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21. 发明授权

US06642216B2 Isoprenoid pathway inhibitors for stimulating bone growth 有权
标题翻译：用于刺激骨生长的异戊二醛途径抑制剂
公开(公告)号：US06642216B2
公开(公告)日：2003-11-04
申请号：US09848839
申请日：2001-05-03
申请人： Shirley R. Gasper , Robert R. West , Theresa Martinez , Kirk G. Robbins , Patricia A. McKernan , Nand Baindur , Virender M. Labroo , Gregory R. Mundy
发明人： Shirley R. Gasper , Robert R. West , Theresa Martinez , Kirk G. Robbins , Patricia A. McKernan , Nand Baindur , Virender M. Labroo , Gregory R. Mundy
IPC分类号： A61K31665
CPC分类号： C07D215/14 , A23L33/10 , A61K31/00 , A61K31/192 , A61K31/22 , A61K31/225 , A61K31/366 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/505 , A61K45/06 , A61K2300/00
摘要： Compounds of the formula wherein X in each of formulas (1) and (2) represents a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2-6C; Y is of the formula or a stereoisomer thereof, wherein R1 is substituted or unsubstituted alkyl; each R2 is independently H, hydroxy, alkoxy (1-6C) or lower alkyl (1-4C); R3 is H, hydroxy, or alkoxy (1-6C); or Y is of the formula wherein each n is 1, Z is N, K comprises a substituted or unsubstituted aromatic carbocyclic or heterocyclic ring system which may optionally be spaced from the linkage position shown in formula (7) by a linker of 1-2C, or in formula (7), Z may be spaced from the carbon bonded to X by ═CR6— wherein R6 is H or linear, branded or cyclic alkyl (1-6C), R5 is H or linear, branched or cyclic alkyl, and R′ represents a cation, H or a substituted or unsubstituted alkyl group of 1-6C, promote bone formation and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation. Also disclosed is a method to identify additional compounds which are inhibitors of enzymes in the isoprenoid scheme especially of HMG-CoA reductase which results in prenylation of proteins and in the synthesis of steroids or of inhibitors of their production which are useful in treating bone disorders.
摘要翻译：式（1）和（2）中的式（Ⅳ）化合物表示取代或未取代的2-6C的亚烷基，亚烯基或亚炔基接头; Y为其立体异构体，其中R 1为取代或每个R 2独立地是H，羟基，烷氧基（1-6C）或低级烷基（1-4C）; R 3是H，羟基或烷氧基（1-6C）; 或Y是每个n是1的烷基，其中Z是N，K包括取代或未取代的芳族碳环或杂环系统，其可以任选地与式（7）所示的连接位置与1-2C的连接体间隔开，或在式（7）中，Z可以与通过= CR 6键合到X的碳隔开，其中R 6是H或直链的，有品牌的或环状的烷基（1-6C），R 5是H或直链，支链或环状的烷基，R'表示1-6个C的阳离子H或取代或未取代的烷基，促进骨形成，因此可用于治疗骨质疏松症，骨折或缺陷，原发性或继发性甲状旁腺功能亢进，牙周病或缺损，转移性骨病，溶骨性骨病，整形后手术，假体后关节手术和牙后植入术。还公开了一种鉴定作为特异性HMG-CoA的异戊二烯方案中的酶抑制剂的其它化合物的方法导致蛋白质异戊烯化的还原酶在合成类固醇或其制备的抑制剂中可用于治疗骨骼疾病。

