US 2024/0264170 A1 · BIOMARKER PAIRS AND TRIPLETS FOR PREDICTING PRETERM BIRTH

Abstract

The disclosure provides a reversal group of biomarkers comprising a reversal pair and a reversal triplet, wherein the reversal pair and reversal triplet exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls. Also provided is a method of determining probability for preterm birth in a pregnant female, the method comprising measuring in a biological sample obtained from the pregnant female, a reversal value for a reversal pair and a reversal triplet to determining the probability of preterm birth in the pregnant female.

Claims188

Dependent claims

A composition comprising at least three pairs of biomarkers selected from the group consisting of IBP4/SHBG, IBP4/TETN, EGLN/SHBG, EGLN/TETN, PRL/SHBG, and PRL/TETN, wherein said pairs of biomarkers exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls.

A composition comprising a reversal group of isolated biomarkers comprising:

(a) a reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(b) a reversal triplet of isolated biomarkers consisting of (EGLN+PRL)/TETN,
wherein said reversal group of isolated biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A composition comprising a reversal group of surrogate peptides for a reversal group of biomarkers comprising:

(a) a reversal pair of biomarkers consisting of IBP4/SHBG;
and
(b) a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN,
wherein said reversal group of biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A composition comprising a reversal group of isolated biomarkers comprising:

(a) a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG,
wherein said reversal group of isolated biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

A composition comprising a reversal group of surrogate peptides for a reversal group of biomarkers comprising:

(a) a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG,
wherein said reversal group of biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

A composition comprising at least two pairs of biomarkers, wherein the at least two pairs of biomarkers comprise a first reversal pair of IBP4/SHBG;

and a second reversal pair selected from Table 22, wherein said pairs of biomarkers exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls.

A composition comprising a reversal group of isolated biomarkers comprising:

(a) a first reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(b) a second reversal pair of isolated biomarkers selected from Table 22,
wherein said reversal group of isolated biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A composition comprising a reversal group of surrogate peptides for a reversal group of biomarkers comprising:

(a) a first reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(b) a second reversal pair of isolated biomarkers selected from Table 22,
wherein said reversal group of biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A panel comprising at least three pairs of biomarkers selected from the group consisting of IBP4/SHBG, IBP4/TETN, EGLN/SHBG, EGLN/TETN, PRL/SHBG, and PRL/TETN, wherein said pairs of biomarkers exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls.

A panel of biomarkers comprising a reversal group of biomarkers comprising:

(a) a reversal pair of biomarkers consisting of IBP4/SHBG;
and
(b) a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN,
wherein said reversal group of biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A panel of surrogate peptides comprising a reversal group of surrogate peptides for a reversal group of biomarkers comprising:

(a) a reversal pair of biomarkers consisting of IBP4/SHBG;
and
(b) a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN,
wherein said reversal group of biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A panel of biomarkers comprising a reversal group of biomarkers comprising:

(a) a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG,
wherein said reversal group of isolated biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

A panel of surrogate peptides comprising a reversal group of surrogate peptides for a reversal group of biomarkers comprising:

(a) a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG,
wherein said reversal group of isolated biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

A panel comprising at least two pairs of biomarkers, wherein the at least two pairs of biomarkers comprise a first reversal pair of IBP4/SHBG;

and a second reversal pair selected from Table 22, wherein said pairs of biomarkers exhibits a change in reversal value between pregnant females at risk for pre-term birth and term controls.

A panel of biomarkers comprising a reversal group of biomarkers comprising:

(a) a first reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(b) a second reversal pair of biomarkers selected from Table 22,
wherein said reversal group of biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A panel of surrogate peptides comprising a reversal group of surrogate peptides for a reversal group of biomarkers comprising:

(a) a first reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(b) a second reversal pair of biomarkers selected from Table 22,
wherein said reversal group of biomarkers exhibits a change in combined reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A method of determining probability for preterm birth in a pregnant female, the method comprising measuring in a biological sample obtained from said pregnant female, at least three pairs of biomarkers selected from the group consisting of IBP4/SHBG, IBP4/TETN, EGLN/SHBG, EGLN/TETN, PRL/SHBG, and PRL/TETN, wherein said pairs of biomarkers exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls.

