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1. 发明申请

WO2004002418A3 COMPOSITIONS AND METHODS COMPRISING PROTEIN ACTIVATED RECEPTOR ANTAGONISTS 审中-公开
公开(公告)号：WO2004002418A3
公开(公告)日：2004-01-08
申请号：PCT/US2003/020366
申请日：2003-06-26
申请人： ENTREMED, INC , HEMBROUGH, Todd , PRIBLUDA, Victor
发明人： HEMBROUGH, Todd , PRIBLUDA, Victor
IPC分类号： A61K38/00
摘要： Compositions and methods comprising protein activated receptor antagonists are provided. More particularly, the present invention relates to the use of proteins, peptides and biomolecules that bind to protein activated receptor 2, and inhibit the processes associated with the activation of that receptor. More specifically, the present invention provides novel compositions and methods for the treatment of disorders and diseases such as those associated with abnormal cellular proliferation, angiogenesis, inflammation and cancer.

2. 发明申请

WO2011087868A1 INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR (IGF-1R) PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译：胰岛素样生长因子1受体（IGF-1R）蛋白SRM / MRM测定
公开(公告)号：WO2011087868A1
公开(公告)日：2011-07-21
申请号：PCT/US2010/061924
申请日：2010-12-22
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N33/50
CPC分类号： G01N33/6851 , G01N33/6848 , G01N33/74 , G01N2333/71
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Insulin-Like Growth Factor 1 Receptor (IGF- I R) protein that are particularly advantageous for quantifying the IGF-IR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin- fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the IGF- I R protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IGF-I R peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供来自胰岛素样生长因子1受体（IGF-1R）蛋白的特定肽和衍生的电离特征，其特别有利于直接在固定的生物样品中对IGF-1R蛋白进行定量在福尔马林中，通过选择反应监测（SRM）质谱法或还可以称为多反应监测（MRM）质谱法。这样的生物样品是化学保存和固定的，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从所述生物样品制备蛋白质样品，并且通过SRM / MRM质谱法的方法在液体组织样品中定量IGF-1R蛋白，通过在蛋白质样品中定量至少一种或多种描述的肽。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 IGF-I R肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基的磷酸化。

3. 发明申请

WO2012097276A2 BCL-2-LIKE PROTEIN 11 SRM/MRM ASSAY 审中-公开
标题翻译： BCL-2样蛋白11 SRM / MRM测定
公开(公告)号：WO2012097276A2
公开(公告)日：2012-07-19
申请号：PCT/US2012/021283
申请日：2012-01-13
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li
IPC分类号： C12Q1/37
CPC分类号： G01N33/6893 , C07K14/4747 , C07K16/2863 , C07K16/32 , C07K2317/76 , C12Q1/485 , C12Q1/6886 , C12Q2600/158 , G01N33/5088 , G01N33/574 , G01N33/6848 , G01N2333/4703 , G01N2800/44 , G01N2800/52 , G01N2800/56
摘要： Specific peptides, and derived ionization characteristics of those peptides, from the Bcl-2-like protein 11 (BIM) are provided that are particularly advantageous for quantifying the BIM protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM). Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin- fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol, and the BIM protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a BIM peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：提供了来自Bcl-2样蛋白11（BIM）的那些肽的特异性肽和衍生的电离特征，其特别有利于通过选择反应的方法在福尔马林中固定的生物样品中直接定量BIM蛋白监测（SRM）质谱，或什么也可以称为多反应监测（MRM）。在生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从生物样品制备蛋白质样品，并且通过SRM / MRM质谱法通过在蛋白质样品中定量至少一种或多种的蛋白质样品，在Liquid TissueTM样品中定量BIM蛋白质描述的肽。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 BIM肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基的磷酸化。

4. 发明申请

WO2012092531A1 HER3 PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译： HER3蛋白SRM / MRM测定
公开(公告)号：WO2012092531A1
公开(公告)日：2012-07-05
申请号：PCT/US2011/067998
申请日：2011-12-29
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： C07K16/18
CPC分类号： G01N33/6848 , G01N33/574 , G01N33/6893 , G01N33/74 , G01N2333/485 , G01N2333/71 , G01N2333/912 , G01N2333/9121
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-3, or Her3. that are particularly advantageous for quantifying the Her3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.
摘要翻译：目前的公开内容提供了来自受体酪氨酸 - 蛋白激酶erbB-3或Her3的肽的特定肽和衍生的电离特征。这特别有利于通过选择反应监测（SRM）质谱法或还可以称作多重反应监测（MRM）质谱法的方法，在已经在福尔马林中固定的生物样品中直接定量Her3蛋白。这样的生物样品是化学保存和固定的，其中所述生物样品选自用含甲醛的试剂固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块和细胞）处理的组织和细胞从那些块和已经被福尔马林固定和石蜡包埋的组织培养细胞。

