公开(公告)号：US20090269772A1

公开(公告)日：2009-10-29

申请号：US12432579

申请日：2009-04-29

申请人： Andrea Califano ,  Riccardo Dalla-Favera ,  Owen A. O'Connor

发明人： Andrea Califano ,  Riccardo Dalla-Favera ,  Owen A. O'Connor

IPC分类号： C12Q1/68 ,  C12Q1/02 ,  G06N5/02

CPC分类号： G01N33/5008 ,  G16B5/00 ,  G16B20/00 ,  G16C20/50

摘要： Systems, methods, and apparatus for searching for a combination of compounds of therapeutic interest are provided. Cell-based assays are performed, each cell-based assay exposing a different sample of cells to a different compound in a plurality of compounds. From the cell-based assays, a subset of the tested compounds is selected. For each respective compound in the subset, a molecular abundance profile from cells exposed to the respective compound is measured. Targets of transcription factors and post-translational modulators of transcription factor activity are inferred from the molecular abundance profile data using information theoretic measures. This data is used to construct an interaction network. Variances in edges in the interaction network are used to determine the drug activity profile of compounds in the subset of compounds. The drug activity profiles are used to form a filter set of compound combinations from the subset of compounds.

摘要翻译： 提供了用于搜索治疗感兴趣的化合物的组合的系统，方法和装置。 进行基于细胞的测定，每个基于细胞的测定将不同样品的细胞暴露于多种化合物中的不同化合物。 从基于细胞的测定中，选择测试化合物的一个子集。 对于子集中的每个相应化合物，测量暴露于相应化合物的细胞的分子丰度分布。 转录因子和翻译后调控因子转录因子活性的目标是使用信息理论测量从分子丰度分布数据中推导出来的。 该数据用于构建交互网络。 使用相互作用网络边缘的差异来确定化合物子集中化合物的药物活性谱。 药物活性谱用于形成化合物子集合的化合物组合的过滤器组。

公开(公告)号：US08586726B2

公开(公告)日：2013-11-19

申请号：US12688680

申请日：2010-01-15

申请人： Andrea Califano ,  Riccardo Dalla-Favera

发明人： Andrea Califano ,  Riccardo Dalla-Favera

IPC分类号： C07H21/04 ,  C07H21/02 ,  A61K48/00

CPC分类号： C12N15/113 ,  C12N2310/141

摘要： The invention provides for isolated nucleic acid sequences of newly discovered micro RNAs that have been identified to exist in normal Human B cells and/or in tumor-related Human B cells, using an integrated bioinformatics method and pipeline described herein.

摘要翻译： 本发明提供了使用本文所述的综合生物信息学方法和流程，已经鉴定存在于正常人B细胞和/或肿瘤相关人B细胞中的新发现的微RNA的分离核酸序列。

公开(公告)号：US20100197772A1

公开(公告)日：2010-08-05

申请号：US12688680

申请日：2010-01-15

申请人： Andrea Califano ,  Riccardo Dalla-Favera

发明人： Andrea Califano ,  Riccardo Dalla-Favera

IPC分类号： A61K31/7088 ,  C07H21/00 ,  C12N5/0781 ,  C12N5/071 ,  A61K31/713 ,  A61P43/00

CPC分类号： C12N15/113 ,  C12N2310/141

摘要： The invention provides for isolated nucleic acid sequences of newly discovered micro RNAs that have been identified to exist in normal Human B cells and/or in tumor-related Human B cells, using an integrated bioinformatics method and pipeline described herein.

