Reagents, methods and kits for identifying pregnant human beings at risk for placental bed disorder(s)
AssigneeEdward E. Winger, M.D., Professional Corporation
InventorsEdward WINGER, Jane REED
Life of this patent
Estimating the term…
Abstract
This disclosure provides microRNA (miRNA)-based tests and treatment protocols for identifying and/or treating pregnant human beings at risk for a placental bed disorder during pregnancy, as well as reagents and/or kits relating to the same.
Claims26
A method for identifying at least two characteristic groups in a patient population on the basis of microRNA (miRNA) expression, wherein one characteristic group is associated with a reproductive disorder or a risk of developing such a disorder, comprising the steps of:
- a) quantifying at least one microRNA from a biological sample derived from immune cells;
- and, b) segregating the patient population into the groups on the basis of expression of the at least one miRNA, wherein:
- the miRNA is selected from the group consisting of at least one the miRNAs listed in Table 3, Table 4, Table 5, and/or SEQ ID NOS. 1-100;
- and/or,
- the at least one miRNA is selected from the group consisting of hsa-miR-4485-5p, hsa-miR-551b-3p, hsa-miR-24-1-5p, hsa-miR-6819-3p, hsa-miR-1238-3p, hsa-miR-6737-3p, hsa-miR-1237-3p, hsa-miR-6757-3p, hsa-miR-6889-3p, hsa-miR-6752-3p, hsa-miR-191-3p, hsa-miR-6795-3p, hsa-miR-149-5p, hsa-miR-2116-3p, hsa-miR-7974, hsa-miR-23c, hsa-miR-4310, hsa-miR-98-3p, hsa-miR-3190-5p, and/or hsa-miR-4312.
A method for identifying a pregnant human being as being at risk for a placental bed disorder, the method comprising:
- a) quantifying at least one microRNA (miRNA) from a biological sample derived from immune cells of the pregnant human being;
- b) identifying the pregnant human being as being at risk for a placental bed disorder on the basis of a difference in the expression of the at least one miRNA as compared to a control biological sample;
- and,
- c) optionally treating the pregnant human being identified in step b) as being at risk for a placental bed disorder to ameliorate the likelihood of the occurrence of said placental bed disorder in said pregnant human being, and/or to treat said placental bed disorder in said pregnant human being;
- wherein:
- the at least one miRNA is selected from the group consisting of at least one the miRNAs listed in Table 3, Table 4, Table 5, and/or SEQ ID NOS. 1-100;
- and/or,
- the at least one miRNA is selected from the group consisting of hsa-miR-4485-5p, hsa-miR-551b-3p, hsa-miR-24-1-5p, hsa-miR-6819-3p, hsa-miR-1238-3p, hsa-miR-6737-3p, hsa-miR-1237-3p, hsa-miR-6757-3p, hsa-miR-6889-3p, hsa-miR-6752-3p, hsa-miR-191-3p, hsa-miR-6795-3p, hsa-miR-149-5p, hsa-miR-2116-3p, hsa-miR-7974, hsa-miR-23c, hsa-miR-4310, hsa-miR-98-3p, hsa-miR-3190-5p, and/or hsa-miR-4312.
A method comprising the steps of:
- a) quantifying the expression of one or more microRNAs (miRNAs) in a biological sample of a pregnant human being, the miRNAs being:
- at least one miRNA is selected from the group consisting of at least one miRNAs listed in Table 3, Table 4, Table 5, and/or SEQ ID NOS. 1-100;
- and/or,
- the at least one miRNA is selected from the group consisting of hsa-miR-4485-5p, hsa-miR-551b-3p, hsa-miR-24-1-5p, hsa-miR-6819-3p, hsa-miR-1238-3p, hsa-miR-6737-3p, hsa-miR-1237-3p, hsa-miR-6757-3p, hsa-miR-6889-3p, hsa-miR-6752-3p, hsa-miR-191-3p, hsa-miR-6795-3p, hsa-miR-149-5p, hsa-miR-2116-3p, hsa-miR-7974, hsa-miR-23c, hsa-miR-4310, hsa-miR-98-3p, hsa-miR-3190-5p, and/or hsa-miR-4312;
- b) comparing the expression of the miRNAs quantified in step a) to the expression of the same miRNAs in a control sample to determine whether the pregnant human being is at risk of developing preeclampsia, wherein an increase in expression in the pregnant human being relative to the control biological sample indicates the pregnant human being is at risk of developing a placental bed disorder;
- and,
- c) optionally treating a pregnant human being identified in step b) as being at risk of developing a placental bed disorder.
