SOLUBLE FMS-LIKE TYROSINE KINASE-1 (sFLT-1) ANTIBODY AND RELATED COMPOSITION, KIT, METHODS OF USING, AND MATERIALS AND METHOD FOR MAKING

Abstract

An isolated antibody that specifically binds to sFlt-1 or a fragment thereof having (i) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO: 2, (ii) a variable light domain region comprising the amino acid sequence of SEQ ID NO: 4, or (iii) both (i) and (ii), a pharmaceutical composition and a kit comprising such an antibody, a method of making such an antibody, a method of determining the presence, amount or concentration of sFlt-1 or a fragment thereof in a test sample, a method of treating a patient in therapeutic or prophylactic need of an antagonist of sFlt-1, an isolated nucleic acid comprising a nucleotide sequence encoding the amino acid sequence of (i) SEQ ID NO: 2, (ii) SEQ ID NO: 4, or (iii) both (i) and (ii), optionally as part of a vector, and a host cell comprising and expressing such a nucleic acid.

1 .- 2 . (canceled) 
     
     
         3 . A method of determining the presence, amount or concentration of sFlt-1 or a fragment thereof in a test sample, which method comprises assaying the test sample for sFlt-1 (or a fragment thereof) by an immunoassay employing at least one antibody and at least one detectable label and comprising comparing a signal generated by the detectable label as a direct or indirect indication of the presence, amount or concentration of sFlt-1 (or a fragment thereof) in the test sample to a signal generated as a direct or indirect indication of the presence, amount or concentration of sFlt-1 (or a fragment thereof) in a control or a calibrator, which is optionally part of a series of calibrators in which each of the calibrators differs from the other calibrators in the series by the concentration of sFlt-1 (or a fragment thereof), wherein one of the at least one antibody is an isolated antibody, which specifically binds to sFlt-1 (or a fragment thereof) and which has (i) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO: 2, (ii) a variable light domain region comprising the amino acid sequence of SEQ ID NO: 4, or (iii) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO: 2 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 4, whereupon the presence, amount or concentration of sFlt-1 (or a fragment thereof) in the test sample is determined. 
     
     
         4 . The method of  claim 3 , wherein the method comprises the following steps:
 (i) contacting the test sample with at least one capture antibody, which binds to an epitope on sFlt-1 (or a fragment thereof) so as to form a capture antibody/sFlt-1 (or a fragment thereof) complex,   (ii) contacting the capture antibody/sFlt-1 (or a fragment thereof) complex with at least one detection antibody, which comprises a detectable label and binds to an epitope on sFlt-1 (or a fragment thereof) that is not bound by the capture antibody, to form a capture antibody/sFlt-1 (or a fragment thereof)/detection antibody complex, and   (iii) determining the presence, amount or concentration of sFlt-1 (or a fragment thereof) in the test sample based on the signal generated by the detectable label in the capture antibody/sFlt-1 (or a fragment thereof)/detection antibody complex formed in (ii), whereupon the presence, amount or concentration of sFlt-1 (or a fragment thereof) in the test sample is determined.   
     
     
         5 . The method of  claim 3 , wherein the method comprises the following steps:
 (i) contacting the test sample with at least one capture antibody, which binds to an epitope on sFlt-1 (or a fragment thereof) so as to form a capture antibody/sFlt-1 (or a fragment thereof) complex, and simultaneously or sequentially, in either order, contacting the test sample with detectably labeled sFlt-1 (or a fragment thereof), which can compete with any sFlt-1 (or a fragment thereof) in the test sample for binding to the at least one capture antibody, wherein any sFlt-1 (or a fragment thereof) present in the test sample and the detectably labeled sFlt-1 compete with each other to form a capture antibody/sFlt-1 (or a fragment thereof) complex and a capture antibody/detectably labeled sFlt-1 (or a fragment thereof) complex, respectively, and   (ii) determining the presence, amount or concentration of sFlt-1 in the test sample based on the signal generated by the detectable label in the capture antibody/detectably labeled sFlt-1 (or a fragment thereof) complex formed in (ii),   wherein the signal generated by the detectable label in the capture antibody/detectably labeled sFlt-1 (or a fragment thereof) complex is inversely proportional to the amount or concentration of sFlt-1 in the test sample,   whereupon the presence, amount or concentration of sFlt-1 in the test sample is determined.   
     