摘要翻译： 本发明提供了使用本文所述的综合生物信息学方法和流程，已经鉴定存在于正常人B细胞和/或肿瘤相关人B细胞中的新发现的微RNA的分离核酸序列。

公开(公告)号：US20070141579A1

公开(公告)日：2007-06-21

申请号：US11254841

申请日：2005-10-20

申请人： Riccardo Dalla-Favera

发明人： Riccardo Dalla-Favera

IPC分类号： C40B30/06 ,  C40B40/08 ,  C12Q1/68

CPC分类号： C07K16/32 ,  A61K38/00 ,  C07K14/4702 ,  C07K14/82

摘要： This invention provides a method of determining a chromosomal breakpoint in a subject suffering from multiple myeloma which comprises steps of: (a) obtaining a DNA sample from the subject suffering from multiple myeloma; (b) determining whether there is J and C disjunction in the immunoglobulin heavy chain gene in the obtained DNA sample; (c) obtaining a genomic library having clones which contain genomic DNA fragments from the DNA sample which shows positive J and C disjunction; (d) selecting and isolating clones of the obtained library which show positive hybridization with a probe which is capable of specifically hybridizing with the C but not the J region of the immunoglobulin heavy chain gene; (e) preparing fluorescent probes from the genomic DNA fragments of the isolated clones from step (d); (f) hybridizing said fluorescent probes with metaphase chromosomes; and (g) determining the identity of the chromosomes which are capable of hybridizing to said fluorescent probes, wherein the identification of a chromosome other than chromosome 14 would indicate that the chromosomal breakpoint is between chromosome 14 and the identified chromosome, thereby determining a chromosomal breakpoint in a subject suffering from multiple myeloma. This invention also provides the identified gene altered by a chromosomal breakpoint and various uses thereof.

摘要翻译： 本发明提供了确定患有多发性骨髓瘤的受试者的染色体断裂点的方法，其包括以下步骤：（a）从患有多发性骨髓瘤的受试者获得DNA样品; （b）确定获得的DNA样品中免疫球蛋白重链基因中是否存在J和C分离; （c）获得具有克隆的基因组文库，所述克隆含有显示阳性J和C分离的DNA样品的基因组DNA片段; （d）选择和分离获得的文库的克隆，其与能够与免疫球蛋白重链基因的C而不是J区特异性杂交的探针显示阳性杂交; （e）从步骤（d）的分离的克隆的基因组DNA片段制备荧光探针; （f）将所述荧光探针与中期染色体杂交; 和（g）确定能够与所述荧光探针杂交的染色体的身份，其中染色体14以外的染色体的鉴定将指示染色体断裂点位于染色体14和所鉴定的染色体之间，由此确定染色体断点 在患有多发性骨髓瘤的受试者中。 本发明还提供了通过染色体断裂点改变的鉴定的基因及其各种用途。

公开(公告)号：US06958386B1

公开(公告)日：2005-10-25

申请号：US09585023

申请日：2000-06-01

申请人： Riccardo Dalla-Favera

发明人： Riccardo Dalla-Favera

IPC分类号： C12N15/09 ,  A61K31/00 ,  A61K31/70 ,  A61K31/7088 ,  A61K35/76 ,  A61K36/00 ,  A61K38/00 ,  A61K48/00 ,  A61P35/00 ,  A61P35/02 ,  C07K14/47 ,  C07K14/82 ,  C07K16/32 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/68 ,  C07K14/00

CPC分类号： C07K16/32 ,  A61K38/00 ,  C07K14/4702 ,  C07K14/82

摘要： This invention provides a method of determining a chromosomal breakpoint in a subject suffering from multiple myeloma which comprises steps of: (a) obtaining a DNA sample from the subject suffering from multiple myeloma; (b) determining whether there is J and C disjunction in the immunoglobulin heavy chain gene in the obtained DNA sample; (c) obtaining a genomic library having clones which contain genomic DNA fragments from the DNA sample which shows positive J and C disjunction; (d) selecting and isolating clones of the obtained library which show positive hybridization with a probe which is capable of specifically hybridizing with the C but not the J region of the immunoglobulin heavy chain gene; (e) preparing fluorescent probes from the genomic DNA fragments of the isolated clones from step (d); (f) hybridizing said fluorescent probes with metaphase chromosomes; and (g) determining the identity of the chromosomes which are capable of hybridizing to said fluorescent probes, wherein the identification of a chromosome other than chromosome 14 would indicate that the chromosomal breakpoint is between chromosome 14 and the identified chromosome, thereby determining a chromosomal breakpoint in a subject suffering from multiple myeloma. This invention also provides the identified gene altered by a chromosomal breakpoint and various uses thereof.

