US2014155411A1PendingUtilityA1

Tuberculosis Biomarkers and Uses Thereof

63
Assignee: SOMALOGIC INCPriority: Apr 13, 2012Filed: Apr 12, 2013Published: Jun 5, 2014
Est. expiryApr 13, 2032(~5.7 yrs left)· nominal 20-yr term from priority
Inventors:Urs OchsnerDavid SterlingNebojsa Janjic
C12Q 2600/106G01N 33/5695G01N 2800/60C12Q 2600/158G01N 2800/52C12Q 1/6883A61K 31/496G01N 2570/00G01N 33/6893
63
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

The present application includes biomarkers, methods, devices, reagents, systems, and kits for the detection, treatment and diagnosis of tuberculosis (TB). In one aspect, the present application includes the identification of biomarkers that can be used alone or in various combinations for the detection of TB, including those set forth in Tables 1, 2, 4, 5, and 8 to 12. In another aspect, the application provides biomarkers that can be used alone or in various combinations to diagnose or prognose TB or follow treatment response. In another aspect, methods are provided for diagnosing TB in an individual, where the methods include detecting, in a biological sample from an individual, at least one biomarker value corresponding to at least one biomarker selected from the group of biomarkers provided in Tables 1, 2, 4, 5, and 8 to 12, wherein the individual is classified as having TB, or the likelihood of the individual having TB is determined, based on the at least one biomarker value.

Claims

exact text as granted — not AI-modified
1 . A method of diagnosing an individual as having or not having the TB comprising:
 providing a biomarker panel comprising N of the biomarker proteins listed in Tables 1, 2, 4, 5 or 8 to 12; wherein N is an integer from 1 to 239 and   detecting biomarker proteins, in a biological sample from an individual, to give biomarker values that each correspond to one of said N biomarker proteins in the panel, wherein said individual is classified as having or not having TB based on said biomarker values.   
     
     
         2 . The method of  claim 1 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         3 . The method of  claim 2 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         4 . The method of  claim 3 , wherein said at least one capture reagent is an aptamer. 
     
     
         5 . The method according to any one of  claims 2  to  4 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         6 . The method according to any one of  claims 1  to  5 , wherein an individual is classified as having TB, or the likelihood of the individual having TB is determined, based on a classification score that deviates from a predetermined threshold. 
     
     
         7 . The method according to any one of  claims 1  to  6 , wherein the biological sample is sputum, urine, lung or other infected tissue and wherein the biomarker values derive from a histological or cytological analysis of said tissue. 
     
     
         8 . The method according to any one of  claims 1  to  7 , wherein the biological sample is selected from the group consisting of sputum, whole blood, plasma, urine, body (e.g. pleural) fluid and serum. 
     
     
         9 . The method according to any one of  claims 1  to  7 , wherein the biological sample is sputum. 
     
     
         10 . The method according to any one of  claims 1  to  9 , wherein the individual is a human. 
     
     
         11 . The method according to any one of  claims 1  to  10 , wherein N=3 to 239. 
     
     
         12 . The method according to any one of  claims 1  to  10 , wherein N=4 to 239. 
     
     
         13 . The method according to any one of  claims 1  to  10 , wherein N=5 to 239. 
     
     
         14 . The method according to any one of  claims 1  to  10 , wherein N=10 to 239. 
     
     
         15 . The method according to any one of  claims 1  to  10 , wherein N=15 to 239. 
     
     
         16 . The method according to any one of  claims 1  to  15  wherein at least one biomarker is selected from the group consisting of Table 1 and/or Table 4 and/or Table 5 and/or Tables 8 to 12. 
     
     
         17 . The method according to any one of  claims 1  to  16  wherein at least one biomarker is selected from the group consisting of TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, LBP, Coagulation factor V, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. 
     
     
         18 . A computer-implemented method for classifying an individual as either having a first evaluation of NED, or as having a second evaluation of EVD, said method comprising:
 a) retrieving on a computer biomarker information for an individual, wherein the biomarker information comprises a biomarker value that corresponds to at least one biomarker of Tables 1, 2, 4, 5 or 8 to 12;   b) comparing said biomarker value of step a) to a biomarker value of a control population to determine if there is differential expression; and   c) classifying the individual as having a first evaluation of NED when there is no differential expression in step b) of the biomarker value relative to said control population, and as having a second evaluation of EVD when there is differential expression of the biomarker value relative to the control population.   
     
     
         19 . The method of  claim 18 , wherein said evaluation comprises a diagnosis, prognosis, determination of recurrence of TB, and/or a combination thereof. 
     
     
         20 . The method of  claim 19 , wherein said evaluation of NED can be indicative of a diagnosis of no TB, a prognosis of an outcome of no TB at a selected future time point, a determination of no recurrence of TB, and/or a combination thereof. 
     
     
         21 . The method of  claim 19 , wherein said evaluation of EVD can be indicative of a diagnosis of TB, a prognosis of an outcome of treatment for TB at a selected future time point, a determination of recurrence of TB, and/or a combination thereof. 
     
