Biomarker signature method, and apparatus and kits thereof
Inventors
Brandon, Richard Bruce • MCHUGH, Leo Charles
Assignees
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Publication Number
US-11047010-B2
Publication Date
2021-06-29
Expiration Date
Abstract
The present invention discloses methods, kits, and apparatus as well as reagents and compositions associated therewith for deriving an indicator for use in diagnosing the presence, absence or degree of at least one condition in a biological subject or in prognosing at least one condition in a biological subject. Also disclosed is a biomarker signature for use in diagnosing the presence, absence or degree of at least one condition in a biological subject or in prognosing at least one condition in a biological subject. The present invention further discloses methods, kits and apparatus, as well as reagents and compositions associated therewith, for identifying biomarkers for use in a biomarker signature.
Core Innovation
The invention relates to a biomarker signature and indicator framework for infection-negative systemic inflammatory response syndrome (inSIRS) and infection-positive systemic inflammatory response syndrome (ipSIRS) in a human subject. Immune system biomarkers are measured or derived from a blood sample taken from the subject, and at least one pair of biomarker values is used to determine at least one derived biomarker value indicative of a ratio of concentrations of a corresponding pair of immune system biomarkers. The ratio is correlated with an increased likelihood of inSIRS or an increased likelihood of ipSIRS.
An indicator is determined based on the derived biomarker value or values and is used to assess the likely presence of inSIRS or ipSIRS. In embodiments, at least two pairs of biomarker values are used, first and second derived biomarker values are determined from respective ratios of biomarker concentrations, and the indicator is determined based on a combination of the derived biomarker values. The biomarker pairs include polynucleotide expression products of PLA2G7 and PLAC8, and CEACAM4 and LAMP1.
The framework correlates immune response biomarker signatures with treatment outcomes and supports diagnosis, prognosis, and treatment monitoring. Reference biomarker signatures are defined from control signatures, and sample biomarker signatures are defined from signatures obtained from subjects after starting therapy. The signature is used to correlate with positive therapeutic response, negative therapeutic response, or side effects.
Claims Coverage
Two independent method claims are directed to measuring immune system biomarker pairs in a blood sample, deriving ratio-based values that correlate with likely inSIRS versus ipSIRS, and using the resulting indicator to select a treatment regimen. Across the claims, the inventive content centers on biomarker-ratio indicator determination and indicator-guided selection of anti-inflammatory or anti-pyretic treatment versus antibiotic treatment for inhibiting the development or progression of inSIRS or ipSIRS.
Ratio-based indicator for inSIRS versus ipSIRS likelihood
Determining at least one pair of biomarker values for corresponding immune system biomarkers in a blood sample; determining at least one derived biomarker value indicative of a ratio of concentrations of a corresponding pair of immune system biomarkers; and determining an indicator based on the derived biomarker value to indicate likely inSIRS when the correlation is with inSIRS and likely ipSIRS when the correlation is with ipSIRS.
PLA2G7/PLAC8 polynucleotide expression product biomarker pair
Wherein the at least one pair of biomarker values comprises a first pair including a first immune system biomarker representing a polynucleotide expression product of the PLA2G7 gene and a second immune system biomarker representing a polynucleotide expression product of the PLAC8 gene.
Indicator-guided treatment regimen selection for inhibiting progression
Exposing the subject to a treatment regimen for treating inSIRS comprising administration of an anti-inflammatory or anti-pyretic agent based on the indicator indicating a likely presence of inSIRS, or exposing the subject to a treatment regimen for treating ipSIRS comprising administration of an antibiotic agent based on the indicator indicating a likely presence of ipSIRS.
Combination of multiple ratio-derived biomarker values to form the indicator
Determining the indicator based on a combination of at least the first derived biomarker value and the second derived biomarker value, wherein at least two biomarker pairs are used and the second pair includes polynucleotide expression products of the CEACAM4 and LAMP1 genes.
PLA2G7/PLAC8 and CEACAM4/LAMP1 biomarker pair definitions
Wherein one pair represents a polynucleotide expression product of the PLA2G7 gene and a polynucleotide expression product of the PLAC8 gene, and another pair represents a polynucleotide expression product of the CEACAM4 gene and a polynucleotide expression product of the LAMP1 gene.
The claims cover methods that measure immune-system biomarker expression products from a blood sample, convert at least one or at least two biomarker pairs into ratio-based derived values, combine the derived values into an indicator that discriminates likely inSIRS versus likely ipSIRS, and select an anti-inflammatory or anti-pyretic regimen or an antibiotic regimen accordingly. The biomarker scheme explicitly includes PLA2G7/PLAC8 and CEACAM4/LAMP1 polynucleotide expression product pairs.
Stated Advantages
Inhibiting the development or progression of infection-negative systemic inflammatory response syndrome (inSIRS) or infection-positive systemic inflammatory response syndrome (ipSIRS) in a human subject.
Assessing a likelihood of the presence of inSIRS or ipSIRS in a subject and selecting a treatment regimen accordingly.
Correlating IRS biomarker signatures with treatment outcomes, including positive therapeutic response, negative therapeutic response, and side effects.
Documented Applications
Assessing the likelihood of the presence of inSIRS or ipSIRS in a subject and exposing the subject to a treatment regimen for treating inSIRS or treating ipSIRS based on the indicator.
Correlating IRS biomarker signatures with treatment outcomes, including positive therapeutic response, negative therapeutic response, and side effects, in inSIRS/ipSIRS contexts such as mild sepsis, severe sepsis, and septic shock.
Using immune system biomarker signatures and indicators for diagnosis, prognosis, and treatment monitoring in inSIRS/ipSIRS.
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