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`EXHIBIT 2
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`I IIIII IIIIIIII Ill lllll lllll lllll lllll lllll lllll lllll lllll 111111111111111111
`US007727720B2
`
`c12) United States Patent
`Dhallan
`
`(IO) Patent No.:
`(45) Date of Patent:
`
`US 7,727,720 B2
`Jun. 1, 2010
`
`(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 ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 501 days.
`
`(21) Appl. No.: 11/212,812
`
`(22) Filed:
`
`Aug. 26, 2005
`
`(65)
`
`Prior Publication Data
`
`US 2006/0121452 Al
`
`Jun. 8,2006
`
`Related U.S. Application Data
`
`(63) Continuation of application No. PCT/US2004/
`006337, filed on Mar. 1, 2004, which is a continuation(cid:173)
`in-part of application No. PCT/US03/06198, filed on
`Feb. 28, 2003, application No. 11/212,812, which is a
`continuation of application No. 10/661,165, filed on
`Sep. 11, 2003, which is a continuation-in-partofappli(cid:173)
`cation No. PCT/US03/06198, filed on Feb. 28, 2003,
`and a continuation-in-part of application No. PCT/
`US03/27308, filed on Aug. 29, 2003.
`
`(60) Provisional application No. 60/378,354, filed on May
`8, 2002.
`
`(51)
`
`Int. Cl.
`C12Q 1/68
`(2006.01)
`C07H 21/00
`(2006.01)
`C07H 21/02
`(2006.01)
`C07H 21/04
`(2006.01)
`(52) U.S. Cl. ......................... 435/6; 536/22.1; 536/23.1;
`536/24.3; 536/25.4; 536/25.41
`(58) Field of Classification Search ..................... 435/6,
`435/91.2; 536/23.1, 24.3
`See application file for complete search history.
`
`(56)
`
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`(Continued)
`
`Primary Examiner-Ethan Whisenant
`(74) Attorney, Agent, or Firm-Whyte Hirschboeck Dudek
`S.C.
`
`(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.
`
`30 Claims, 33 Drawing Sheets
`
`

`

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