摘要翻译： 本发明提供了确定患有多发性骨髓瘤的受试者的染色体断裂点的方法，其包括以下步骤：（a）从患有多发性骨髓瘤的受试者获得DNA样品; （b）确定获得的DNA样品中免疫球蛋白重链基因中是否存在J和C分离; （c）获得具有克隆的基因组文库，所述克隆含有显示阳性J和C分离的DNA样品的基因组DNA片段; （d）选择和分离获得的文库的克隆，其与能够与免疫球蛋白重链基因的C而不是J区特异性杂交的探针显示阳性杂交; （e）从步骤（d）的分离的克隆的基因组DNA片段制备荧光探针; （f）将所述荧光探针与中期染色体杂交; 和（g）确定能够与所述荧光探针杂交的染色体的身份，其中染色体14以外的染色体的鉴定将指示染色体断裂点位于染色体14和所鉴定的染色体之间，由此确定染色体断点 在患有多发性骨髓瘤的受试者中。 本发明还提供了通过染色体断裂点改变的鉴定的基因及其各种用途。

公开(公告)号：US20070148176A1

公开(公告)日：2007-06-28

申请号：US11520183

申请日：2006-09-12

申请人： Riccardo Dalla-Favera

发明人： Riccardo Dalla-Favera

IPC分类号： G01N33/574 ,  C07H21/04 ,  C12P21/06 ,  A61K39/395 ,  C12N5/06

CPC分类号： C07K16/283 ,  A61K47/6849 ,  A61K51/1027

摘要： This invention provides an isolated nucleic acid molecule which encodes immunoglobulin receptor, Immunoglobulin superfamily Receptor Translocation Associated, IRTA, protein. Provided too, are the IRTA proteins encoded by the isolated nucleic acid molecules, IRTA1, IRTA2, IRTA3, IRTA4 or IRTA5 proteins, having the amino acid sequences set forth in any of FIGS. 18A, 18B-1-18B-3, 18C-1-18C-2, 18D-1-18D-2 or 18E-1-18E-2. Oligonucleotides of the isolated nucleic acid molecules are provided. Antibodies directed to an epitope of a purified IRTA1, IRTA2, IRTA3, IRTA4 or IRTA5 proteins are also provided, as are pharmaceutical compositions comprising such antibodies or oligonucleotides. Methods for detecting a B cell malignancy in a sample from a subject; diagnosing B cell malignancy in a sample from a subject; detecting human IRTA protein in a sample; and treating a subject having a B cell cancer are also provided.

摘要翻译： 本发明提供编码免疫球蛋白受体，免疫球蛋白超家族受体易位相关的IRTA，蛋白质的分离的核酸分子。 由分离的核酸分子IRTA1，IRTA2，IRTA3，IRTA4或IRTA5蛋白质编码的IRTA蛋白质也是具有图1至图6中任一项所述的氨基酸序列的。 18 A，18 B- 1 - 18 B- 3，18 C- 1 - 18 C -2,18 D 1 - 18 D- 2或18 E- 1 - 18 E- 2。 提供分离的核酸分子的寡核苷酸。 还提供了针对纯化的IRTA1，IRTA2，IRTA3，IRTA4或IRTA5蛋白的表位的抗体，以及包含此类抗体或寡核苷酸的药物组合物。 用于检测来自受试者的样品中B细胞恶性肿瘤的方法; 诊断受试者样本中的B细胞恶性肿瘤; 检测样品中的人类IRTA蛋白; 还提供了治疗患有B细胞癌的受试者。

公开(公告)号：US06783945B2

公开(公告)日：2004-08-31

申请号：US09761117

申请日：2001-01-16

申请人： Raju S. K. Chaganti ,  Riccardo Dalla-Favera

发明人： Raju S. K. Chaganti ,  Riccardo Dalla-Favera

IPC分类号： G01N3353

CPC分类号： C07K14/82 ,  Y10S436/813

摘要： This invention provides an isolated vertebrate nucleic acid molecule the bcl-6 locus. This invention also provides an isolated human nucleic acid molecule of bcl-6 locus. This invention further provides a nucleic acid molecule comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of the nucleic acid molecule of bcl-6 locus. This invention provides an isolated vertebrate nucleic acid molecule of bcl-6 operatively linked to a promoter of RNA transcription. This invention provides a vector which comprises the nucleic acid molecule of bcl-6 locus. This invention provides a host vector system for the production of a polypeptide encoded by bcl-6 locus, which comprises the vector of bcl-6 locus in a suitable host. This invention provides a polypeptide encoded by the isolated vertebrate nucleic acid molecule of bcl-6 locus. This invention provides an antibody capable of binding to polypeptide encoded by bcl-6 locus. This invention provides an antagonist capable of blocking the expression of the polypeptide encoded by bcl-6. This invention provides an antisense molecule capable of hybridizing to the nucleic acid molecule of bcl-6. This invention provides an assay for non-Hodgkin's lymphoma, a method for screening putative therapeutic agents for treatment of non-Hodgkin's lymphoma and a method for diagnosing B-cell lymphoma in a subject. Finally, this invention provides a method of treating a subject with non-Hodgkin's lymphoma.

