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1. 发明授权

US06943189B2 Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG CO-A reductase inhibitors 失效
标题翻译：使用回肠胆汁酸转运抑制苯并噻二嗪和HMG CO-A还原酶抑制剂的联合治疗
公开(公告)号：US06943189B2
公开(公告)日：2005-09-13
申请号：US10620460
申请日：2003-07-17
申请人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
发明人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
IPC分类号： A61K31/22 , A61K31/366 , A61K31/38 , A61K31/405 , A61K45/06 , C07D337/06 , C07D337/08 , C07D409/10 , C07D495/04 , C07D495/10 , C08G65/329 , A01N43/02 , C07D337/00
CPC分类号： C08G65/329 , A61K31/22 , A61K31/366 , A61K31/38 , A61K31/405 , A61K45/06 , C07D337/06 , C07D337/08 , C07D409/10 , C07D495/04 , C07D495/10 , A61K2300/00
摘要： Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals. Also provided are compositions and methods for combination therapy employing ileal bile acid transport inhibitors and HMG Co-A reductase inhibitors for the treatment of hyperlipidemic conditions.
摘要翻译：提供了新的苯并噻庚因，衍生物和类似物; 含有它们的药物组合物; 以及在医学中使用这些化合物和组合物的方法，特别是用于预防和治疗哺乳动物中高脂血症的疾病，例如与动脉粥样硬化或高胆固醇血症有关的那些。还提供了使用回肠胆汁酸转运抑制剂和HMG Co-A还原酶抑制剂联合治疗高脂血症的组合物和方法。

2. 发明授权

US06268392B1 Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors 失效
标题翻译：使用回肠胆汁酸转运抑制苯并噻二嗪和HMG Co-A还原酶抑制剂的联合治疗
公开(公告)号：US06268392B1
公开(公告)日：2001-07-31
申请号：US09037308
申请日：1998-03-09
申请人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
发明人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
IPC分类号： A61K3138
CPC分类号： C07D495/04 , A61K31/22 , A61K31/366 , A61K31/38 , A61K31/405 , A61K45/06 , C07D337/06 , C07D337/08 , C07D409/10 , C07D495/10 , C08G65/329 , A61K2300/00
摘要： Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals. Also provided are compositions and methods for combination therapy employing ileal bile acid transport inhibitors and EG Co-A reductase inhibitors for the treatment of hyperlipidemic conditions.
摘要翻译：提供了新的苯并噻庚因，衍生物和类似物; 含有它们的药物组合物; 以及在医学中使用这些化合物和组合物的方法，特别是用于预防和治疗哺乳动物中高脂血症的疾病，例如与动脉粥样硬化或高胆固醇血症有关的那些。还提供了使用回肠胆汁酸转运抑制剂和EG Co-A还原酶抑制剂联合治疗高脂血症的组合物和方法。

3. 发明授权

US06642268B2 Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors 失效
公开(公告)号：US06642268B2
公开(公告)日：2003-11-04
申请号：US10076091
申请日：2002-02-15
申请人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
发明人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
IPC分类号： A61K3138
CPC分类号： C08G65/329 , A61K31/22 , A61K31/366 , A61K31/38 , A61K31/405 , A61K45/06 , C07D337/06 , C07D337/08 , C07D409/10 , C07D495/04 , C07D495/10 , A61K2300/00
摘要： Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals. Also provided are compositions and methods for combination therapy employing ileal bile acid transport inhibitors and HMG Co—A reductase inhibitors for the treatment of hyperlipidemic conditions.

4. 发明授权

US06420417B1 Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors 失效
标题翻译：使用回肠胆汁酸转运抑制苯并噻二嗪和HMG Co-A还原酶抑制剂的联合治疗
公开(公告)号：US06420417B1
公开(公告)日：2002-07-16
申请号：US09676466
申请日：2000-09-29
申请人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
发明人： Bradley T. Keller , Kevin C. Glenn , Robert E. Manning
IPC分类号： A61K3138
CPC分类号： C07D495/04 , A61K31/22 , A61K31/366 , A61K31/38 , A61K31/405 , A61K45/06 , C07D337/06 , C07D337/08 , C07D409/10 , C07D495/10 , C08G65/329 , A61K2300/00
摘要： Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals. Also provided are compositions and methods for combination therapy employing ileal bile acid transport inhibitors and HMG Co-A reductase inhibitors for the treatment of hyperlipidemic conditions.
摘要翻译：提供了新的苯并噻庚因，衍生物和类似物; 含有它们的药物组合物; 以及在医学中使用这些化合物和组合物的方法，特别是用于预防和治疗哺乳动物中高脂血症的疾病，例如与动脉粥样硬化或高胆固醇血症有关的那些。还提供了使用回肠胆汁酸转运抑制剂和HMG Co-A还原酶抑制剂联合治疗高脂血症的组合物和方法。

