Granted Patent
B2
US 12,195,799 · App. 16/915,944 · Granted Jan 14, 2025
Risk calculation for evaluation of fetal aneuploidy
Inventors:
Arnold Oliphant (San Jose, CA); Andrew Sparks (San Jose, CA); Eric Wang (Milpitas, CA); Craig Struble (Glendale, WI)
Assignee:
Ariosa Diagnostics, Inc.
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Abstract
The present invention provides processes for determining accurate risk probabilities for fetal aneuploidies. Specifically, the invention provides non-invasive evaluation of genomic variations through chromosome-selective sequencing and non-host fraction data analysis of maternal samples.
Claims (51)
1. A method to calculate a risk that a first fetal chromosome in a maternal sample from a pregnant female comprising maternal and fetal nucleic acids is aneuploid, the method comprising:
providing first one or more sequence-specific oligonucleotide probes directed to a plurality of non-polymorphic loci on each of at least a first and second chromosome;
providing second one or more sequence-specific oligonucleotide probes directed to a plurality of polymorphic loci on at least a third chromosome;
amplifying the plurality of non-polymorphic and polymorphic loci using the first and second sequence-specific oligonucleotide probes;
determining a number of each amplified non-polymorphic locus on the at least first and second chromosomes;
determining a number of alleles at each amplified polymorphic locus on the at least third chromosome;
estimating a chromosome frequency for the at least first and second chromosomes based on the number of amplified non-polymorphic loci on the at least the first and second chromosomes; calculating a fetal nucleic acid proportion in the maternal sample based on the number of alleles at the amplified polymorphic loci;
calculating a value of likelihood that the first fetal chromosome is disomic using the fetal nucleic acid proportion to adjust the estimated chromosome frequency of the first and second chromosomes;
calculating a value of likelihood that the first fetal chromosome is aneuploid using the fetal nucleic acid proportion to adjust the estimated chromosome frequency of the first and second chromosomes; and
calculating the risk of a fetal aneuploidy of the first fetal chromosome by comparing the values of likelihood to a first mathematic model assuming a disomic first fetal chromosome and a second mathematic model assuming an aneuploid first fetal chromosome.
2. The method of claim 1 , wherein the calculated risk is an odds ratio comparing the first mathematic model assuming a disomic first fetal chromosome and a second mathematic model assuming a trisomic first fetal chromosome.
3. The method of claim 1 , wherein the fetal nucleic acid proportion is determined using the frequency of alleles on two or more chromosomes in the maternal sample.
4. The method of claim 1 , wherein the fetal aneuploidy is a result of one or no copies of a chromosome or part of a chromosome.
5. The method of claim 1 , wherein the fetal aneuploidy is a result of three or more copies of a chromosome or part of a chromosome.
6. The method of claim 1 , wherein the maternal sample is maternal plasma or serum.
7. The method of claim 1 , further comprising a step of adjusting the calculated risk using extrinsic information on prior risk.
8. The method of claim 1 , further comprising a step of adjusting the calculated risk using information on prior risk associated with maternal age or gestational age.
9. The method of claim 1 , further comprising the step of identifying a set of non-polymorphic loci best able to discriminate trisomy samples from normal samples.
10. A method to calculate a risk that a first fetal chromosome in a maternal sample from a pregnant female comprising maternal and fetal nucleic acids is aneuploid, the method comprising:
providing first one or more sequence-specific oligonucleotide probes directed to a plurality of non-polymorphic loci on each of at least a first and second chromosome;
providing second one or more sequence-specific oligonucleotide probes directed to a plurality of polymorphic loci on at least a third chromosome;
amplifying the plurality of non-polymorphic and polymorphic loci using the first and second sequence-specific oligonucleotide probes;
determining a number of each amplified non-polymorphic locus on the at least first and second chromosomes;
determining a number of alleles at each amplified polymorphic locus on the at least third chromosome;
estimating a chromosome frequency for the at least first and second chromosomes based on the number of the amplified non-polymorphic loci on the at least the first and second chromosomes;
calculating a fetal nucleic acid proportion in the maternal sample based on the number of alleles at the amplified polymorphic loci;
calculating a value of likelihood that the first fetal chromosome is disomic;
calculating a value of likelihood that the first fetal chromosome is aneuploid using the fetal nucleic acid proportion in the maternal sample to adjust the estimated chromosome frequency of the first and second chromosomes;
calculating the risk of a fetal aneuploidy of the first fetal chromosome by comparing the values of likelihood to a first mathematic model assuming a disomic first fetal chromosome and a second mathematic model assuming an aneuploid first fetal chromosome; and
adjusting the calculated risk using extrinsic information on prior risk.
11. The method of claim 10 , wherein the calculated risk is an odds ratio comparing the first mathematic model assuming a disomic first fetal chromosome and a second mathematic model assuming a trisomic first fetal chromosome.
12. The method of claim 10 , wherein the fetal nucleic acid proportion is determined using the frequency of alleles on two or more chromosomes in the maternal sample.
13. The method of claim 10 , wherein the fetal aneuploidy is a result of one or no copies of a chromosome or part of a chromosome.
14. The method of claim 10 , wherein the fetal aneuploidy is a result of three or more copies of a chromosome or part of a chromosome.
15. The method of claim 10 , wherein the maternal sample is maternal plasma or serum.
16. The method of claim 10 , further comprising a step of adjusting the calculated risk using extrinsic information on prior risk.
17. The method of claim 10 , further comprising a step of adjusting the calculated risk using information on prior risk associated with maternal age or gestational age.
18. The method of claim 10 , further comprising the step of identifying a set of non-polymorphic loci best able to discriminate trisomy samples from normal samples.