A method of determining probability for preterm birth in a pregnant female, the method comprising measuring in a biological sample obtained from said pregnant female a reversal group of biomarkers comprising:

(a) a reversal pair of biomarker consisting of IBP4/SHBG;
and
(b) a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN,
wherein said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

1 more element

(a) a reversal pair of biomarkers consisting of IBP4/SHBG;
and
(b) a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN,
wherein said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

1 more element

A method of determining probability for preterm birth in a pregnant female, the method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) measuring a reversal group of biomarkers comprising:
(i) a reversal pair of biomarkers consisting of IBP4/SHBG;
and
(ii) a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN;
and
(c) determining the combined reversal value of said reversal group,
wherein said combined reversal value of said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

5 more elements

A method of determining probability for preterm birth in a pregnant female, the method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) measuring a reversal pair of biomarkers consisting of IBP4/SHBG;
(c) determining a first reversal value of said reversal pair;
(d) measuring a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN;
(e) determining a second reversal value of said reversal triplet;
(f) combining the first reversal value and the second reversal value into a combined reversal value,
wherein said combined reversal value exhibits a change between pregnant females at risk for pre-term birth and term controls.

4 more elements

(a) a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG,
wherein said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

(a) a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG,
wherein said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

A method of determining probability for preterm birth in a pregnant female, the method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) measuring a reversal group of biomarkers comprising:
(i) a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG;
and
(c) determining a combined reversal value of said reversal group,
wherein said combined reversal value of said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

3 more elements

A method of determining probability for preterm birth in a pregnant female, the method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) measuring a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG;
and
(c) determining a combined reversal value of said reversal triplet;
wherein said combined reversal value exhibits a change between pregnant females at risk for pre-term birth and term controls.

2 more elements

A method of determining probability for preterm birth in a pregnant female, the method comprising measuring a biological sample obtained from said pregnant female, at least two pairs of biomarkers, wherein the at least two pairs of biomarkers comprise a first reversal pair of IBP4/SHBG;

and a second reversal pair selected from Table 22, wherein said pairs of biomarkers exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls.

A method of determining probability for preterm birth in a pregnant female, the method comprising measuring a biological sample obtained from said pregnant female a reversal group of biomarkers comprising:

(a) a first reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(b) a second reversal pair of isolated biomarkers selected from Table 22;
wherein said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

1 more element

(a) a first reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(b) a second reversal pair of isolated biomarkers selected from Table 22,
wherein said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

1 more element

A method of determining probability for preterm birth in a pregnant female, the method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) measuring a reversal group of biomarkers comprising:
(i) a first reversal pair of isolated biomarkers consisting of IBP4/SHBG;
and
(ii) a second reversal pair of isolated biomarkers selected from Table 22;
and
(c) determining the reversal value of said reversal group,
wherein said reversal value of said reversal group of biomarkers exhibits a change between pregnant females at risk for pre-term birth and term controls.

5 more elements

A method of determining probability for preterm birth in a pregnant female, the method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) measuring a reversal group of biomarkers comprising a first reversal pair of biomarkers consisting of IBP4/SHBG;
(c) determining a first reversal value of said first reversal pair;
(d) measuring a second reversal pair of biomarkers selected from Table 22;
(e) determining a second reversal value of said second reversal pair;
(f) combining the first reversal value and the second reversal value into a combined reversal value,
wherein said combined reversal value exhibits a change between pregnant females at risk for pre-term birth and term controls.

4 more elements

A method of detecting at least three pairs of biomarkers selected from the group consisting of IBP4/SHBG, IBP4/TETN, EGLN/SHBG, EGLN/TETN, PRL/SHBG, and PRL/TETN in a pregnant female, said method comprising,

(a) obtaining a biological sample from said pregnant female;
and
(b) detecting whether the at least three pairs of biomarkers is present in the biological sample,
wherein said pairs of biomarkers exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A method of detecting at least two pairs of biomarkers in a pregnant female, wherein the at least two pairs of biomarkers comprise a first reversal pair of IBP4/SHBG and a second reversal pair selected from Table 22, said method comprising,

(a) obtaining a biological sample from said pregnant female;
and
(b) detecting whether the at least two pairs of biomarkers is present in the biological sample,
wherein said pairs of biomarkers exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls.

1 more element

A method of detecting a reversal group of biomarkers comprising a reversal pair of biomarkers consisting of IBP4/SHBG and a reversal triplet of biomarkers consisting of (EGLN+PRL)/TETN in a pregnant female, said method comprising:

(a) obtaining a biological sample from said pregnant female;
and
(b) detecting whether the reversal group of biomarkers is present in the biological sample,
wherein said detecting comprises subjecting said sample to a proteomics work-flow comprised of mass spectrometry (MS) quantification.

1 more element

A method of detecting a reversal group of biomarkers comprising a reversal pair of biomarkers consisting of IBP4/SHBG and a reversal triplet consisting of (EGLN+PRL)/TETN in a pregnant female, said method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) first detecting whether the reversal pair of biomarkers is present in the biological sample;
and
(c) second detecting whether the reversal triplet of biomarkers is present in the biological sample,
wherein said first detecting step and/or said second detecting step comprises subjecting said sample to a proteomics work-flow comprised of mass spectrometry (MS) quantification.

