# US 2025/0085293 A1 · Biomarkers for predicting preterm birth due to preterm premature rupture of membranes (pprom) versus idiopathic spontaneous labor (ptl) > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0085293 A1 - Document ID: US20250085293A1 - Status: Published application - Kind: A1 - Application number: 18/745,657 - Filed: 2024-06-17 - Published: 2025-03-13 - Earliest claimed: 2016-08-05 - Assignees: Sera Prognostics, Inc. - Applicants: Sera Prognostics, Inc. - Inventors: John Jay Boniface; Julja Burchard; Gregory Charles Critchfield; Tracey Cristine Fleischer; Durlin Edward Hickok; Chien Hsu - Web page: https://patentgrep.com/patent/US20250085293A1 ## CPC - G01N 33/6848: {Methods of protein analysis involving mass spectrometry} - C12Q 1/6883: for diseases caused by alterations of genetic material - C40B 40/10: Libraries containing peptides or polypeptides, or derivatives thereof - G01N 33/689: {related to pregnancy or the gonads} - C12Q 2600/156: Polymorphic or mutational markers - C12Q 2600/158: Expression markers - G01N 2560/00: Chemical aspects of mass spectrometric analysis of biological material - G01N 2800/368: Pregnancy complicated by disease or abnormalities of pregnancy, e.g. preeclampsia, preterm labour - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60) ## Abstract The present invention provides compositions and methods for predicting the probability of preterm birth in a pregnant female. The present invention provides a composition comprising one or more biomarkers selected from the group consisting of the biomarkers set forth in FIGS. 1 and 2 and Tables 1 through 3, 6 through 38, and 44 through 68. In one embodiment, the invention provides a method of determining probability for preterm birth in a pregnant female, optionally preterm birth associated with preterm premature rupture of membranes (PPROM) or preterm birth associated idiopathic spontaneous labor (PTL), the method comprising measuring in a biological sample obtained from the pregnant female one or biomarkers selected from one or more of the biomarkers set forth in FIGS. 1 and 2 and Tables 1 through 3, 6 through 38, and 44 through 68 to determine the probability for preterm birth in said pregnant female. ## Claims ### Claim 1 A composition comprising one or more biomarkers, wherein the biomarkers comprise Notum or ISM2. ### Claim 2 A method of determining probability for preeclampsia in a pregnant female, the method comprising: (a) detecting the presence or amount of one or more biomarkers in a biological sample obtained from a pregnant female; and (b) measuring a reversal value for said one or more biomarkers, wherein said reversal value predicts the probability for preeclampsia in said pregnant female in a predictive model, wherein detecting comprises subjecting said biological sample to: (i) a proteomics work-flow comprised of mass spectrometry (MS) quantification; or (ii) an assay that utilizes a capture agent that binds to at least one biomarker of said one or more biomarkers, and wherein the one or more biomarkers comprise Notum or ISM2. ### Claim 3 (canceled) ### Claim 4 (canceled) ### Claim 5 (depends on 1) The composition of claim 1, wherein the one or more biomarkers comprising Notum or ISM2 further comprise PRG4. ### Claim 6 (depends on 5) The composition of claim 5, wherein the composition comprises Notum and PRG4. ### Claim 7 (depends on 5) The composition of claim 5, wherein the composition comprises ISM2 and PRG4. ### Claim 8 (depends on 1) The composition of claim 1, wherein: (a) the one or more biomarkers comprising Notum comprises a peptide fragment comprising the amino acid sequence GLADSGWFLDNK (SEQ ID NO: 123); (b) the one or more biomarkers comprising Notum comprises a peptide fragment comprising the amino acid sequence LYIQNLGR (SEQ ID NO: 166); (c) the one or more biomarkers comprising ISM2 comprises a peptide fragment comprising the amino acid sequence FDTTPWILCK (SEQ ID NO: 130); or (d) the one or more biomarkers comprising ISM2 comprises a peptide fragment comprising the amino acid sequence TRPCGYGCTATETR (SEQ ID NO: 149). ### Claim 9 (depends on 5) The composition of claim 5, wherein the one or more biomarkers comprising PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 10 (depends on 6) The composition of claim 6, wherein: (a) Notum comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of GLADSGWFLDNK (SEQ ID NO: 123) or LYIQNLGR (SEQ ID NO: 166); and (b) PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 11 (depends on 7) The composition of claim 7, wherein: (a) ISM2 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of FDTTPWILCK (SEQ ID NO: 130) or TRPCGYGCTATETR (SEQ ID NO: 149); and (b) PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 12 (depends on 2) The method of claim 2, wherein the pregnant female is between 17 and 28 weeks of gestation at the time the biological sample is collected. ### Claim 13 (depends on 2) The method of claim 2, wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. ### Claim 14 (depends on 2) The method of claim 2, wherein said detecting comprises mass spectrometry (MS). ### Claim 15 (depends on 14) The method of claim 14, wherein said MS is selected from the group consisting of matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS; MALDI-TOF post-source-decay (PSD); MALDI-TOF/TOF; surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF) MS; electrospray ionization mass spectrometry (ESI-MS); ESI-MS/MS; ESI-MS/(MS)n (n is an integer greater than zero); ESI 3D or linear (2D) ion trap MS; ESI triple quadrupole MS; ESI quadrupole orthogonal TOF (Q-TOF); ESI Fourier transform MS systems; desorption/ionization on silicon (DIOS); secondary ion mass spectrometry (SIMS); atmospheric pressure chemical ionization mass spectrometry (APCI-MS); APCI-MS/MS; APCI-(MS)n (n is an integer greater than zero); ion mobility spectrometry (IMS); inductively coupled plasma mass spectrometry (ICP-MS); atmospheric pressure photoionization mass spectrometry (APPI-MS); APPI-MS/MS; and APPI-(MS)n (n is an integer greater than zero). ### Claim 16 (depends on 14) The method of claim 14, wherein said MS comprises affinity-capture MS (AC-MS), co-immunoprecipitation-mass spectrometry (co-IP MS), liquid chromatography-mass spectrometry (LC-MS), multiple reaction monitoring (MRM) or selected reaction monitoring (SRM). ### Claim 17 (depends on 2) The method of claim 2, wherein said detecting comprises said assay that utilizes a capture agent that binds to at least one biomarker of said one or more biomarkers. ### Claim 18 (depends on 17) The method of claim 17, wherein said capture agent is selected from the group consisting of an antibody, antibody fragment, nucleic acid-based protein binding reagent, small molecule or variant thereof. ### Claim 19 (depends on 17) The method of claim 17, wherein said assay is selected from the group consisting of enzyme immunoassay (EIA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). ### Claim 20 (depends on 2) The method of claim 2, wherein the one or more biomarkers comprising Notum or ISM2 further comprise PRG4. ### Claim 21 (depends on 20) The method of claim 20, wherein the one or more biomarkers comprise Notum and PRG4. ### Claim 22 (depends on 20) The method of claim 20, wherein the one or more biomarkers comprise ISM2 and PRG4. ### Claim 23 (depends on 2) The method of claim 2, wherein: (a) the one or more biomarkers comprising Notum comprises a peptide fragment comprising the amino acid sequence GLADSGWFLDNK (SEQ ID NO: 123); (b) the one or more biomarkers comprising Notum comprises a peptide fragment comprising the amino acid sequence LYIQNLGR (SEQ ID NO: 166); (c) the one or more biomarkers comprising ISM2 comprises a peptide fragment comprising the amino acid sequence FDTTPWILCK (SEQ ID NO: 130); or (d) the one or more biomarkers comprising ISM2 comprises a peptide fragment comprising the amino acid sequence TRPCGYGCTATETR (SEQ ID NO: 149). ### Claim 24 (depends on 20) The method of claim 20, wherein the one or more biomarkers comprising PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 25 (depends on 21) The method of claim 21, wherein: (a) Notum comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of GLADSGWFLDNK (SEQ ID NO: 123) or LYIQNLGR (SEQ ID NO: 166); and (b) PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 26 (depends on 22) The method of claim 22, wherein: (a) ISM2 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of FDTTPWILCK (SEQ ID NO: 130) or TRPCGYGCTATETR (SEQ ID NO: 149); and (b) PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 27 A method of detecting a reversal value for one or more isolated biomarkers or a pair of isolated biomarkers in a biological sample obtained from a pregnant female, the method comprising: (a) detecting the presence or amount of said one or more isolated biomarkers or pair of isolated biomarkers in said biological sample; and (b) measuring a reversal value for said pair of isolated biomarkers, wherein detecting comprises subjecting said biological sample to: (i) a proteomics work-flow comprised of mass spectrometry (MS) quantification; or (ii) an assay that utilizes a capture agent that binds to at least one biomarker of said one or more isolated biomarkers or said pair of isolated biomarkers, wherein said biological sample is selected from the group consisting of whole blood, plasma, and serum, and wherein said one or more isolated biomarkers or said pair of isolated biomarkers comprises Notum or ISM2. ### Claim 28 (depends on 27) The method of claim 27, wherein the one or more isolated biomarkers or pair of isolated biomarkers comprising Notum or ISM2 further comprise PRG4. ### Claim 29 (depends on 28) The method of claim 28, wherein the one or more isolated biomarkers or pair of isolated biomarkers comprise Notum and PRG4. ### Claim 30 (depends on 28) The method of claim 28, wherein the one or more isolated biomarkers or pair of isolated biomarkers comprise ISM2 and PRG4. ### Claim 31 (depends on 27) The method of claim 27, wherein: (a) the one or more isolated biomarkers or pair of isolated biomarkers comprising Notum comprises a peptide fragment comprising the amino acid sequence GLADSGWFLDNK (SEQ ID NO: 123); (b) the one or more isolated biomarkers or pair of isolated biomarkers comprising Notum comprises a peptide fragment comprising the amino acid sequence LYIQNLGR (SEQ ID NO: 166); (c) the one or more isolated biomarkers or pair of isolated biomarkers comprising ISM2 comprises a peptide fragment comprising the amino acid sequence FDTTPWILCK (SEQ ID NO: 130); or (d) the one or more isolated biomarkers or pair of isolated biomarkers comprising ISM2 comprises a peptide fragment comprising the amino acid sequence TRPCGYGCTATETR (SEQ ID NO: 149). ### Claim 32 (depends on 28) The method of claim 28, wherein the one or more isolated biomarkers or pair of isolated biomarkers comprising PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 33 (depends on 29) The method of claim 29, wherein: (a) Notum comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of GLADSGWFLDNK (SEQ ID NO: 123) or LYIQNLGR (SEQ ID NO: 166); and (b) PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156). ### Claim 34 (depends on 30) The method of claim 30, wherein: (a) ISM2 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of FDTTPWILCK (SEQ ID NO: 130) or TRPCGYGCTATETR (SEQ ID NO: 149); and (b) PRG4 comprises a peptide fragment comprising an amino acid sequence selected from the group consisting of ITEVWGIPSPIDTVFTR (SEQ ID NO: 46), DQYYNIDVPSR (SEQ ID NO: 114), and GLPNVVTSAISLPNIR (SEQ ID NO: 156).