摘要翻译： 本发明提供了一种分离的脊椎动物核酸分子bcl-6基因座。 本发明还提供了bcl-6基因座的分离的人核酸分子。 本发明还提供了一种核酸分子，其包含能够与bcl-6基因座的核酸分子的序列中包含的序列特异性杂交的至少15个核苷酸的核酸分子。 本发明提供了与RNA转录启动子有效连接的bcl-6的分离的脊椎动物核酸分子。 本发明提供了包含bcl-6基因座的核酸分子的载体。 本发明提供了用于产生由bcl-6基因座编码的多肽的宿主载体系统，其包含合适宿主中bcl-6基因座的载体。 本发明提供了由bcl-6基因座的分离的脊椎动物核酸分子编码的多肽。 本发明提供能够结合由bcl-6基因座编码的多肽的抗体。 本发明提供能够阻断由bcl-6编码的多肽的表达的拮抗剂​​。 本发明提供能够与bcl-6的核酸分子杂交的反义分子。 本发明提供了非霍奇金淋巴瘤的检测方法，用于筛选用于治疗非霍奇金淋巴瘤的推定治疗剂的方法和用于诊断受试者的B细胞淋巴瘤的方法。 最后，本发明提供了用非霍奇金淋巴瘤治疗受试者的方法。

公开(公告)号：US08299220B2

公开(公告)日：2012-10-30

申请号：US12981400

申请日：2010-12-29

申请人： Riccardo Dalla-Favera

发明人： Riccardo Dalla-Favera

IPC分类号： C07K14/00 ,  C07K16/00 ,  C07K17/00 ,  C07K17/14 ,  A61K35/14 ,  C12P21/00 ,  C12P21/08

CPC分类号： C07K16/283 ,  A61K47/6849 ,  A61K51/1027

摘要： This invention provides an isolated nucleic acid molecule which encodes immunoglobulin receptor, Immunoglobulin superfamily Receptor Translocation Associated, IRTA, protein. Provided too, are the IRTA proteins encoded by the isolated nucleic acid molecules, IRTA1, IRTA2, IRTA3, IRTA4 or IRTA5 proteins, having the amino acid sequences set forth in any of FIG. 18A, 18B-1-18B-3, 18C-1-18C-2, 18D-1-18D-2 or 18E-1-18E-2. Oligonucleotides of the isolated nucleic acid molecules are provided. Antibodies directed to an epitope of a purified IRTA1, IRTA2, IRTA3, IRTA4 or IRTA5 proteins are also provided, as are pharmaceutical compositions comprising such antibodies or oligonucleotides. Methods for detecting a B cell malignancy in a sample from a subject; diagnosing B cell malignancy in a sample from a subject; detecting human IRTA protein in a sample; and treating a subject having a B cell cancer are also provided.

摘要翻译： 本发明提供编码免疫球蛋白受体，免疫球蛋白超家族受体易位相关的IRTA，蛋白质的分离的核酸分子。 由分离的核酸分子IRTA1，IRTA2，IRTA3，IRTA4或IRTA5蛋白质编码的IRTA蛋白质也具有图中任何一个所示的氨基酸序列。 18A，18B-1-18B-3,18C-1-18C-2,18D-1-18D-2或18E-1-18E-2。 提供分离的核酸分子的寡核苷酸。 还提供了针对纯化的IRTA1，IRTA2，IRTA3，IRTA4或IRTA5蛋白的表位的抗体，以及包含此类抗体或寡核苷酸的药物组合物。 用于检测来自受试者的样品中B细胞恶性肿瘤的方法; 诊断受试者样本中的B细胞恶性肿瘤; 检测样品中的人类IRTA蛋白; 还提供了治疗患有B细胞癌的受试者。

公开(公告)号：US20080280297A1

公开(公告)日：2008-11-13

申请号：US11995719

申请日：2006-07-17

申请人： Riccardo Dalla-Favera

发明人： Riccardo Dalla-Favera

IPC分类号： G01N33/574 ,  C12Q1/68 ,  C07K16/00

CPC分类号： C12Q1/6886 ,  C07K16/3061 ,  C12Q2600/118 ,  C12Q2600/158 ,  C12Q2600/16 ,  G01N33/5047 ,  G01N33/57426

摘要： The invention provides compositions and methods for determining a prognosis of a B cell chronic lymphocytic leukemia (CLL) in a subject based on the level of expression of at least one marker gene. Marker genes provided by the invention are SEPTlO, KIAA0799, Hs.23133, and ADAM29. The marker genes can be used to differentially diagnose CLL in a subject based on relative gene expression levels in the subject compared to reference gene expression levels established from a clinically characterized population of patients. The invention also provides diagnostic reagents and compositions and kits based on the marker genes.

