Soluble human st-2 antibodies and assays

Abstract

Provided herein are antibodies and antigen-binding antibody fragments that bind to human soluble Growth Stimulation-Expressed Gene 2 (ST2) protein, kits containing these antibodies and antibody fragments, and methods of using these antibodies and antibody fragments.

What is claimed is: 
     
         1 . An isolated antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof binds competitively with an antibody produced by the hybridoma deposited at the American Type Culture Collection (ATTC) and designated by Patent Deposit Designation PTA-10431 or PTA-10432. 
     
     
         2 . The antibody or fragment of  claim 1 , wherein the antibody or fragment thereof does not bind competitively with D066-3 or D067-3 antibody, has a K D  for binding to human soluble ST2 equal to or less than 1.51×10 −9 M, or has a K D  for binding to human soluble ST2 equal to or less than 8.59×10 −10 M. 
     
     
         3 . The antibody or fragment of  claim 1 , wherein the antibody or fragment thereof is chimeric or humanized. 
     
     
         4 . The antibody or fragment of  claim 1 , wherein the fragment is selected from the group consisting of: a Fab fragment, a F(ab′) 2  fragment, and a scFv fragment. 
     
     
         5 . The antibody or fragment of  claim 1 , wherein the antibody or fragment thereof comprises one or more of the complementary determining regions of the light or heavy chain of the antibody produced by the hybridoma deposited at the ATTC and designated by the Patent Deposit Designation PTA-10431 or PTA-10432. 
     
     
         6 . The antibody or fragment of  claim 1 , wherein the antibody is the antibody produced by the hybridoma deposited at the ATTC and designated by the Patent Deposit Designation PTA-10431 or PTA-10432, or is an antigen-binding fragment of the antibody produced by the hybridoma deposited at the ATTC and designated by the Patent Deposit Designation PTA-10431 or PTA-10432. 
     
     
         7 . The antibody or fragment of  claim 1 , wherein the antibody or fragment thereof is labeled. 
     
     
         8 . An isolated antibody or antigen-binding fragment thereof that specifically binds to human soluble ST2, wherein the antibody or antigen-binding fragment thereof is produced by a process that includes immunizing a non-human mammal with a recombinant human soluble ST2 isolated from a human cell. 
     
     
         9 . The antibody or fragment of  claim 8 , wherein the human cell is a human embryonic kidney cell. 
     
     
         10 . A hybridoma selected from the group consisting of: the hybridoma deposited at the American Type Culture Collection (ATCC) and designated by the Patent Deposit Designation PTA-10431 and the hybridoma deposited at the ATCC and designated by the Patent Deposit Designation PTA-10432. 
     
     
         11 . A method of quantitating a level of human soluble ST2 in a sample from a subject, the method comprising:
 contacting the sample with at least one antibody or fragment thereof of  claim 1 ; and   detecting binding of the antibody or fragment thereof to human soluble ST2.   
     
     
         12 . The method of  claim 11 , wherein the subject is undiagnosed or is not presenting with one or more symptoms of a disease. 
     
     
         13 . The method of  claim 11 , wherein the subject has been diagnosed as having a disease or has been identified as being at risk of developing a disease. 
     
     
         14 . The method of  claim 13 , wherein the disease is selected from the group consisting of: heart failure, coronary artery disease, cardiovascular disease, acute coronary syndrome, renal insufficiency, and stroke. 
     
     
         15 . The method of  claim 11 , wherein the subject has one or more of:
 hypertriglyceridemia, hypercholesterolemia, hypertension, and a body mass index of ≥30.   
     
     
         16 . The method of  claim 11 , wherein the sample comprises blood, serum, or plasma. 
     
     
         17 . A method of predicting the risk of death within one year in a subject, the method comprising:
 obtaining a sample from a subject; and   determining the level of human soluble ST2 in the sample using at least one antibody or fragment thereof of  claim 1 ;   wherein an elevated level of human soluble ST2 in the sample compared to a reference level of human soluble ST2 indicates that the subject has an increased risk of death within one year, and a decreased or an equal level of human soluble ST2 in the sample compared to a reference level of human soluble ST2 indicates that the subject has a decreased risk of death within one year.   
     
     
         18 . The method of  claim 17 , wherein the reference level of human soluble ST2 is a threshold level of human soluble ST2. 
     
     
         19 . The method of  claim 18 , wherein the threshold level of human soluble ST2 is an average level of human soluble ST2 in a healthy patient population. 
     
     
         20 . The method of any of  claims 17 , wherein the reference level is a level of human soluble ST2 present in a sample of a subject not diagnosed as having a disease or not presenting with one or more symptoms of a disease. 
     
     
         21 . A method of determining whether to discharge or to initiate or continue treatment of a subject on an inpatient basis, the method comprising:
 obtaining a sample from a subject; and   determining the level of human soluble ST2 in the sample using at least one antibody or fragment thereof of  claim 1 ;   wherein an elevated level of human soluble ST2 in the sample compared to a reference level of human soluble ST2 indicates that inpatient treatment of the subject should be initiated or continued, and a decreased or an equal level of human soluble ST2 in the sample compared to a reference level of human soluble ST2 in the sample indicates that the subject should be discharged.   
     
     
         22 . The method of  claim 21 , wherein the subject has at least one or more of the following symptoms: chest pain or discomfort, shortness of breath, nausea, vomiting, eructation, sweating, palpitations, lightheadedness, fatigue, and fainting. 
     
     
         23 . A method of selecting a subject for participation in a clinical study, the method comprising:
 obtaining a sample from a subject;   determining the level of human soluble ST2 in the sample using at least one antibody or fragment thereof of  claim 1 ; and   selecting the subject for participation in a clinical study if the subject's level of human soluble ST2 relative to a reference level of human soluble ST2 indicates that the subject should be selected for participation in a clinical study.   
     
     
         24 . The method of  claim 23 , wherein the presence of an elevated level of human soluble ST2 indicates that the subject should be selected for participation in a clinical study. 
     
     
         25 . A kit comprising at least one antibody or antigen-binding fragment thereof of  claim 1 . 
     
     
         26 . The kit of  claim 25 , wherein at least one of the antibodies or fragments has a K D  for binding to human soluble ST2 equal to or less than 8.59×10 −10 M. 
     
     
         27 . The kit of  claim 25 , wherein the kit is provided as an enzyme-linked immunosorbent assay. 
     
     
         28 . The kit of  claim 25 , further comprising a recombinant human soluble ST2 isolated from a human cell.