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1. 发明申请

US20130072581A1 Secreted Protein Acidic and Rich in Cysteine (SPARC) Protein SRM Assay 有权
标题翻译：分泌蛋白酸和丰富的半胱氨酸（SPARC）蛋白SRM测定
公开(公告)号：US20130072581A1
公开(公告)日：2013-03-21
申请号：US13529907
申请日：2012-06-21
申请人： David B. KRIZMAN , Todd Hembrough , Sheeno Thyparambil
发明人： David B. KRIZMAN , Todd Hembrough , Sheeno Thyparambil
IPC分类号： G01N33/68 , C07K7/08 , C07K16/18 , C07K7/06
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 from the Secreted Protein Acidic and Rich in Cysteine (SPARC) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying SPARC directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. SPARC protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of SPARC peptides include those bearing 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）蛋白的特异性肽以及这些肽的衍生电离特征，其有利于通过选择反应监测（SRM）的方法直接定量福尔马林固定生物样品中的SPARC。质谱。这样的固定生物样品包括：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组织块和来自那些块的细胞，以及福尔马林固定和石蜡包埋的组织培养细胞。通过定量一种或多种本文所述的肽，通过SRM / MRM质谱法的方法在生物样品中定量SPARC蛋白质。如果它们以修饰或未修饰的形式存在，则可定量肽。 SPARC肽的潜在修饰形式的实例包括在肽序列内具有酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基磷酸化的那些。

2. 发明申请

US20060063930A1 Compositions and methods comprising proteinase activated receptor antagonists 审中-公开
标题翻译：包含蛋白酶活化受体拮抗剂的组合物和方法
公开(公告)号：US20060063930A1
公开(公告)日：2006-03-23
申请号：US11208460
申请日：2005-08-19
申请人： Gregory Agoston , Todd Hembrough , Theresa LaVallee , Jamshed Shah , Lita Suwandi , Anthony Treston
发明人： Gregory Agoston , Todd Hembrough , Theresa LaVallee , Jamshed Shah , Lita Suwandi , Anthony Treston
IPC分类号： C07D261/18 , C07D235/30 , C07D403/02
CPC分类号： C07D295/185 , C07D205/04 , C07D207/34 , C07D213/56 , C07D213/82 , C07D231/40 , C07D233/64 , C07D235/26 , C07D235/30 , C07D241/26 , C07D249/04 , C07D261/18 , C07D275/03 , C07D277/46 , C07D403/06 , C07D487/04
摘要： Compositions and methods comprising proteinase activated receptor antagonists are provided. More particularly, the present invention relates to the use of proteins, peptides and molecules that bind to proteinase 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.
摘要翻译：提供了包含蛋白酶激活的受体拮抗剂的组合物和方法。更具体地，本发明涉及结合蛋白酶活化受体2的蛋白质，肽和分子的用途，并且抑制与该受体活化相关的过程。更具体地，本发明提供了用于治疗疾病和疾病的新型组合物和方法，例如与异常细胞增殖，血管生成，炎症和癌症相关的疾病和疾病。

3. 发明授权

US09417246B2 Insulin receptor substrate 1 (IRS1) protein SRM/MRM assay 有权
标题翻译：胰岛素受体底物1（IRS1）蛋白SRM / MRM测定
公开(公告)号：US09417246B2
公开(公告)日：2016-08-16
申请号：US13529902
申请日：2012-06-21
申请人： David B. Krizman , Todd Hembrough , Sheeno Thyparambil
发明人： David B. Krizman , Todd Hembrough , Sheeno Thyparambil
IPC分类号： C12Q1/37 , G01N33/68
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 from the Insulin Receptor Substrate 1 (IRS1) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying IRS1 directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. IRS1 protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of IRS1 peptides include those bearing 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（IRS1）蛋白的特异性肽和这些肽的衍生电离特征，其有利于通过选择反应监测（SRM）质谱法直接定量福尔马林固定生物样品中的IRS1。这样的固定生物样品包括：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组织块和来自那些块的细胞，以及福尔马林固定和石蜡包埋的组织培养细胞。通过定量本文所述的一种或多种肽，通过SRM / MRM质谱法测定生物样品中的IRS1蛋白质。如果它们以修饰或未修饰的形式存在，则可定量肽。 IRS1肽的潜在修饰形式的实例包括在肽序列内具有酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基磷酸化的那些。

