公开(公告)号：US5506247A

公开(公告)日：1996-04-09

申请号：US87676

申请日：1994-01-21

申请人： Robert D. Sindelar ,  Barton J. Bradbury ,  Teodoro S. Kaufman ,  Stephen H. Ip ,  Henry C. Marsh, Jr. ,  Chew Lee

发明人： Robert D. Sindelar ,  Barton J. Bradbury ,  Teodoro S. Kaufman ,  Stephen H. Ip ,  Henry C. Marsh, Jr. ,  Chew Lee

IPC分类号： C07D307/94 ,  A61K31/42 ,  A61K31/41

CPC分类号： C07D307/94

摘要： The present invention is directed to compounds which suppress immune responses and/or selectively inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the pharmaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activities, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.

摘要翻译： PCT No.PCT / US91 / 09303 Sec。 371 1991年12月6日第 102（e）日期1991年12月6日PCT 1991年12月6日PCT PCT。 WO92 / 10096 PCT公开号 日期：1992年6月25日。本发明涉及抑制免疫应答和/或选择性抑制补体的化合物。 这些化合物含有芳环，是取代的二氢苯并呋喃，螺苯并呋喃-2（3H） - 环烷及其开链中间体。 本发明的化合物及其药学上可接受的盐中断了C5对生物活性成分的蛋白水解加工，表现出免疫抑制活性，并且具有改善由补体和/或免疫活性介导的疾病和病症的治疗效用。

公开(公告)号：US5981481A

公开(公告)日：1999-11-09

申请号：US470652

申请日：1995-06-06

申请人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

发明人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

IPC分类号： A61K38/00 ,  C07K14/705 ,  A61K38/18 ,  C07K14/46 ,  C12P21/00

CPC分类号： C07K14/70596 ,  A61K38/00

摘要： The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

摘要翻译： 本发明涉及C3b / C4b受体（CR1）基因及其编码蛋白。 本发明进一步提供CR1蛋白及其片段的表达。 本发明的基因和蛋白质在诊断和治疗涉及补体活性的疾病以及各种免疫系统或炎性疾病中具有应用。 在下文实施例部分详述的本发明的具体实施方案中，描述了全长CR1 cDNA及其片段的克隆，核苷酸序列和推导的氨基酸序列。 还描述了CR1蛋白及其片段的表达。 还描述了缺乏跨膜区的分泌型CR1分子的表达。 分泌的CR1分子显示可用于减少由炎症引起的损伤和降低心肌梗死面积并防止再灌注损伤。

公开(公告)号：US5456909A

公开(公告)日：1995-10-10

申请号：US927099

申请日：1992-08-07

申请人： Henry C. Marsh, Jr. ,  Richard A. G. Smith ,  Chang-Jing G. Yeh ,  John Lifter ,  Anne M. Freeman ,  Michael L. Gosselin

发明人： Henry C. Marsh, Jr. ,  Richard A. G. Smith ,  Chang-Jing G. Yeh ,  John Lifter ,  Anne M. Freeman ,  Michael L. Gosselin

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/16 ,  A61K38/46 ,  A61K38/49 ,  A61P7/02 ,  A61P29/00 ,  A61P37/02 ,  A61P37/06 ,  C07K14/705 ,  C12N15/12 ,  C12P21/00 ,  A61K38/36

CPC分类号： C07K14/705 ,  A61K38/166 ,  A61K38/49

摘要： The present invention relates to novel glycoforms and preparations of the soluble complement receptor type 1 (sCR1), and their uses in the therapy of complement mediated diseases and disorders involving inflammation and inappropriate complement activation and in thrombotic or shock state conditions. The invention provides novel glycoforms and methods for producing, detecting, enriching and purifying such glycoforms. The invention further provides methods of specifically producing a glycoform by recombinant or chemical means. Preferred embodiments of the invention include sialylated glycoforms and glycoforms with a pI.ltoreq.5.1 determined by chromatofocusing or with a sialic acid to mannose molar ratio of >0.25. The glycoforms may be formulated alone in therapeutic compositions or in combination with thrombolytic agents.