     
         6 . The method of  claim 3 , which further comprises simultaneously or sequentially, in either order, determining the amount or concentration of vascular endothelial growth factor (VEGF) (or a fragment thereof) and/or placental growth factor (P1GF) (or a fragment thereof) in the test sample, which method comprises assaying the test sample for VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) by an assay employing at least one specific binding partner for VEGF (or a fragment thereof) and/or at least one specific binding partner for P1GF (or a fragment thereof), respectively, and at least one detectable label and comprising a signal generated by the detectable label as a direct or indirect indication of the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample to a signal generated as a direct or indirect indication of the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof), respectively, in a control or calibrator, which is optionally part of a series of calibrators in which each of the calibrators differs from the other calibrators in the series by the concentration of VEGF or P1GF, respectively, whereupon the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample is determined. 
     
     
         7 . The method of  claim 4 , which further comprises simultaneously or sequentially, in either order, determining the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample, which method comprises assaying the test sample for VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) by an assay employing at least one specific binding partner for VEGF (or a fragment thereof) and/or at least one specific binding partner for P1GF (or a fragment thereof), respectively, and at least one detectable label and comprising comparing a signal generated by the detectable label as a direct or indirect indication of the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample to a signal generated as a direct or indirect indication of the amount or concentration of VEGF and/or P1GF, respectively, in a control or calibrator, which is optionally part of a series of calibrators in which each of the calibrators differs from the other calibrators in the series by the amount concentration of VEGF or P1GF, respectively, whereupon the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample is determined. 
     
     
         8 . The method of  claim 5 , which further comprises simultaneously or sequentially, in either order, determining the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample, which method comprises assaying the test sample for VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) by an assay employing at least one specific binding partner for VEGF (or a fragment thereof) and/or at least one specific binding partner for P1GF (or a fragment thereof), respectively, and at least one detectable label and comprising comparing a signal generated by the detectable label as a direct or indirect indication of the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample to a signal generated as a direct or indirect indication of the amount or concentration of VEGF and/or P1GF, respectively, in a control or calibrator, which is optionally part of a series of calibrators in which each of the calibrators differs from the other calibrators in the series by the concentration of VEGF or P1GF, respectively, whereupon the amount or concentration of VEGF (or a fragment thereof) and/or P1GF (or a fragment thereof) in the test sample is determined. 
     
     
         9 . The method of  claim 3 , wherein the test sample is from a patient and the method further comprises diagnosing, prognosticating, or assessing the efficacy of therapeutic/prophylactic treatment of the patient, wherein, if the method further comprises assessing the efficacy of therapeutic/prophylactic treatment of the patient, the method optionally further comprises modifying the therapeutic/prophylactic treatment of the patient as needed to improve efficacy. 
     
     
         10 . The method of  claim 4 , wherein the test sample is from a patient and the method further comprises diagnosing, prognosticating, or assessing the efficacy of therapeutic/prophylactic treatment of the patient, wherein, if the method further comprises assessing the efficacy of therapeutic/prophylactic treatment of the patient, the method optionally further comprises modifying the therapeutic/prophylactic treatment of the patient as needed to improve efficacy. 
     
     
         11 . The method of  claim 5 , wherein the test sample is from a patient and the method further comprises diagnosing, prognosticating, or assessing the efficacy of therapeutic/prophylactic treatment of the patient, wherein, if the method further comprises assessing the efficacy of therapeutic/prophylactic treatment of the patient, the method optionally further comprises modifying the therapeutic/prophylactic treatment of the patient as needed to improve efficacy. 
     
     
         12 . The method of  claim 3 , wherein the method is adapted for use in an automated system or a semi-automated system. 
     
     
         13 . The method of  claim 4 , wherein the method is adapted for use in an automated system or a semi-automated system. 
     
     
         14 . The method of  claim 5 , wherein the method is adapted for use in an automated system or a semi-automated system. 
     
     
         15 .- 21 . (canceled)