19. A method to calculate a risk that a first fetal chromosome in a maternal sample from a pregnant female comprising maternal and fetal nucleic acids is triploid, the method comprising:
providing first one or more sequence-specific oligonucleotide probes directed to a plurality of non-polymorphic loci on each of at least a first and second chromosome;
identifying a set of non-polymorphic loci best able to discriminate trisomy samples from normal samples;
providing second one or more sequence-specific oligonucleotide probes directed to a plurality of polymorphic loci on at least a third chromosome;
amplifying a plurality of non-polymorphic loci using the identified non-polymorphic loci best able to discriminate trisomy samples from normal samples and amplifying a plurality of polymorphic loci using the first and second sequence-specific oligonucleotide probes;
determining a number of each amplified non-polymorphic locus on the at least first and second chromosomes;
determining a number of alleles at each amplified polymorphic locus on the at least third chromosome;
estimating a chromosome frequency for the at least first and second chromosomes based on the number of amplified non-polymorphic loci on the at least the first and second chromosomes;
calculating a fetal nucleic acid proportion in the maternal sample based on the number of alleles at the amplified polymorphic loci;
calculating a value of likelihood that the first fetal chromosome is disomic using the fetal nucleic acid proportion to adjust the estimated chromosome frequency of the first and second chromosomes;
calculating a value of likelihood that the first fetal chromosome is triploid using the fetal nucleic acid proportion to adjust the estimated chromosome frequency of the first and second chromosomes; and
calculating the risk of a fetal trisomy of the first fetal chromosome by comparing the values of likelihood to a first mathematic model assuming a disomic first fetal chromosome and a second mathematic model assuming an triploid first fetal chromosome.
20. The method of claim 19 , wherein the fetal nucleic acid proportion is determined using the frequency of alleles on two or more chromosomes in the maternal sample.
Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE CORRECT ASSIGNMENT RECORDAL BY REMOVING PATENT NUMBER 8399195 PREVIOUSLY RECORDED ON REEL 056969 FRAME 0905. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT.
Recorded Apr 22, 2022
From: ARIOSA DIAGNOSTICS, INC.
To: ROCHE MOLECULAR SYSTEMS, INC.
Reel/Frame 059847/0803 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 23, 2021
From: ARIOSA DIAGNOSTICS, INC.
To: ROCHE MOLECULAR SYSTEMS, INC.
Reel/Frame 056969/0905 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 26, 2021
From: OLIPHANT, ARNOLD; SPARKS, ANDREW; WANG, ERIC; STRUBLE, CRAIG
To: ARIOSA DIAGNOSTICS, INC.
Reel/Frame 056364/0323 →
Continuity (7)
References Cited (400)
US 4683195A
· Mullis et al.
· 1987
[cited by applicant]
US 4988617A
· Landegren et al.
· 1991
[cited by applicant]
US 5143854A
· Pirrung et al.
· 1992
[cited by applicant]
US 5242794A
· Whiteley et al.
· 1993
[cited by applicant]
US 5270184A
· Walker et al.
· 1993
[cited by applicant]
US 5399491A
· Kacian et al.
· 1995
[cited by applicant]
US 5409818A
· Davey et al.
· 1995
[cited by applicant]
US 5413909A
· Bassam et al.
· 1995
[cited by applicant]
US 5422252A
· Walker et al.
· 1995
[cited by applicant]
US 5437975A
· McClelland
· 1995
[cited by applicant]
US 5494810A
· Barany et al.
· 1996
[cited by applicant]
US 5547839A
· Dower et al.
· 1996
[cited by applicant]
US 5554517A
· Davey et al.
· 1996
[cited by applicant]
US 5578832A
· Trulson et al.
· 1996
[cited by applicant]
US 5631734A
· Stern et al.
· 1997
[cited by applicant]
US 5648245A
· Fire et al.
· 1997
[cited by applicant]
US 5800992A
· Fodor et al.
· 1998
[cited by applicant]
US 5808041A
· Padhye et al.
· 1998
[cited by applicant]
US 5830711A
· Barany et al.
· 1998
[cited by applicant]
US 5834758A
· Trulson et al.
· 1998
[cited by applicant]
US 5856092A
· Dale et al.
· 1999
[cited by applicant]
US 5861245A
· McClelland et al.
· 1999
[cited by applicant]
US 5871928A
· Fodor et al.
· 1999
[cited by applicant]
US 5874219A
· Rava et al.
· 1999
[cited by applicant]
US 5876924A
· Zhang et al.
· 1999
[cited by applicant]
US 5888740A
· Han
· 1999
[cited by applicant]
US 5898071A
· Hawkins
· 1999
[cited by applicant]
US 5902723A
· Dower et al.
· 1999
[cited by applicant]
US 5936324A
· Montagu
· 1999
[cited by applicant]
US 5952170A
· Stroun et al.
· 1999
[cited by applicant]
US 5981956A
· Stern
· 1999
[cited by applicant]
US 6025601A
· Trulson et al.
· 2000
[cited by applicant]
US 6027889A
· Barany et al.
· 2000
[cited by applicant]
US 6045996A
· Cronin et al.
· 2000
[cited by applicant]
US 6054564A
· Barany et al.
· 2000
[cited by applicant]
US 6063603A
· Davey et al.
· 2000
[cited by applicant]
US 6090555A
· Fiekowsky et al.
· 2000
[cited by applicant]
US 6136229A
· Cui et al.
· 2000
[cited by applicant]
US 6141096A
· Stern et al.
· 2000
[cited by applicant]
US 6143495A
· Lizardi et al.
· 2000
[cited by applicant]
US 6156504A
· Gocke et al.
· 2000
[cited by applicant]
US 6185030B1
· Overbeck
· 2001
[cited by applicant]
US 6201639B1
· Overbeck
· 2001
[cited by applicant]
US 6210891B1
· Nyren et al.
· 2001
[cited by applicant]
US 6218803B1
· Montagu et al.
· 2001
[cited by applicant]
US 6225625B1
· Pirrung et al.
· 2001
[cited by applicant]
US 6258540B1
· Lo et al.
· 2001
[cited by applicant]
US 6268148B1
· Barany et al.