The method of any preceding claim wherein the biological sample is obtained during the first trimester of pregnancy.
The method of any preceding claim wherein the placental bed disorder is selected from the group consisting of preeclampsia, preterm birth, HELLP Syndrome, gestational diabetes, miscarriage, implantation failure, fetal growth restriction, and premature rupture of the membranes (P.R.O.M.).
The method of any preceding claim, wherein the placental bed disorder is preeclampsia.
The method of any preceding claim wherein the control biological sample is representative of a pregnant human being without a placental bed disorder.
The method of any preceding claim wherein the biological sample comprises mononuclear cells.
The method of any preceding claim wherein the biological sample is peripheral blood.
The method of any preceding claim, further comprising the additional step of isolating mononuclear cells from the biological sample.
The method of any preceding claim wherein the biological sample is derived from peripheral blood.
The method of any preceding claim, further comprising the step of extracting miRNA-comprising RNA from the biological sample.
A method of any preceding claim further comprising the steps of quantifying at least one microRNA from a biological sample derived from immune cells from an additional pregnant and identifying the additional pregnant human being as being at risk for a placental bed disorder on the basis of expression of the at least one microRNA.
A method for identifying at least one miRNA that distinguishes a first population individuals at risk for a placental bed disorder from at least one second population comprising individuals not at risk for a placental bed disorder, the method comprising calculating a ratio (HC ratio) of expression of said at least one miRNA, wherein said ratio comprises:
- a numerator equal to the difference between the mean value of expression of the at least one miRNA in the first population and the mean value of the second population and the denominator comprises the average of the two standard deviations of the values for the first and second populations.
A component of a diagnostic assay comprising at least one miRNA listed in Table 3, Table 4, Table 5, and/or SEQ ID NOS. 1-100;
- and/or, at least one of hsa-miR-4485-5p, hsa-miR-551b-3p, hsa-miR-24-1-5p, hsa-miR-6819-3p, hsa-miR-1238-3p, hsa-miR-6737-3p, hsa-miR-1237-3p, hsa-miR-6757-3p, hsa-miR-6889-3p, hsa-miR-6752-3p, hsa-miR-191-3p, hsa-miR-6795-3p, hsa-miR-149-5p, hsa-miR-2116-3p, hsa-miR-7974, hsa-miR-23c, hsa-miR-4310, hsa-miR-98-3p, hsa-miR-3190-5p, and/or hsa-miR-4312.
A microarray, solid support, or collection of solid supports, comprising at least one miRNA listed in Table 3, Table 4, Table 5, and/or SEQ ID NOS. 1-100;
- and/or, at least one of hsa-miR-4485-5p, hsa-miR-551b-3p, hsa-miR-24-1-5p, hsa-miR-6819-3p, hsa-miR-1238-3p, hsa-miR-6737-3p, hsa-miR-1237-3p, hsa-miR-6757-3p, hsa-miR-6889-3p, hsa-miR-6752-3p, hsa-miR-191-3p, hsa-miR-6795-3p, hsa-miR-149-5p, hsa-miR-2116-3p, hsa-miR-7974, hsa-miR-23c, hsa-miR-4310, hsa-miR-98-3p, hsa-miR-3190-5p, and/or hsa-miR-4312;
- and/or a binding partner for at least one of said miRNAs.
Dependencies are inferred from the claim text.