5. 发明授权

US06562860B1 Combinations of ileal bile acid transport inhibitors and bile acid sequestering agents for cardiovascular indications 失效
标题翻译：回肠胆汁酸运输抑制剂和心血管适应症胆汁酸螯合剂的组合
公开(公告)号：US06562860B1
公开(公告)日：2003-05-13
申请号：US09466592
申请日：1999-12-17
申请人： Bradley T. Keller , Kevin C. Glenn , Joseph R. Schuh
发明人： Bradley T. Keller , Kevin C. Glenn , Joseph R. Schuh
IPC分类号： A61K3138
CPC分类号： A61K31/585 , A61K31/55 , A61K31/575 , A61K31/785 , A61K45/06 , Y10S514/824 , A61K2300/00
摘要： The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an ileal bile acid transport inhibitor combined with a bile acid sequestrant.
摘要翻译：本发明提供用于预防或治疗包括高胆固醇血症，动脉粥样硬化或高脂血症的心血管疾病的心血管治疗化合物的组合。公开的组合包括与胆汁酸螯合剂组合的回肠胆汁酸转运抑制剂。

6. 发明授权

US06458851B1 Combinations of ileal bile acid transport inhibitors and cholesteryl ester transfer protein inhibitors for cardiovascular indications 失效
标题翻译：回肠胆汁酸转运抑制剂与心血管适应症胆固醇酯转运蛋白抑制剂的组合
公开(公告)号：US06458851B1
公开(公告)日：2002-10-01
申请号：US09466415
申请日：1999-12-17
申请人： Bradley T. Keller , James A. Sikorski , Kevin C. Glenn , Daniel T. Connolly , Mark E. Smith , Joseph R. Schuh
发明人： Bradley T. Keller , James A. Sikorski , Kevin C. Glenn , Daniel T. Connolly , Mark E. Smith , Joseph R. Schuh
IPC分类号： A61K314995
CPC分类号： A61K31/585 , A61K31/55 , A61K31/575 , A61K31/785 , A61K45/06 , Y10S514/824 , A61K2300/00
摘要： The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an ileal bile acid transport inhibitor combined with a cholesteryl ester transfer protein (CETP) inhibitor.
摘要翻译：本发明提供用于预防或治疗包括高胆固醇血症，动脉粥样硬化或高脂血症的心血管疾病的心血管治疗化合物的组合。公开的组合包括与胆固醇酯转移蛋白（CETP）抑制剂组合的回肠胆汁酸转运抑制剂。

7. 发明授权

US06638969B1 Combinations of ileal bile acid transport inhibitors and fibric acid derivatives for cardiovascular indications 失效
标题翻译：回肠胆汁酸转运抑制剂和纤维酸衍生物用于心血管适应症的组合
公开(公告)号：US06638969B1
公开(公告)日：2003-10-28
申请号：US09465642
申请日：1999-12-17
申请人： Bradley T. Keller , Kevin C. Glenn , Joseph R. Schuh
发明人： Bradley T. Keller , Kevin C. Glenn , Joseph R. Schuh
IPC分类号： A61K3138
CPC分类号： A61K45/06 , A61K31/192 , A61K31/216 , A61K31/554 , Y10S514/824 , A61K2300/00
摘要： The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an ileal bile acid transport inhibitor combined with a fibric acid derivative.
摘要翻译：本发明提供用于预防或治疗包括高胆固醇血症，动脉粥样硬化或高脂血症的心血管疾病的心血管治疗化合物的组合。公开的组合包括与纤维酸衍生物组合的回肠胆汁酸转运抑制剂。

8. 发明授权

US06462091B1 Combinations of cholesteryl ester transfer protein inhibitors and HMG coA reductase inhibitors for cardiovascular indications 失效
标题翻译：胆固醇酯转运蛋白抑制剂和HMG coA还原酶抑制剂用于心血管适应症的组合
公开(公告)号：US06462091B1
公开(公告)日：2002-10-08
申请号：US09466414
申请日：1999-12-17
申请人： Bradley T. Keller , James A. Sikorski , Kevin C. Glenn , Daniel T. Connolly , Mark E. Smith
发明人： Bradley T. Keller , James A. Sikorski , Kevin C. Glenn , Daniel T. Connolly , Mark E. Smith
IPC分类号： A61K31136
CPC分类号： A61K31/585 , A61K31/135 , A61K31/22 , A61K31/36 , A61K31/405 , A61K31/55 , A61K31/575 , A61K31/785 , A61K45/06 , Y10S514/824 , A61K2300/00
摘要： The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an HMG CoA reductase inhibitor combined with a cholesteryl ester transfer protein (CETP) inhibitor.
摘要翻译：本发明提供用于预防或治疗包括高胆固醇血症，动脉粥样硬化或高脂血症的心血管疾病的心血管治疗化合物的组合。所公开的组合包括与胆固醇酯转移蛋白（CETP）抑制剂组合的HMG CoA还原酶抑制剂。