     
         22 . A computer program product comprising a computer readable medium embodying program code executable by a processor of a computing device or system, the program code comprising:
 a) code that retrieves data attributed to a biological sample from an individual, wherein the data comprises a biomarker value that corresponds to the at least one biomarker of Tables 1, 2, 4, 5 or 8 to 12;   b) code for comparing the biomarker value of step a) to a biomarker value of a control population; and   c) code that executes a classification method that indicates a first evaluation of NED when there is no differential expression of the individual's biomarker value in step b) relative to the control population, or second evaluation of EVD when there is differential expression of the individual's biomarker value relative to the control population.   
     
     
         23 . A method of evaluating an individual for tuberculosis (TB), wherein said evaluating comprises diagnosing the individual as having or not having TB, prognosing a future course of the TB, determining treatment response, recurrence or reactivation of TB in an individual who had been apparently cured of the TB, or any combination thereof the method comprising:
 providing a biomarker panel comprising N of the biomarker proteins listed in Table 1, 2, 4, 5 or 8 to 12; wherein N is an integer from 2 to 239 and   detecting biomarker proteins, in a biological sample from an individual, to give values that each correspond to one of said N biomarker proteins in the panel, wherein said individual is classified as having or not having TB based on said biomarker values.   
     
     
         24 . The method of  claim 23 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         25 . The method of  claim 24 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         26 . The method of  claim 25 , wherein said at least one capture reagent is an aptamer. 
     
     
         27 . The method of  claim 24 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         28 . The method according to any one of  claims 23  to  27 , wherein an individual is classified as having TB, or the likelihood of the individual having TB is determined, based on a classification score that deviates from a predetermined threshold. 
     
     
         29 . The method according to any one of  claims 23  to  28 , wherein the biological sample is lung, sputum, urine or other infected tissue and wherein the biomarker values derive from a histological or cytological analysis of said sample. 
     
     
         30 . The method of  claims 23  to  28 , wherein the biological sample is selected from the group consisting of sputum, whole blood, plasma, other infected tissue or fluids and serum. 
     
     
         31 . The method according to any one of  claims 23  to  28 , wherein the biological sample is sputum. 
     
     
         32 . The method according to any one of  claims 23  to  31 , wherein the individual is a human. 
     
     
         33 . The method according to any one of  claims 23  to  32 , wherein N=3 to 239. 
     
     
         34 . The method according to any one of  claims 23  to  32 , wherein N=4 to 239. 
     
     
         35 . The method according to any one of  claims 23  to  32 , wherein N=5 to 239. 
     
     
         36 . The method according to any one of  claims 23  to  32 , wherein N=10 to 239. 
     
     
         37 . The method according to any one of  claims 23  to  32 , wherein N=15 to 239. 
     
     
         38 . The method according to any one of  claims 23  to  37  wherein at least one biomarker is selected from the group consisting of Table 1 and/or Table 4 and/or Table 5 and/or Tables 8 to 12. 
     
     
         39 . The method according to any one of  claims 23  to  38  wherein at least one biomarker is selected from the group consisting of TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, LBP, Coagulation factor V, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. 
     
     
         40 . A method for treating tuberculosis infection in an individual, comprising:
 diagnosing tuberculosis infection by causing to be determined a biomarker value corresponding N biomarker(s) of Tables 1, 2, 4, 5, or 8 to 12 in a biological sample of the individual,   
       wherein said determination comprises comparing the biomarker value of the individual to the biomarker value in a control population for differential expression of the biomarker, 
       wherein differential expression of the biomarker indicates the presence of tuberculosis infection in the individual, 
       wherein N is at least one; and
 administering treatment for tuberculosis infection to the individual thereby diagnosed with tuberculosis infection. 
 
     
     
         41 . The method  claim 40 , wherein the biological sample is sputum, urine, lung or other infected tissue and wherein the biomarker values derive from a histological or cytological analysis of said tissue. 
     
     
         42 . The method of  claim 40 , wherein the biological sample is selected from the group consisting of sputum, whole blood, plasma, urine, body (e.g. pleural) fluid and serum. 
     
     
         43 . The method of  claim 40 , wherein the biological sample is sputum. 
     
     
         44 . The method according to any of  claims 40  to  43 , wherein the individual is a human. 
     
     
         45 . The method according to any one of  claims 40  to  44 , wherein N=2 to 239. 
     
     
         46 . The method according to any one of  claims 40  to  44 , wherein N=3 to 239. 
     
     
         47 . The method according to any one of  claims 40  to  44 , wherein N=4 to 239. 
     
     
         48 . The method according to any one of  claims 40  to  44 , wherein N=5 to 239. 
     
     
         49 . The method according to any one of  claims 40  to  44 , wherein N=10 to 239. 
     
     
         50 . The method according to any one of  claims 40  to  44 , wherein N=15 to 239. 
     
     
         51 . The method according to any one of  claims 40  to  50 , wherein at least one biomarker is selected from the group consisting of Table 1 and/or Table 4 and/or Table 5 and/or Tables 8 to 12. 
     