· 2001
[cited by applicant]
US 6309824B1
· Drmanac
· 2001
[cited by applicant]
US 6310199B1
· Smith et al.
· 2001
[cited by applicant]
US 6312892B1
· Barany et al.
· 2001
[cited by applicant]
US 6329179B1
· Kopreski
· 2001
[cited by applicant]
US 6342387B1
· Hayashizaki et al.
· 2002
[cited by applicant]
US 6386749B1
· Watts et al.
· 2002
[cited by applicant]
US 6391623B1
· Besemer et al.
· 2002
[cited by applicant]
US 6401267B1
· Drmanac
· 2002
[cited by applicant]
US 6410276B1
· Burg et al.
· 2002
[cited by applicant]
US 6506594B1
· Barany et al.
· 2003
[cited by applicant]
US 6534262B1
· McKernan et al.
· 2003
[cited by applicant]
US 6534293B1
· Barany et al.
· 2003
[cited by applicant]
US 6562573B2
· Halaka
· 2003
[cited by applicant]
US 6573103B1
· Wald
· 2003
[cited by applicant]
US 6576453B2
· Barany et al.
· 2003
[cited by applicant]
US 6797470B2
· Barany et al.
· 2004
[cited by applicant]
US 6828100B1
· Ronghi
· 2004
[cited by applicant]
US 6833246B2
· Balasubramanian
· 2004
[cited by applicant]
US 6852487B1
· Barany et al.
· 2005
[cited by applicant]
US 6858412B2
· Willis et al.
· 2005
[cited by applicant]
US 6864052B1
· Drmanac et al.
· 2005
[cited by applicant]
US 6911345B2
· Quake et al.
· 2005
[cited by applicant]
US 6914137B2
· Baker
· 2005
[cited by applicant]
US 6927028B2
· Dennis et al.
· 2005
[cited by applicant]
US 6949370B1
· Barany et al.
· 2005
[cited by applicant]
US 6977162B2
· Barany et al.
· 2005
[cited by applicant]
US 7014994B1
· Barany et al.
· 2006
[cited by applicant]
US 7083917B2
· Barany et al.
· 2006
[cited by applicant]
US 7097980B2
· Barany et al.
· 2006
[cited by applicant]
US 7166434B2
· Barany et al.
· 2007
[cited by applicant]
US 7198894B2
· Barany et al.
· 2007
[cited by applicant]
US 7208274B2
· Dhallan
· 2007
[cited by applicant]
US 7232656B2
· Balasubramanian
· 2007
[cited by applicant]
US 7244233B2
· Krantz et al.
· 2007
[cited by applicant]
US 7244831B2
· Barany et al.
· 2007
[cited by applicant]
US 7312039B2
· Barany et al.
· 2007
[cited by applicant]
US 7315787B2
· Orlandi et al.
· 2008
[cited by applicant]
US 7320865B2
· Barany et al.
· 2008
[cited by applicant]
US 7332277B2
· Dhallan
· 2008
[cited by applicant]
US 7332285B2
· Barany et al.
· 2008
[cited by applicant]
US 7343190B2
· Krantz et al.
· 2008
[cited by applicant]
US 7358048B2
· Krantz et al.
· 2008
[cited by applicant]
US 7364858B2
· Barany et al.
· 2008
[cited by applicant]
US 7429453B2
· Barany et al.
· 2008
[cited by applicant]
US 7442506B2
· Dhallan
· 2008
[cited by applicant]
US 7455965B2
· Barany et al.
· 2008
[cited by applicant]
US 7459311B2
· Nyren et al.
· 2008
[cited by applicant]
US 7527929B2
· McKernan et al.
· 2009
[cited by applicant]
US 7556924B2
· Barany et al.
· 2009
[cited by applicant]
US 7582420B2
· Oliphant et al.
· 2009
[cited by applicant]
US 7598060B2
· Dhallan
· 2009
[cited by applicant]
US 7601491B2
· Collis et al.
· 2009
[cited by applicant]
US 7622281B2
· Ronaghi et al.
· 2009
[cited by applicant]
US 7645576B2
· Lo et al.
· 2010
[cited by applicant]
US 7648824B2
· Nyren et al.
· 2010
[cited by applicant]
US 7700323B2
· Willis et al.
· 2010
[cited by applicant]
US 7709194B2
· Lo et al.
· 2010
[cited by applicant]
US 7709201B2
· Barany et al.
· 2010
[cited by applicant]
US 7718367B2
· Lo et al.
· 2010
[cited by applicant]
US 7718370B2
· Dhallan
· 2010
[cited by applicant]
US 7727720B2
· Dhallan
· 2010
[cited by applicant]
US 7727727B2
· Collis
· 2010
[cited by applicant]
US 7754428B2
· Lo et al.
· 2010
[cited by applicant]
US 7780600B2
· Krantz et al.
· 2010
[cited by applicant]
US 7799531B2
· Mitchell et al.
· 2010
[cited by applicant]
US 7807431B2
· Barany et al.
· 2010
[cited by applicant]
US 7888017B2
· Quake et al.
· 2011
[cited by applicant]
US 7901884B2
· Lo et al.
· 2011
[cited by applicant]
US 7989614B2
· Deggerdal et al.
· 2011
[cited by applicant]
US 8008018B2
· Quake et al.
· 2011
[cited by applicant]
US 8195415B2
· Fan et al.
· 2012
[cited by applicant]
US 8296076B2
· Fan et al.
· 2012
[cited by applicant]
US 8318430B2
· Chuu et al.
· 2012
[cited by applicant]
US 8700338B2
· Oliphant et al.
· 2014
[cited by applicant]
US 8756020B2
· Struble et al.
· 2014
[cited by applicant]
US 9567639B2
· Oliphant et al.
· 2017
[cited by applicant]
US 20010051341A1
· Lo et al.
· 2001
[cited by applicant]
US 20020045176A1
· Lo et al.
· 2002
[cited by applicant]
US 20020160361A1
· Loehrlein et al.
