公开(公告)号：US06826488B1

公开(公告)日：2004-11-30

申请号：US09533466

申请日：2000-03-23

申请人： Frank R. Collart ,  Eliezer Huberman ,  Andrezej Joachimiak ,  Rongguang Zhang ,  Edwin M. Westbrook

发明人： Frank R. Collart ,  Eliezer Huberman ,  Andrezej Joachimiak ,  Rongguang Zhang ,  Edwin M. Westbrook

IPC分类号： G06F1900

CPC分类号： C12N9/0006 ,  C07K2299/00 ,  C12Y101/01205

摘要： The present invention relates to a data storage medium encoded with the structural coordinates of crystallized molecules and molecular complexes which comprise the active site binding pockets of bacterial IMPDH. Such data storage material is capable of displaying such molecules and molecular complexes, or their structural homologues, as a graphical three-dimensional representation on a computer screen. This invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. In addition, this invention relates to methods of using the structure coordinates to screen and design compounds, including inhibitory compounds, that bind to IMPDH or homologues thereof. This invention also relates to molecules and molecular complexes that comprise the active site binding pockets of IMPDH or close structural homologues of the active site binding pockets. This invention also relates to compounds and pharmaceutical compositions which are inhibitors of bacterial IMPDH.

摘要翻译： 本发明涉及用结构化分子和分子复合物的结构坐标编码的数据存储介质，其包含细菌IMPDH的活性位点结合口袋。 这样的数据存储材料能够在计算机屏幕上显示这样的分子和分子复合物或其结构同系物作为图形三维表示。 本发明还涉及使用结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。 此外，本发明涉及使用结构坐标来筛选和设计结合IMPDH或其同系物的化合物（包括抑制性化合物）的方法。 本发明还涉及包含IMPDH的活性位点结合袋或活性位点结合口袋的紧密结构同系物的分子和分子复合物。 本发明还涉及作为细菌IMPDH抑制剂的化合物和药物组合物。

公开(公告)号：US5665583A

公开(公告)日：1997-09-09

申请号：US232302

申请日：1988-08-12

申请人： Frank R. Collart ,  Eliezer Huberman

发明人： Frank R. Collart ,  Eliezer Huberman

IPC分类号： A61K48/00 ,  C07K16/40 ,  C12N1/21 ,  C12N9/04 ,  C12N15/53 ,  C12P19/32 ,  C12N15/52 ,  C12N15/63 ,  C12N15/85

CPC分类号： C12N9/0006 ,  C07K16/40 ,  C12P19/32 ,  C12Y101/01205 ,  A61K48/00

摘要： Disclosed are purified and isolated DNA sequences encoding eukaryotic proteins possessing biological properties of inosine 5'-monophosphate dehydrogenase ("IMPDH"). Illustratively, mammalian (e.g., human) IMPDH-encoding DNA sequences are useful in transformation or transfection of host cells for the large scale recombinant production of the enzymatically active expression products and/or products (e.g., GMP) resulting from IMPDH catalyzed synthesis in cells. Vectors including IMPDH-encoding DNA sequences are useful in gene amplification procedures. Recombinant proteins and synthetic peptides provided by the invention are useful as immunological reagents and in the preparation of antibodies (including polyclonal and monoclonal antibodies) for quantitative detection of IMPDH.

摘要翻译： 公开了编码具有肌苷5'-单磷酸脱氢酶（“IMPDH”）的生物学性质的真核蛋白质的纯化和分离的DNA序列。 说明性地，哺乳动物（例如，人）IMPDH编码DNA序列可用于宿主细胞的转化或转染，用于大规模重组产生由细胞内的IMPDH催化合成产生的酶活性表达产物和/或产物（例如，GMP） 。 包含IMPDH编码DNA序列的载体可用于基因扩增过程。 本发明提供的重组蛋白质和合成肽可用作免疫学试剂和用于定量检测IMPDH的抗体（包括多克隆和单克隆抗体）的制备。