2 more elements

(a) obtaining a biological sample from said pregnant female;
and
(b) detecting whether the pair of isolated biomarkers is present in the biological sample by contacting the biological sample with a first capture agent that specifically binds a first member of said pair and a second capture agent that specifically binds a second member of said pair;
and,
(c) detecting binding between the first biomarker of said pair and the first capture agent and between the second member of said pair and the second capture agent,
wherein said detecting comprises an assay that utilizes the capture agent.

3 more elements

(a) obtaining a biological sample from the pregnant female;
(b) detecting whether the reversal group of biomarkers is present in the biological sample by contacting the biological sample with a capture agent that specifically binds an individual biomarker of the reversal group;
and
(c) detecting binding between the capture agent and the individual biomarker of the reversal group,
wherein said detecting comprises an assay that utilizes the capture agent.

2 more elements

A method of detecting a reversal group of biomarkers comprising a reversal triplet of isolated biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG in a pregnant female, said method comprising:

(a) obtaining a biological sample from said pregnant female;
and
(b) detecting whether the reversal group of biomarkers is present in the biological sample,
wherein said detecting comprises subjecting said sample to a proteomics work-flow comprised of mass spectrometry (MS) quantification.

1 more element

A method of detecting a reversal group of biomarkers comprising a reversal triplet of biomarkers consisting of (EGLN+IBP4)/SHBG or (PAPP2+IBP4)/SHBG in a pregnant female, said method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) detecting whether the reversal group of biomarkers is present in the biological sample by contacting the biological sample with a capture agent that specifically binds an individual biomarker of the reversal group;
and
(c) detecting binding between the capture agent and the individual biomarker of the reversal group,
wherein said detecting comprises an assay that utilizes the capture agent.

2 more elements

A method of detecting a reversal group of biomarkers in a pregnant female comprising a first reversal pair of biomarkers consisting of IBP4/SHBG and a second reversal pair of biomarkers selected from Table 22, said method comprising:

(a) obtaining a biological sample from said pregnant female;
and
(b) detecting whether the reversal group of biomarkers is present in the biological sample,
wherein said detecting comprises subjecting said sample to a proteomics work-flow comprised of mass spectrometry (MS) quantification.

1 more element

(a) obtaining a biological sample from the pregnant female;
(b) first detecting whether the first reversal pair of biomarkers is present in the biological sample;
and
(c) second detecting whether the second reversal pair of biomarkers is present in the biological sample,
wherein said first detecting step and/or said second detecting step comprises subjecting said sample to a proteomics work-flow comprised of mass spectrometry (MS) quantification.

2 more elements

(a) obtaining a biological sample from said pregnant female;
and
(b) detecting whether the pairs of isolated biomarkers are present in the biological sample by contacting the biological sample with a first capture agent that specifically binds a first member of said pairs and a second capture agent that specifically binds a second member of said pairs;
and,
(c) detecting binding between the first biomarker of said pairs and the first capture agent and between the second member of said pairs and the second capture agent,
wherein said detecting comprises an assay that utilizes the capture agent.

3 more elements

A method of detecting a reversal group of biomarkers comprising a first reversal pair of biomarkers consisting of IBP4/SHBG and a second reversal pair of biomarkers selected from Table 22 in a pregnant female, said method comprising:

(a) obtaining a biological sample from the pregnant female;
(b) detecting whether the reversal group of biomarkers is present in the biological sample by contacting the biological sample with a capture agent that specifically binds an individual biomarker of the reversal group;
and
(c) detecting binding between the capture agent and the individual biomarker of the reversal group,
wherein said detecting comprises an assay that utilizes the capture agent.

2 more elements

A method of treating or preventing preterm birth in a pregnant female the method comprising:

(a) obtaining a biological sample from said pregnant female;
(b) detecting a reversal group of biomarkers in said sample;
(c) providing a risk score for said pregnant female;
(d) prognosing said pregnant female as having an increased risk of preterm birth;
and
(e) administering one or more therapies to said pregnant female to prevent preterm birth.

3 more elements

A method of treating and/or preventing preterm birth, the method comprising:

(a) obtaining a biological sample from a pregnant female;
(b) detecting a reversal group of biomarkers in said sample;
(c) providing a test risk score for said pregnant female based at least in part on the detected level of said reversal group in said sample;
and
(d) administering one or more preterm birth interventions to said pregnant female when the risk score exceeds a reference risk score.

2 more elements

Dependencies are inferred from the claim text.

Biomarker pairs and triplets for predicting preterm birth

Life of this patent

Biomarker pairs and triplets for predicting preterm birth

Life of this patent

Abstract

Claims188