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    Analogs of 2-Phthalimidinoglutaric acid
    1.
    发明授权
    Analogs of 2-Phthalimidinoglutaric acid 有权
    2-邻苯二甲酰氨基嘌呤酸的类似物

    公开(公告)号：US06673828B1

    公开(公告)日：2004-01-06

    申请号：US09309464

    申请日：1999-05-11

    申请人： Shawn J. Green ,  Glenn M. Swartz, Jr. ,  Jamshed H. Shah ,  John Madsen ,  Adonia E. Papathanassiu ,  William Fogler

    发明人： Shawn J. Green ,  Glenn M. Swartz, Jr. ,  Jamshed H. Shah ,  John Madsen ,  Adonia E. Papathanassiu ,  William Fogler

    IPC分类号： A61K314035

    CPC分类号： C07D209/46

    摘要： The invention provides new and useful analogs of 2-phthalimidinoglutaric acid. These analogs include DL-2-methyl-2-phthalimidinoglutaric acid and hydroxylated analogs of 2-phthalimidinoglutaric. The invention also provides processes for making these analogs. The invention also provides the two individual enantiomers of DL-2-methyl-2-phthalimidinoglutaric acid, (R)-(+)-2-methyl-2-phthalimidinoglutaric acid and (S)-(−)-2-methyl-2-phthalimidinoglutaric acid, and processes for separating these individual enantiomers from the racemate. Further, the invention provides methods for inhibiting angiogenesis and treating angiogenesis-associated diseases, including cancer and macular degeneration, by administering one or more of these compounds.

    摘要翻译： 本发明提供了新的和有用的2-邻苯二甲酰亚氨基戊二酸的类似物。 这些类似物包括DL-2-甲基-2-邻苯二甲酰亚氨基戊二酸和2-邻苯二甲酰亚氨基嘌呤的羟基化类似物。 本发明还提供了制备这些类似物的方法。 本发明还提供DL-2-甲基-2-邻苯二甲酰亚氨基戊二酸的两种单独的对映异构体，（R） - （+） - 2-甲基-2-邻苯二甲酰亚氨基戊二酸和（S） - （ - ） - 2-甲基-2 - 邻苯二甲酰氨基嘌呤酸，以及从外消旋体中分离这些单独的对映异构体的方法。 此外，本发明提供了通过施用这些化合物中的一种或多种来抑制血管发生和治疗血管生成相关疾病（包括癌症和黄斑变性）的方法。

    Methods of treating undesired angiogenesis with 2-methyl-EM-138
    2.
    发明授权
    Methods of treating undesired angiogenesis with 2-methyl-EM-138 有权
    用2-甲基-MEM-138治疗不需要的血管生成的方法

    公开(公告)号：US07112602B2

    公开(公告)日：2006-09-26

    申请号：US10732867

    申请日：2003-12-09

    申请人： Robert J. D'Amato ,  Shawn J. Green ,  John W. Madsen ,  William Fogler ,  Glenn M. Swartz, Jr. ,  Adonia E. Papathanassiu ,  Jamshed H. Shah

    发明人： Robert J. D'Amato ,  Shawn J. Green ,  John W. Madsen ,  William Fogler ,  Glenn M. Swartz, Jr. ,  Adonia E. Papathanassiu ,  Jamshed H. Shah

    IPC分类号： A61K31/40

    CPC分类号： C07D209/46

    摘要： The invention provides new and useful analogs of 2-phthalimidinoglutaric acid. These analogs include DL-2-methyl-2-phthalimidinoglutaric acid and hydroxylated analogs of 2-phthalimidinoglutaric. The invention also provides processes for making these analogs. The invention also provides the two individual enantiomers of DL-2-methyl-2-phthalimidinoglutaric acid, (R)-(+)-2-methyl-2-phthalimidinoglutaric acid and (S)-(−)-2-methyl-2-phthalimidinoglutaric acid, and processes for separating these individual enantiomers from the racemate. Further, the invention provides methods for inhibiting angiogenesis and treating angiogenesis-associated diseases, including cancer and macular degeneration, by administering one or more of these compounds.

    摘要翻译： 本发明提供了新的和有用的2-邻苯二甲酰亚氨基戊二酸的类似物。 这些类似物包括DL-2-甲基-2-邻苯二甲酰亚氨基戊二酸和2-邻苯二甲酰亚氨基嘌呤的羟基化类似物。 本发明还提供了制备这些类似物的方法。 本发明还提供DL-2-甲基-2-邻苯二甲酰亚氨基戊二酸的两种单独的对映异构体，（R） - （+） - 2-甲基-2-邻苯二甲酰亚氨基戊二酸和（S） - （ - ） - 2-甲基-2 - 邻苯二甲酰氨基嘌呤酸，以及从外消旋体中分离这些单独对映异构体的方法。 此外，本发明提供了通过施用这些化合物中的一种或多种来抑制血管发生和治疗血管生成相关疾病（包括癌症和黄斑变性）的方法。

    Compositions and methods for inhibiting cellular proliferation
    6.
    发明授权
    Compositions and methods for inhibiting cellular proliferation 失效
    抑制细胞增殖的组合物和方法

    公开(公告)号：US06734163B2

    公开(公告)日：2004-05-11

    申请号：US09766778

    申请日：2001-01-22

    申请人： Adonia E. Papathanassiu ,  Shawn J. Green

    发明人： Adonia E. Papathanassiu ,  Shawn J. Green

    IPC分类号： A61K3855

    CPC分类号： C07K14/8114 ,  A61K38/57

    摘要： Compositions and methods for inhibiting cellular proliferation wherein the composition contains Tissue Factor Pathway Inhibitor (TFPI), a TFPI homolog, or an active fragment thereof. TFPI exhibits potent anti-proliferative activity on human and other animal cells, particularly endothelial cells. More particularly, the TFPI, TFPI homolog, and inhibitory fragment thereof may be combined with a pharmaceutically acceptable excipient or carrier and used to inhibit angiogenesis and angiogenesis-related diseases such as cancer, arthritis, macular degeneration, and diabetic retinopathy.

