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Patent US5324668A successfully refreshed from Google Patents.
US5324668A
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US
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Method for detecting trisomy 13 and Down syndrome by non-invasive maternal blood screening
Assignee: PerkinElmer Singapore Pte Ltd
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Filing: 1993-02-03
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Granted: 1994-06-28
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Expires: 2013-02-03
Abstract
Abstract A method and apparatus for determining if a pregnant woman is at significant risk of carrying a fetus with Down syndrome, The method comprises measuring the pregnant woman's maternal blood levels of the free beta subunit of human chorionic gonadotropin. The level of free beta subunit of human chorionic gonadotropin individually or with other markers may be compared to reference data. A computerized apparatus for making the determination preferably using a probability density function generated from a set of reference data by a linear discriminant analysis procedure is disclosed.
Inventors
- 👤 James N. Macri
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 19:43
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/74; G01N33/76; G16; G16H; G16H50/00; G16H50/20; G16H50/30; Y; Y10; Y10S; Y10S436/00; Y10S436/815; Y10S436/817; Y10S436/818
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
110 words
A screening method for determining a pregnant woman's risk of carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for free beta (human chorionic gonadotropin (HCG)) level, comparing said level of free beta (HCG), and said pregnant woman's gestational age, to reference values at various gestational ages of the level for free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of said pregnant woman's risk of carrying a fetus with Down syndrome, wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 2
Dependent Claim
110 words
A screening method for determining a pregnant woman's risk of carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for free beta (human chorionic gonadotropin (HCG)) level, comparing said level of free beta (HCG), and said pregnant woman's gestational age, to reference values at various gestational ages of the level for free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of said pregnant woman's risk of carrying a fetus with Down syndrome, wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 3
Dependent Claim
79 words
The method of claim 1 further comprising: measuring said pregnant woman's maternal blood for intact human chorionic gonadotropin molecule (Intact HCG) level and incorporating said level for Intact HCG and reference values at various gestational ages of the levels Intact HCG in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses into said comparison wherein a higher level of Intact HCG is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 4
Dependent Claim
90 words
The method of claim 2 further comprising: measuring said pregnant woman's maternal blood for alpha-fetoprotein (AFP) level and said pregnant woman's maternal blood for unconjugated estriol (UE) level and incorporating said level of AFP, said level of UE, and reference values at various gestational ages of said levels of AFP and UE in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses into said comparison wherein lower levels of AFP and UE are indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 5
Dependent Claim
89 words
The method of claim 3 further comprising: incorporating a ratio of said measurement of said level of said free beta (HCG) to said measurement of said level of said Intact HCG and reference values at various gestational ages of the ratio of the level of free beta (HCG) to the level of Intact HCG in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, into said comparison wherein a higher ratio is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 6
Dependent Claim
111 words
The method of claim 2, further comprising: measuring said pregnant woman's maternal blood for alpha-fetoprotein (AFP) level and incorporating said measurement of said level of AFP, a ratio of said level of said free beta (HCG) to said level of said intact HCG and reference values at various gestational ages of the ratio of the level of free beta (HCG) to the level of Intact HCG and the level of AFP in (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses into said comparison wherein lower levels of AFP and a higher ratio are indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 7
Dependent Claim
15 words
The method of claim 1 wherein the assay comprises a one step free beta-hCG assay.
Claim 8
Independent Claim
117 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood level of a fragment of free beta (human chorionic gonadotropin (HCG)) and comparing the measurement of said level of the fragment of free beta (HCG) to reference data containing reference values at various gestational ages of the level of the fragment of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the fragment of free beta (HCG) is indicative of a high probability of carrying a fetus with Down syndrome.
Claim 9
Independent Claim
117 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood level of a fragment of free beta (human chorionic gonadotropin (HCG)) and comparing the measurement of said level of the fragment of free beta (HCG) to reference data containing reference values at various gestational ages of the level of the fragment of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the fragment of free beta (HCG) is indicative of a high probability of carrying a fetus with Down syndrome.
