公开(公告)号：US09012455B2

公开(公告)日：2015-04-21

申请号：US12296720

申请日：2007-04-10

Applicant: Wen-Hwa Lee ,  Phang-Lang Chen ,  Longen Zhou ,  Jiewen Zhu

Inventor： Wen-Hwa Lee ,  Phang-Lang Chen ,  Longen Zhou ,  Jiewen Zhu

IPC: A61K31/4725 ,  A61K31/506 ,  A61K31/4745

CPC classification number: A61K31/4745

Abstract: Chronic myelogenous leukemia (CML), and in particular imatinib resistant CML is treated using compositions and methods in which a Rad51-inhibitor and a kinase inhibitor are administered. Most preferably, the Rad51 inhibitor comprises an indolyl isoquinoline structure and the kinase inhibitor is a BCR-ABL inhibitor.

Abstract translation: 使用其中施用Rad51抑制剂和激酶抑制剂的组合物和方法治疗慢性骨髓性白血病（CML），特别是伊马替尼耐药性CML。 最优选地，Rad51抑制剂包含吲哚基异喹啉结构，激酶抑制剂是BCR-ABL抑制剂。

公开(公告)号：US07105156B1

公开(公告)日：2006-09-12

申请号：US08472760

申请日：1995-06-07

Applicant: Wen-Hwa Lee ,  H. Michael Shepard ,  Richard J. Gregory ,  Ken N. Wills ,  Daniel C. Maneval ,  Eva Lee ,  David Goodrich ,  Nan-Ping Wang

Inventor： Wen-Hwa Lee ,  H. Michael Shepard ,  Richard J. Gregory ,  Ken N. Wills ,  Daniel C. Maneval ,  Eva Lee ,  David Goodrich ,  Nan-Ping Wang

IPC: A61K35/00 ,  A61K48/00

CPC classification number: A61K38/1709 ,  A61K48/005 ,  C07K14/4736 ,  C12N2710/10043

Abstract: Disclosed are methods of controlling cell cycle progression by introducing into a cell to be controlled a composition selected from the group consisting of p56RB protein, a fragment of the p56RB protein, and the gene encoding p56RB protein to alter the cell cycle progression while maintaining the viability of the cell. The p56RB protein has been found to have the unexpected and surprising characteristic of being soluble in low concentrations of glycerol, thereby enhancing its value in pharmaceutical applications and the gene encoding p56RB when delivered to the hyperproliferating cell inhibits cellular proliferation.

Abstract translation: 公开了通过将细胞引入被控制的细胞中来控制细胞周期进程的方法，所述细胞选自由p56Rb蛋白质组成的组，p56RB蛋白质的片段， 和编码p56PN蛋白的基因，以改变细胞周期进程，同时保持细胞的活力。 已经发现p56RBP蛋白具有可溶于低浓度甘油的意想不到的令人惊奇的特征，从而提高了其在药物应用中的价值，并且编码p56Rb / 当递送到过度增殖细胞时抑制细胞增殖。

公开(公告)号：US6133424A

公开(公告)日：2000-10-17

申请号：US485042

申请日：1995-06-07

Applicant: Wen-Hwa Lee ,  Eva Y. -H. P. Lee

Inventor： Wen-Hwa Lee ,  Eva Y. -H. P. Lee

IPC: A61K38/00 ,  C07K14/47 ,  G01N33/567 ,  G01N33/574 ,  A61K38/17

CPC classification number: C07K14/4746 ,  G01N33/567 ,  G01N33/5748 ,  A61K38/00 ,  C12N2799/026 ,  Y10S436/813 ,  Y10S530/828

Abstract: This invention relates in general to a phosphoprotein product of the retinoblastoma susceptibility gene. In particular, this invention relates to a phosphoprotein ppRB.sup.110 primarily located in the cell nucleus which has a DNA binding activity. The invention also relates to the amino acid sequence of the phosphoprotein and to the specific purified anti-retinoblastoma phosphoprotein antibody. The invention further relates to a method of diagnosing retinoblastoma and other retinoblastoma gene involved cancers, treating such kind of cancers and regulating the oncogenicity of other genes.