    摘要翻译： 用于抑制细胞增殖的组合物和方法，其中所述组合物含有组织因子途径抑制剂（TFPI），TFPI同源物或其活性片段。 TFPI对人和其他动物细胞，特别是内皮细胞表现出有效的抗增殖活性。 更具体地，TFPI，TFPI同源物及其抑制片段可以与药学上可接受的赋形剂或载体组合，并用于抑制血管生成和血管生成相关疾病如癌症，关节炎，黄斑变性和糖尿病性视网膜病变。

    Compositions and methods for inhibiting cellular proliferation comprising TFPI fragments
    7.
    发明授权
    Compositions and methods for inhibiting cellular proliferation comprising TFPI fragments 失效
    用于抑制包含TFPI片段的细胞增殖的组合物和方法

    公开(公告)号：US06946439B2

    公开(公告)日：2005-09-20

    申请号：US10086176

    申请日：2002-02-28

    申请人： Todd Hembrough ,  Victor P. Pribluda ,  Adonia E. Papathanassiu ,  Shawn J. Green

    发明人： Todd Hembrough ,  Victor P. Pribluda ,  Adonia E. Papathanassiu ,  Shawn J. Green

    IPC分类号： A61K38/00 ,  A61K38/57 ,  C07K14/81 ,  A61K38/16

    CPC分类号： C07K14/8114 ,  A61K38/57

    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.

    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。 组合物包含含有蛋白酶抑制剂如TFPI的C末端部分的全部或活性部分的天然存在或合成的蛋白质，肽或蛋白质片段。 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。

    Compositions and methods for inhibiting cellular proliferation
    8.
    发明授权
    Compositions and methods for inhibiting cellular proliferation 失效
    抑制细胞增殖的组合物和方法

    公开(公告)号：US5981471A

    公开(公告)日：1999-11-09

    申请号：US796850

    申请日：1997-02-06

    申请人： Adonia E. Papathanassiu ,  Shawn J. Green

    发明人： Adonia E. Papathanassiu ,  Shawn J. Green

    IPC分类号： A61K38/00 ,  A61K38/57 ,  A61P35/00 ,  C07K14/81 ,  A61K38/55 ,  A61K38/06

    CPC分类号： C07K14/8114 ,  A61K38/57

    摘要： Compositions and methods for inhibiting cellular proliferation wherein the composition contains Tissue Factor Pathway Inhibitor (TFPI), a TFPI homolog, or an active fragment thereof. TFPI exhibits potent anti-proliferative activity on human and other animal cells, particularly endothelial cells. More particularly, the TFPI, TFPI homolog, and inhibitory fragment thereof may be combined with a pharmaceutically acceptable excipient or carrier and used to inhibit angiogenesis and angiogenesis-related diseases such as cancer, arthritis, macular degeneration, and diabetic retinopathy.

    摘要翻译： 用于抑制细胞增殖的组合物和方法，其中所述组合物含有组织因子途径抑制剂（TFPI），TFPI同源物或其活性片段。 TFPI对人和其他动物细胞，特别是内皮细胞表现出有效的抗增殖活性。 更具体地，TFPI，TFPI同源物及其抑制片段可以与药学上可接受的赋形剂或载体组合，并用于抑制血管生成和血管生成相关疾病如癌症，关节炎，黄斑变性和糖尿病性视网膜病变。

    Compositions and methods of use of ligands that bind components of the blood coagulation/clotting pathway for the treatment of cancer and angiogenic-based disease
    9.
    发明授权
    Compositions and methods of use of ligands that bind components of the blood coagulation/clotting pathway for the treatment of cancer and angiogenic-based disease 失效
    用于结合血液凝固/凝血途径的组分用于治疗癌症和基于血管生成的疾病的配体的组合物和方法

    公开(公告)号：US06593291B1

    公开(公告)日：2003-07-15

    申请号：US09418546

    申请日：1999-10-14

    申请人： Shawn J. Green ,  Adonia E. Papathanassiu

    发明人： Shawn J. Green ,  Adonia E. Papathanassiu

    IPC分类号： A01N3718

    CPC分类号： C07K14/8114 ,  A61K38/4833 ,  A61K38/4846 ,  A61K38/57 ,  A61K2039/505

    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 naturally occurring, or synthetic proteins, peptides, or protein fragments capable of binding to components of the blood coagulation pathway. The compositions may be administered using a pharmaceutically acceptable carrier. 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。 组合物包含能够结合凝血途径成分的天然存在的或合成的蛋白质，肽或蛋白质片段。 组合物可以使用药学上可接受的载体给药。 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种肿瘤的生长或扩张。