摘要翻译： 本发明涉及新型糖形式和可溶性补体受体1型（sCR1）的制剂，以及它们在治疗补体介导的涉及炎症和不适当补体活化以及血栓形成或休克状态的疾病和病症中的用途。 本发明提供了用于生产，检测，富集和纯化这些糖型的新型糖型和方法。 本发明还提供了通过重组或化学方法特异性产生糖型的方法。 本发明的优选实施方案包括通过色谱聚焦或唾液酸与甘露糖摩尔比> 0.25测定的唾液酸化糖形式和糖形式，其具有pI = 5.1。 糖形式可以单独配制在治疗组合物中或与溶栓剂组合。

公开(公告)号：US5256642A

公开(公告)日：1993-10-26

申请号：US588128

申请日：1990-09-24

申请人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas; C. Makrides ,  Henry C. Marsh, Jr.

发明人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas; C. Makrides ,  Henry C. Marsh, Jr.

IPC分类号： A61K38/00 ,  A61K38/16 ,  A61K38/36 ,  A61K38/43 ,  A61K38/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  A61P37/06 ,  C07K1/18 ,  C07K14/00 ,  C07K14/315 ,  C07K14/705 ,  C07K14/715 ,  C07K14/745 ,  C07K16/28 ,  C07K19/00 ,  C12N20060101 ,  C12N1/21 ,  C12N5/10 ,  C12N9/70 ,  C12N9/72 ,  C12N15/09 ,  C12N15/12 ,  C12N15/62 ,  C12N15/74 ,  C12P19/34 ,  C12P21/00 ,  C12P21/02 ,  C12R1/19 ,  C12R1/91 ,  A61K37/02 ,  A61K37/547 ,  C07K13/00

CPC分类号： C07K14/3153 ,  C07K14/70596 ,  C07K16/2896 ,  C12N9/6462 ,  C12Y304/21073 ,  A61K38/00 ,  Y10S514/885 ,  Y10S514/886

摘要： The present invention relates to compositions comprising soluble complement receptor 1 (CR1) and a thrombolytic agent. In a specific embodiment, the thrombolytic agent is anisoylated human plasminogen-streptokinase activator complex (ASPAC). The invention further relates to methods for treating thrombotic conditions in humans and animals by administering a composition comprising soluble CR1 and a thrombolytic agent. In particular, the compositions and methods are useful both for reducing reperfusion injury and ameliorating the other effects of myocardial infarction.

摘要翻译： 本发明涉及包含可溶性补体受体1（CR1）和溶栓剂的组合物。 在具体实施方案中，溶栓剂是茴香酰化的人纤溶酶原 - 链激酶复合物（ASPAC）。 本发明还涉及通过施用包含可溶性CR1和溶栓剂的组合物来治疗人和动物血栓形成病症的方法。 特别地，组合物和方法对于减少再灌注损伤和改善心肌梗死的其它作用是有用的。

公开(公告)号：US6057131A

公开(公告)日：2000-05-02

申请号：US186827

申请日：1998-11-05

申请人： Henry C. Marsh, Jr. ,  Richard A. G. Smith ,  Chang-Jing Grace Yeh ,  John Lifter ,  Anne Mary Freeman ,  Michael L. Gosselin

发明人： Henry C. Marsh, Jr. ,  Richard A. G. Smith ,  Chang-Jing Grace Yeh ,  John Lifter ,  Anne Mary Freeman ,  Michael L. Gosselin

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/16 ,  A61K38/46 ,  A61K38/49 ,  A61P7/02 ,  A61P29/00 ,  A61P37/02 ,  A61P37/06 ,  C07K14/705 ,  C12N15/12 ,  C12P21/00 ,  A61K38/17 ,  C07K14/47

CPC分类号： C07K14/705 ,  A61K38/166 ,  A61K38/49

摘要： Provided are methods of making preparations of recombinant soluble Complement Receptor type 1 (sCR1) defined with respect to the distribution of sCR1 glycoforms and therapeutic methods using them. The preparations are suitable for treatment of allograft or xenograft rejection, diseases involving inflammation or inappropriate complement activation, and thrombotic or shock state conditions. Preferred methods employ sCR1 glycoforms that are sialylated, have a pI of .ltoreq.5.1, or have a sialic acid: mannose molar ratio of .gtoreq.0.25.

