Diagnostic marker compounds and their use

Patent metadata

Field	Value
Publication number	US-10080811-B2
Application number	US-201314382728-A
Country	US
Kind code	B2
Filing date	Mar 7, 2013
Priority date	Mar 7, 2012
Publication date	Sep 25, 2018
Grant date	Sep 25, 2018

Abstract

The present Invention relates to the monitoring of biological substances, such as non-invasive monitoring of such substances in animal, for examples biomarkers and metabolites. Specifically, the invention further relates to such monitoring using rare earth tagged marker compounds. The invention further relates to such monitoring using laser spectroscopy or Raman spectroscopy. The invention further relates to the use of such monitoring in disease states, such as stroke, neurological disorders and cardiovascular disorders. The invention further relates to novel rare-earth conjugated marker compounds and processes for preparing said rare-earth conjugated compounds

First claim

The invention claimed is:

1. A method for the measurement of a metabolites in an animal comprising:
(a) using spectroscopy, detecting a rare earth metal-conjugated marker formed from a rare earth metal conjugated with the metabolite, wherein the spectroscopy is laser spectroscopy or Raman spectroscopy, and wherein the spectroscopy uses an excitation wavelength and a measurement wavelength, each being in the range of about 600 nm to about 2100 nm; and
(b) measuring the metabolite based on the detected rare earth metal-conjugated marker.

2. A method according to claim 1 wherein the measured-metabolite correlates with a disease condition.

3. A method according to claim 2 wherein the disease condition is cardiovascular diseases, neuropsychiatric diseases, neurological diseases or cancer.

4. A method according to claim 3 wherein the rare earth metal-conjugated marker is Eu 3+ -conjugated lactic acid.

5. A method according to claim 2 wherein the rare earth metal-conjugated marker is Eu 3+ -conjugated lactic acid.

6. A method according to claim 1 wherein the detecting is non-invasive.

7. A method according to claim 6 wherein the rare earth metal-conjugated marker is Eu 3+ -conjugated lactic acid.

8. A method according to claim 1 wherein the metabolite is
(i) a small molecule metabolite;
(ii) a lipid;
(iii) a peptide;
(iv) a protein; or
(v) an enzyme.

9. A method according to claim 8 wherein the metabolite is:
(i) an amino acid or related compounds selected from taurine, glutamine, N-acetyl-L-asparate (NAA), and homocysteine;
(ii) Lipids and related intermediates selected from phosphatidylcholine and phosphocholine;
(iii) lipid binding proteins selected from lipoprotein A, HDL and LDL;
(iv) Peptides/Proteins selected from PARK 7, Nucleoside Diphosphate Kinase A (NDKA), amyloid beta peptide, Tau (e.g. hyperphosphorylated Tau), CD68, CD64, carcino-embryonic antigen (CEA), tumor-associated glycoprotein 72 (Tag72), folate receptor-α, Alpha actin, Toll-like receptors (TLRs) Creatine, Creatinine, amyloid precursor protein (APP), troponin, C-reactive protein, Fibrinogen and B-type natriuretic peptide (BNP)
(v) Enzymes selected from phospholipases, β-secretase, γ-secretase, succinate dehydrogenase (SDH), fumarate hydratase (FH), neprilysin (NEP), endothelin-converting enzyme (ECE), insulysin (IDE), angiotensin-converting enzyme (ACE) and matrix metalloproteinase 1-9 (MMP 1-9), Creatine kinase (CK) and creatine kinase isoenzyme MB (CKMB)
(vi) Cytokines selected from IL(1-6) and TNFα; or
(vii) small molecule metabolites selected from lactate, glucose, acetyladehyde hydrate, acetate, choline, inositol.

10. A method according to claim 9 , wherein the metabolite is lactic acid.

11. A method according to claim 8 wherein the rare earth metal is Cerium, Dysprosium, Erbium, Europium, Gadolinium, Holmium, Neodymium Praseodymium, Samarium, Terbium, Thulium or Ytterbium.

12. A method according to claim 1 wherein the rare earth metal is Cerium, Dysprosium, Erbium, Europium, Gadolinium, Holmium, Neodymium Praseodymium, Samarium, Terbium, Thulium or Ytterbium.

13. A method according to claim 12 wherein the rare earth metal is Ce 4+,3+ , Yb 3+ , Eu 3+ , Sm 3+ , Tm 3+ , Tb 3+ or Nd 3+ .

14. A method according to claim 13 , wherein the rare earth metal is Eu 3+ .

15. A method according to claim 1 wherein the rare earth metal-conjugated marker is Eu 3+ -conjugated lactic acid.

16. A method according to claim 1 , wherein a photoluminescence intensity ratio (PLIR) imaging technique is used to calculate the level or a change in level of the metabolite.

Assignees

• Univ Leeds Innovations Ltd

Inventors

• Saha Sikha
• Jose Gin
• Jha Animesh

Classifications

• A61K49/0004 Primary

  Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions · CPC title

• A61K47/52

  the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient · CPC title

• A61K49/0019 Primary

  characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules · CPC title

• A61B5/1455

  using optical sensors, e.g. spectral photometrical oximeters · CPC title

• A61B5/0059

  using light, e.g. diagnosis by transillumination, diascopy, fluorescence (photoacoustic A61B5/0093; optical measurement of heart rate A61B5/02416; optical measurement of blood flow A61B5/0261; optical measurement of analytes A61B5/1455) · CPC title