`
`1111111111111111111111111111111111111111111111111111111111111
`US007332277B2
`
`c12) United States Patent
`Db allan
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 7,332,277 B2
`Feb.19,2008
`
`(54) METHODS FOR DETECTION OF GENETIC
`DISORDERS
`
`(75)
`
`Inventor: Ravinder S. Dhallan, Bethesda, MD
`(US)
`
`(73) Assignee: RavGen, Inc., Columbia, MD (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 367 days.
`
`(21) Appl. No.: 10/661,165
`
`(22) Filed:
`
`Sep. 11, 2003
`
`(65)
`
`Prior Publication Data
`
`US 2004/0137470 Al
`
`Jul. 15, 2004
`
`Related U.S. Application Data
`
`(63) Continuation-in-part of application No. PCT/US03/
`06198, filed on Feb. 28, 2003, which is a continua(cid:173)
`tion-in-part of application No. 10/093,618, filed on
`Mar. 11, 2002, now Pat. No. 6,977,162, application
`No. 10/661,165, which is a continuation-in-part of
`application No. PCTIUS03/27308, filed on Aug. 29,
`2003, which is a continuation-in-part of application
`No. 10/376,770, filed on Feb. 28, 2003, now Pat. No.
`7,208,274, which is a continuation-in-part of appli(cid:173)
`cation No. 10/093,618, filed on Mar. 11, 2002, now
`Pat. No. 6,977,162.
`
`(60) Provisional application No. 60/378,354, filed on May
`8, 2002, provisional application No. 60/360,232, filed
`on Mar. 1, 2002.
`
`(51)
`
`Int. Cl.
`C12Q 1168
`(2006.01)
`C07H 21102
`(2006.01)
`C07H 21104
`(2006.01)
`(52) U.S. Cl. ......................... 435/6; 536/23.1; 536/24.3
`(58) Field of Classification Search .................... 435/6;
`536/22.1, 23.1, 24.3, 25.4
`See application file for complete search history.
`
`(56)
`
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`(Continued)
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`FOREIGN PATENT DOCUMENTS
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`EP
`
`0 994 963
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`
`(Continued)
`
`OTHER PUBLICATIONS
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`The Stratagene Cartalog, p. 39 ( 1988). *
`
`(Continued)
`
`Primary Examiner-Ethan Whisenant
`(74) Attorney, Agent, or Firm-Morrison & Foerster LLP
`
`(57)
`
`ABSTRACT
`
`The invention provides a method useful for detection of
`genetic disorders. The method comprises determining the
`sequence of alleles of a locus of interest, and quantitating a
`ratio for the alleles at the locus of interest, wherein the ratio
`indicates the presence or absence of a chromosomal abnor(cid:173)
`mality. The present invention also provides a non-invasive
`method for the detection of chromosomal abnormalities in a
`fetus. The invention is especially useful as a non-invasive
`method for determining the sequence of fetal DNA. The
`invention further provides methods of isolation of free DNA
`from a sample.
`
`140 Claims, 33 Drawing Sheets
`
`Ariosa Exhibit 1004, p. 1
`
`
`
`US 7,332,277 B2
`Page 2
`
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`12/2005 Dhallan
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`
`10/2003 Dhallan
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`435/6
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