摘要翻译： 提供了关于sCR1糖型分布和使用它们的治疗方法定义的重组可溶性补体受体1型（sCR1）的制备方法。 该制剂适用于治疗同种异体移植物或异种移植物排斥反应，涉及炎症或不适当补体活化的疾病以及血栓形成或休克状态。 优选的方法使用sial1，其唾液酸化，pI = 5.1，或唾液酸：甘露糖摩尔比≥0.25。

公开(公告)号：US5856297A

公开(公告)日：1999-01-05

申请号：US472038

申请日：1995-06-06

申请人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

发明人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

IPC分类号： A61K38/00 ,  A61K38/16 ,  A61K38/36 ,  A61K38/43 ,  A61K38/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  A61P37/06 ,  C07K1/18 ,  C07K14/00 ,  C07K14/315 ,  C07K14/705 ,  C07K14/715 ,  C07K14/745 ,  C07K16/28 ,  C07K19/00 ,  C12N20060101 ,  C12N1/21 ,  C12N5/10 ,  C12N9/70 ,  C12N9/72 ,  C12N15/09 ,  C12N15/12 ,  C12N15/62 ,  C12N15/74 ,  C12P19/34 ,  C12P21/00 ,  C12P21/02 ,  C12R1/19 ,  C12R1/91 ,  A01N37/18

CPC分类号： C07K14/3153 ,  C07K14/70596 ,  C07K16/2896 ,  C12N9/6462 ,  C12Y304/21073 ,  A61K38/00 ,  Y10S514/885 ,  Y10S514/886

摘要： Human complement receptor type 1 (CR1). Nucleic acid molecules encoding full-length CR1 protein and fragments thereof having complement regulatory activity are described, as well as recombinant CR1 protein and polypeptides, vectors for their expression, and cell lines expressing or bearing DNA molecules encoding such proteins and polypeptides, including a soluble CR1 polypeptide consisting of the extracellular 30 short consensus repeat domains of the mature CR1 protein. The nucleic acids and polypeptides described are useful in diagnosis and treatment of disorders involving complement activity and inflammation. Compositions useful in therapeutic applications are also disclosed.

摘要翻译： 人类补体受体1型（CR1）。 描述了编码具有补体调节活性的全长CR1蛋白及其片段的核酸分子，以及重组CR1蛋白和多肽，用于其表达的载体，以及表达或携带编码此类蛋白质和多肽的DNA分子的细胞系，包括可溶性 CR1多肽由成熟CR1蛋白的细胞外30个短共有重复区组成。 所述的核酸和多肽可用于诊断和治疗涉及补体活性和炎症的疾病。 还公开了可用于治疗应用的组合物。

公开(公告)号：US5472939A

公开(公告)日：1995-12-05

申请号：US138825

申请日：1993-10-19

申请人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

发明人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

IPC分类号： A61K38/00 ,  A61K38/16 ,  A61K38/36 ,  A61K38/43 ,  A61K38/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  A61P37/06 ,  C07K1/18 ,  C07K14/00 ,  C07K14/315 ,  C07K14/705 ,  C07K14/715 ,  C07K14/745 ,  C07K16/28 ,  C07K19/00 ,  C12N20060101 ,  C12N1/21 ,  C12N5/10 ,  C12N9/70 ,  C12N9/72 ,  C12N15/09 ,  C12N15/12 ,  C12N15/62 ,  C12N15/74 ,  C12P19/34 ,  C12P21/00 ,  C12P21/02 ,  C12R1/19 ,  C12R1/91

CPC分类号： C07K14/3153 ,  C07K14/70596 ,  C07K16/2896 ,  C12N9/6462 ,  C12Y304/21073 ,  A61K38/00 ,  Y10S514/885 ,  Y10S514/886

摘要： The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention also relates to CR1 nucleic acid sequences and fragments thereof comprising 70 nucleotides and their encoded peptides or proteins comprising 24 amino acids. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