· 2002
[cited by applicant]
US 20030054386A1
· Antonarakis et al.
· 2003
[cited by applicant]
US 20030064366A1
· Hardin et al.
· 2003
[cited by applicant]
US 20040009518A1
· Lo et al.
· 2004
[cited by applicant]
US 20040086864A1
· Lo et al.
· 2004
[cited by applicant]
US 20040214175A9
· McKernan et al.
· 2004
[cited by applicant]
US 20050100939A1
· Namsaraev et al.
· 2005
[cited by applicant]
US 20060204495A1
· Zang
· 2006
[cited by applicant]
US 20060275789A1
· Willis et al.
· 2006
[cited by applicant]
US 20070087345A1
· Olson-Munoz et al.
· 2007
[cited by applicant]
US 20070178478A1
· Dhallan
· 2007
[cited by applicant]
US 20070207482A1
· Church et al.
· 2007
[cited by applicant]
US 20080090239A1
· Shoemaker et al.
· 2008
[cited by applicant]
US 20080096766A1
· Lee
· 2008
[cited by applicant]
US 20100112575A1
· Fan
· 2010
[cited by applicant]
US 20100120076A1
· Braun et al.
· 2010
[cited by applicant]
US 20100184043A1
· Mitchell et al.
· 2010
[cited by applicant]
US 20100184044A1
· Mitchell et al.
· 2010
[cited by applicant]
US 20100267034A1
· Lo et al.
· 2010
[cited by applicant]
US 20100291571A1
· Stoughton et al.
· 2010
[cited by applicant]
US 20100291572A1
· Stoughton et al.
· 2010
[cited by applicant]
US 20110003293A1
· Stoughton et al.
· 2011
[cited by applicant]
US 20110027771A1
· Deng
· 2011
[cited by applicant]
US 20110086357A1
· Lo et al.
· 2011
[cited by applicant]
US 20110171638A1
· Stoughton et al.
· 2011
[cited by applicant]
US 20110178719A1
· Rabinowitz
· 2011
[cited by applicant]
US 20110224087A1
· Quake et al.
· 2011
[cited by applicant]
US 20110245085A1
· Rava et al.
· 2011
[cited by applicant]
US 20110312503A1
· Chuu
· 2011
[cited by applicant]
US 20120003650A1
· Lo et al.
· 2012
[cited by applicant]
US 20120010085A1
· Rava
· 2012
[cited by applicant]
US 20120034603A1
· Oliphant et al.
· 2012
[cited by applicant]
US 20120100548A1
· Rava et al.
· 2012
[cited by applicant]
US 20120165203A1
· Quake et al.
· 2012
[cited by applicant]
US 20120184449A1
· Hixson
· 2012
[cited by applicant]
US 20120190557A1
· Oliphant et al.
· 2012
[cited by applicant]
US 20120219950A1
· Oliphant et al.
· 2012
[cited by applicant]
US 20120225798A1
· Cantor et al.
· 2012
[cited by applicant]
US 20120237928A1
· Rava et al.
· 2012
[cited by applicant]
US 20120270739A1
· Rava et al.
· 2012
[cited by applicant]
US 20130040375A1
· Sparks et al.
· 2013
[cited by applicant]
US 20130089863A1
· Oliphant et al.
· 2013
[cited by applicant]
US 20130122500A1
· Sparks et al.
· 2013
[cited by applicant]
US 20130172211A1
· Oliphant et al.
· 2013
[cited by applicant]
US 20130172212A1
· Oliphant et al.
· 2013
[cited by applicant]
US 20130172213A1
· Oliphant et al.
· 2013
[cited by applicant]
US 20130210640A1
· Sparks et al.
· 2013
[cited by applicant]
US 20130288252A1
· Sparks et al.
· 2013
[cited by applicant]
US 20140342940A1
· Oliphant et al.
· 2014
[cited by applicant]
GB 2299166
· 1996
[cited by applicant]
GB 9704440
· 1997
[cited by applicant]
GB 97044440
· 1997
[cited by applicant]
WO WO87006270A1
· 1987
[cited by applicant]
WO WO9006995A1
· 1990
[cited by applicant]
WO WO9839474A1
· 1998
[cited by applicant]
WO WO9947964A1
· 1999
[cited by applicant]
WO WO0004193A1
· 2000
[cited by applicant]
WO WO0056927
· 2000
[cited by applicant]
WO WO2003038120
· 2003
[cited by applicant]
WO WO2007100243A1
· 2007
[cited by applicant]
WO WO2007126377A1
· 2007
[cited by applicant]
WO WO2008118998
· 2008
[cited by applicant]
WO WO2009036525
· 2009
[cited by applicant]
WO WO2009102632
· 2009
[cited by applicant]
WO WO2011066476
· 2011
[cited by applicant]
WO WO2011090556A1
· 2011
[cited by applicant]
WO WO2011090557A1
· 2011
[cited by applicant]
WO WO2011090558A1
· 2011
[cited by applicant]
WO WO2012019187
· 2012
[cited by applicant]
WO WO2012019193
· 2012
[cited by applicant]
WO WO2012019200
· 2012
[cited by applicant]
WO WO2012088456
· 2012
[cited by applicant]
WO WO2012102945A1
· 2012
[cited by applicant]
WO WO2012103031
· 2012
[cited by applicant]
WO WO2013009175A1
· 2013
[cited by applicant]
WO WO2013192292A1
· 2013
[cited by applicant]
WO WO2016018986A1
· 2016
[cited by applicant]
Rebrikov et al. Real-time PCR: A review of approaches to data analysis. Applied Biochemistry and Microbiology, vol. 42, pp. 455-463. (Year: 2006).
[cited by examiner]
Mikhaylov, V.M. et al., (Jun. 1989). “Changes in the quantity and synthesis of DNA in the nuclei of large decidual cells of rats in the course of their differentiation”, Tsitologiya (Cytology) 31(6):677-683.