Abstract translation: 本发明一般涉及视网膜母细胞瘤易感基因的磷蛋白产物。 特别地，本发明涉及主要位于具有DNA结合活性的细胞核中的磷蛋白ppRB110。 本发明还涉及磷蛋白和特异性纯化的抗视网膜母细胞瘤磷蛋白抗体的氨基酸序列。 本发明还涉及诊断视网膜母细胞瘤和其他视网膜母细胞瘤基因涉及的癌症，治疗这种癌症并调节其他基因的致癌性的方法。

公开(公告)号：US6051396A

公开(公告)日：2000-04-18

申请号：US58784

申请日：1993-05-07

Applicant: Wen-Hwa Lee ,  Eva Y.-H. P. Lee

Inventor： Wen-Hwa Lee ,  Eva Y.-H. P. Lee

IPC: A61K38/00 ,  A61K48/00 ,  C07K14/47 ,  C07K16/18 ,  C12N9/16 ,  C12N15/85 ,  C12N15/866 ,  C12P21/04 ,  C12Q1/68 ,  G01N33/567 ,  G01N33/574 ,  C12N15/00 ,  C12N5/00 ,  C12P21/06

CPC classification number: G01N33/5748 ,  C07K14/47 ,  C07K14/4736 ,  C07K14/4746 ,  C07K16/18 ,  C12N15/8509 ,  C12N15/86 ,  C12N9/16 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q1/6886 ,  G01N33/567 ,  G01N33/574 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2267/01 ,  A61K38/00 ,  A61K48/00 ,  C12N2710/14143

Abstract: A method that produces substantial quantities of a desired polypeptide, by delivering genetic material into insect cells. For example, cloned genes, or gene fragments or, derivates may be defined, utilizing as appropriate vector, into host cells for high level production of high purity protein in substantial quantities.

Abstract translation: 通过将遗传物质递送到昆虫细胞中产生大量所需多肽的方法。 例如，可以将克隆的基因或基因片段或衍生物以适当的载体定义为宿主细胞，用于大量生产高纯度蛋白质。

公开(公告)号：US5858771A

公开(公告)日：1999-01-12

申请号：US337855

申请日：1994-11-14

Applicant: Wen-Hwa Lee ,  Huei-Jen Su Huang ,  Eva Y. H. P. Lee

Inventor： Wen-Hwa Lee ,  Huei-Jen Su Huang ,  Eva Y. H. P. Lee

IPC: A01K67/027 ,  A61K38/00 ,  A61K48/00 ,  C07K14/47 ,  C07K16/18 ,  C12N9/16 ,  C12N15/85 ,  C12Q1/68 ,  G01N33/567 ,  G01N33/574 ,  C12N15/00

CPC classification number: C12N15/8509 ,  A01K67/0271 ,  A01K67/0276 ,  C07K14/47 ,  C07K14/4746 ,  C07K16/18 ,  C12N9/16 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q1/6886 ,  G01N33/567 ,  G01N33/574 ,  G01N33/5748 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  A61K38/00 ,  A61K48/00 ,  C12N2799/026 ,  C12Q2600/158

Abstract: A method for gene therapy for cancers wherein chromosomal location of an inactive or defective cancer suppressing gene is established, a replacement gene which is preferably cloned is then used to replace the inactive or defective cancer suppressing gene in the chromosome. In addition to its uses in therapy, the present invention provides a means for prophylactically treating individuals having a genetic predisposition to cancer and provides an animal model for testing for carcinogenicity of environmental substances.

公开(公告)号：US5578701A

公开(公告)日：1996-11-26

申请号：US225099

申请日：1994-04-08

Applicant: Wen-Hwa Lee ,  Eva Y.-H. P. Lee

Inventor： Wen-Hwa Lee ,  Eva Y.-H. P. Lee

IPC: A61K38/00 ,  C07K14/47 ,  G01N33/567 ,  G01N33/574 ,  C07K16/30 ,  A61K39/395

CPC classification number: C07K14/4746 ,  G01N33/567 ,  G01N33/5748 ,  A61K38/00 ,  C12N2799/026 ,  Y10S436/813 ,  Y10S530/828

Abstract: This invention relates in general to a phosphoprotein product of the retinoblastoma susceptibility gene. In particular, this invention relates to a phosphoprotein ppRB.sup.110 primarily located in the cell nucleus which has a DNA binding activity. The invention also relates to the amino acid sequence of the phosphoprotein and to the specific purified anti-retinoblastoma phosphoprotein antibody. The invention further relates to a method of diagnosing retinoblastoma and other retinoblastoma gene involved cancers, treating such kind of cancers and regulating the oncogenicity of other genes.

