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公开(公告)号：EP1907018A2
公开(公告)日：2008-04-09
申请号：EP06784805.1
申请日：2006-06-12
IPC分类号： A61K49/00
CPC分类号： A61K49/0008 , A61K49/0004 , G01N33/60 , G01N33/6893 , G01N2800/042
摘要： Provided are methods for determining concurrently with a simple, minimally invasive test, the adequacy of pancreatic beta-cell compensation and/or the presence of tissue insulin resistance in a subject human or an experimental animal. The methods allow for the determination of a subject's or experimental animal's susceptibility to developing type 2 diabetes mellitus (DM2) or to progression to more advanced forms of DM2. Among other uses, the methods allow for diagnostic classification of subjects for decisions regarding therapeutic interventions, clinical differentiation between type 1 DM and DM2, clinical monitoring of treatments intended to reduce risk of developing DM2 in non-diabetic subjects, clinical monitoring of agents intended to improve existing DM2 and to prevent progression of DM2, clinical development and testing of new compounds, candidate agents, or candidate therapies for preventing progression to DM2 or disease progression in existing DM2, and preclinical screening of candidate agents or candidate therapies in experimental animals to identify and characterize agents having insulin-sensitizing properties, pancreatic stimulatory or regenerative properties or other desirable actions.
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2.发明公开MOLECULAR FLUX RATES THROUGH CRITICAL PATHWAYS MEASURED BY STABLE ISOTOPE LABELING IN VIVO, AS BIOMARKERS OF DRUG ACTION AND DISEASE ACTIVITY 审中-公开稳定同位素MARK IN体内测分子速度流经CRITICAL方式的生物标记药物作用与疾病活动
公开(公告)号：EP1759326A2
公开(公告)日：2007-03-07
申请号：EP05733311.4
申请日：2005-02-22
IPC分类号： G06G7/48
CPC分类号： G01N33/6881 , G01N33/5008 , G01N33/5011 , G01N33/5014 , G01N33/5038 , G01N33/5088 , G01N33/58 , G01N33/60 , G01N33/6887 , G01N33/6893 , G01N33/92 , G01N2500/00 , G01N2800/042 , G01N2800/044 , G01N2800/323
摘要： The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through metabolic pathways of interest.
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3.发明公开METHOD FOR AUTOMATED, LARGE-SCALE MEASUREMENT OF THE MOLECULAR FLUX RATES OF THE PROTEOME OR THE ORGANEOME USING MASS SPECTROMETRY 审中-公开自动测量过程中的分子流大规模蛋白质组的速度或质量ORGANOMS手段
公开(公告)号：EP1546364A2
公开(公告)日：2005-06-29
申请号：EP03771855.8
申请日：2003-07-25
IPC分类号： C12Q1/02
CPC分类号： G01N33/6848 , A61K49/0002 , G01N33/6803 , G01N2458/15 , G01N2500/10 , G01N2570/00 , G01N2800/52 , G06Q50/22 , Y10T436/24
摘要： Disclosed here is a method for measuring the kinetics (i.e., the molecular flux rates - synthesis and breakdown or removal rates) of a plurality of proteins or organic metabolites inn living systems. The methods may be accomplished in a high-throughput, large-scale automated manner, by using existing mass spectrometric profiling techniques and art well known in the fields of static proteomics and static organeomics, without the need for additional biochemical preparative steps or analytic/instrumental devices.
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4.发明公开MEASUREMENT OF PROTEIN SYNTHESIS RATES IN HUMANS AND EXPERIMENTAL SYSTEMS BY USE OF ISOTOPICALLY LABELED WATER 有权在人类和实验系统蛋白质合成价格由使用同位素标记的水计量
公开(公告)号：EP1437966A1
公开(公告)日：2004-07-21
申请号：EP02806603.3
申请日：2002-10-23
IPC分类号： A61B10/00
CPC分类号： G01N33/68 , G01N33/6848 , G01N33/6893 , G01N33/92
摘要： Provided herein are methods for measuring protein biosynthesis by using 2H2O or radioactive 3H2O and applicable uses thereof.
