公开(公告)号：WO2003035008A3

公开(公告)日：2003-05-01

申请号：PCT/US2002/034497

申请日：2002-10-28

Applicant: OXIGENE, INC. ,  CHAPLIN, David, J. ,  GARNER, Charles, Manly, III ,  KANE, Robert, Ronald ,  PINNEY, Kevin, G. ,  PREZIOSO, Joseph, Anthony ,  EDVARDSEN, Klaus

Inventor： CHAPLIN, David, J. ,  GARNER, Charles, Manly, III ,  KANE, Robert, Ronald ,  PINNEY, Kevin, G. ,  PREZIOSO, Joseph, Anthony ,  EDVARDSEN, Klaus

IPC: C07C43/20

Abstract: Novel stilbenoid compounds and their prodrug forms are disclosed, which serve as potent vascular targeting agents useful for the treatment of solid tumor cancers and other diseases associated with unwanted neovascularization. The novel stilbenoid compounds are tubulin-binding stilbenoid analogs structurally related to combretastatin A-1 and combretastatin A-4. The prodrug forms serve as potent vascular targeting agents (VTAs) useful for the treatment of solid tumor cancers and diseases associated with retinal neovascularization.

公开(公告)号：WO2004087061B1

公开(公告)日：2005-05-12

申请号：PCT/US2004009417

申请日：2004-03-26

Applicant: OXIGENE INC ,  UNIV BAYLOR ,  PINNEY KEVIN G ,  MOCHARLA VANI P ,  CHEN ZHI ,  GARNER CHARLES M ,  GHATAK ANJAN ,  HADIMANI MALLINATH ,  KESSLER JIMMY ,  DORSEY JAMES M ,  EDVARDSON KLAUS ,  CHAPLIN DAVID J ,  PREZIOSO JOSEPH ,  JELINEK CHRISTOPHER

Inventor： PINNEY KEVIN G ,  MOCHARLA VANI P ,  CHEN ZHI ,  GARNER CHARLES M ,  GHATAK ANJAN ,  HADIMANI MALLINATH ,  KESSLER JIMMY ,  DORSEY JAMES M ,  EDVARDSON KLAUS ,  CHAPLIN DAVID J ,  PREZIOSO JOSEPH ,  JELINEK CHRISTOPHER

IPC: A61K20060101 ,  A61K31/075 ,  C07C41/00 ,  C07C43/215 ,  C07C43/23 ,  C07C45/51 ,  C07C45/64 ,  C07C49/84 ,  C07C205/45 ,  C07C217/84 ,  C07C217/94 ,  C07C225/22 ,  C07D233/54 ,  C07D307/80 ,  C07D307/81 ,  C07D333/56 ,  C07D333/64 ,  C07F9/12 ,  C07F9/18 ,  C07F9/24 ,  C07F9/655 ,  C07F9/6553

CPC classification number: C07C43/23 ,  A61K31/075 ,  A61K31/66 ,  C07C43/215 ,  C07C45/512 ,  C07C45/64 ,  C07C45/673 ,  C07C49/755 ,  C07C49/84 ,  C07C205/37 ,  C07C205/45 ,  C07C217/84 ,  C07C217/94 ,  C07C223/06 ,  C07C225/22 ,  C07C237/08 ,  C07C2602/08 ,  C07C2602/10 ,  C07D307/80 ,  C07D307/81 ,  C07D333/56 ,  C07D333/64 ,  C07F9/12 ,  C07F9/18 ,  C07F9/247 ,  C07F9/65517 ,  C07F9/655354

Abstract: A diverse set of tubulin binding agents have been discovered which are structurally characterized, in a general sense, by a semi-rigid molecular framework capable of maintaining aryl-aryl, pseudo pi stacking distances appropriate for molecular recognition of tubulin. In phenolic or amino form, these ligands may be further functionalized to prepare phosphate esters, phosphate salts, phosphoramidates, and other prodrugs capable of demonstrating selective targeting and destruction of tumor cell vasculature.