22. 发明授权

US06492333B1 Treatment of myeloma bone disease with proteasomal and NF-&kgr;B activity inhibitors 失效
标题翻译：用蛋白酶体和NF-κB活性抑制剂治疗骨髓瘤骨病
公开(公告)号：US06492333B1
公开(公告)日：2002-12-10
申请号：US09289229
申请日：1999-04-09
申请人： Gregory R. Mundy
发明人： Gregory R. Mundy
IPC分类号： A61K3800
CPC分类号： A61K38/06 , A61K31/165 , A61K31/166 , A61K31/40 , A61K31/435 , A61K31/66 , A61K38/05
摘要： The present invention involves the identification and use of compositions for treating myeloma bone disease. The compositions inhibit proteasomal activity and decrease the activity of the transcription factor NF-&kgr;B. Assessment of a candidate compound for its ability to inhibit production or activity of proteasomal enzymes or NF-&kgr;B provides a useful means to identify agents to treat myeloma bone disease.
摘要翻译：本发明涉及用于治疗骨髓瘤骨病的组合物的鉴定和使用。该组合物抑制蛋白酶体活性并降低转录因子NF-κB的活性。评估候选化合物抑制蛋白酶体酶或NF-κB生产或活性的能力为鉴定骨髓瘤骨病的药物提供了有用的手段。

23. 发明授权

US6083690A Methods and compositions for identifying osteogenic agents 失效
标题翻译：用于鉴定成骨剂的方法和组合物
公开(公告)号：US6083690A
公开(公告)日：2000-07-04
申请号：US458434
申请日：1995-06-02
申请人： Stephen E. Harris , Gregory R. Mundy , Nandini Ghosh-Choudhury , Jian Q. Feng
发明人： Stephen E. Harris , Gregory R. Mundy , Nandini Ghosh-Choudhury , Jian Q. Feng
IPC分类号： C12N15/09 , C07K14/51 , C12Q1/68 , C07H21/04 , C12N15/85 , C12Q1/02
CPC分类号： C12Q1/6897 , C07K14/51
摘要： Methods and compositions for identifying osteogenic agents are disclosed, wherein a bone morphogenetic protein promoter is utilized in an assay system to modulate the production of an assayable product of a reporter gene.
摘要翻译：公开了用于鉴定成骨剂的方法和组合物，其中在测定系统中使用骨形态发生蛋白启动子来调节报告基因的可测定产物的产生。

24. 发明授权

US5939444A Compositions and methods for treating bone deficit conditions 失效
公开(公告)号：US5939444A
公开(公告)日：1999-08-17
申请号：US808740
申请日：1997-02-28
申请人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Gregory R. Mundy
发明人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Gregory R. Mundy
IPC分类号： A61K31/428 , A61K31/549 , A61K31/655 , A61K31/421
CPC分类号： A61K31/428 , A61K31/549 , A61K31/655
摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

25. 发明授权

US5922753A Methods for treating bone deficit conditions with benzothiazole 失效
标题翻译：用苯并噻唑治疗骨缺损病症的方法
公开(公告)号：US5922753A
公开(公告)日：1999-07-13
申请号：US808742
申请日：1997-02-28
申请人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Laurence H. Hurley , Sean M. Kerwin , Gregory R. Mundy
发明人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Laurence H. Hurley , Sean M. Kerwin , Gregory R. Mundy
IPC分类号： A61K31/4184 , A61K31/428 , A61K31/38 , A61K31/385
CPC分类号： A61K31/428 , A61K31/4184
摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.
摘要翻译：包含通过含有一个或多个原子的接头共价连接的两个芳族体系的化合物或定义为包含共价键本身的“连接体”，以使芳族体系在距离为1.5-15安培的范围内空间有效地处理与骨缺损。化合物可以单独施用于脊椎动物，或者与促进骨生长或抑制骨吸收的其它试剂组合施用。可以通过评估其在影响与骨形态发生蛋白相关的启动子相关的报告基因的转录和/或刺激模型动物系统中颅骨生长的能力的能力来筛选其给药前的活性。

26. 发明授权

US5919808A Compositions and methods for treating bone deficit conditions 失效
公开(公告)号：US5919808A
公开(公告)日：1999-07-06
申请号：US808743
申请日：1997-02-28
申请人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Maria Kontoyianni , Gregory R. Mundy
发明人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Maria Kontoyianni , Gregory R. Mundy
IPC分类号： A61K31/196 , A61K31/4184 , A61K31/428 , A61K31/444 , A61K31/47 , A61K31/4709 , A61K31/498 , A61K31/517 , A61K31/53 , A61K31/655 , A61K31/425 , A61K31/415 , A61K31/42
CPC分类号： A61K31/655 , A61K31/196 , A61K31/4184 , A61K31/428 , A61K31/444 , A61K31/47 , A61K31/4709 , A61K31/498 , A61K31/517 , A61K31/53
摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15.ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