公开(公告)号：US06479628B1

公开(公告)日：2002-11-12

申请号：US09712372

申请日：2000-11-13

申请人： Frank R. Collart ,  Eliezer Huberman

发明人： Frank R. Collart ,  Eliezer Huberman

IPC分类号： A61K3800

CPC分类号： C12N9/0006 ,  A61K48/00 ,  C07K16/40 ,  C12P19/32 ,  C12Y101/01205

摘要： Disclosed are purified and isolated DNA sequences encoding eukaryotic proteins possessing biological properties of inosine 5′-monophosphate dehydrogenase (“IMPDH”). Illustratively, mammalian (e.g., human) IMPDH-encoding DNA sequences are useful in transformation or transfection of host cells for the large scale recombinant production of the enzymatically active expression products and/or products (e.g., GMP) resulting from IMPDH catalyzed synthesis in cells. Vectors including IMPDH-encoding DNA sequences are useful in gene amplification procedures. Recombinant proteins and synthetic peptides provided by the invention are useful as immunological reagents and in the preparation of antibodies (including polyclonal and monoclonal antibodies) for quantitative detection of IMPDH.

摘要翻译： 公开了编码具有肌苷5'-单磷酸脱氢酶（“IMPDH”）的生物学性质的真核蛋白质的纯化和分离的DNA序列。 说明性地，哺乳动物（例如，人）IMPDH编码DNA序列可用于宿主细胞的转化或转染，用于大规模重组产生由细胞内的IMPDH催化合成产生的酶活性表达产物和/或产物（例如，GMP） 。 包含IMPDH编码DNA序列的载体可用于基因扩增过程。 本发明提供的重组蛋白质和合成肽可用作免疫学试剂和用于定量检测IMPDH的抗体（包括多克隆和单克隆抗体）的制备。

公开(公告)号：US06153398A

公开(公告)日：2000-11-28

申请号：US997758

申请日：1997-12-24

申请人： Frank R. Collart ,  Eliezer Huberman

发明人： Frank R. Collart ,  Eliezer Huberman

IPC分类号： C12N1/21 ,  C12N9/04 ,  C12N15/53 ,  C12Q1/32 ,  C12N1/20 ,  C12N5/00

CPC分类号： C12N9/0006

摘要： This invention relates to methods to identify specific inhibitors of the purine nucleotide synthesis enzyme, IMP dehydrogenase (IMPDH). IMPDH is an essential enzyme found in all free-living organisms from humans to bacteria and is an important therapeutic target. The invention allows the identification of specific inhibitors of any IMPDH enzyme which can be expressed in a functional form in a recombinant host cell. A variety of eukaryotic or prokaryotic host systems commonly used for the expression of recombinant proteins are suitable for the practice of the invention. The methods are amenable to high throughput systems for the screening of inhibitors generated by combinatorial chemistry or other methods such as antisense molecule production. Utilization of exogenous guanosine as a control component of the methods allows for the identification of inhibitors specific for IMPDH rather than other causes of decreased cell proliferation.

摘要翻译： 本发明涉及鉴定嘌呤核苷酸合成酶，IMP脱氢酶（IMPDH）的特异性抑制剂的方法。 IMPDH是从人类到细菌的所有自由生物体中发现的必需酶，是重要的治疗靶点。 本发明允许鉴定可以在重组宿主细胞中以功能形式表达的任何IMPDH酶的特异性抑制剂。 通常用于表达重组蛋白质的各种真核或原核宿主系统适用于本发明的实践。 该方法适用于筛选通过组合化学或其它方法如反义分子生产产生的抑制剂的高通量系统。 利用外源鸟苷作为方法的对照组分允许鉴定特异于IMPDH的抑制剂，而不是其它导致细胞增殖减少的原因。