[cited by applicant]
Moreno and Gomella, (Nov. 1998). “Circulating Prostate Cancer Cells Detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR: What do they mean?”, Cancer Control Journal, 5(6):507-512.
[cited by applicant]
Mulcahy, H.E. et al. (Apr. 2000). “Plasma DNA K-ras Mutations in Patients with Gastrointestinal Malignancies,” Annals New York Academy of Sciences, 906:25-28.
[cited by applicant]
Abadia-Molina, et al., “Immune phenotype and cytotoxic activity of lymploycytes from human term decidua against trophoblast”, J. of Reproductive Immunology, n31:109-23 (1996).
[cited by applicant]
Advisory Action Received on Jan. 29, 2013 for U.S. Appl. No. 13/293,419 (inventor A. Sparks, filed Nov. 10, 2011), entire document.
[cited by applicant]
Agostini, et al., “Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving pre-operative chemotherapy”, Ann. Surg. Oncol., 18(9):2461-68 (2011).
[cited by applicant]
Alexandrov, et al., (May 11, 1993). “Definition of a new alpha satellite suprachromosomal family characterized by monomeric organization”, Nucleic Acids Research, 21(9):2209-2215.
[cited by applicant]
Anker, et al., Information carried by the DNA release by antigen-stimulated lymphocytes:, Immunology, 37:753-63 (1979).
[cited by applicant]
Anker, et al., “K-ras Mutations are found in DNA extreacted from the plasma of patients with colorectal cancer,” Gastroenterology, 112:1114-20 (1997).
[cited by applicant]
Anker, et al., “Spontaneous Release of DNA by Human Blood Lymphocytes as Shown in an in Vitro System”, Cancer Research, 35:2375-82 (1975).
[cited by applicant]
Arnheim, et al., “Molecular evidence for genetic exchanges among ribosomal genes on nonhomologous chromosomes in man and apes”, PNAS USA, 77(12):7323-27 (1980).
[cited by applicant]
Ashoor, et al., “Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18”, Am. J. of Obstet. Gynecol., (2012), doi: 10.1016/j.ajog.2012.01.029.
[cited by applicant]
Ashoor, et al., Fetal Fraction in Maternal Plasma Cell-Free DNA at 11-13 Weeks' Gestation: Effect of Maternal and Fetal Factors, Fetal Dian Ther D01:10.1159/000337373 (Pub'd online May 4, 2012).
[cited by applicant]
Australian Patent Examination Report No. 1 dated Feb. 20, 2014 for 2011285512, entire document.
[cited by applicant]
Australian Patent Examination Report No. 1 dated Feb. 7, 2014 for 2011285477, entire document.
[cited by applicant]
Australian Patent Examination Report No. 1 dated Mar. 4, 2014 for 2011285518, entire document.
[cited by applicant]
Avent, N.D. (2008). “RHD genotyping from maternal plasma: guidelines and technical challenges,” Methods in Molecular Biology 444:185-201.
[cited by applicant]
Bandyopadhyay, et al, “Identification and characterization of satellite III subfamilies to the acrocentric chromosomes”, Chromosome Research, 9:223-33 (2001).
[cited by applicant]
Batzer and Deininger, “ALU Repeats and Human Genomic Diversity”, Nature, 3:370-79 (2002).
[cited by applicant]
Beard, “Embryological Aspects and Etiology of Carcinoma”, The Lancet, Jun. 21, 1902, pp. 1758-1761.
[cited by applicant]
Belokhvostov, et al., “Changes in the Fractional Composition of the Nucleic Acids in Blood Serum upon Rediation Damage Early Stage Abnormalities Following Gamma-Irradiation of Rats”, Tsitologiia (Cytology) 1986.
[cited by applicant]
Bianchi, “Isolation of fetal DNA from nucleated erythrocytes in maternal blood”, PNAS USA, 87:3279-83 (1990).
[cited by applicant]
Bianchi, “PCR Quantitation of Fetal Cells in Maternal Blood in Normal and Aneuploid Pregnancies”, Am J. Hum. Genet., 61:822-29 (1997).
[cited by applicant]
Bianchi, “Prenatal diagnosis by analysis of fetal cells in maternal blood”, J. of Pediatrics, 127(6):847-56 (1995).
[cited by applicant]
Bianchi, et al., “Large Amounts of Cell-free DNAS Are Present in Amniotic Fluid”, Clin. Chem., 47(10) 1867-69 (2001).
[cited by applicant]
Biran, “On the Oncodevelopmental Rold of Human Imprinted Genes”, 43:119-23 (1994).
[cited by applicant]
Blaschke and Rappold, “The Pseudoautosomal regions, SHOX and disease”, Curr. Opin. Gene. Dev., 16(3):23-29 (2006).
[cited by applicant]
Bodurtha and Strauss, “Genomics and Prenatal Care”, New Eng. J. of Medicine, 366:64-73 (2012).
[cited by applicant]
Bombard, et al., “Fetal RHD genotype detection from circulating cell-free DNA in maternal plasma in non-sensitized RhD negative women”, Prenat Diagn, 31:802-08 (2011).
[cited by applicant]
Boyle, E.A. et al (Sep. 15, 2014, e-published May 26, 2014). “MIPgen: optimized modeling and design of molecular inversion probes for targeted resequencing,” Bioinformatics 30(18):2670-2672.
[cited by applicant]
Bradstock, et al., “Functional and phenotypic assessment of neonatal human leucocytes expressing natural killer cell-associated antigen”, Immunology and Cell Biology (71:535-42 (1993).
[cited by applicant]
Bustamante-Aragones et al. (Mar. 2010). “Noninvasive prenatal diagnosis using ccffDNA in maternal blood:state of the art,”
[cited by applicant]
Camaschella, et al., “Prenatal Diagnosis of Fetal Hemoglobin Lepore-Boston Disease on Maternal Peripheral Blood”, Blood, 75(11):2102-06 (1990).