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5.发明公开METHODS FOR DETERMINING TOTAL BODY SKELETAL MUSCLE MASS 有权VERFAHREN ZUR BESTIMMUNG DERGESAMTKÖRPERSKELETTMUSKELMASSE
公开(公告)号：EP3008471A1
公开(公告)日：2016-04-20
申请号：EP14737418.5
申请日：2014-06-12
申请人： The Regents of the University of California , Glaxosmithkline Intellectual Property (No. 2) Limited
IPC分类号： G01N33/70
CPC分类号： G01N33/70 , G01N2458/15
摘要： The present invention is based on the finding that enrichment of isotope-labeled creatinine in a urine sample following oral administration of a single defined dose of isotope-labeled can be used to calculate total-body creatine pool size and total body skeletal muscle mass in a subject. The invention further encompasses methods for detecting creatinine and isotope-labeled creatinine in a single sample. The methods of the invention find use,
inter alia , in diagnosing disorders related to skeletal muscle mass, and in screening potential therapeutic agents to determine their effects on muscle mass.摘要翻译： 本发明是基于以下发现：在口服给予单一定义剂量的同位素标记的尿液样品中，同位素标记的肌酸酐的富集可以用于计算全身肌酸蛋白酶体积和全身肌肉骨骼质量 学科。 本发明还包括在单个样品中检测肌酐和同位素标记的肌酸酐的方法。 本发明的方法尤其用于诊断与骨骼肌质量相关的疾病，并且在筛选潜在的治疗剂以确定其对肌肉质量的影响。
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6.发明公开METHOD FOR REPLACING BIOMARKERS OF PROTEIN KINETICS FROM TISSUE SAMPLES BY BIOMARKERS OF PROTEIN KINETICS FROM BODY FLUIDS AFTER ISOTOPIC LABELING IN VIVO 审中-公开方法更换的生物标志物蛋白动力学组织样品BY生物标志物蛋白动力学体液同位素后体内MARK
公开(公告)号：EP2972389A1
公开(公告)日：2016-01-20
申请号：EP14722040.4
申请日：2014-03-14
IPC分类号： G01N33/68
CPC分类号： G01N33/6848 , G01N2333/9123 , G01N2800/52
摘要： Provided herein are method for measuring the rate of synthesis, breakdown, transport, or other kinetic parameters of a protein in a tissue of medical interest, without requiring physical sampling of the tissue, by a measurement of the protein in a body fluid. Methods may include selecting one or more target proteins in a tissue; administering an isotope-labeled molecule to a subject for a period of time sufficient for said isotope-labeled molecule to enter into and label the one or more target proteins to produce one or more isotope-labeled target proteins; collecting a volume of a body fluid, wherein the volume comprises one or more isotope-labeled target proteins that escaped or were released from the tissue; enriching or isolating the one or more isotope-labeled target proteins from the volume; performing a mass spectrometric measurement of the isotopic content, rate of incorporation, and/or pattern or rate of change in isotopic content and/or pattern of isotope labeling of the one or more enriched or isolated isotope-labeled target proteins; and calculating at least one kinetic parameter of the one or more enriched or isolated isotope-labeled target proteins, where the kinetic parameter of the one or more isotope-labeled target proteins from the volume of a body fluid reflects the corresponding kinetic parameter of the one or more target proteins in the tissue; and inferring the at least one kinetic parameter of the one or more target proteins in the tissue based on the corresponding at least one kinetic parameter of the one or more target proteins in the body fluid.
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7.发明公开METHODS FOR MEASURING RATES OF RESERVE CHOLESTEROL TRANSPORT IN VIVO, AS AN INDEX OF ANTI-ATHEROGENESIS 有权法测量胆固醇逆转运的速度在体内指数抗动脉粥样硬化
公开(公告)号：EP1546373A2
公开(公告)日：2005-06-29
申请号：EP03749756.7
申请日：2003-09-15
CPC分类号： A61K49/0004 , A61K51/04 , A61K51/0493 , A61K51/1224
摘要： The present invention relates to biochemical methods for determining reverse cholesterol transport. Specifically, the rates of the two arms of reverse cholesterol transport (HDL or first arm and post-HDL or second arm) are obtained by measuring the flow of unlabeled cholesterol from tissues into plasma HDL and from plasma HDL to bile acids.
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8.发明授权METHODS FOR MEASURING RATES OF REVERSE CHOLESTEROL TRANSPORT IN VIVO, AS AN INDEX OF ANTI-ATHEROGENESIS 有权法测量胆固醇逆转运的速度在体内指数抗动脉粥样硬化
公开(公告)号：EP1546373B1
公开(公告)日：2008-11-26
申请号：EP03749756.7
申请日：2003-09-15
IPC分类号： C12Q1/60 , C12Q1/00 , G01N31/00 , G01N33/92 , A61K51/00 , A61M36/14 , A61K49/00 , A61K51/04 , A61K51/12 , G01N33/60
CPC分类号： A61K49/0004 , A61K51/04 , A61K51/0493 , A61K51/1224
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9.发明授权MEASUREMENT OF BIOSYNTHESIS AND BREAKDOWN RATES OF BIOLOGICAL MOLECULES THAT ARE INACCESSIBLE OR NOT EASILY ACCESSIBLE TO DIRECT SAMPLING, NON-INVASIVELY, BY LABEL INCORPORATION INTO METABOLIC DERIVATIVES AND CATABOLITIC PRODUCTS 有权非创伤性测量和减少生物分子衍生工具及代谢分解代谢产物的生物合成SPEEDS，覆盖率的或直接取样不容易接触，通过合并MARK OF
公开(公告)号：EP1483399B1
公开(公告)日：2008-10-29
申请号：EP03713429.3
申请日：2003-02-12
CPC分类号： A61K51/0493 , G01N33/5091 , G01N33/58 , G01N33/60 , G01N33/6842 , G01N33/6848 , G01N2800/52 , Y10T436/24 , Y10T436/25
摘要： Methods of determining rate of biosynthesis or breakdown of biological molecules from metabolic derivatives and catabolic products are disclosed herein. In particular, methods of measuring the rates of biosynthesis and breakdown of biological molecules inaccessible or not easily accessible to direct sampling by sampling metabolic derivatives and catabolic products in accessible biological samples are disclosed herein.
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公开(公告)号：EP1879627A2
公开(公告)日：2008-01-23
申请号：EP06759050.5
申请日：2006-05-03
CPC分类号： A61K51/0493
摘要： The present invention relates to biochemical methods for determining reverse cholesterol transport (RCT). Specifically, the three components of RCT (efflux, plasma, and excretion) are measured in vivo by administering an isotope-labeled cholesterol or cholesterol-related molecule or cholesterol-related complex, and then measuring the dilution or appearance of isotopes in the various cholesterol or cholesterol-related molecules or cholesterol-related complexes, as well as recovery in sterol end-products, that are part of RCT. A parameter of Global RCT flux, representing for the first time in living organisms that combined rate of cholesterol efflux from tissues into blood and excretion from blood out of the body, is generated. Such methods find use in drug discovery and development, diagnosis and prognosis of atherosclerosis and other blood vessel diseases and conditions, the selection of proper doses for treating disease, and selecting subjects for therapies targeting RCT flux.
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