公开(公告)号：US6147194A

公开(公告)日：2000-11-14

申请号：US925230

申请日：1997-09-08

申请人： Frank R. Collart ,  Eliezer Huberman

发明人： Frank R. Collart ,  Eliezer Huberman

IPC分类号： A61K48/00 ,  C07K16/40 ,  C12N1/21 ,  C12N9/04 ,  C12N15/53 ,  C12P19/32 ,  C07K16/00 ,  C12N9/64

CPC分类号： C12N9/0006 ,  C07K16/40 ,  C12P19/32 ,  C12Y101/01205 ,  A61K48/00

摘要： Disclosed are purified and isolated DNA sequences encoding eukaryotic proteins possessing biological properties of inosine 5'-monophosphate dehydrogenase ("IMPDH"). Illustratively, mammalian (e.g., human) IMPDH-encoding DNA sequences are useful in transformation or transfection of host cells for the large scale recombinant production of the enzymatically active expression products and/or products (e.g., GMP) resulting from IMPDH catalyzed synthesis in cells. Vectors including IMPDH-encoding DNA sequences are useful in gene amplification procedures. Recombinant proteins and synthetic peptides provided by the invention are useful as immunological reagents and in the preparation of antibodies (including polyclonal and monoclonal antibodies) for quantitative detection of IMPDH.

摘要翻译： 公开了编码具有肌苷5'-单磷酸脱氢酶（“IMPDH”）的生物学性质的真核蛋白质的纯化和分离的DNA序列。 说明性地，哺乳动物（例如，人）IMPDH编码DNA序列可用于转化或转染宿主细胞，用于大规模重组产生由细胞内的IMPDH催化合成产生的酶活性表达产物和/或产物（例如，GMP） 。 包含IMPDH编码DNA序列的载体可用于基因扩增过程。 本发明提供的重组蛋白质和合成肽可用作免疫学试剂和用于定量检测IMPDH的抗体（包括多克隆和单克隆抗体）的制备。

公开(公告)号：US20050260158A1

公开(公告)日：2005-11-24

申请号：US10968385

申请日：2004-10-18

申请人： Eliezer Huberman ,  Yong Zhao

发明人： Eliezer Huberman ,  Yong Zhao

IPC分类号： A61K35/15 ,  A61K48/00 ,  C12N5/071 ,  C12N5/0786 ,  C12N5/08

CPC分类号： A61K35/15 ,  C12N5/0607 ,  C12N5/0645 ,  C12N5/0676 ,  C12N2501/22 ,  C12N2501/2306 ,  C12N2501/235 ,  C12N2506/03 ,  C12N2506/115

摘要： Monocyte derived adult stem cells (MDSCs) isolated from peripheral blood of mammals are provided, along with pharmaceutical compositions containing an MDSC, kits containing a pharmaceutical composition, and methods of preparing, propagating and using MDSCs or differentiated derivatives thereof. The uses of these biological materials include methods of treating disorders or diseases, as well as methods of ameliorating a symptom associated with any such disorder or disease, including disorders or diseases associated with aberrant function or presence (i.e., level) of pancreatic islet β-cell-like macrophages.

摘要翻译： 提供从哺乳动物的外周血分离的单核细胞来源的成体干细胞（MDSC），以及含有MDSC的药物组合物，含有药物组合物的试剂盒，以及制备，增殖和使用MDSC或其差异衍生物的方法。 这些生物材料的用途包括治疗疾病或疾病的方法，以及改善与任何此类疾病或疾病相关的症状的方法，包括与胰岛β细胞的异常功能或存在（即水平）相关的疾病或疾病， 细胞样巨噬细胞。

公开(公告)号：US06673623B1

公开(公告)日：2004-01-06

申请号：US09660107

申请日：2000-09-12

申请人： Eliezer Huberman

发明人： Eliezer Huberman

IPC分类号： G01N3300

CPC分类号： G01N33/502 ,  G01N33/5008 ,  Y10S436/805

摘要： The present invention relates generally to the use of lipogenins, proteins, e.g. human extra-cellular matrix protein 1 (ECM-1), human glia-derived nexin I alpha protein (NP-I), human tissue inhibitor of metalloproteinase-2 (TIMP-2) and human histone H2A (H2A) singly or in various combinations to control lipogenesis in a mammal.