Claim 10
Independent Claim
121 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for a protein portion of free beta (human chorionic gonadotropin (HCG)) level and comparing the measurement of said level for the protein portion of free beta (HCG) to reference data containing reference values at various gestational ages of the level for said protein portion of free beta (HCG) in (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the protein portion of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 11
Independent Claim
121 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for a protein portion of free beta (human chorionic gonadotropin (HCG)) level and comparing the measurement of said level for the protein portion of free beta (HCG) to reference data containing reference values at various gestational ages of the level for said protein portion of free beta (HCG) in (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the protein portion of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 12
Independent Claim
121 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for a carbohydrate portion of free beta (human chorionic gonadotropin (HCG)) level and comparing the measurement of said level for the carbohydrate portion of free beta (HCG) to reference data containing reference values at various gestational ages of the level for said carbohydrate portion of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the carbohydrate portion of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 13
Independent Claim
121 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for a carbohydrate portion of free beta (human chorionic gonadotropin (HCG)) level and comparing the measurement of said level for the carbohydrate portion of free beta (HCG) to reference data containing reference values at various gestational ages of the level for said carbohydrate portion of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the carbohydrate portion of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 14
Independent Claim
141 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for a portion of free beta (human chorionic gonadotropin (HCG)) located at about the junction of the carbohydrate and the protein portions of free beta (HCG) and comparing the measurement of said level to reference data containing reference values at various gestational ages of the level of said portion of free beta (HCG) located at about the junction of the carbohydrate and the protein portions of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the portion of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 15
Independent Claim
141 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring said pregnant woman's maternal blood for a portion of free beta (human chorionic gonadotropin (HCG)) located at about the junction of the carbohydrate and the protein portions of free beta (HCG) and comparing the measurement of said level to reference data containing reference values at various gestational ages of the level of said portion of free beta (HCG) located at about the junction of the carbohydrate and the protein portions of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of the portion of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 16
Independent Claim
104 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring a pregnant woman's maternal blood for free beta (human chorionic gonadotropin (HCG)) level and comparing the measurement for the level of free beta (HCG) to a set of reference data containing reference values of the level for free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 17
Independent Claim
104 words
A method for determining the risk that a pregnant woman is carrying a fetus with Down syndrome comprising: measuring a pregnant woman's maternal blood for free beta (human chorionic gonadotropin (HCG)) level and comparing the measurement for the level of free beta (HCG) to a set of reference data containing reference values of the level for free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of the pregnant woman's risk wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 18
Dependent Claim
65 words
The method of claim 11 further comprising measuring the pregnant woman's maternal blood for alpha-fetoprotein (AFP) level and incorporating said level of AFP and reference values at various ages of the levels AFP in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, into said comparison wherein a lower level of AFP is indicative of a higher probability of risk.
Claim 19
Dependent Claim
111 words
A screening method for determining a pregnant woman's risk of carrying a fetus with trisomy 13 comprising: measuring said pregnant woman's maternal blood for free beta (human chorionic gonadotropin (HCG)) level and comparing said level of free beta (HCG) and said pregnant woman's gestational age to reference values at various gestational ages of the level of free beta (HCG) in: (1) pregnant women carrying trisomy 13 fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of said pregnant woman's risk of carrying a fetus with trisomy 13 wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with trisomy 13.
Claim 20
Dependent Claim
111 words
A screening method for determining a pregnant woman's risk of carrying a fetus with trisomy 13 comprising: measuring said pregnant woman's maternal blood for free beta (human chorionic gonadotropin (HCG)) level and comparing said level of free beta (HCG) and said pregnant woman's gestational age to reference values at various gestational ages of the level of free beta (HCG) in: (1) pregnant women carrying trisomy 13 fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of said pregnant woman's risk of carrying a fetus with trisomy 13 wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with trisomy 13.
Claim 21
Independent Claim
114 words
A method for determining whether a pregnant woman's risk of carrying a fetus with Down syndrome warrants further testing comprising: measuring said pregnant woman's maternal blood level of an analyte using an assay that employs an antibody raised against free beta (HCG) and comparing the level of the analyte to a set of reference data containing reference values of the level of the analyte in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of pregnant woman's risk of carrying a fetus with Down syndrome wherein a higher level of the analyte is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 22
Independent Claim
114 words
A method for determining whether a pregnant woman's risk of carrying a fetus with Down syndrome warrants further testing comprising: measuring said pregnant woman's maternal blood level of an analyte using an assay that employs an antibody raised against free beta (HCG) and comparing the level of the analyte to a set of reference data containing reference values of the level of the analyte in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, said comparison being indicative of pregnant woman's risk of carrying a fetus with Down syndrome wherein a higher level of the analyte is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 23
Dependent Claim
17 words
The method of claim 14 wherein the assay comprises an enzyme linked immunosorbent assay for free beta-hCG.
Claim 24
Dependent Claim
15 words
The method of claim 14 wherein the assay comprises a one step free beta-hCG assay.