Abstract translation: 本发明一般涉及视网膜母细胞瘤易感基因的磷蛋白产物。 特别地，本发明涉及主要位于具有DNA结合活性的细胞核中的磷蛋白ppRB110。 本发明还涉及磷蛋白和特异性纯化的抗视网膜母细胞瘤磷蛋白抗体的氨基酸序列。 本发明还涉及诊断视网膜母细胞瘤和其他视网膜母细胞瘤基因涉及的癌症，治疗这种癌症并调节其他基因的致癌性的方法。

公开(公告)号：US08293764B2

公开(公告)日：2012-10-23

申请号：US11577445

申请日：2005-10-19

Applicant: Wen-Hwa Lee ,  Phang-Lang Chen ,  Jiewen Zhu

Inventor： Wen-Hwa Lee ,  Phang-Lang Chen ,  Jiewen Zhu

IPC: C07D215/38 ,  A61K31/04

CPC classification number: A61K31/4725

Abstract: Contemplated compounds disrupt interaction between BRCA2 and RAD51, likely by binding to RAD51. Based on the crucial role of the BRCA2-RAD51 complex formation in DNA repair and the role of RAD51 in the control of entry into S-phase from G1, numerous compositions and methods are presented. Among other advantageous uses, contemplated compounds may be employed as protective agents for non-neoplastic cells in chemotherapy before exposure of the cells to a chemotherapeutic drug, and/or as DNA-damage sensitizer for neoplastic cells.

Abstract translation: 考虑的化合物可能通过结合RAD51扰乱BRCA2和RAD51之间的相互作用。 基于BRCA2-RAD51复合物形成在DNA修复中的关键作用和RAD51在控制从G1进入S期的作用，提出了许多组合物和方法。 除了其它有利的用途之外，预期的化合物可以在细胞暴露于化学治疗药物之前和/或作为肿瘤细胞的DNA损伤敏化剂中用作化疗中的非肿瘤细胞的保护剂。

公开(公告)号：US20090312324A1

公开(公告)日：2009-12-17

申请号：US12296720

申请日：2007-04-10

Applicant: Wen-Hwa Lee ,  Phang-Lang Chen ,  Longen Zhou ,  Jiewen Zhu

Inventor： Wen-Hwa Lee ,  Phang-Lang Chen ,  Longen Zhou ,  Jiewen Zhu

IPC: A61K31/5377 ,  A61K31/47 ,  A61K31/496 ,  A61K31/505 ,  C07D217/22 ,  C07D413/14 ,  A61P35/02

CPC classification number: A61K31/4745

Abstract: Chronic myelogenous leukemia (CML), and in particular imatinib resistant CML is treated using compositions and methods in which a Rad51-inhibitor and a kinase inhibitor are administered. Most preferably, the Rad51 inhibitor comprises an indolyl isoquinoline structure and the kinase inhibitor is a BCR-ABL inhibitor.

Abstract translation: 使用其中施用Rad51抑制剂和激酶抑制剂的组合物和方法治疗慢性骨髓性白血病（CML），特别是伊马替尼耐药性CML。 最优选地，Rad51抑制剂包含吲哚基异喹啉结构，激酶抑制剂是BCR-ABL抑制剂。

公开(公告)号：US5710022A

公开(公告)日：1998-01-20

申请号：US328254

申请日：1994-10-24

Applicant: Xueling Zhu ,  Wen-Hwa Lee

Inventor： Xueling Zhu ,  Wen-Hwa Lee

IPC: G01N33/53 ,  A61K35/12 ,  A61K38/00 ,  A61K38/45 ,  A61K39/395 ,  A61K48/00 ,  A61P13/02 ,  A61P15/00 ,  A61P17/00 ,  A61P35/00 ,  A61P35/02 ,  C07H21/04 ,  C07K14/47 ,  C07K16/18 ,  C12N1/21 ,  C12N15/09 ,  C12P21/02 ,  C12P21/08 ,  G01N33/566 ,  C07K14/435 ,  C12N15/12 ,  C12N15/63