摘要翻译： 本发明一般涉及脂质成分，蛋白质等的用途。 人类细胞外基质蛋白1（ECM-1），人神经胶质来源的nexinIα蛋白（NP-I），金属蛋白酶-2（TIMP-2）和人组蛋白H2A（H2A）的人组织抑制剂单独或各种 用于控制哺乳动物脂肪生成的组合。

公开(公告)号：US20050003534A1

公开(公告)日：2005-01-06

申请号：US10854962

申请日：2004-05-26

申请人： Eliezer Huberman ,  Yong Zhao

发明人： Eliezer Huberman ,  Yong Zhao

IPC分类号： A61K48/00 ,  C12N5/02 ,  C12N5/074 ,  E02D27/42 ,  C12N5/08

CPC分类号： C12N5/0607 ,  C12N2501/22 ,  C12N2501/2306 ,  C12N2501/235

摘要： Monocyte derived adult stem cells (MDSCs) isolated from peripheral blood of mammals are provided, along with pharmaceutical compositions containing an MDSC, kits containing a pharmaceutical composition, and methods of preparing, propagating and using MDSCs or differentiated derivatives thereof. The uses of these biological materials include methods of treating disorders or diseases, as well as methods of ameliorating a symptom associated with any such disorder or disease including disorders or diseases associated with platelets.

摘要翻译： 提供从哺乳动物的外周血分离的单核细胞来源的成体干细胞（MDSC），以及含有MDSC的药物组合物，含有药物组合物的试剂盒，以及制备，增殖和使用MDSC或其差异衍生物的方法。 这些生物材料的用途包括治疗疾病或疾病的方法，以及改善与任何此类疾病或疾病相关的症状（包括与血小板相关的疾病或疾病）的方法。

公开(公告)号：US07183106B1

公开(公告)日：2007-02-27

申请号：US10856409

申请日：2004-05-28

申请人： Eliezer Huberman ,  Mekhine J. Baccam

发明人： Eliezer Huberman ,  Mekhine J. Baccam

IPC分类号： C12N15/00

CPC分类号： C12N9/0006

摘要： The present invention relates to a nucleic acid sequence and its corresponding protein sequence useful as a dominant selectable marker in eukaryotes. More specifically the invention relates to a nucleic acid encoding a bacterial IMPDH gene that has been engineered into a eukaryotic expression vectors, thereby permitting bacterial IMPDH expression in mammalian cells. Bacterial IMPDH expression confers resistance to MPA which can be used as dominant selectable marker in eukaryotes including mammals. The invention also relates to expression vectors and cells that express the bacterial IMPDH gene as well as gene therapies and protein synthesis.

摘要翻译： 本发明涉及可用作真核生物中显性选择标记的核酸序列及其相应的蛋白质序列。 更具体地，本发明涉及编码细菌IMPDH基因的核酸，其已经被工程化成真核表达载体，从而允许在哺乳动物细胞中表达细菌IMPDH。 细菌IMPDH表达赋予对MPA的抗性，其可以用作包括哺乳动物在内的真核生物的显性选择标记。 本发明还涉及表达细菌IMPDH基因以及基因治疗和蛋白质合成的表达载体和细胞。

公开(公告)号：US20140249178A1

公开(公告)日：2014-09-04

申请号：US14240583

申请日：2012-08-23

申请人： Eliezer Huberman

发明人： Eliezer Huberman

IPC分类号： A61K31/437

CPC分类号： A61K31/437 ,  A61K31/44 ,  Y02A50/385 ,  Y02A50/393

摘要： Substituted perhydro pyrrolopyridines and methods for their use in the treatment of HIV infections, AIDS, and AIDS-related diseases, and in the treatment of BVDV infections are described herein. Also, pharmaceutical compositions comprising the substituted perhydro pyrrolopyridines are useful for the treatment of HIV infections, AIDS, and AIDS-related diseases. The compositions include one or more carriers, diluents, or excipients, or a combination thereof.

摘要翻译： 本文描述了取代的全氢吡咯并吡啶及其用于治疗HIV感染，AIDS和AIDS相关疾病以及用于治疗BVDV感染的方法。 此外，包含取代的全氟吡咯并吡啶的药物组合物可用于治疗HIV感染，AIDS和AIDS相关疾病。 组合物包括一种或多种载体，稀释剂或赋形剂，或其组合。