摘要翻译： 本发明涉及C3b / C4b受体（CR1）基因及其编码蛋白。 本发明还涉及包含70个核苷酸的CR1核酸序列及其片段及其编码的肽或包含24个氨基酸的蛋白质。 本发明进一步提供CR1蛋白及其片段的表达。 本发明的基因和蛋白质在诊断和治疗涉及补体活性的疾病以及各种免疫系统或炎性疾病中具有应用。 在下文实施例部分详述的本发明的具体实施方案中，描述了全长CR1 cDNA及其片段的克隆，核苷酸序列和推导的氨基酸序列。 还描述了CR1蛋白及其片段的表达。 还描述了缺乏跨膜区的分泌型CR1分子的表达。 分泌的CR1分子显示可用于减少由炎症引起的损伤和降低心肌梗死面积并防止再灌注损伤。

公开(公告)号：US5401767A

公开(公告)日：1995-03-28

申请号：US997266

申请日：1992-12-21

申请人： Robert D. Sindelar ,  Barton J. Bradbury ,  Teodoro Kaufman ,  Stephen H. Ip ,  Henry C. Marsh, Jr.

发明人： Robert D. Sindelar ,  Barton J. Bradbury ,  Teodoro Kaufman ,  Stephen H. Ip ,  Henry C. Marsh, Jr.

IPC分类号： C07D307/94 ,  A61K31/335 ,  A61K31/16 ,  A61K31/34

CPC分类号： C07D307/94 ,  Y10S514/825 ,  Y10S514/885

摘要： The present invention is directed to compounds which suppress immune responses and/or selectively inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the pharmaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activities, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.

公开(公告)号：US06316604B1

公开(公告)日：2001-11-13

申请号：US08463959

申请日：1995-06-05

申请人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

发明人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

IPC分类号： C07K14435

CPC分类号： C07K14/70596 ,  A61K38/00 ,  Y02A50/473

摘要： The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention also relates to CR1 nucleic acid sequences and fragments thereof comprising 70 nucleotides and their encoded peptides or proteins comprising 24 amino acids. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

摘要翻译： 本发明涉及C3b / C4b受体（CR1）基因及其编码蛋白。 本发明还涉及包含70个核苷酸的CR1核酸序列及其片段及其编码的肽或包含24个氨基酸的蛋白质。 本发明进一步提供CR1蛋白及其片段的表达。 本发明的基因和蛋白质在诊断和治疗涉及补体活性的疾病以及各种免疫系统或炎性疾病中具有应用。 在下文实施例部分详述的本发明的具体实施方案中，描述了全长CR1 cDNA及其片段的克隆，核苷酸序列和推导的氨基酸序列。 还描述了CR1蛋白及其片段的表达。 还描述了缺乏跨膜区的分泌型CR1分子的表达。 分泌的CR1分子显示可用于减少由炎症引起的损伤和降低心肌梗死面积并防止再灌注损伤。

公开(公告)号：US5858969A

公开(公告)日：1999-01-12

申请号：US470867

申请日：1995-06-06

申请人： Henry C. Marsh, Jr. ,  Richard A.G. Smith ,  Chang-Jing Grace Yeh ,  John Lifter ,  Anne Mary Freeman ,  Michael L. Gosselin

发明人： Henry C. Marsh, Jr. ,  Richard A.G. Smith ,  Chang-Jing Grace Yeh ,  John Lifter ,  Anne Mary Freeman ,  Michael L. Gosselin

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/16 ,  A61K38/46 ,  A61K38/49 ,  A61P7/02 ,  A61P29/00 ,  A61P37/02 ,  A61P37/06 ,  C07K14/705 ,  C12N15/12 ,  C12P21/00 ,  A61K38/17

CPC分类号： C07K14/705 ,  A61K38/166 ,  A61K38/49

摘要： Provided are therapeutic methods employing preparations of recombinant soluble Complement Receptor type 1 (sCR1) defined with respect to the distribution of sCR1 glycoforms. The methods are suitable for treatment of disease involving inflammation, inappropriate complement activation, and in thrombotic or shock state conditions. Preferred methods employ sCR1 glycoforms that are sialylated, have a pI of .ltoreq.5.1, or have a sialic acid:mannose molar ratio of .gtoreq.0.25.

摘要翻译： 提供了使用关于sCR1糖型分布定义的重组可溶性补体受体1型（sCR1）制剂的治疗方法。 该方法适用于治疗涉及炎症，不适当补体活化以及血栓形成或休克状态的疾病。 优选的方法使用sial1，其唾液酸化，pI = 5.1，或唾液酸：甘露糖摩尔比≥0.25。