4. 发明授权

US09128102B2 Her3 protein SRM/MRM assay 有权
标题翻译： Her3蛋白SRM / MRM检测
公开(公告)号：US09128102B2
公开(公告)日：2015-09-08
申请号：US13932883
申请日：2013-07-01
申请人： David Krizman , Todd Hembrough , Sheeno Thyparambil
发明人： David Krizman , Todd Hembrough , Sheeno Thyparambil
IPC分类号： G01N30/72 , G01N33/68 , G01N33/574 , G01N33/74
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. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the Her3 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 Her3 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，其特别有利于直接在通过福尔马林固定的福尔马林生物样品中定量Her3蛋白选择反应监测（SRM）质谱法的方法，或称为多反应监测（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 Tissue TM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Liquid Tissue TM样品中定量Her3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。 Her3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。

5. 发明申请

US20130289142A1 HER3 PROTEIN SRM/MRM ASSAY 有权
标题翻译： HER3蛋白SRM / MRM测定
公开(公告)号：US20130289142A1
公开(公告)日：2013-10-31
申请号：US13932883
申请日：2013-07-01
申请人： David Krizman , Todd Hembrough , Sheeno Thyparambil
发明人： David Krizman , Todd Hembrough , Sheeno Thyparambil
IPC分类号： G01N33/68
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. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the Her3 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 Her3 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，其特别有利于直接在通过福尔马林固定的福尔马林生物样品中定量Her3蛋白选择反应监测（SRM）质谱法的方法，或称为多反应监测（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 Tissue TM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质谱法通过在蛋白质样品中定量至少定量在Liquid Tissue TM样品中定量Her3蛋白描述的一种或多种肽。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 Her3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。

6. 发明申请

US20120302650A1 Insulin-Like Growth Factor 1 Receptor (IGF1R) Protein SRM/MRM Assay 有权
标题翻译：胰岛素样生长因子1受体（IGF1R）蛋白SRM / MRM测定
公开(公告)号：US20120302650A1
公开(公告)日：2012-11-29
申请号：US13529875
申请日：2012-06-21
申请人： David B. Krizman , Todd Hembrough , Sheeno Thyparambil
发明人： David B. Krizman , Todd Hembrough , Sheeno Thyparambil
IPC分类号： G01N27/72 , C07K7/06 , G01N33/566 , C07K7/08 , C07K16/28 , A61P35/00 , A61K35/00 , C07K14/71
CPC分类号： G01N33/6851 , G01N33/6848 , G01N33/74 , G01N2333/71
摘要： The current disclosure provides for specific peptides from the Insulin-Like Growth Factor 1 Receptor (IGF-1R) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying the IGF-1R directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. IGF-1R protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of an IGF-1R peptides include those bearing 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样生长因子1受体（IGF-1R）蛋白的特异性肽以及这些肽的衍生电离特征，其有利于通过选择的方法直接在福尔马林固定生物样品中定量IGF-1R 反应监测（SRM）质谱。这样的固定生物样品包括：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组织块和来自那些块的细胞，以及福尔马林固定和石蜡包埋的组织培养细胞。通过定量一种或多种本文所述的肽，通过SRM / MRM质谱法的方法在生物样品中定量IGF-1R蛋白质。如果它们以修饰或未修饰的形式存在，则可定量肽。 IGF-1R肽的潜在修饰形式的实例包括在肽序列内具有酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基的磷酸化的那些。