[cited by applicant]
Campbell, et al., “Subclonal phylogenetic structions in cancer revealed by ultra-deep sequencing”, PNAS, 105(35):13081-86 (2008).
[cited by applicant]
Cappuzzo, et al., “Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer”, J. Nati Cancer Inst., 97(9):643-55 (2005).
[cited by applicant]
Centre for Genomics Education, “Changes to Chromosome Structure—Translocations”, The Australasian Genetics Resource Book, www.aenetics corn, pp. 1-5 (2007).
[cited by applicant]
Chen, et al., “Microsatellite alterations in plasma DNA of small cell lung cancer patients”, Nature Medicine, 2(9):1033-35 (1996).
[cited by applicant]
Chen, et al., “Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing”, PLos One, 6:e21791 (2011).
[cited by applicant]
Chim, et al., “Detection of the placental epigenetic signature of the maspin gene in maternal plasma”, PNAS USA, 102(41):14753-58 (2005).
[cited by applicant]
Chinen, P.A. et al. (Nov. 2010), e-published Apr. 20, 2010). “Noninvasive determination of fetal rh blood group, D antigen status by cell-free DNA analysis in maternal plasma: experience in a Brazilian population,”
[cited by applicant]
Chiu and Lo, “Non-invasive prenatal diagnosis by fetal nucleic acid analysis in maternal plasma: the coming of age”, Semin. Fetal Neonatal Med., 16(2):88-93 (2011).
[cited by applicant]
Chiu, et al., “Effects of Blood-Processing Protocols on Fetal and Total DNA Quantification in Maternal Plasma”, Clin. Chem., 47(9):1607-1613 (2001).
[cited by applicant]
Chiu, et al., “Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma”, PNAS USA 105:20458-63 (2008), 17 pages supporting information.
[cited by applicant]
Chiu, et al., “Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21”, Clinical Chemistry 56:459-63 (2010).
[cited by applicant]
Chiu, et al., “Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study”, Br Med J. 342:c7401 (2011).
[cited by applicant]
Chiu, et al., “Non-invasive prenatal diagnosis by single molecule counting technologies”, Trends in Genomics, 25(7):324-31 (2009).
[cited by applicant]
Choo, et al., “A Chromosome 14-specific Human Satellite III DNA Subfamily That Shows Variable Presence on Different Chromosomes 14”, Am J. Hum. Genet., 50:706-16 (1992).
[cited by applicant]
Choo, et al., “A homologous subfamily of satellite III DNA on human chromosomes 14 and 22”, Nucleic Acids Research, 18(19):5641-47 (1990).
[cited by applicant]
Chromosome 14 Map (Mar. 14, 1996). The Genethon Human Genetic Linkage Map, Collections, Supplements,
[cited by applicant]
Chu, et al., “A novel approach toward the challenge of accurately quantifying fetal DNA in maternal plasma”, Prenat. Diag., 30:1226-29 (2010).
[cited by applicant]
Ciccodicola, et al., “Differentially regulated and evolved genes in the fully sequences Xq/Yq pseudoautosomal region”, Hum. Mol. Genet., 9(3):395-401 (2000).
[cited by applicant]
Cicuttini and Boyd, “Hemopoietic and Lymphoid Progenitro Cells in Human Umbilical Cord Blood”, Developmental Immunology, 4:1-11 (1994).
[cited by applicant]
Cirigiliano, et al., “Clinical application of multiplex quantitative fluorescent polymerase chain reaction QF-PCR for the repaid prenatal detection of common chromosome aneuploidies”, Molecular Human Reproduction, 7(10)…
[cited by applicant]
Cirigiliano, et al., “Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR, results of 9 years of clinical experience”, Prenatal diagnosis, 29:40-49 (2009).
[cited by applicant]
Cockwell, et al., “Distribution of the D15A1 copy number polymorphism”, European J. of Hum. Genet., 15:441-45 (2007).
[cited by applicant]
Conover, Practical Nonparametric Statistics, pp. 295-01 (John Wiley & Sons, NY)(1971).
[cited by applicant]
Costa, et al., “New strategy for prenatal diagnosis of X-linked disorders”, N. Engl J. Med., 346:1502 (2002).
[cited by applicant]
Datta, et al., “Sensitive Detection of Occult Breast Cancer by the Reverse-Transcriptase Polymerase Chain Reaction”, J. of Clinical Oncology, 12(3): 475-82 (1994).
[cited by applicant]
Dear, et al., “A High-Resolution Metric HAPPY Map of Human Chromosome 14” Genmoics, 48 232-41 (1998).
[cited by applicant]
Dennin, “DNA of Free and Complexed Origin in Human Plasma: Concentration and Length Distribution”, Klin. Wochenschr., 57:451-56 (1979).
[cited by applicant]
Dhallan, et al., “A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study”, Lancet, 369(9560):474-81 (2007).
[cited by applicant]
Dobrzycka, et al., “Circulating free DNA and p53 antibodies in plasma of patients with ovarian epithelial cancers”, Annals of Oncology, 22:1133-40 (2011).
[cited by applicant]
Dobrzycka, et al., “Prognostic significance of VEGF and its receptors in endometrioid endometrial cancer”, Ginekol Pol. 81(6):422-25 (2010).
[cited by applicant]
Duan, et al., “PstSNP-HapMap3: a database of SNPs with high population differentiation for HapMap3”, Bioinformation, 3(3):139-41 (2008).
[cited by applicant]
Earle, et al., “Identification of DNA Sequences Flanking the Breakpoin of Human t(14q21q) Robertsonian Translocations”, Am J. Hum Genet., 50:717-24 (1992).
[cited by applicant]
Ehrich, et al., “Noninvasive detection of fetal trisomy 21 by sequencing of fetal DNA in maternal blood: a study in a clinical setting”, Am J. Obstet Gynecol, 2011:204:205 el-11 (2011).
[cited by applicant]
Enders, et al., “Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases”, Prenatal Diagnosis, 24:513-18 (2004).