Abstract translation: 已经发现了各种各样的微管蛋白结合剂，其结构特征在于一般意义上是能够维持适于分子识别微管蛋白的芳基 - 芳基，伪π层叠距离的半刚性分子框架。 在酚类或氨基形式中，这些配体可进一步官能化以制备能够显示肿瘤细胞脉管系统的选择性靶向和破坏的磷酸酯，磷酸盐，氨基磷酸酯和其它前体药物。

公开(公告)号：WO2004078126A2

公开(公告)日：2004-09-16

申请号：PCT/US2004/006175

申请日：2004-03-01

Applicant: OXIGENE, INC. ,  CHAPLIN, David, J. ,  EDVARDSEN, Klaus ,  PINNEY, Kevin, G. ,  PREZIOSO, Joseph, Anthony ,  WOOD, Mark

Inventor： CHAPLIN, David, J. ,  EDVARDSEN, Klaus ,  PINNEY, Kevin, G. ,  PREZIOSO, Joseph, Anthony ,  WOOD, Mark

IPC: A61K

CPC classification number: A61K31/6615 ,  A61K31/09 ,  C07C43/23 ,  C07C205/35 ,  C07D205/08 ,  C07F9/12

Abstract: Novel quinone and catechol compositions, compositions containing prodrugs of quinone and catechol compositions, and methods of use for the treatment of solid tumor cancers and other vascular proliferative disorders. The disclosure particularly relates to the discovery of dual activity agents capable of generating both a vascular targeting effect and direct tumor cell cytotoxicity in order to achieve an enhanced anti-tumor response in a patient.

Abstract translation: 新型醌和儿茶酚组合物，含有醌和儿茶酚组合物的前药的组合物，以及用于治疗实体瘤癌症和其它血管增生性疾病的方法。 本公开特别涉及能够产生血管靶向效应和直接肿瘤细胞毒性的双重活性试剂的发现，以便在患者体内实现增强的抗肿瘤反应。

公开(公告)号：WO2006078422A3

公开(公告)日：2006-07-27

申请号：PCT/US2005/046960

申请日：2005-12-22

Applicant: OXIGENE, INC. ,  CHAPLIN, David, J. ,  EDVARDSEN, Klaus ,  YOUNG, Scott

Inventor： CHAPLIN, David, J. ,  EDVARDSEN, Klaus ,  YOUNG, Scott

IPC: A61K31/09 ,  A61P35/00 ,  A61K31/337 ,  A61K31/555 ,  G01N33/50

Abstract: Methods and pharmaceutical compositions for modulating tumor growth or metastasis and methods for prognosing treatment therewith are provided.

公开(公告)号：WO2006078422A2

公开(公告)日：2006-07-27

申请号：PCT/US2005046960

申请日：2005-12-22

Applicant: OXIGENE INC ,  CHAPLIN DAVID J ,  EDVARDSEN KLAUS ,  YOUNG SCOTT

Inventor： CHAPLIN DAVID J ,  EDVARDSEN KLAUS ,  YOUNG SCOTT

IPC: A61K31/09 ,  A61K45/00 ,  A61K31/05 ,  A61K31/282 ,  A61K31/337 ,  A61K31/4745 ,  A61K31/555 ,  A61K31/661 ,  A61K33/24 ,  A61K36/18 ,  A61K45/06 ,  A61P9/00 ,  A61P35/00 ,  A61P35/04 ,  A61P43/00 ,  G01N33/50

CPC classification number: A61K31/09 ,  A61K31/05 ,  A61K31/337 ,  A61K31/555 ,  A61K33/24 ,  A61K45/06 ,  A61K2300/00

Abstract: Methods and pharmaceutical compositions for modulating tumor growth or metastasis and methods for prognosing treatment therewith are provided.

Abstract translation: 提供了调节肿瘤生长或转移的方法和药物组合物及其预防方法。

公开(公告)号：WO2004078126A3

公开(公告)日：2005-08-11

申请号：PCT/US2004006175

申请日：2004-03-01

Applicant: OXIGENE INC ,  CHAPLIN DAVID J ,  EDVARDSEN KLAUS ,  PINNEY KEVIN G ,  PREZIOSO JOSEPH ANTHONY ,  WOOD MARK

Inventor： CHAPLIN DAVID J ,  EDVARDSEN KLAUS ,  PINNEY KEVIN G ,  PREZIOSO JOSEPH ANTHONY ,  WOOD MARK

IPC: A01N31/14 ,  A61K20060101 ,  A61K31/075 ,  A61K31/16 ,  A61K31/36 ,  A61K31/66 ,  C07C9/02 ,  C07C41/00 ,  C07C43/02 ,  C07C43/20

CPC classification number: A61K31/6615 ,  A61K31/09 ,  C07C43/23 ,  C07C205/35 ,  C07D205/08 ,  C07F9/12

Abstract: Novel quinone and catechol compositions, compositions containing prodrugs of quinone and catechol compositions, and methods of use for the treatment of solid tumor cancers and other vascular proliferative disorders. The disclosure particularly relates to the discovery of dual activity agents capable of generating both a vascular targeting effect and direct tumor cell cytotoxicity in order to achieve an enhanced anti-tumor response in a patient.

