Adrenomedullin assays and methods for determining mature andrendomedullin
Inventors
Assignees
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Publication Number
US-12247988-B2
Publication Date
2025-03-11
Expiration Date
Abstract
An in vitro method for therapy follow-up in septic patients wherein the concentration of mature ADM 1-52 and/or mature ADM 1-52-Gly in a sample of bodily fluid of said septic patient is determined using an assay containing two binders that bind to two different regions within the region of mature adrenomedullin and/or adrenomedullin-Gly that is amino acid 21-52-amid SEQ ID No. 1 or amino acid 21-52-Gly SEQ ID No. 2 wherein each of said regions contains at least 4 or 5 amino acids, and further assays and calibration methods.
Core Innovation
The invention relates to an in vitro method for use with a human patient suspected of having sepsis. A complex is formed in a sample of plasma or whole blood, where the complex comprises mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly and two antibodies that bind to two different regions within the region of mature adrenomedullin and/or adrenomedullin-Gly that is SEQ ID No. 1 or SEQ ID No. 2, and each of said regions comprises at least 4 or 5 amino acids.
The method measures the amount of complex formed as being above a predetermined amount, and the measured amount is used to stratify human patients into groups according to the measurement, or in combination with at least one other clinical and/or laboratory parameter and/or clinical score, and at least one group is indicated as having sepsis. The method proceeds to treat the human patient or patients indicated to have sepsis, with the condition that the treatment is not provided as a follow-up treatment.
In a related aspect, the same type of complex is formed in plasma or whole blood and the amount of mature ADM 1-52 and/or mature ADM 1-52-Gly bound in the complex in the sample is measured. The measured bound amount is greater than defined pg/ml thresholds, including greater than 40 pg/ml, and after measuring within the defined threshold, at least one treatment selected from steroids, vasopressors, antibiotics, and fluid therapy is administered, with the condition that the treatment is not provided as a follow-up treatment.
Claims Coverage
The independent claims cover four inventive features: a two-antibody complex for sepsis-associated measurement and treatment, a patient stratification approach based on the measured complex amount, a bound-mature ADM threshold with specified treatment administration, and a sample composition with a bound ADM concentration and antibody identity constraint.
Two-antibody complex with region-defined SEQ ID targets and threshold measurement for sepsis treatment
forming a complex in a sample of plasma or whole blood from a human patient suspected of having sepsis, said complex comprising mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly and two antibodies that bind to two different regions within the region of mature adrenomedullin and/or adrenomedullin-Gly that is SEQ ID No. 1 or SEQ ID No. 2, wherein each of said regions comprises at least 4 or 5 amino acids, measuring the amount of complex formed as being above a predetermined amount, treating the human patient suspected of having sepsis, wherein the treatment is not provided as a follow-up treatment
Patient stratification based on measured ADM complex amount for sepsis and treatment without follow-up therapy
forming a complex in an in vitro sample of plasma or whole blood from a human patient suspected of having sepsis, said complex comprising mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly and two antibodies that bind to two different regions within the region of mature adrenomedullin and/or adrenomedullin-Gly that is SEQ ID No. 1 or SEQ ID No. 2 wherein each of said regions comprises at least 4 or 5 amino acids, measuring the amount of complex formed, stratifying the human patients into groups according to the measurement or in combination with at least one other clinical and/or laboratory parameters and/or clinical score wherein at least one group is indicated as having sepsis, treating the human patients in said group indicated to have sepsis, wherein the treatment is not provided as a follow-up treatment
Bound-mature ADM threshold with specific treatment group administration without follow-up therapy
forming a complex in a sample of plasma or whole blood from a human patient suspected of having sepsis, said complex comprising mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly and two antibodies that bind to two different regions within the region of mature adrenomedullin and/or adrenomedullin-Gly that is SEQ ID No. 1 or SEQ ID No. 2, said region of mature adrenomedullin and/or adrenomedullin-Gly that is SEQ ID No. 1 or SEQ ID No. 2 comprises at least 4 or 5 amino acids, measuring the amount of complex formed, wherein the amount of mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly bound in said complex in the sample, is greater than 40 pg/ml, administering at least one of the treatments from the group consisting of steroids, vasopressors, antibiotics and fluid therapy, wherein the treatment is not provided as a follow-up treatment
Sample complex composition with bound ADM concentration and region-binding antibody identity constraint
a complex comprising mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly and at least one antibody to a region within the region of mature adrenomedullin or adrenomedullin-Gly that is SEQ ID No. 1 or SEQ ID No. 2 wherein said region comprises at least 4 or 5 amino acids, wherein the amount of mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly bound in said complex in the sample, is greater than 70 pg/ml, wherein said antibody has an amino acid sequence which is identical to an antibody produced by a process comprising fusing activated B-cells from a mammal previously immunized with a peptide comprising the sequence of mature ADM 1-52, mature ADM 1-52-Gly or a fragment thereof, or with a conjugate of said peptide and a serum protein, with cells of a myeloma cell line and culturing the resulting cells, screening said cultures of said fused cells and selecting recombinant binding IgG antibodies that bind to mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly
Across the independent claims, the core claim coverage is the use of an in vitro two-antibody complex that binds mature adrenomedullin (ADM) 1-52 and/or mature ADM 1-52-Gly to two different regions defined by SEQ ID No. 1 or SEQ ID No. 2 (each region comprising at least 4 or 5 amino acids), followed by measuring the amount of complex or the bound ADM concentration. The measured result is used either to treat patients directly based on a threshold, stratify patients for treatment, or administer one of steroids, vasopressors, antibiotics, or fluid therapy when the bound amount is greater than a defined pg/ml threshold, with treatment expressly not provided as a follow-up treatment. A separate independent sample claim defines a bound-mature ADM concentration and an antibody identity/origin constraint.
Stated Advantages
Documented Applications
In vitro assessment in plasma or whole blood from a human patient suspected of having sepsis to form and measure a mature ADM (ADM 1-52) and/or mature ADM 1-52-Gly complex for use in treating the patient or stratifying patients, with the condition that the treatment is not provided as a follow-up treatment.
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