CPC classification number: C07K14/4738 ,  A61K38/00

Abstract: A novel purified phosphoprotein designated mitosin is provided by this invention. Also provided is the amino acid sequence of mitosin, active fragments of mitosin, and a nucleic acid molecule encoding mitosin. Diagnostic and therapeutic methods of using the protein and nucleic acid molecule are also provided. The nucleic acid molecules are useful to recombinantly produce mitosin and for use as probes. The compositions and methods of this invention are based on the discovery that the intracellular presence of mitosin is necessary for the cell to enter the M phase of mitosis, and that the degradation of mitosin is necessary for the cell to advance to the next stage. Thus, an anti-mitsoin antibody, or a mutant or non-functional analog of mitosin, would inhibit the mitotic cell cycle by preventing cells from entering the M phase, and overexpression of mitosin, or a functional equivalent thereof, would inhibit the cycle by preventing cells from leaving the M phase. Such overexpression could be achieved either by addition of the protein or through gene therapy, i.e., delivery of a gene encoding the protein or a functional equivalent thereof.

Abstract translation: 本发明提供了一种称为丝裂素的新型纯化磷蛋白。 还提供了丝裂原的氨基酸序列，丝裂原的活性片段和编码丝裂原的核酸分子。 还提供了使用蛋白质和核酸分子的诊断和治疗方法。 核酸分子可用于重组产生丝裂霉素并用作探针。 本发明的组合物和方法基于以下发现，即细胞内存在丝裂蛋白是细胞进入有丝分裂M期的必需物质，并且丝裂原的降解对于细胞进展到下一阶段是必需的。 因此，抗mitinin抗体或丝裂肌蛋白的突变或非功能类似物将通过阻止细胞进入M期来抑制有丝分裂细胞周期，并且丝裂原或其功能等同物的过表达将通过 防止细胞离开M相。 这种过表达可以通过添加蛋白质或通过基因治疗即递送编码蛋白质的基因或其功能等同物来实现。

公开(公告)号：US20150105391A1

公开(公告)日：2015-04-16

申请号：US14335893

申请日：2014-07-19

Applicant: Wen-Hwa Lee ,  Jiewen Zhu ,  Chun-Mei Hu

Inventor： Wen-Hwa Lee ,  Jiewen Zhu ,  Chun-Mei Hu

IPC: C07D417/12

CPC classification number: C07D417/12 ,  C07D417/14

Abstract: Certain embodiments of the present invention provide selected compounds having a molecular structure according to Formula 1: In Formula 1, Z is —CO—, —SO—, or —SO2—; Ar is phenyl, heteroaryl, or heterocycloalkyl; Het is heteroaryl; R is R″, X, or NR1R2; R′ is R3, or OR3; R″ is R4, or OR4; R1 and R2 are each independently H, alkyl, or acyl; R3 is H, heteroaryl, or alkyl; R4 is H, heteroaryl, or CnH2n+1 (n>2); and X is F, Br, I, CN, or NO2. In some embodiments, compounds having a molecular structure according to Formula 1 have the property of inhibiting a growth of a cell line selected from HeLa and MB468 with a sub-micromolar IC50.

Abstract translation: 本发明的某些实施方案提供了具有根据式1的分子结构的所选化合物：在式1中，Z是-CO-，-SO-或-SO 2 - ; Ar是苯基，杂芳基或杂环烷基; Het是杂芳基; R是R“，X或NR 1 R 2; R'是R3或OR3; R“是R 4或OR 4; R1和R2各自独立地为H，烷基或酰基; R3是H，杂芳基或烷基; R 4是H，杂芳基或C n H 2n + 1（n> 2）; X是F，Br，I，CN或NO 2。 在一些实施方案中，具有根据式1的分子结构的化合物具有以亚微米IC 50抑制选自HeLa和MB468的细胞系的生长的性质。