continued)
`
`Primary Examiner - Cynthia B Wilder
`(74) Attorney, Agent, or Firm - Wilson Sonsini Goodrich
`& Rosati
`
`(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(cid:173)
`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(cid:173)
`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(cid:173)
`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.
`
`33 Claims, 16 Drawing Sheets
`
`

`

`Case 1:20-cv-01580-LPS Document 22-1 Filed 01/14/21 Page 3 of 786 PageID #: 2891
`
`US 9,902,992 B2
`Page 2
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