9. 发明授权

US06630572B1 Thrombin derived polypeptides: compositions and methods for use 失效
标题翻译：凝血酶衍生多肽：组合物和使用方法
公开(公告)号：US06630572B1
公开(公告)日：2003-10-07
申请号：US09631137
申请日：2000-08-02
申请人： Darrell H. Carney , Kevin C. Glenn
发明人： Darrell H. Carney , Kevin C. Glenn
IPC分类号： C07K400
CPC分类号： C12N9/6429 , A61K38/00 , C12Y304/21005
摘要： Thrombin is now known to mediate a number of potent biological effects on cells bearing high-affinity thrombin receptors. These effects depend, at least in part, upon receptor occupancy signals generated by thrombin's interaction with the high affinity thrombin receptor. The present inventors have formulated synthetic thrombin derivatives capable of selectively stimulating or inhibiting thrombin receptor occupancy signals. The stimulatory thrombin derivatives to bind to cell surface thrombin receptors and stimulate DNA synthesis in cells treated with non-mitogenic concentrations of alpha-thrombin or phorbol myristate acetate. Thus, these peptides, which have both a thrombin receptor binding domain and a segment of amino acids with a sequence common to a number of serine proteases, appear to generate receptor-occupancy dependent mitogenic signals. The inhibitory derivatives, which have no serine esterase conserved amino acid sequences bind to thrombin receptors without generating receptor-occupancy dependent mitogenic signals. This invention describes the peptides and methods for using them to promote cell growth and wound healing or to inhibit scar formation, tissue adhesions, and tumor metastasis and angiogenesis.
摘要翻译：凝血酶现在已知可以介导一些对高亲和力凝血酶受体的细胞的有力的生物学作用。这些作用至少部分取决于凝血酶与高亲和力凝血酶受体相互作用产生的受体占有率信号。本发明人已经制备了能够选择性地刺激或抑制凝血酶受体占据信号的合成凝血酶衍生物。刺激性凝血酶衍生物结合细胞表面凝血酶受体并刺激用非丝分裂浓度的α-凝血酶或佛波酮肉豆蔻酸乙酸酯处理的细胞中的DNA合成。因此，这些具有凝血酶受体结合结构域和具有多个丝氨酸蛋白酶共有序列的氨基酸片段的这些肽似乎产生受体占据依赖的促有丝分裂信号。没有丝氨酸酯酶保守氨基酸序列的抑制性衍生物结合凝血酶受体而不产生受体占有依赖的有丝分裂信号。本发明描述了使用它们促进细胞生长和伤口愈合或抑制瘢痕形成，组织粘连和肿瘤转移和血管生成的肽和方法。

10. 发明授权

US06627731B1 Thrombin derived polypeptides; compositions and methods for use 失效
标题翻译：凝血酶衍生多肽; 组合物和使用方法
公开(公告)号：US06627731B1
公开(公告)日：2003-09-30
申请号：US08538504
申请日：1995-09-29
申请人： Darrell H. Carney , Kevin C. Glenn
发明人： Darrell H. Carney , Kevin C. Glenn
IPC分类号： C07K510
CPC分类号： C12N9/6429 , A61K38/00 , C12Y304/21005
摘要： Thrombin is now known to mediate a number of potent biological effects on cells bearing high-affinity thrombin receptors. These effects depend, at least in part, upon receptor occupancy signals generated by thrombin's interaction with the high affinity thrombin receptor. The present inventors have formulated synthetic thrombin derivatives capable of selectively stimulating or inhibiting thrombin receptor occupancy signals. The stimulatory thrombin derivatives to bind to cell surface thrombin receptors and stimulate DNA synthesis in cells treated with non-mitogenic concentrations of alpha-thrombin or phorbol myristate acetate. Thus, these peptides, which have both a thrombin receptor binding domain and a segment of amino acids with a sequence common to a number of serine proteases, appear to generate receptor-occupancy dependent mitogenic signals. The inhibitory derivatives, which have no serine esterase conserved amino acid sequences bind to thrombin receptors without generating receptor-occupancy dependent mitogenic signals. This invention describes the peptides and methods for using them to promote cell growth and wound healing or to inhibit scar formation, tissue adhesions, and tumor metastasis and angiogenesis.
摘要翻译：凝血酶现在已知可以介导一些对高亲和力凝血酶受体的细胞的有力的生物学作用。这些作用至少部分取决于凝血酶与高亲和力凝血酶受体相互作用产生的受体占有率信号。本发明人已经制备了能够选择性地刺激或抑制凝血酶受体占据信号的合成凝血酶衍生物。刺激性凝血酶衍生物结合细胞表面凝血酶受体并刺激用非丝分裂浓度的α-凝血酶或佛波酮肉豆蔻酸乙酸酯处理的细胞中的DNA合成。因此，这些具有凝血酶受体结合结构域和具有多个丝氨酸蛋白酶共有序列的氨基酸片段的这些肽似乎产生受体占据依赖的促有丝分裂信号。没有丝氨酸酯酶保守氨基酸序列的抑制性衍生物结合凝血酶受体而不产生受体占有依赖的有丝分裂信号。本发明描述了使用它们促进细胞生长和伤口愈合或抑制瘢痕形成，组织粘连和肿瘤转移和血管生成的肽和方法。

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