7. 发明申请

US20080090760A2 Compositions and Methods for Inhibiting Cellular Proliferation 审中-公开
标题翻译：抑制细胞增殖的组合物和方法
公开(公告)号：US20080090760A2
公开(公告)日：2008-04-17
申请号：US11636353
申请日：2006-12-08
申请人： Todd Hembrough , Christopher Holmes , Qun Yin , Genet Zemede , Yvonne Angell , Brian Frederick , Caiding Xu
发明人： Todd Hembrough , Christopher Holmes , Qun Yin , Genet Zemede , Yvonne Angell , Brian Frederick , Caiding Xu
IPC分类号： A61K38/10 , A61K38/08 , C07K7/08 , C07K7/06
CPC分类号： A61K38/08 , A61K38/10 , A61K47/55 , A61K47/60 , A61K47/62 , C07K7/08 , C07K14/001
摘要： Compositions and methods effective in inhibiting abnormal or undesirable cell proliferation, particularly endothelial cell proliferation and angiogenesis related to neovascularization and tumor growth are provided. The compositions comprise peptide molecules, optionally containing one or more individual peptide chains covalently linked, and optionally modified with polyethylene glycol (PEG). The methods involve administering to a human or animal the composition described herein in a dosage sufficient to inhibit cell proliferation, particularly endothelial cell proliferation. The methods are useful for treating diseases and processes mediated by undesired and uncontrolled cell proliferation, such as cancer, particularly by inhibiting angiogenesis. Administration of the composition to a human or animal having prevascularized, metastasized tumors is useful for preventing the growth or expansion of such tumors.
摘要翻译：提供了有效抑制异常或不期望的细胞增殖，特别是与新生血管形成和肿瘤生长相关的内皮细胞增殖和血管发生的组合物和方法。组合物包含肽分子，任选地含有一个或多个共价连接并且任选地用聚乙二醇（PEG）修饰的单个肽链。所述方法包括以足以抑制细胞增殖，特别是内皮细胞增殖的剂量向人或动物施用本文所述的组合物。该方法可用于治疗由不期望的和不受控制的细胞增殖如癌症介导的疾病和过程，特别是通过抑制血管发生。将组合物给予具有血运重建的转移性肿瘤的人或动物可用于预防这些肿瘤的生长或扩张。

8. 发明申请

US20060142203A1 Compositions and methods comprising protein activated receptor antagonists 审中-公开
标题翻译：包含蛋白激活受体拮抗剂的组合物和方法
公开(公告)号：US20060142203A1
公开(公告)日：2006-06-29
申请号：US10608886
申请日：2003-06-26
申请人： Todd Hembrough , Victor Pribluda
发明人： Todd Hembrough , Victor Pribluda
IPC分类号： A61K38/08 , A61K38/06 , A61K38/05 , A61K38/04
CPC分类号： A61K38/07 , A61K38/06 , A61K38/08
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.
摘要翻译：提供了包含蛋白激活受体拮抗剂的组合物和方法更具体地，本发明涉及结合蛋白质活化受体2的蛋白质，肽和生物分子的用途，并且抑制与该受体活化相关的过程。更具体地，本发明提供了用于治疗疾病和疾病的新型组合物和方法，例如与异常细胞增殖，血管生成，炎症和癌症相关的疾病和疾病。

9. 发明申请

US20060025329A1 Compositions and methods for inhibiting cellular proliferation comprising TFPI fragments 审中-公开
公开(公告)号：US20060025329A1
公开(公告)日：2006-02-02
申请号：US11183555
申请日：2005-07-18
申请人： Todd Hembrough , Victor Pribluda , Adonia Papathanassiu , Shawn Green
发明人： Todd Hembrough , Victor Pribluda , Adonia Papathanassiu , Shawn Green
IPC分类号： A61K38/17
CPC分类号： A61K38/1709
摘要： Compositions and methods effective in inhibiting abnormal or undesirable cell proliferation, particularly endothelial cell proliferation and angiogenesis related to neovascularization and tumor growth are provided. The compositions comprise a naturally occurring or synthetic protein, peptide, or protein fragment containing all or an active portion of the C-terminal portion of proteinase inhibitors such as TFPI. The methods involve administering to a human or animal the composition described herein in a dosage sufficient to inhibit cell proliferation, particularly endothelial cell proliferation. The methods are useful for treating diseases and processes mediated by undesired and uncontrolled cell proliferation, such as cancer, particularly by inhibiting angiogenesis. Administration of the composition to a human or animal having prevascularized, metastasized tumors is useful for preventing the growth or expansion of such tumors.

10. 发明授权

US09551719B2 BCL-2-like protein 11 SRM/MRM assay 有权
标题翻译： BCL-2样蛋白11 SRM / MRM测定
公开(公告)号：US09551719B2
公开(公告)日：2017-01-24
申请号：US13942574
申请日：2013-07-15
申请人： David Krizman , Todd Hembrough , Sheeno Thyparambil , Wei-Li Liao
发明人： David Krizman , Todd Hembrough , Sheeno Thyparambil , Wei-Li Liao
IPC分类号： G01N33/68 , C07K14/47 , C12Q1/48 , G01N33/50 , G01N33/574 , C12Q1/68
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（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 Tissue TM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来定量BIM蛋白质在Liquid Tissue TM样品中的肽。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。

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