公开(公告)号：US06521646B1

公开(公告)日：2003-02-18

申请号：US09958812

申请日：2001-10-15

申请人： Wolfgang Stähle ,  Rudolf Gottschlich ,  Simon Goodman

发明人： Wolfgang Stähle ,  Rudolf Gottschlich ,  Simon Goodman

IPC分类号： A61K3144

CPC分类号： C07D213/74 ,  C07C69/757 ,  C07C2603/40

摘要： Compounds of the formula (I) and their physiologically acceptable salts and solvates are useful as integrin-inhibiting substances. They are especially useful in the prophylaxis and treatment of cardiovascular disorders, of thrombosis, cardiac infarction, coronary heart diseases, arteriosclerosis, osteoporosis, in pathological conditions that are caused or propagated by angiogenesis and in tumor therapy.

摘要翻译： 式（I）化合物及其生理学上可接受的盐和溶剂合物可用作整合素抑制物质。 它们在预防和治疗心血管疾病，血栓形成，心肌梗死，冠心病，动脉硬化，骨质疏松症，通过血管发生引起或增殖的病理状况和肿瘤治疗中尤其有用。

公开(公告)号：US06743810B2

公开(公告)日：2004-06-01

申请号：US10203406

申请日：2002-08-09

申请人： Matthias Wiesner ,  Simon Goodman ,  Rudolf Gottschlich

发明人： Matthias Wiesner ,  Simon Goodman ,  Rudolf Gottschlich

IPC分类号： A61K314439

CPC分类号： C07D401/12 ,  C07D209/18 ,  C07D403/12 ,  C07D417/14

摘要： Indol-3-yl derivatives of the general formula I in which A, B, X, R1, R2, R3, R4, R5, n and m are as defined in patent claim 1, and their physiologically acceptable salts or solvates are integrin inhibitors and can be employed for combating thromboses, cardiac infarction, coronary heart diseases, arteriosclerosis, inflammations, tumours, osteoporosis, rheumatic arthritis, macular degenerative disease, diabetic retinopathy, infections and restenosis after angioplasty or in pathological processes maintained or propagated by angiogenesis.

摘要翻译： A，B，X，R 1，R 2，R 3，R 4，R 5，n和m的通式Iin的吲哚-3-基衍生物如 权利要求1，其生理上可接受的盐或溶剂化物是整联蛋白抑制剂，可用于对抗血栓形成，心肌梗死，冠心病，动脉硬化，炎症，肿瘤，骨质疏松症，风湿性关节炎，黄斑变性疾病，糖尿病性视网膜病变，感染和再狭窄 在血管成形术之后或通过血管发生维持或传播的病理过程中。

公开(公告)号：US20120171699A1

公开(公告)日：2012-07-05

申请号：US13390791

申请日：2010-07-15

申请人： Simon Goodman ,  Claudia Wilm

发明人： Simon Goodman ,  Claudia Wilm

IPC分类号： G01N33/567 ,  C12P21/08 ,  C07K14/435 ,  C12N15/12 ,  C07K16/28 ,  C12N15/13

CPC分类号： C07K16/2839 ,  C07K16/00 ,  G01N33/566 ,  G01N2333/70546

摘要： The invention relates to antibodies that are capable to bind the extracellular domain of integrin. Another object of the invention concerns the use of said antibodies for detecting integrins in archival formalin fixed paraffin embedded (FFPE) tissue. The invention also relates to methods for preparing monoclonal rabbit antibodies, wherein the immunogen is an insect expression culture-derived recombinant extracellular integrin domain, and another method for screening anti-integrin antibodies that discriminate between closest integrin homologues and that are especially suited for immunohistochemistry in FFPE material.

摘要翻译： 本发明涉及能够结合整联蛋白的细胞外结构域的抗体。 本发明的另一个目的涉及所述抗体用于检测归档福尔马林固定石蜡包埋（FFPE）组织中的整联蛋白的用途。 本发明还涉及用于制备单克隆兔抗体的方法，其中所述免疫原是来自昆虫表达培养物的重组细胞外整联蛋白结构域，以及用于筛选抗整联蛋白抗体的另一种方法，所述抗整联蛋白抗体区分最接近的整联蛋白同源物并且特别适用于免疫组织化学 FFPE材料。

公开(公告)号：US20060153770A1

公开(公告)日：2006-07-13

申请号：US11378093

申请日：2006-03-17

申请人： Sally DeNardo ,  Patricia Burke ,  Gerald DeNardo ,  Simon Goodman ,  Siegfried Matzku ,  Kerstin Matzku

发明人： Sally DeNardo ,  Patricia Burke ,  Gerald DeNardo ,  Simon Goodman ,  Siegfried Matzku ,  Kerstin Matzku

IPC分类号： A61K51/00 ,  A61K39/395 ,  A61K31/33 ,  A61K38/12

CPC分类号： A61K45/06 ,  A61K31/33 ,  A61K38/12 ,  A61K51/1045 ,  A61K51/1096 ,  A61K2039/505 ,  C07K16/30 ,  C07K16/3092 ,  A61K2300/00

摘要： A method of treating tumors, such as prostate tumors, breast tumors, non-Hodgkin's lymphoma, and the like, includes the sequential steps of administering to the patient at least one dose of an antiangiogenic cyclo-arginine-glycine-aspartic acid-containing pentapeptide (cRGD pentapeptide); administering to the patient an anti-tumor effective amount of a radioimmunotherapeutic agent (RIT); and then administering to the patient at least one additional dose of cRGD pentapeptide. The cRGD pentapeptide is preferably cyclo-(Arg-Gly-Asp-D-Phe-[N-Me]-Val), and the RIT is preferably a radionuclide-labeled chelating agent-ligand complex in which chelating agent is chemically bonded to a tumor-targeting molecule, such as a monoclonal antibody.

