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(12) Patent Application Publication (10) Pub. No.: US 2011/0166166A1 Henkin (43) Pub US 2011 01661. 66A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0166166A1 Henkin (43) Pub. Date: Jul. 7, 2011 (54) METHODS FOR DETECTION OF Publication Classification BOLOGICAL SUBSTANCES (51) Int. Cl. (76) Inventor: Robert I. Henkin, Bethesda, MD A6II 3/522 (2006.01) (US) CI2O 1/70 (2006.01) CI2O I/68 (2006.01) (21) Appl. No.: 12/523,040 GOIN 33/53 (2006.01) GOIN 33/573 (2006.01) (22) PCT Filed: Jan. 31, 2008 (86). PCT No.: PCT/US08/52712 (52) U.S. Cl. .......... 514/263.34; 43.5/5:435/7.1:435/7.4: S371 (c)(1), 435/6.17 (2), (4) Date: Jan. 13, 2010 Related U.S. Application Data (57) ABSTRACT (60) Provisional application No. 60/887,587, filed on Jan. 31, 2007, provisional application No. 60/915,008, Methods and compositions are provided for detection of bio filed on Apr. 30, 2007. logical Substances in nasal specimen. Patent Application Publication Jul. 7, 2011 Sheet 1 of 12 US 2011/O1661.66 A1 aseas?pau?asoufield O Patent Application Publication Jul. 7, 2011 Sheet 2 of 12 US 2011/O1661.66 A1 zoz seolaeqqndimo?ndul –003 Patent Application Publication Jul. 7, 2011 Sheet 3 of 12 US 2011/O1661.66 A1 Patent Application Publication Jul. 7, 2011 Sheet 4 of 12 US 2011/O1661.66 A1 lanes 1-7 HLA M Mol, wt markers 8-14 B-globin F.G. 4 Patent Application Publication Jul. 7, 2011 Sheet 5 of 12 US 2011/O1661.66 A1 ed Lp(-)p- eoueoSeon Patent Application Publication Jul. 7, 2011 Sheet 6 of 12 US 2011/0166166A1 P Name Calculate. CrOS. 1 WBPOS Cont 0.000E-00 22.67 2 R. Bk <0.000E+00 >41.00 3 Specimen #1 0.000E-00 19.02 4 Specimen #2 0.000E+00 27.42 5 Specimen #1+Pos Cont O.000E+00 18,18 6 Specimen #1 + Pos Cont 0.000E+00 18.62 7 R. BK <0.000E-00 D41.00 Cycie Number FIG. 6 Patent Application Publication Jul. 7, 2011 Sheet 7 of 12 US 2011/O1661.66 A1 Patent Application Publication Jul. 7, 2011 Sheet 8 of 12 US 2011/016616.6 A1 P Name Calculate CrOS 8 WBPOS Cont 0.000E+00 24.24 9 RBIk 0.000E--00 40.28 10 Specimen #1 0.000E+00 28,85 11 Specimen #2 12 Specimen #1 + Pos Cont 0.000E+00 22.13 13 Specimen #1 + Pos Cont 14 R. BIk 2.3. 1 t O. 5 Cycle Number F.G. 8 Patent Application Publication Jul. 7, 2011 Sheet 9 of 12 US 2011/0166166A1 P Name Calculate. Cros... 1 WBPOS COnt 0.000E+OO 22.67 2 R. Bk <0.000E+00 D41.00 3 Specimen #1 0.000E+00 19.02 4 Specimen #2 0.000E+00 27.42 5 Specimen #1 + Pos Cont 0.000E+00 18.18 6 Specimen #1 + Pos Cont O,000E+00 18.62 7 R. Bik C0.000E-00 D41.00 8 WBPOS COnt 0.000E+00 24.24 9 RBIk 0.000E-00 40.28 10 Specimen #1 0.000E+00 28.85 11 Specimen #2 12 Specimen #1 + Pos Cont 0.000E+00 22.13 13 Specimen #1 + Pos Cont 14 R. BEk 3. : 1 O 34 -w- O 5 10 15 20 25 Cycle Number FIG. 9 Patent Application Publication Jul. 7, 2011 Sheet 10 of 12 US 2011/O1661.66 A1 38Ie?O?ssew An asISuelu I 3Anean Patent Application Publication US 2011/O1661.66 A1 Patent Application Publication US 2011/O1661.66 A1 US 2011/01661.66 A1 Jul. 7, 2011 METHODS FOR DETECTION OF uid chromatography, electrophoresis, arrays, or biologic sen BOLOGICAL SUBSTANCES sors. In one aspect detection of a biological Substance or element is performed on a point of care device. BACKGROUND OF THE INVENTION 0007. In one aspect, the detected element is a metal. In 0001. Detection and identification of biological sub another element the metal is copper or zinc. stances in tissue samples is used for the diagnosis, prognosis, 0008. In one aspect, the disease or condition associated and monitoring of diseases. Efficient identification of biologi with a detected biological Substance or element is preeclamp cal Substances aids in devising effective treatment strategies. sia, a bacterial infection, a viral infection, a parasitic infec 0002 Most of the current diagnostic techniques involve tion, a metabolic disease, a gastrointestinal disease, a cardio invasive procedures for the removal of tissue samples or vascular disease, a neurologic disease, a hematologic disease, blood. Hence, there is need for the development of minimally an endocrine disease, a malignant disease, an autoimmune invasive procedures for biological sample retrieval. disease, or an inflammatory disease. 0003. The present invention provides methods and com 0009. In another aspect, the method also includes diagnos positions for detection of biological Substances, diagnosis of ing a disease or condition. In a still further aspect, the method diseases based on this detection and methods for treatment of includes administering atherapeutically effective amount of a the diseases after the diagnosis. drug or active agent to treat the diagnosed disease or condi tion. In another aspect, the administration route is oral admin SUMMARY OF THE INVENTION istration, transmucosal administration, buccal administra 0004. In one embodiment, a method is provided for detect tion, nasal administration, parental administration, ing a biological Substance or element from a nasal specimen intravenous administration, Subcutaneous administration, of a patient to detect a biological Substance or element that is intramuscular administration, transdermal administration, or associated with a disease or condition, and where the disease rectal administration. In one aspect, the administration route is not a respiratory disease. is by nasal administration. 