Kits and methods for prediction and treatment of preeclampsia
Inventors
TARCA, Adi L. • Chaemsaithong, Piya • Chaiworapongsa, Tinnakorn • Hassan, Sonia S. • Romero, Roberto
Assignees
Wayne State University • US Department of Health and Human Services
Publication Number
US-12270814-B2
Publication Date
2025-04-08
Expiration Date
2036-11-07
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Abstract
Biomarkers tests which can be used to predict a positive or negative risk of preeclampsia are described. More specifically, a panel of biomarkers including MMP-7 and gpIIbIIIa, described. The test is useful to predict preeclampsia when a biological sample is obtained between the 16th and 22nd week of pregnancy. Prediction later in pregnancy can be achieved by a combination of Siglec-6, Activin A, ALCAM, and/or FCN2.
Core Innovation
The invention provides kits and methods for the early prediction of preeclampsia in pregnant women by measuring specific biomarkers in biological samples. Six biomarkers are identified for this purpose: Matrilysin (MMP-7), Integrin alpha-IIb: beta-3 complex (gpIIbIIIa), Sialic acid-binding Ig-like lectin 6 (Siglec-6), Activin A, ALCAM, and Ficolin-2 (FCN2). The test is designed to predict the risk of preeclampsia when samples are obtained in defined gestational intervals, with different combinations of biomarkers being relevant at specific stages of pregnancy.
The current problem is that preeclampsia, a severe pregnancy complication leading to maternal and fetal morbidity and mortality, is usually diagnosed only after clinical manifestations, such as hypertension and proteinuria, which appear later in pregnancy. Early prediction is challenging due to the lack of reliable biomarkers and results in missed opportunities for timely intervention. Existing single biomarker tests display limited sensitivity, thereby underperforming in early identification of at-risk patients.
The core innovation lies in utilizing a panel of up to six biomarkers measured from maternal plasma or serum to provide a sensitive and specific prediction of preeclampsia before clinical symptoms appear. The kits include detection mechanisms for these biomarkers and instructions for generating and interpreting biomarker datasets to assess risk. By evaluating biomarker levels at key gestational intervals, the methods allow stratification of risk and determination of the need for preventive treatment regimens, potentially before the onset of symptoms.
Claims Coverage
There are three main inventive features presented in the independent claims of the patent.
Simultaneous detection of Siglec-6 and Activin A in maternal plasma or serum during 22nd to 28th week of gestation
A method consisting of: - Obtaining a plasma or serum sample from a pregnant human subject in the 22nd to 28th week of gestation. - Contacting the sample with at least two binding ligands in one or more wells, where at least one binding ligand binds Sialic acid-binding Ig-like lectin 6 (Siglec-6) and at least one binding ligand binds Activin A. - This enables detection and measurement of both biomarkers in the same biological sample within the specified gestational window.
Sequential measurement of Siglec-6, Activin A, ALCAM, and FCN2 in plasma or serum at specific gestational intervals
A method consisting of: 1. Obtaining a first plasma or serum sample from a pregnant human subject in the 22nd to 28th week of gestation, and contacting it with binding ligands for Siglec-6 and Activin A. 2. Obtaining a second plasma or serum sample from the same subject in the 28th to 32nd week of gestation, and contacting it with one or more binding ligands that bind one or more of Siglec-6, CD166 antigen (ALCAM), and Ficolin-2 (FCN2). - The inventive feature is the use of sequential sampling and detection of these key biomarkers at critical pregnancy windows for preeclampsia assessment.
Assaying expression levels of Siglec-6 and Activin A in maternal plasma or serum between 22 and 28 weeks using well-coated binding ligands
A method consisting of: - Assaying a serum or plasma sample from a pregnant human subject in the 22nd to 28th week of gestation for expression levels of Siglec-6 and Activin A. - The assay involves loading samples into one or more wells that are coated with binding ligands specific to these biomarkers. - This enables quantitative measurement of Siglec-6 and Activin A for preeclampsia risk assessment within this gestational interval.
The three inventive features focus on the detection and measurement of a defined panel of biomarkers at specific gestational intervals for the prediction and assessment of preeclampsia risk, using well-based binding ligand assays in plasma or serum samples.
Stated Advantages
Allows earlier identification of women at risk of preeclampsia before 22 weeks of gestation compared to other technologies.
Provides better prediction performance (higher sensitivity and specificity) for preeclampsia within the same gestational age intervals than known single biomarker tests.
Enables potential for therapeutic intervention to prevent, reduce, or delay symptoms of preeclampsia before symptom onset.
Can be performed on blood samples taken during routine prenatal visits, facilitating integration into standard care.
Documented Applications
Prediction of preeclampsia risk in pregnant women based on biomarker measurements at specific gestational windows.
Prediction of related pregnancy complications in early gestation, such as implantation failure and threatened or spontaneous miscarriage.
Assessment of the need for therapeutic intervention to prevent or reduce the symptoms of preeclampsia.
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