公开(公告)号：US20050153902A1

公开(公告)日：2005-07-14

申请号：US10503616

申请日：2003-01-15

申请人： Wolfgang Staehle ,  Oliver Schadt ,  Alfred Jonczyk ,  Simon Goodman

发明人： Wolfgang Staehle ,  Oliver Schadt ,  Alfred Jonczyk ,  Simon Goodman

IPC分类号： A61K31/44 ,  A61K31/4402 ,  A61P1/04 ,  A61P1/18 ,  A61P3/14 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P13/02 ,  A61P13/12 ,  A61P15/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P19/10 ,  A61P25/00 ,  A61P27/02 ,  A61P29/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  C07D213/74 ,  A61K38/04 ,  C07D213/72

CPC分类号： C07D213/74

摘要： Novel biphenyl derivatives of the general formula I in which R1, R1′, R1″, R2, R2′, R3 and n are as defined in Patent claim 1, stereoisomers thereof and physiologically acceptable salts or solvates thereof are novel integrin inhibitors which preferentially inhibit the αvβ6 integrin receptor. The novel compounds can be used, in particular, as medicaments.

摘要翻译： 通式I的新型联苯衍生物，其中R 1，R 1，R 1，R 2，R 2， R 3和R 2如在专利权利要求1中所定义，其立体异构体和其生理学上可接受的盐或溶剂合物是优选抑制α-角蛋白6整联蛋白受体的新型整联蛋白抑制剂。 新化合物特别可用作药物。

公开(公告)号：US06649613B1

公开(公告)日：2003-11-18

申请号：US10030691

申请日：2002-01-14

申请人： Günter Hölzemann ,  Simon Goodman ,  Horst Kessler ,  Christoph Gibson ,  Gabór Sulyok

发明人： Günter Hölzemann ,  Simon Goodman ,  Horst Kessler ,  Christoph Gibson ,  Gabór Sulyok

IPC分类号： C07C24338

CPC分类号： C07D213/74 ,  C07C243/24 ,  C07C279/18 ,  C07C281/02 ,  C07C2603/18

摘要： Diacylhydrazine derivatives of general formula (I) wherein X, Y, Z, R1, 2 and R3 are as defined herein, and their physiologically acceptable salts or solvates thereof, are integrin inhibitors and can be used to combat thromboses, myocardial infarcts, coronary cardiac diseases, arteriosclerosis, inflammations, tumors, osteoporosis, infections, and restenosis following angioplasty or during pathological processes that are maintained or propagated by angiogenesis.

摘要翻译： 其中X，Y，Z，R 1，R 2和R 3如本文所定义的通式（I）的二酰基肼衍生物及其生理上可接受的盐或溶剂合物是整联蛋白抑制剂，可用于 抗血栓形成，心肌梗死，冠心病，动脉硬化，炎症，肿瘤，骨质疏松症，感染和血管成形术后或病理过程中的再狭窄等。

公开(公告)号：US5985278A

公开(公告)日：1999-11-16

申请号：US574699

申请日：1995-12-19

申请人： Francesc Mitjans ,  Jaume Piulats ,  Elisabet Rosell ,  Jaume Adan ,  Simon Goodman ,  Diane Hahn

发明人： Francesc Mitjans ,  Jaume Piulats ,  Elisabet Rosell ,  Jaume Adan ,  Simon Goodman ,  Diane Hahn

IPC分类号： C12N15/02 ,  A61K38/00 ,  A61K39/00 ,  A61K39/395 ,  A61P35/00 ,  C07K16/00 ,  C07K16/18 ,  C07K16/28 ,  C12N5/00 ,  C12N5/10 ,  C12N5/12 ,  C12N5/20 ,  C12N15/06 ,  C12N15/13 ,  C12N15/16 ,  C12P21/08 ,  C12R1/91 ,  G01N33/00 ,  G01N33/574 ,  G01N33/577

CPC分类号： C07K16/2839 ,  A61K38/00

摘要： The invention relates to a novel monoclonal antibody, a hybridoma cell line producing said antibody, DNA sequences coding for said antibody, and amino acid sequences. The monoclonal antibody, a preferred embodiment of which is named 17E6, has the following properties:reacting only with the .alpha.V-chain of human .alpha.V-integrins,blocking the attachment to the integrin substrate of the .alpha.V-integrin bearing cell,triggering reversal of established cell matrix interaction caused by .alpha.V-integrins,blocking tumor development, andshowing no cytotoxic activity.