Abstract translation: 新型醌和儿茶酚组合物，含有醌和儿茶酚组合物的前药的组合物，以及用于治疗实体瘤癌症和其它血管增生性疾病的方法。 本公开特别涉及能够产生血管靶向效应和直接肿瘤细胞毒性的双重活性试剂的发现，以便在患者体内实现增强的抗肿瘤反应。

公开(公告)号：WO2003035008A2

公开(公告)日：2003-05-01

申请号：PCT/US2002/034497

申请日：2002-10-28

Applicant: OXIGENE, INC. ,  CHAPLIN, David, J. ,  GARNER, Charles, Manly, III ,  KANE, Robert, Ronald ,  PINNEY, Kevin, G. ,  PREZIOSO, Joseph, Anthony

Inventor： CHAPLIN, David, J. ,  GARNER, Charles, Manly, III ,  KANE, Robert, Ronald ,  PINNEY, Kevin, G. ,  PREZIOSO, Joseph, Anthony

IPC: A61K

CPC classification number: C07C43/23 ,  C07C45/63 ,  C07C47/575 ,  C07C205/37 ,  C07C207/04 ,  C07C217/84 ,  C07C237/04 ,  C07F9/12

Abstract: Novel stilbenoid compounds and their prodrug forms are disclosed, which serve as potent vascular targeting agents useful for the treatment of solid tumor cancers and other diseases associated with unwanted neovascularization. The novel stilbenoid compounds are tubulin-binding stilbenoid analogs structurally related to combretastatin A-1 and combretastatin A-4. The prodrug forms serve as potent vascular targeting agents (VTAs) useful for the treatment of solid tumor cancers and diseases associated with retinal neovascularization.

Abstract translation: 公开了新的芪类化合物及其前体药物形式，其用作治疗实体瘤癌症和与不想要的新生血管形成相关的其它疾病的有效的血管靶向剂。 新型芪类化合物是与科替布他汀A-1和考布他汀A-4结构相关的微管蛋白结合芪类似物。 前药形式可用作治疗实体瘤癌症和与视网膜新生血管形成相关疾病的有效的血管靶向剂（VTA）。

公开(公告)号：WO2009103076A1

公开(公告)日：2009-08-20

申请号：PCT/US2009/034318

申请日：2009-02-17

Applicant: OXIGENE, INC. ,  CHAPLIN, David, J. ,  SIIM, Bronwyn, G.

Inventor： CHAPLIN, David, J. ,  SIIM, Bronwyn, G.

IPC: A61K31/4412 ,  A61K31/517 ,  A61K31/66 ,  A61K31/661 ,  A61P35/00

CPC classification number: A61K31/66 ,  A61K31/44 ,  A61K31/517 ,  A61K31/661 ,  A61K2300/00

Abstract: This invention relates to methods for treating, preventing and/or managing cancer in a subject including enhacing the efficacy of a Receptor Tyrosine Kinase inhibitor (e.g., a small molecule RTK inhibitor, e.g., Sorafenib or Erlotinib) by administering to the subject a Vascular Disrupting Agent (e.g., a Combretastatin or derivative thereof) sequentially or simultaneously in combination with said RTK inhibitor. Pharmaceutical compositions comprising a combination of a RTK inhibitor and a VDA are also provided.

Abstract translation: 本发明涉及用于治疗，预防和/或控制受试者中的癌症的方法，所述方法包括通过向受试者施用受体酪氨酸激酶抑制剂（例如，小分子RTK抑制剂，例如索拉非尼或埃洛替尼）来实现血管破坏 与所述RTK抑制剂组合，代理（例如，Combretastatin或其衍生物）顺序地或同时地。 还提供了包含RTK抑制剂和VDA的组合的药物组合物。

公开(公告)号：WO2004087061A2

公开(公告)日：2004-10-14

申请号：PCT/US2004009417

申请日：2004-03-26

Applicant: OXIGENE INC ,  UNIV BAYLOR ,  PINNEY KEVIN G ,  MOCHARLA VANI P ,  CHEN ZHI ,  GARNER CHARLES M ,  GHATAK ANJAN ,  HADIMANI MALLINATH ,  KESSLER JIMMY ,  DORSEY JAMES M ,  EDVARDSON KLAUS ,  CHAPLIN DAVID J ,  PREZIOSO JOSEPH ,  JELINEK CHRISTOPHER