[cited by applicant]
EPO Examination Report dated Nov. 21, 2013 for App. No. 11745880.2, entire document.
[cited by applicant]
EPO Examination Report dated Nov. 21, 2013 for App. No. 11745881.1, entire document.
[cited by applicant]
EPO Examination Report dated Nov. 28, 2013 for App. No. 11745883.6, entire document.
[cited by applicant]
Fan, et al., “Analysis of the Size Distributions of Fetal and Maternal Cell-Free DNA by Paired-End Sequencing”, Clin. Chem., 56(8):1279-80 (2010).
[cited by applicant]
Fan, et al., “Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood”, PNAS USA, 105(42):16266-71 (2008).
[cited by applicant]
Fan, et al., “Sensitivity of noninvasive prenatal detection of fetal aneuploidy from maternal plasma using shotgun sequencing is limited only by counting statistics”, PLoS One, 5:e10439 (2010).
[cited by applicant]
Fejgin, et al., “Fetal cells in the uterine cervix: a source for early non-invasive prenatal diagnosis”, Prenat. Diag., 21:619-21 (2001).
[cited by applicant]
Final Office Action Received on Jul. 8, 2013 for U.S. Appl. No. 13/689,206 (inventor A. Oliphant, filed Nov. 30, 2012), entire document.
[cited by applicant]
Final Office Action Received on Oct. 12, 2012 for U.S. Appl. No. 13/293,419 (inventor A. Sparks, filed Nov. 10, 2011), entire document.
[cited by applicant]
Finning, et al., “Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study”, Br Med J., 336:816-18 (2008).
[cited by applicant]
Fisher, et al., “Genetic evidence that placental site trophoblastic tumours can originate from a hydatidiform mole or a normal conceptus”, Br. J. Cancer, 65:355-58 (1992).
[cited by applicant]
Fournie, et al., “Plasma DNA as Cell Death Marker in Elderly Patients”, Gerontology, 39:215-221 (1993).
[cited by applicant]
Fowke, Genetic analysis of human DNA recovered from minute amounts of serum and plasma, J. of Immunol. Meth., 180:45-51 (1995).
[cited by applicant]
Geifman-Holzman, et al., “Fetal RhD genotyping in fetal cells flow sorted from maternal blood”, Am. J.Obstet. Gynecol., 174(3):818-22 (1996).
[cited by applicant]
Ghanta, S. et al. (Oct. 8, 2010). “Non-invasive prenatal detection of trisomy 21 using tandem single nucleotide polymorphisms,”
[cited by applicant]
Ghossein, et al.. “Detection of Circulating Tumor Cells in Patients with Localized and Metastatic Prostatic Carcinoma Clinical Implications”, J. of Clin. Oncology, 13(5):1995-200 (1995).
[cited by applicant]
Gold, “Cancer and Pregnancy: Parallels in Growth, Invasion, and Immune Modulation and Implicationsa for Cancer Therapeutic Agents”, Mayo Clin. Proc., 84(11):985-1000 (2009).
[cited by applicant]
Gosden, et al., “Satellite DNA Sequences in the Human Acrocentric Chromosomes: Information from Translocations and Heteromorphisms”, Am. J. Hum. Genet., 33:243-51 (1981).
[cited by applicant]
Guo, Q. et al. (Sep. 2010, e-published Jul. 9, 2010). “Simultaneous detection of trisomies 13, 18, and 21 with multiplex ligation-dependent probe amplification-based real-time PCR,” Clin Chem 56(9):1451-1459.
[cited by applicant]
Greeley, et al., “Get ready for the flood of fetal gene screening”, Nature, 469:289-91 (2011).
[cited by applicant]
Green, et al., “Gestational Trophoblastic Disease: A Spectrum of Radiologic Diagnosis”, Radiographics, 16(6):1371-84 (1996).
[cited by applicant]
Gribben, et al., “Detection of Residual Lymphoma Cells by Polymerase Chain Reaction in Peripheral Blood is Significantly Less Predictive for Relapse Than Detection in Bone Marrow”, Blood, 83(12):3800-07 (1994).
[cited by applicant]
Guatelli, et al., “Isothermal, in vitro amplification of nucleic acids by a multienzyme reaction modeled after retroviral replication”, PNAS USA, 87(5):1874—(1990).
[cited by applicant]
Han, et al., “Molecular Chytogenetic Characterization of 17 rob(13q14q) Robertsonian Translocations by FISH, Narrowing the Region Containing the Breakpoints”, Am J. Hum. Genet., 55:960-67 (1994).
[cited by applicant]
Hardenbol et al., Multiplexed genotyping with sequence-tagged molecular inversion probes. Nat Biotechnol. Jun. 2003;21(6):673-8.
[cited by applicant]
Hardingham, et al., “Detection of Circulating Tumor Cells in Colorectal Cancer by Immunogead-PCR is a Sensitive Prognostic marker for Relapse of Disease”, Molecular Medicine, 1(7):789-94 (1995).
[cited by applicant]
Harrell, Regression modeling strategies, §§9.2.2 and 1.10.5 (Springer Vertag)(2001).
[cited by applicant]
Hayden, et al., “Multiplex-Ready Pcr: A new method for multiplexed SSR and SNP genotyping”, BMC Genomics, 9:80:1-12 (2007).
[cited by applicant]
Heid, et al., “Real Time Quantitative PCR”, Genome Res., 6:986-94 (1996).
[cited by applicant]
Heilig, et al., “The DNA sequence and analysis of human chromosome 14”, Nature, 421:601-09 (2003).
[cited by applicant]
Ho, et al., “Activation Status of T and NK Cells in the Endometrium Throughout Menstrual Cycle and Normal and Abnormal Early Pregnancy”, Human Immunology, 49:130-36 (1996).