     
         52 . The method according to any one of  claims 40  to  51  wherein at least one biomarker is selected from the group consisting of TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, LBP, Coagulation factor V, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. 
     
     
         53 . An assay for diagnosing tuberculosis infection in an individual, comprising:
 causing to be determined a biomarker value corresponding to N biomarker(s) of Tables 1, 2, 4, 5, or 8 to 12 in a biological sample of the individual,   
       wherein said determining comprises comparing the biomarker value of the individual to the biomarker value in a control population for differential expression of the biomarker, 
       wherein differential expression of the biomarker indicates the presence of tuberculosis infection in the individual, 
       wherein N is at least one and
 diagnosing an individual to have tuberculosis infection based on said differential expression of the biomarker. 
 
     
     
         54 . The method of  claim 53 , wherein the biological sample is selected from the group consisting of sputum, whole blood, plasma, urine, body (e.g. pleural) fluid, serum. 
     
     
         55 . The method  claim 53 , wherein the biological sample is infected tissue and said biomarker value derives from a histological or cytological analysis of said tissue. 
     
     
         56 . The method of  claim 53 , wherein the biological sample is sputum. 
     
     
         57 . The method according to any one of  claims 53  to  56 , wherein the individual is a human. 
     
     
         58 . The method according to any one of  claims 53  to  57 , wherein N=2 to 239. 
     
     
         59 . The method according to any one of  claims 53  to  57 , wherein N=3 to 239. 
     
     
         60 . The method according to any one of  claims 53  to  57 , wherein N=4 to 239. 
     
     
         61 . The method according to any one of  claims 53  to  57 , wherein N=5 to 239. 
     
     
         62 . The method according to any one of  claims 53  to  57 , wherein N=10 to 239. 
     
     
         63 . The method according to any one of  claims 53  to  57 , wherein N=15 to 239. 
     
     
         64 . The method according to any one of  claims 53  to  63 , wherein at least one biomarker is selected from the group consisting of Table 1 and/or Table 4 and/or Table 5 and/or Tables 8 to 12. 
     
     
         65 . The method according to any one of  claims 53  to  64 , wherein at least one biomarker is selected from the group consisting of TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, LBP, Coagulation factor V, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. 
     
     
         66 . A method for determining whether treatment for tuberculosis infection should be administered to a patient, comprising:
 a) causing an assay to be conducted for determining a biomarker value corresponding N biomarker(s) of Tables 1, 2, 4, 5, or 8 to 12 in a biological sample of the individual,   
       wherein said determining comprises comparing the biomarker value of the individual to the biomarker value in a control population for differential expression of the biomarker, 
       wherein differential expression of the biomarker indicates the presence of tuberculosis infection in the individual, 
       wherein N is at least one
 b) diagnosing an individual to have tuberculosis infection based on said differential expression of the biomarker; and 
 c) administering treatment for tuberculosis infection. 
 
     
     
         67 . A method for determining whether treatment for tuberculosis infection should be administered to a patient, comprising:
 a) obtaining a biological sample from said patient   b) causing an assay to be conducted for determining a biomarker value corresponding to N biomarker(s) of Tables 1, 2, 4, 5, or 8 to 12 in said biological sample of the individual,   
       wherein said determining comprises comparing the biomarker value of the individual to the biomarker value in a control population for differential expression of the biomarker, 
       wherein differential expression of the biomarker indicates the presence of tuberculosis infection in the individual, 
       wherein N is at least one;
 c) diagnosing an individual to have tuberculosis infection based on said differential expression of the biomarker; and 
 d) administering treatment for tuberculosis infection. 
 
     
     
         68 . A method for treating recurrence or reactivation of tuberculosis infection in an individual, comprising:
 diagnosing recurrence or reactivation of tuberculosis infection by causing to be determined a biomarker value corresponding to N biomarker(s) of Tables 1, 2, 4, 5, or 8 to 12 in a biological sample of the individual,   
       wherein said determination comprises comparing the biomarker value of the individual to the biomarker value in a control population for differential expression of the biomarker, 
       wherein differential expression of the biomarker indicates the recurrence or reactivation of tuberculosis infection in the individual, and
 administering treatment for recurrence or reactivation of tuberculosis infection to the individual thereby diagnosed with recurrent or reactivated tuberculosis infection. 
 
     
     
         69 . A method for modifying treatment of tuberculosis infection in an individual, comprising
 evaluating the status of tuberculosis infection by causing to be determined a biomarker value corresponding to N biomarker(s) of Tables 8 to 12 in a biological sample of the individual,   
       wherein said evaluation comprises comparing the biomarker value of the individual to the biomarker value in a control population for differential expression of the biomarker, 
       wherein differential expression of the biomarker indicates the need to intensify treatment of tuberculosis infection in the individual, and
 modifying treatment for tuberculosis infection to the individual thereby evaluated as in need of modified treatment of tuberculosis infection.

Join the waitlist — get patent alerts

Track US2014155411A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.