I IIIII IIIIIIII Ill lllll lllll lllll lllll lllll lllll lllll lllll 111111111111111111
`US009323888B2
`
`c12) United States Patent
`Rava et al.
`
`(IO) Patent No.:
`(45) Date of Patent:
`
`US 9,323,888 B2
`Apr. 26, 2016
`
`(54) DETECTING AND CLASSIFYING COPY
`NUMBER VARIATION
`
`(75)
`
`Inventors: Richard P. Rava, Redwood City, CA
`(US); Anupama Srinivasan, Redwood
`City, CA (US)
`
`(73) Assignee: Verinata Health, Inc., San Diego, CA
`(US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 810 days.
`
`(21) Appl. No.: 13/600,043
`
`(22) Filed:
`
`Aug. 30, 2012
`
`(65)
`
`Prior Publication Data
`
`US 2013/0096011 Al
`US 2016/0070853 A9
`
`Apr. 18, 2013
`Mar. 10, 2016
`
`Related U.S. Application Data
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`(63)
`
`(60)
`
`Continuation-in-part of application No. 13/555,037,
`filed on Jul. 20, 2012, which is a continuation-in-part
`of application No. 13/191,366, filed on Jul. 26, 2011,
`which is a continuation-in-part of application No.
`12/958,352, filed on Dec. 1, 2010, application No.
`13/600,043, which
`is a continuation-in-part of
`application No. 13/400,028, filed on Feb. 17, 2012,
`now abandoned, and a continuation-in-part of
`application No. 13/009,708, filed on Jan. 19, 2011,
`now Pat. No. 8,700,341, application No. 13/600,043,
`which is a continuation-in-part of application No.
`13/445,778, filed on Apr. 12, 2012, application No.
`13/600,043, which
`is a continuation-in-part of
`applicationNo.12/958,347, filed on Dec. I, 2010, now
`abandoned, application No. 13/600,043, which is a
`continuation-in-part of application No. 12/958,356,
`filed on Dec. 1, 2010, now abandoned, application No.
`13/600,043, which
`is a continuation-in-part of
`application No. 13/482,964, filed on May 29, 2012,
`now abandoned, which is a continuation-in-part of
`application No. 12/958,353, filed on Dec. 1, 2010,
`application No.
`13/600,043, which
`1s
`a
`continuation-in-part
`of
`application
`No.
`PCT/US2012/031625,
`filed on Mar. 30, 2012,
`application No.
`13/600,043, which
`is
`a
`continuation-in-part of application No. 13/087,842,
`filed on Apr. 15, 2011, now Pat. No. 8,532,936.
`
`Provisional application No. 61/296,464, filed on Jan.
`19, 2010, provisional application No. 61/474,362,
`filed on Apr. 12, 2011, provisional application No.
`61/296,358, filed on Jan. 19, 2010, provisional
`application No. 61/407,017, filed on Oct. 26, 2010,
`provisional application No. 61/360, 83 7, filed on Jul. 1,
`2010, provisional application No. 61/455,849, filed on
`Oct. 26, 2010, provisional application No. 61/469,236,
`filed on Mar. 30, 2011.
`
`(51)
`
`Int. Cl.
`G06F 19/22
`GllC 17/00
`
`(2011.01)
`(2006.01)
`
`G06F 15/00
`C12Ql/68
`G06F 19/24
`(52) U.S. Cl.
`CPC
`
`(2006.01)
`(2006.01)
`(2011.01)
`
`G06F 19/22 (2013.01); C12Q 1/6809
`(2013.01); C12Q 1/6869 (2013.01); G06F
`19/24 (2013.01); Cl2Q 1/6883 (2013.01);
`Cl2Q 1/6886 (2013.01); Cl2Q 2537/16
`(2013.01); Cl2Q 2600/106 (2013.01)
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`
`John S Brusca
`Primary Examiner -
`(74) Attorney, Agent, or Firm - Weaver Austin Villeneuve
`& Sampson LLP
`
`(57)
`
`ABSTRACT
`
`The invention provides a method for determining copy num(cid:173)
`ber variations (CNV) ofa sequence ofinterest in a test sample
`that comprises a mixture of nucleic acids that are known or are
`suspected to differ in the amount of one or more sequence of
`interest. The method comprises a statistical approach that
`accounts for accrued variability stemming from process-re(cid:173)
`lated, interchromosomal and inter-sequencing variability.
`The method is applicable to determining CNV of any fetal
`aneuploidy, and CNVs known or suspected to be associated
`with a variety of medical conditions. CNV that can be deter(cid:173)
`mined according to the method include trisomies and mono(cid:173)
`somies of any one or more of chromosomes 1-22, X and Y,
`other chromosomal polysomies, and deletions and/or dupli(cid:173)
`cations of segments of any one or more of the chromosomes,
`which can be detected by sequencing only once the nucleic
`acids of a test sample.
`
`24 Claims, 88 Drawing Sheets
`
`Page 1
`
`FOUNDATION EXHIBIT 1055
`IPR2019-00634
`
`

`

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