公开(公告)号：US20100093008A1

公开(公告)日：2010-04-15

申请号：US11681521

申请日：2007-03-02

申请人： Valerie GOSS ,  Roberto Polakiewicz ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz ,  Jiong Wu

发明人： Valerie GOSS ,  Roberto Polakiewicz ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz ,  Jiong Wu

IPC分类号： C12Q1/48 ,  C07K16/40 ,  C12N5/12

CPC分类号： G01N33/573 ,  C07K16/2863 ,  C07K16/44 ,  C07K2317/34 ,  G01N33/57426 ,  G01N2333/9121 ,  G01N2800/52

摘要： The invention discloses a newly discovered Flt3 phosphorylation site, tyrosine 969 (Tyr969) in the intracellular domain, and provides reagents, including polyclonal and monoclonal antibodies, that selectively bind to Flt3 when phosphorylated at this site. Also provided are assays utilizing this reagent, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibody, that binds to Flt3 only when phosphorylated at Tyr969. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).

摘要翻译： 本发明公开了新发现的Flt3磷酸化位点，细胞内结构域中的酪氨酸969（Tyr969），并提供了在该位点磷酸化时选择性结合Flt3的试剂，包括多克隆和单克隆抗体。 还提供了使用该试剂的测定法，包括用于测定生物样品中Flt3的磷酸化的方法，选择适合Flt3抑制剂治疗的患者，在测试组织中分析Flt3活化，以及鉴定在测试中调节Flt3的磷酸化的化合物 通过使用仅在Tyr969磷酸化时与Flt3结合的可检测试剂，例如所公开的抗体。 样品或测试组织可以从疑似患有癌症的受试者中获取，例如急性骨髓性白血病（AML）。

公开(公告)号：US20090285796A1

公开(公告)日：2009-11-19

申请号：US12161512

申请日：2007-01-19

申请人： Valerie Goss ,  Ting-lei Gu ,  Roberto Polakiewicz ,  Brian Druker ,  Denise Walters

发明人： Valerie Goss ,  Ting-lei Gu ,  Roberto Polakiewicz ,  Brian Druker ,  Denise Walters

IPC分类号： A61K39/395 ,  C07H21/04 ,  C07K14/00 ,  C12N15/63 ,  C12N5/10 ,  C12N9/12 ,  C07K16/00 ,  C12Q1/68 ,  G01N33/53 ,  A61K31/7088 ,  A61P35/02

CPC分类号： C12N9/1205 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136

摘要： In accordance with the invention, a novel activating mutation (alanine 572 to valine) in JAK3 kinase has been discovered in human acute myelogenous leukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant protein and enables new methods for determining the presence of mutant JAK3 kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the mutant proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

摘要翻译： 根据本发明，已经在人类急性骨髓性白血病（AML）中发现JAK3激酶中的新的活化突变（丙氨酸572至缬氨酸）。 证实突变型JAK3激酶能够驱动急性巨核细胞白血病（AML-M7）的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变体JAK3激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测突变体多肽的试剂。 所公开的这种新的突变蛋白的鉴定并且使得能够确定生物样品中突变体JAK3激酶多肽的存在的新方法，用于筛选抑制突变蛋白质的化合物的方法，以及用于抑制突变体特征的癌症进展的方法 多核苷酸或多肽，其也由本发明提供。

公开(公告)号：US20090220991A1

公开(公告)日：2009-09-03

申请号：US12074214

申请日：2008-02-29

申请人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

发明人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

IPC分类号： G01N33/53 ,  G01N33/536 ,  C07K16/18 ,  C12N5/18

CPC分类号： C07K16/40 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/2896 ,  C07K16/3061 ,  C07K2317/34 ,  G01N33/57426 ,  G01N33/6854

摘要： The invention discloses nearly 480 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, acetyltransferases, actin binding proteins, adhesion proteins, apoptosis proteins, calcium-binding proteins, cell cycle regulation proteins, cell surface proteins, channel proteins, chaperone proteins, contractile proteins, cytokine proteins, cytoskeletal proteins, G protein regulators and GTPase activating proteins, guanine nucleotide exchange factors, helicase proteins, immunoglobulin superfamily proteins, inhibitor proteins, protein kinases, lipid kinases, ligases, lipid binding proteins, methytransferases, motor proteins, oxidoreductases, phosphotases, phosphodiesterases, phospholipases, proteases, receptor proteins, trascription factors, transferases, translation/transporter proteins, and ubiquitin conjugating system proteins.

摘要翻译： 本发明公开了在信号转导蛋白中识别的近480个新的磷酸化位点和人类白血病下游的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质 作为使用试剂用于此目的的方法。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，乙酰转移酶，肌动蛋白结合蛋白，粘附蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，细胞表面蛋白，通道蛋白，伴侣蛋白 鸟嘌呤核苷酸交换因子，解旋酶蛋白，免疫球蛋白超家族蛋白，抑制蛋白，蛋白激酶，脂质激酶，连接酶，脂质结合蛋白，甲基转移酶，运动蛋白，肌动蛋白， 氧化还原酶，磷酸二酯酶，磷脂酶，蛋白酶，受体蛋白，trascription因子，转移酶，翻译/转运蛋白和泛素缀合系统蛋白。

公开(公告)号：US20070059845A1

公开(公告)日：2007-03-15

申请号：US11503336

申请日：2006-08-11

申请人： Albrecht Moritz ,  Kimberly Lee ,  John Rush ,  Roberto Polakiewicz

发明人： Albrecht Moritz ,  Kimberly Lee ,  John Rush ,  Roberto Polakiewicz

IPC分类号： G01N33/543

CPC分类号： G01N33/6872 ,  C12Q1/25 ,  C12Q1/485 ,  G01N33/6842

摘要： The invention discloses 95 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of the T-cell receptor, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Actin Binding proteins, Adaptor/Scaffold proteins, Adhesion proteins, Calcium-binding proteins, Cell Cycle Regulation or Channel proteins, Chaperones, Cofactor proteins, Cytoskeletal proteins, DNA Binding proteins, G protein or GTPase Activating proteins, Ligases, Lipid Kinases and Binding proteins, Oxidoreductases, Protein Kinases, Protein Phosphatases, Receptor proteins, RNA Binding proteins, Transcription Factor/Initiation Complex proteins, Transcription Coactivator/Corepressor proteins, Translation Initiation Complex proteins, Ubitquitin Conjugating System proteins, and Vesicle proteins.

摘要翻译： 本发明公开了在T细胞受体下游的信号转导蛋白和途径中鉴定的95个新的磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/ 蛋白质，以及使用试剂用于此目的的方法。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：肌动蛋白结合蛋白，衔接/支架蛋白，粘附蛋白，钙结合蛋白，细胞周期调节或通道蛋白，伴侣蛋白，辅因子蛋白，细胞骨架蛋白，DNA结合蛋白， G蛋白或GTPase激活蛋白，连接酶，脂质激酶和结合蛋白，氧化还原酶，蛋白激酶，蛋白磷酸酶，受体蛋白，RNA结合蛋白，转录因子/起始复合蛋白​​，转录共激活因子/ Corepressor蛋白，翻译起始复合蛋白​​，Ubitquitin缀合 系统蛋白和囊泡蛋白。