Inventor： PINNEY KEVIN G ,  MOCHARLA VANI P ,  CHEN ZHI ,  GARNER CHARLES M ,  GHATAK ANJAN ,  HADIMANI MALLINATH ,  KESSLER JIMMY ,  DORSEY JAMES M ,  EDVARDSON KLAUS ,  CHAPLIN DAVID J ,  PREZIOSO JOSEPH ,  JELINEK CHRISTOPHER

IPC: A61K20060101 ,  A61K31/075 ,  C07C41/00 ,  C07C43/215 ,  C07C43/23 ,  C07C45/51 ,  C07C45/64 ,  C07C49/84 ,  C07C205/45 ,  C07C217/84 ,  C07C217/94 ,  C07C225/22 ,  C07D233/54 ,  C07D307/80 ,  C07D307/81 ,  C07D333/56 ,  C07D333/64 ,  C07F9/12 ,  C07F9/18 ,  C07F9/24 ,  C07F9/655 ,  C07F9/6553 ,  A61K

CPC classification number: C07C43/23 ,  A61K31/075 ,  A61K31/66 ,  C07C43/215 ,  C07C45/512 ,  C07C45/64 ,  C07C45/673 ,  C07C49/755 ,  C07C49/84 ,  C07C205/37 ,  C07C205/45 ,  C07C217/84 ,  C07C217/94 ,  C07C223/06 ,  C07C225/22 ,  C07C237/08 ,  C07C2602/08 ,  C07C2602/10 ,  C07D307/80 ,  C07D307/81 ,  C07D333/56 ,  C07D333/64 ,  C07F9/12 ,  C07F9/18 ,  C07F9/247 ,  C07F9/65517 ,  C07F9/655354

Abstract: A diverse set of tubulin binding agents have been discovered which are structurally characterized, in a general sense, by a semi-rigid molecular framework capable of maintaining aryl-aryl, pseudo pi stacking distances appropriate for molecular recognition of tubulin. In phenolic or amino form, these ligands may be further functionalized to prepare phosphate esters, phosphate salts, phosphoramidates, and other prodrugs capable of demonstrating selective targeting and destruction of tumor cell vasculature.

Abstract translation: 已经发现了一组不同的微管蛋白结合剂，其在结构上通常通过能够维持适于分子识别微管蛋白的芳基 - 芳基，伪pi堆叠距离的半刚性分子框架来表征。 在酚类或氨基形式中，这些配体可进一步官能化以制备能够显示肿瘤细胞脉管系统的选择性靶向和破坏的磷酸酯，磷酸盐，氨基磷酸酯和其它前体药物。

公开(公告)号：WO2005113532A1

公开(公告)日：2005-12-01

申请号：PCT/US2005/015276

申请日：2005-05-03

Applicant: OXIGENE, INC. ,  BAYLOR UNIVERSITY ,  PINNEY, Kevin, G. ,  ARTHASARY, Phyllis ,  SHIRALI, Anupama ,  EDVARDSEN, Klaus ,  CHAPLIN, David, J.

Inventor： PINNEY, Kevin, G. ,  ARTHASARY, Phyllis ,  SHIRALI, Anupama ,  EDVARDSEN, Klaus ,  CHAPLIN, David, J.

IPC: C07D311/58

CPC classification number: C07D311/58

Abstract: Trimethoxyphenyl substituted chromene derivatives of formula (I) have been discovered which demostrate impressive cytotoxicity as well as a remarkable ability to inhibit tubulin polymerization. Such compounds as well as related derivatives are excellent clinical candidates for the treatment of cancer in humans. In addition, certain of these ligands, as pro-drugs, may well prove to be tumor selective vascular targeting chemotherapeutic agents or to have vascular targeting activity resulting in the selective prevention and/or destruction of nonmalignant proliferating vasculature.

Abstract translation: 已经发现了式（I）的三甲氧基苯基取代的色烯衍生物，其表现出令人印象深刻的细胞毒性以及抑制微管蛋白聚合的显着能力。 这些化合物以及相关衍生物是用于治疗人类癌症的优异临床候选物。 此外，作为前药的这些配体中的某些可以很好地证明是肿瘤选择性血管靶向化学治疗剂或具有导致选择性预防和/或破坏非恶性增殖血管的血管靶向活性。