Claim 25
Independent Claim
180 words
A method for screening a pregnant woman to determine if said pregnant woman's risk of carrying a fetus with Down syndrome warrants further testing comprising: selecting a risk cut-off level that will determine whether said pregnant woman should be offered further testing; assigning a prior risk level for said pregnant woman's risk of carrying a fetus with Down syndrome; measuring said pregnant woman's blood for free beta (human chorionic gonadotropin (HCG)) level; determining said pregnant woman's gestational age; and comparing said level of free beta (HCG) and said pregnant woman's gestational age to a set of reference data, containing reference values at various gestational ages of the blood level of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses said comparison in conjunction with said prior risk being indicative of whether said pregnant woman's risk of carrying a fetus with Down syndrome is greater than the selected risk cut-off level wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 26
Independent Claim
180 words
A method for screening a pregnant woman to determine if said pregnant woman's risk of carrying a fetus with Down syndrome warrants further testing comprising: selecting a risk cut-off level that will determine whether said pregnant woman should be offered further testing; assigning a prior risk level for said pregnant woman's risk of carrying a fetus with Down syndrome; measuring said pregnant woman's blood for free beta (human chorionic gonadotropin (HCG)) level; determining said pregnant woman's gestational age; and comparing said level of free beta (HCG) and said pregnant woman's gestational age to a set of reference data, containing reference values at various gestational ages of the blood level of free beta (HCG) in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses said comparison in conjunction with said prior risk being indicative of whether said pregnant woman's risk of carrying a fetus with Down syndrome is greater than the selected risk cut-off level wherein a higher level of free beta (HCG) is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 27
Dependent Claim
97 words
The method of claim 17 further comprising: measuring said pregnant woman's blood level of alpha-fetoprotein (AFP) and incorporating said levels of AFP and a set of reference data containing reference values at various gestational ages of the blood levels of AFP in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses into said comparison in conjunction with said prior risk wherein a higher level of AFP is indicative of a higher probability that the pregnant woman's risk of carrying a fetus with Down syndrome is greater than the selected risk cut-off level.
Claim 28
Dependent Claim
104 words
The method of claim 17 further comprising: measuring said pregnant woman's blood for intact human chorionic gonadotropin (Intact HCG) level and incorporating said level for Intact HCG and a set of reference data containing reference values at various gestational ages of the blood levels of Intact HCG in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses into said comparison in conjunction with said prior risk wherein a higher level of Intact HCG is indicative of a higher probability that said pregnant woman's risk of carrying a fetus with Down syndrome is greater than the selected risk cut-off level.
Claim 29
Dependent Claim
102 words
The method of claim 18 further comprising: measuring said pregnant woman's blood for intact Human chorionic gonadotropin level and incorporating said level of Intact HCG and a set of reference data containing reference values at various gestational ages of the blood levels of Intact HCG in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses into said comparison in conjunction with said prior risk wherein a higher level of Intact HCG is indicative of a higher probability that said pregnant woman's risk of carrying a fetus with Down syndrome is greater than the selected risk cut-off level.
Claim 30
Dependent Claim
99 words
The method of claim 20 further comprising: measuring said pregnant woman's blood for unconjugated estriol (UE) level and incorporating said level of UE and a set of reference data containing reference values at various gestational ages of the levels of UE in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses into said comparison in conjunction with said prior risk wherein a higher level of free beta (HCG) is indicative of a higher probability that said pregnant woman's risk of carrying a fetus with Down syndrome is greater than the selected risk cut-off level.
Claim 31
Dependent Claim
72 words
The method of claim 1 further comprising: measuring said pregnant woman's maternal blood level of alpha-fetoprotein (AFP) and incorporating said level of AFP and reference values at various gestational ages of the levels of AFP in: (1) pregnant women carrying Down syndrome fetuses and (2) pregnant women carrying normal fetuses, into said comparison wherein a higher level of AFP is indicative of a higher probability of carrying a fetus with Down syndrome.
Claim 32
Independent Claim
27 words
The method of any one of claims 1, 2, 3, 4, 5 and 17-22 wherein the free beta (HCG) is an aberrant form of free beta (HCG).
Claim 33
Independent Claim
34 words
The method of any one of claims 1, 2, 3, 4, 5 and 22 wherein said pregnant woman's prior risk of carrying a fetus with Down syndrome is a factor incorporated into said comparison.
Claim 34
Independent Claim
27 words
The method of any one of claims 13-21 wherein said pregnant woman's prior risk of carrying a fetus with Down syndrome is based on her maternal age.
References Cited (Backward Citations)
US4016250A
Cited
US4123224A
Cited
JPS54126723A
Cited
US4565687A
Cited
EP0158973A2
Cited
US4874693A
Cited
WO1989000696A1
Cited
US5037305A
Cited
WO1990008325A1
Cited
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