Non-invasive biomarker to identify subject at risk of preterm delivery

• US 10,408,838 B2
• Filed: 09/19/2017
• Issued: 09/10/2019
• Est. Priority Date: 10/24/2012
• Status: Active Grant

• Current Assignee: NYU Winthrop Hospital
• Original Assignee: NYU Winthrop Hospital
• Inventors: Ragolia, Louis
• Primary Examiner(s): Heyer, Dennis
• Application Number:
  US15/708,582
• Publication Number:
  US 20180003713A1
• Time in Patent Office: 721 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: G01N 2333/99 Isomerases (5.)
• CPC Class Codes: G01N 2800/368 Pregnancy complicated by disease or abnormalities of pregnancy, e.g. preeclampsia, preterm labour
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

Methods for diagnosis to allow prediction of the likelihood of preterm birth based upon the concentration of lipocalin-type prostaglandin D2 synthase (L-PGDS) in cervical vaginal secretions. In addition, specific prostaglandin D2 receptor antagonists may represent novel tocolytic therapeutics.

Claims

1. A method for predicting preterm delivery of a fetus, comprising:

collecting a cervical vaginal secretion sample from a pregnant woman having an intact amniotic membrane;

measuring with an immunoassay lipocalin-type prostaglandin D2 synthase (L-PGDS) concentration in the collected cervical vaginal secretion sample; and

determining a likelihood of preterm delivery based on a comparison of the measured lipocalin-type prostaglandin D2 synthase concentration to corresponding values from a gestational age-matched population.

2. The method of claim 1, wherein the L-PGDS concentration in the cervical vaginal secretion rises prior to rupture in membranes.

3. The method of claim 1, wherein measuring lipocalin-type prostaglandin D2 synthase concentration comprises measuring ratios of isoforms of L-PGDS in the collected cervical vaginal secretion sample.

4. The method of claim 1, wherein the cervical vaginal secretion is collected with a sponge.

5. The method of claim 4, wherein the sponge is treated with at least a protease inhibitor and a bacteriocide.

6. The method of claim 1, wherein L-PGDS levels of above 1.8 μ

g/ml indicate the increased likelihood of preterm delivery.

7. The method of claim 1, wherein the likelihood of preterm delivery is the likelihood of preterm delivery within a period greater than 2 weeks.

8. The method of claim 1, wherein the pregnant woman is at week 28 of gestation or later.

9. The method of claim 1, further comprising repeating cervical vaginal secretion collection from the pregnant woman and L-PGDS measurement every two weeks.

10. The method of claim 1, further comprising delaying the preterm delivery by administering to the pregnant woman a composition comprising a tocolytic agent.

11. The method of claim 10, wherein the tocolytic agent is a β

2 agonist, an NSAID cyclooxygenase inhibitor, a calcium channel blocker, a prostaglandin DP1 or DP2 receptor antagonist, or an oxytocin inhibitor.

12. The method of claim 1, wherein the L-PGDS concentration is measured using a radioimmunoassay, enzyme-linked immunoassay, or fluorescent immunoassay.

13. The method of claim 1, wherein measuring L-PGDS comprises contacting the cervical vaginal secretion sample with at least one antibody against L-PGDS.

14. The method of claim 2, wherein measuring L-PGDS concentration comprises contacting the cervical vaginal secretion sample with multiple antibodies against isoforms of L-PGDS.

15. The method of claim 1, wherein the cervical vaginal secretion sample is collected at or after 25 weeks gestation.