摘要翻译： 本发明提供了基于至少一种标记基因的表达水平来确定受试者中B细胞慢性淋巴细胞性白血病（CLL）的预后的组合物和方法。 本发明提供的标记基因是SEPT10，KIAA0799，Hs.23133和ADAM29。 基于与临床表征的患者群体建立的参考基因表达水平相比，标记基因可以用于基于受试者中的相对基因表达水平来区分受试者中的CLL。 本发明还提供了基于标记基因的诊断试剂和组合物和试剂盒。

公开(公告)号：US5888820A

公开(公告)日：1999-03-30

申请号：US347326

申请日：1994-12-01

申请人： Riccardo Dalla-Favera ,  Alessandro Massimo Gianni

发明人： Riccardo Dalla-Favera ,  Alessandro Massimo Gianni

IPC分类号： A01K67/027 ,  A61K31/70 ,  A61K39/395 ,  A61K48/00 ,  A61P43/00 ,  C07H21/04 ,  C07K16/40 ,  C12N5/10 ,  C12N9/00 ,  C12N9/02 ,  C12N15/09 ,  C12N15/85 ,  C12N15/867 ,  C12P21/08 ,  C12Q1/68 ,  G01N33/536 ,  G01N33/573 ,  G01N33/577 ,  C12N15/00 ,  C12N15/63

CPC分类号： C12N15/8509 ,  C12N15/86 ,  C12N9/0008 ,  C12N9/93 ,  C12Y102/01003 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2267/02 ,  C12N2740/13043

摘要： This invention provides viral and retroviral vectors which comprises a nucleic acid molecule encoding a human cytosolic aldehyde dehydrogenase or a glutamylcysteine synthetase or combinations thereof. Further, this invention provides an isolated mammalian nucleic acid molecule encoding a cytosolic aldehyde dehydrogenase and glutamylecysteine synthetase. In addition, this invention provides a method for reducing the toxic effects of a cyclophosphamide in a subject which comprises replacing the subject's hematopoietic cells with hematopoietic cells having the retroviral vector. Further, this invention provides a method for introducing a selectable marker into a mammalian cell which comprises transfecting the cell with a nucleic acid molecule encoding human cytosolic aldehyde dehydrogenase or glutamylcysteine synthetase. Lastly, this invention provides a method for selecting mammalian cells expressing protein of interest which comprises: a) introducing into the cells a nucleic acid molecule comprising a nucleic acid molecule encoding the protein of interest and the nucleic acid molecule encoding human cytosolic aldehyde dehdrogenase: b) culturing the resulting transfected cells; and c) selecting cells which express human cytosolic aldehyde dehdrogenase.

摘要翻译： PCT No.PCT / US94 / 03624 Sec。 371 1994年12月1日第 102（e）日期1994年12月1日PCT 1994年4月1日PCT PCT。 WO94 / 23015 PCT公开 日期：1994年10月13日本发明提供包含编码人细胞溶质醛脱氢酶或谷氨酰半胱氨酸合成酶或其组合的核酸分子的病毒和逆转录病毒载体。 此外，本发明提供了编码胞质醛脱氢酶和谷氨酰半胱氨酸合成酶的分离的哺乳动物核酸分子。 此外，本发明提供减少受试者中环磷酰胺的毒性作用的方法，其包括用具有逆转录病毒载体的造血细胞代替受试者的造血细胞。 此外，本发明提供了将选择标记引入哺乳动物细胞的方法，其包括用编码人细胞溶质醛脱氢酶或谷氨酰半胱氨酸合成酶的核酸分子转染细胞。 最后，本发明提供了选择表达目的蛋白质的哺乳动物细胞的方法，其包括：a）将包含编码目标蛋白的核酸分子和编码人细胞溶质醛脱氢酶的核酸分子的核酸分子引入细胞：b ）培养所得转染细胞; 和c）选择表达人胞浆醛脱氢酶的细胞。