[cited by applicant]
Hoon, et al., “Detection of Occult Melanoma Cells in Blood With a Multiple-Marker Polymerase Chain Reaction Assay”, J. of Clinical Oncology, 13(8):2109-116 (1995).
[cited by applicant]
Hosny, et al., “TP53 mutations in circulating fee DNA from Egyptian patients with non-Hodgkin's lymphoma”, Cancer Lett., 275(2):234-39 (2009).
[cited by applicant]
Hsuih, et al., “Novel, ligation-depdent PCR assay for detection of hepatitis C in serum”, J. of Clin. Microbiology, 34(3):501-07 (1996).
[cited by applicant]
Huang, et al., “Identification of a family of alternatively splied mRNA species of angiopoietin-1”, Blood, 95:1993-99 (2000).
[cited by applicant]
Indolfi, et al., “Perinatal Transmission of Hepatitis C Virus Infection”, J. Med. Virol., 81:836- 43 (2009).
[cited by applicant]
International Human Genome Sequencing Consortium, “Initial sequencing and analysis of the human genome”, Nature, 409:860-921 (2001).
[cited by applicant]
Irizarry, et al., “Summaries of Affymetrix GeneChip probe level data”, Nuc. Acid Res., 31(4):e5 (2003).
[cited by applicant]
Jiang, et al., Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies. BMC Med Genomics. Dec. 1, 2012;5:57.
[cited by applicant]
Kamnasaran and Cox, “Current status of chromosome 14”, J. Med. Genet., 39:81-90 (2002).
[cited by applicant]
Kazakov, et al., “Extracellular DNA in the Blood of Pregnant Women”, Tsitologiia (Cytology), 37(3):232-37 (1995).
[cited by applicant]
Kogan, et al., “An improved method for prenatal diagnosis ofgenetic diseases by analysis of amplified DNA sequences”, New England J. of Medicine, 317(6):985-90 (1987).
[cited by applicant]
Koumbaris, G. et al. (Jun. 2016, e-published Apr. 26, 2016). “Cell-Free DNA Analysis of Targeted Genomic Regions in Maternal Plasma for Non-Invasive Prenatal Testing of Trisomy 21, Trisomy 18, Trisomy 13, and Fetal Sex,…
[cited by applicant]
Krebs, et al., “The Unitarian or Trophoblastic Thesis of Cancer” Medical Record, 163:149-74 (Jul. 1950).
[cited by applicant]
Landegren, et al., “A ligase-mediated gene detection technique”, Science, 241:1077 (1988).
[cited by applicant]
Lapair, et al., “Cell-Free DNA in Amniotic Fluid: Unique Fragmentation Signatures in Euploid and Aneuploid Fetuses”, Clinical Chem., 53(3):405-11 (2007).
[cited by applicant]
Leon, “Free DNA in the Serum of Cancer Patients and the Effect of Therapy”, Cancer Res., 37:646-50 (1977).
[cited by applicant]
Li, et al., “A photocleavable fluorescent nucleotide for DNA sequencing and analysis”, PNAS USA, 100(2):414-19 (2003).
[cited by applicant]
Liao, et al., “Targeted massively parallel sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles”, Clin Che, 57:92-101 (2011).
[cited by applicant]
Lo, “Fetal nucleic acids in maternal blood: the promises”, Clin. Chem. Lab Med., 50(5):xxx-xxx (DOI 10.1515/CCLM.2011.765) (2011).
[cited by applicant]
Lo, et al., “Detection of single-copy fetal DNA sequence from maternal blood”, The Lancet, 335:1463-64 (1990).
[cited by applicant]
Lo, et al., “Digital PCR for the molecular detection of fetal chromosomal aneuploidy”, PNAS USA, 104:13116-21 (2007).
[cited by applicant]
Lo, et al., Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med, 2:61ra91 (2010).
[cited by applicant]
Lo, et al., “Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection”, Nat. Med., 13:218-23 (2007).
[cited by applicant]
Lo, et al., “Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma”, N Engl J Med, 339:1734-38 (1998).
[cited by applicant]
Lo, et al., “Presence of fetal DNA in maternal plasma and serum”, The Lancet, 350:485-86 (1997).
[cited by applicant]
Lo, et al., “Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis”, Am J. Hum. Genetics, 62:768-75 (1998).
[cited by applicant]
Lo, et al., “Rapid clearance of fetal DNA from maternal plasma”, Am J. Hum. Genetics, 64:218-24 (1999).
[cited by applicant]
Lo, et al., “Two-way cell traffic between mother and fetus: biological and clinical implications”, Blood, 88:4390-95 (1996).
[cited by applicant]
Lun, et al., “Microfluidics Digital PCR Reveals a Higher than Expected Fraction of Fetal DNA in Maternal Plasma”, Clin. Chem., 54(10):1664-72 (2008).
[cited by applicant]
Lun, et al., “Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma”, PNAS USA, 105(50):19920-25 (2008).
[cited by applicant]
Makrigiorgos, et al., “A PCR-based amplification method retaining the quantitative difference between two complex genomes”, Nat. Biotech., 20:936-39 (2002).
[cited by applicant]
Mangs, Curr. Genomics, “The Human Pseudoautosomal Region (PAR): Origin, Function and Future”, 8(2):129-36 (2007).
[cited by applicant]
Mansfield, “Diagnosis of Down syndrome and other aneuploidies using quantitative polymerase chain reaction and small tandem repeat polymorphisms”, Human Molecular Genetics, 2(1):43-50 (1993).
[cited by applicant]
Mantzaris, et al., “Preliminary report: correct diagnosis of sex in fetal cells isolated from cervical mucus during early pregnancy”, ANZJOG, 45(6):529-32 (2005).
[cited by applicant]
Mardis, et al., “The impact of next-generation sequencing technology on genetics”, Trends in Genetics, 24(3):133-41 (2007).
[cited by applicant]
Margulies, et al., “Genome sequencing in microfabricated high-density picolitre reactors”, Nature, 437(15):376-80 and errata (2005).
[cited by applicant]