5. 发明申请

WO2011087865A1 EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译： EPIDERM生长因子受体（EGFR）蛋白SRM / MRM测定
公开(公告)号：WO2011087865A1
公开(公告)日：2011-07-21
申请号：PCT/US2010/061916
申请日：2010-12-22
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N33/50
CPC分类号： G01N33/6863 , A61K31/517 , A61K31/5377 , C07K14/71 , C07K16/2863 , C07K2317/24 , G01N33/57407 , G01N33/6842 , G01N33/6848 , G01N33/74 , G01N2333/485 , G01N2333/71 , G01N2560/00
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Epidermal Growth Factor Receptor (EGFR) protein that are particularly advantageous for quantifying the EGFR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the EGFR protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an EGFR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供了来自表皮生长因子受体（EGFR）蛋白质的特定肽和衍生的离子化特征，其特别有利于通过所选择的方法在福尔马林中固定的生物样品中直接定量EGFR蛋白质反应监测（SRM）质谱法，还可以称作多反应监测（MRM）质谱。这些生物样品被化学保存和固定，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从所述生物样品中制备蛋白质样品，并且通过SRM / MRM质谱法的方法将蛋白质定量在液体组织样品中，通过在蛋白质样品中定量至少一种或多种肽描述。如果它们以修饰或未修饰的形式存在，则可定量这些肽。 EGFR肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基的磷酸化。

6. 发明申请

WO2012092302A1 CMET PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译： CMET蛋白SRM / MRM测定
公开(公告)号：WO2012092302A1
公开(公告)日：2012-07-05
申请号：PCT/US2011/067439
申请日：2011-12-27
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N30/72 , G01N33/483 , A61K38/18
CPC分类号： G01N33/6872 , G01N33/4833 , G01N33/68 , G01N33/6848 , G01N33/74 , G01N2030/8831 , G01N2333/71 , G01N2333/82 , G01N2560/00 , G01N2800/52 , G01N2800/56
摘要： Specific peptides are provided, and derived ionization characteristics of those peptides, from the Hepatocyte Growth Factor Receptor (cMET) protein. The peptides are advantageous for quantifying, by the method of Selected Reaction Monitoring (SRM) mass spectrometry, the cMET protein directly in biological samples that have been fixed in formalin, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including: formalin-fixed tissue/cells; formalinfixed/ paraffin embedded (FFPE) tissue/cells; FFPE tissue blocks and cells from those blocks; and tissue culture cells that have been formalin fixed and or paraffin embedded.
摘要翻译：提供特异性肽，并从肝细胞生长因子受体（cMET）蛋白提供这些肽的衍生电离特征。这些肽通过选择反应监测（SRM）质谱法的方法定量，直接在已经在福尔马林中固定的生物样品中的cMET蛋白质，或者也称为多反应监测（MRM）质谱法是有利的。这种生物样品被化学保存和固定，其中生物样品选自用含甲醛的试剂/固定剂处理的组织和细胞，包括：福尔马林固定的组织/细胞; 福尔马林固定/石蜡包埋（FFPE）组织/细胞; FFPE组织块和来自这些区块的细胞; 和已被福尔马林固定和石蜡包埋的组织培养细胞。

7. 发明申请

WO2011087869A1 SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE (SPARC) PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译：分泌蛋白酸和CYCTEINE（SPARC）蛋白SRM / MRM测定
公开(公告)号：WO2011087869A1
公开(公告)日：2011-07-21
申请号：PCT/US2010/061925
申请日：2010-12-22
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N31/00 , A61K38/00
CPC分类号： G01N33/68 , A61K38/08 , A61K38/10 , C07K7/06 , C07K7/08 , C07K14/47 , C07K16/18 , G01N33/6851 , G01N33/6887 , G01N2333/4727 , G01N2333/96433
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Secreted Protein Acidic and Rich in Cysteine (SPARC) protein that are particularly advantageous for quantifying the SPARC protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fϊxed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue TM reagents and protocol and the SPARC protein is quantitated in the Liquid Tissue TM sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an SPARC peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供了来自分泌蛋白酸性和富含半胱氨酸（SPARC）蛋白质的肽的特定肽和衍生的电离特征，其特别有利于直接在通过由福尔马林固定在福尔马林中的生物样品中量化SPARC蛋白选择反应监测（SRM）质谱法的方法，或也称为多反应监测（MRM）质谱的方法。这样的生物样品被化学保存和固定，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织）处理的组织和细胞块和来自这些块的细胞，以及已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从所述生物样品制备蛋白质样品，并且通过SRM / MRM质谱法的方法在SPT蛋白质中定量SPARC蛋白质，通过在蛋白质样品中定量至少一种或多种肽描述。如果它们以修饰或未修饰的形式存在，则可定量这些肽。 SPARC肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基的磷酸化。

8. 发明申请

WO2011087862A1 INSULIN RECEPTOR SUBSTRATE 1 (IRS1) PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译：胰岛素受体底物1（IRS1）蛋白SRM / MRM测定
公开(公告)号：WO2011087862A1
公开(公告)日：2011-07-21
申请号：PCT/US2010/061909
申请日：2010-12-22
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N31/00 , A61K38/00
CPC分类号： G01N33/57496 , G01N33/574 , G01N33/6848 , G01N2333/4703 , G01N2333/62 , G01N2333/72 , G01N2440/14 , G01N2440/38 , G01N2560/00 , G01N2800/52
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Insulin Receptor Substrate 1 (IRS 1 ) protein that are particularly advantageous for quantifying the IRS 1 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the IRS 1 protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IRS 1 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供了来自胰岛素受体底物1（IRS 1）蛋白质的特异性肽和衍生的离子化特征，其特别有利于通过该方法在福尔马林中固定的生物样品中直接定量IRS 1蛋白的选择反应监测（SRM）质谱，或什么也可以称为多反应监测（MRM）质谱。这样的生物样品被化学保存和固定，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从所述生物样品制备蛋白质样品，并且通过SRM / MRM质谱法的方法在液体组织样品中定量IRS 1蛋白质，通过在蛋白质样品中定量至少一种或多种描述的肽。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 IRS 1肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基的磷酸化。

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