摘要翻译： 本发明涉及新型单克隆抗体，产生所述抗体的杂交瘤细胞系，编码所述抗体的DNA序列和氨基酸序列。 单克隆抗体，其优选实施方案名为17E6，具有以下性质：仅与人α-V-整联蛋白的αV链反应，阻断与负载αV-整联蛋白的细胞的整合素底物的连接，触发 逆转由α-V整合素引起的建立的细胞基质相互作用，阻断肿瘤发展，并且不显示细胞毒性活性。

公开(公告)号：US20110223167A1

公开(公告)日：2011-09-15

申请号：US12882541

申请日：2010-09-15

申请人： Simon Goodman ,  Hans-Georg Kreysch

发明人： Simon Goodman ,  Hans-Georg Kreysch

IPC分类号： A61K39/395 ,  A61P35/00

CPC分类号： C07K16/30 ,  A61K38/08 ,  A61K39/39558 ,  A61K41/0038 ,  A61K2039/505 ,  A61K2300/00

摘要： The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of receptor tyrosine kinase antagonists/inhibitors, especially ErbB receptor antagonists, more preferably EGF receptor (Her 1) antagonists and anti-angiogenic agents, preferably integrin antagonists, optionally together with agents or therapy forms that have additive or synergistic efficacy when administered together with the combination of antagonists/inhibitors, such as chemotherapeutic agents and or radiation therapy. The therapy can result in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone.

摘要翻译： 本发明涉及用于治疗肿瘤和肿瘤转移的组合疗法，其包括施用受体酪氨酸激酶拮抗剂/抑制剂，特别是ErbB受体拮抗剂，更优选EGF受体（Her1）拮抗剂和抗血管生成剂，优选整联蛋白拮抗剂，任选地 以及当与拮抗剂/抑制剂如化学治疗剂和/或放射治疗的组合一起施用时具有添加或协同效力的药剂或治疗形式。 该治疗可以导致每个单独治疗剂对肿瘤细胞增殖的抑制作用的协同增加，产生比通过单独施用单独组分所发现的更有效的治疗。

公开(公告)号：US20090130098A1

公开(公告)日：2009-05-21

申请号：US12161195

申请日：2007-01-18

申请人： Simon Goodman ,  Martin Andreas Picard ,  Tom Mikkelsen ,  Johannes Nippgen ,  Ulrike Grimm ,  Roger Stupp ,  Michael Weller ,  Andreas Harstrick ,  Matthias Grell

发明人： Simon Goodman ,  Martin Andreas Picard ,  Tom Mikkelsen ,  Johannes Nippgen ,  Ulrike Grimm ,  Roger Stupp ,  Michael Weller ,  Andreas Harstrick ,  Matthias Grell

IPC分类号： A61K39/395 ,  A61K38/12 ,  A61P35/00

CPC分类号： A61K45/06 ,  A61K31/4188 ,  A61K38/08 ,  A61K38/12 ,  A61K41/00 ,  A61K2300/00

摘要： The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.

摘要翻译： 本发明涉及用于治疗肿瘤和肿瘤转移的组合疗法，其包括整联蛋白配体，优选整联蛋白拮抗剂，以及当与所述配体连续施用时具有协同效力的共同治疗剂或治疗形式，例如化学治疗剂和 或放射治疗。 该治疗导致每个单独治疗剂对肿瘤细胞增殖的抑制作用的协同增加，产生比在本发明的剂量方案中同时或不同时单独施用单独组分的治疗更有效的治疗。

公开(公告)号：US20090035270A1

公开(公告)日：2009-02-05

申请号：US11849685

申请日：2007-09-04

申请人： Matthias Grell ,  Simon Goodman ,  Curzio Ruegg

发明人： Matthias Grell ,  Simon Goodman ,  Curzio Ruegg

IPC分类号： A61K38/21 ,  A61K38/12 ,  A61K39/395

CPC分类号： A61K38/08 ,  A61K38/191 ,  A61K38/217 ,  A61K39/39541 ,  A61K2300/00

摘要： The invention relates to a combination therapy for the treatment of tumors metastases comprising administration of anti-angiogenic agents and rumor necrosis factor alpha (TNFa) optionally together with other cytotoxic agents, such as interferon gamma (IFNy) or chemotherapeutic agents such as anti-EGFR antibodies. The method and the pharmaceutical compositions comprising said agents can result in a synergistic potentiation of the tumor cell proliferation inhibition effect of each individual therapeutic agent, yielding more effective treatment than found by administering an individual component alone.

摘要翻译： 本发明涉及用于治疗肿瘤转移的组合疗法，其包括任选地与其它细胞毒剂如干扰素γ（IFNγ）或化学治疗剂如抗EGFR一起施用抗血管生成剂和肿瘤坏死因子α（TNFa） 抗体。 包含所述试剂的方法和药物组合物可以导致每种单独治疗剂的肿瘤细胞增殖抑制作用的协同增强作用，产生比通过单独施用单独组分发现的更有效的治疗。