0005. In one aspect, the detected biological substance is 0010. In one embodiment, a method is provided to detect agouti related protein, alpha fetoprotein (AFP), brain derived a biological Substance or element in nasal mucus that is asso neurotrophic factor (BDNF), bone morphogenetic protein-2 ciated with the likelihood of occurrence of a disease or con (BMP-2), ciliary neurotrophic factor (CNTF), thymus and dition, and where the disease is not a respiratory disease. activation-regulated chemokines (CCL17/TARC) CC 0011. In one aspect, the biological substance associated chemokines, cystatin, D-dimer, E selectin, endoglin, epider with the likelihood of occurrence of a disease is agouti related mal growth factor, (EGF), endothelial nitric oxide synthase, protein, alpha fetoprotein (AFP), brain derived neurotrophic (eNOS), FAS ligand, fibroblastic growth factor basic (FGF factor (BDNF), bone morphogenetic protein-2 (BMP-2), cili basis), granulocyte macrophage colony stimulating factor ary neurotrophic factor (CNTF), thymus and activation-regu (GM-CSF), hepatocyte growth factor (HGF), inducible nitric lated chemokines (CCL17/TARC) CC chemokines, cystatin, oxide synthase (iNOS), insulin-like growth factor 1 (IGF-1), d-dimer, E selectin, endoglin, epidermal growth factor, interferon alpha (INF-C.), interferon beta (INF-B), interferon (EGF), endothelial nitric oxide synthase, (eNOS), FAS gamma (INF-Y), interferon omega (INF-co), intracellular ligand, fibroblastic growth factor basic (FGF basis), granulo adhesion molecule 1 (ICAM-1), interleukin-1 (IL-1), inter cyte macrophage colony stimulating factor (GM-CSF), hepa leukin-1 receptor (IL-1 receptor), interleukin-2 (IL-2), inter tocyte growth factor (HGF), inducible nitric oxide synthase leukin-2 receptor (IL-2 receptor), interleukin-3 (IL-3), inter (iNOS), insulin-like growth factor 1 (IGF-1), interferon alpha leukin-6 (IL-6), interleukin-15 (IL-15), interleukin-17 (IL (INF-C.), interferon beta (INF-B), interferon gamma (INF-Y), 17), interleukin-18 (IL-18), keratinocyte growth factor interferon omega (INF-()), intracellular adhesion molecule 1 (KGF), L-selectin, leptin, leukemia inhibitor factor (LIF), (ICAM-1), interleukin-1 (IL-1), interleukin-1 receptor (IL-1 matrix metalloproteinase 1 (MMP-1), migrating inhibitory receptor), interleukin-2 (IL-2), interleukin-2 receptor (IL-2 factor (MIF), nerve growth factor (NGF), Pselectin, placental receptor), interleukin-3 (IL-3), interleukin-6 (IL-6), interleu growth factor (PlGF), platelet derived growth factor-AA kin-15 (IL-15), interleukin-17 (IL-17), interleukin-18 (IL (PDGF-AA), platelet derived growth factor-BB (PDGF-BB), 18), keratinocyte growth factor (KGF), L-selectin, leptin, pro-B type natiuretic peptide, receptor for abdominal glyca leukemia inhibitor factor (LIF), matrix metalloproteinase 1 tion end product (RAGE), stem cell factor (SCF), substance P. (MMP-1), migrating inhibitory factor (MIF), nerve growth triggering receptor expressed on myeloid cells (TREM-1), factor (NGF), P selectin, placental growth factor (P1GF), transforming growth factor alpha (TGF-alpha), transforming platelet derived growth factor-AA (PDGF-AA), platelet growth factor beta (TGF-beta), tumor necrosis factor (TNF). derived growth factor-BB (PDGF-BB), pro-B type natiuretic tumor necrosis factor receptor 1 (TNF-R1), tumor necrosis peptide, receptor for abdominal glycation end product factor receptor 2 (TNF-R2), TNF-related apoptosis-inducing (RAGE), stem cell factor (SCF), substance P. triggering ligand (TRAIL), vascular cell adhesion molecule 1 receptor expressed on myeloid cells (TREM-1), transforming (VCAM1), vascular endothelial growth factor C (VEGF-C), growth factor alpha (TGF-alpha), transforming growth factor vascular growth factor D (VEGF-D), vascular endothelia beta (TGF-beta), tumor necrosis factor (TNF), tumor necrosis growth factor receptor 1 (VEGFR1), or vascular endothelia factor receptor 1 (TNF-R1), tumor necrosis factor receptor 2 growth factor receptor 2 (VEGFR2). (TNF-R2), TNF-related apoptosis-inducing ligand (TRAIL), 0006. In another aspect, the detected biological substance vascular cell adhesion molecule 1 (VCAM1), vascular endot is a nucleic acid, a protein, a carbohydrate, a lipid, a metabo helial growth factor C (VEGF-C), vascular growth factor D lite, a hormone, or a combination of these. In a further aspect, (VEGF-D), vascular endothelia growth factor receptor 1 the biological Substance is a protein.
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