27. 发明授权

US5626845A Method to ameliorate osteolysis and metastasis 失效
标题翻译：改善骨质溶解和转移的方法
公开(公告)号：US5626845A
公开(公告)日：1997-05-06
申请号：US376359
申请日：1995-01-23
申请人： Toshiyuki Yoneda , Gregory R. Mundy
发明人： Toshiyuki Yoneda , Gregory R. Mundy
IPC分类号： A61K38/00 , A61K45/06 , A61P19/08 , A61P35/00 , C07K16/22 , C07K16/24 , C07K16/26 , A61K39/395
CPC分类号： A61K45/06 , C07K16/22 , C07K16/241 , C07K16/244 , C07K16/26 , A61K38/00 , Y10S514/885
摘要： Materials immunoreactive with parathyroid hormone-related protein (PTH-rp) are used in the invention method to prevent and treat metastasis and cancer cell growth in bone as well as osteolysis and symptomatic sequelae thereof. Humanized antibodies are included in the invention for application of the invention method to human subjects.
摘要翻译：在本发明方法中使用与甲状旁腺激素相关蛋白（PTH-rp）免疫反应的材料以预防和治疗骨中的转移和癌细胞生长以及骨质溶解和其症状后遗症。人源化抗体包括在本发明中，用于将本发明方法应用于人类受试者。

28. 发明申请

US20100183599A1 Methods of treating multiple myeloma and myeloma-induced bone resorption using integrin antagonists 审中-公开
标题翻译：使用整联蛋白拮抗剂治疗多发性骨髓瘤和骨髓瘤诱导的骨吸收的方法
公开(公告)号：US20100183599A1
公开(公告)日：2010-07-22
申请号：US12620050
申请日：2009-11-17
申请人： Gregory R. Mundy , Toshiyuki Yoneda
发明人： Gregory R. Mundy , Toshiyuki Yoneda
IPC分类号： A61K39/395 , A61P35/00
CPC分类号： C07K14/70542 , A61K38/00 , C07K16/2836 , C07K16/2839 , C07K16/2842
摘要： Antagonists of α4 integrin/α4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are useful in suppressing bone destruction associated with multiple myeloma. The homing of multiple myeloma cells to bone marrow and their α4 integrin-dependent release of bone-resorbing factors, resulting in bone destruction in patients with multiple myeloma, is inhibited.
摘要翻译：描述了抑制这种粘附的生物学作用的α4整联蛋白/α4整联蛋白配体粘附的拮抗剂，并详细说明了其使用方法。这样的拮抗剂可用于抑制与多发性骨髓瘤相关的骨破坏。多发性骨髓瘤细胞归巢到骨髓及其骨吸收因子的α4整联蛋白依赖性释放，导致多发性骨髓瘤患者的骨破坏被抑制。

29. 发明授权

US07101907B2 Topical administration of statins for treatment of bone disorders 有权
标题翻译：用于治疗骨骼疾病的他汀类药物的局部给药
公开(公告)号：US07101907B2
公开(公告)日：2006-09-05
申请号：US10652159
申请日：2003-08-29
申请人： Shirley R. Gasper , Robert R. West , Theresa Martinez , Kirk G. Robbins , Patricia A. McKernan , Nand Baindur , Virender M. Labroo , Gregory R. Mundy
发明人： Shirley R. Gasper , Robert R. West , Theresa Martinez , Kirk G. Robbins , Patricia A. McKernan , Nand Baindur , Virender M. Labroo , Gregory R. Mundy
IPC分类号： A61K31/335
CPC分类号： C07D215/14 , A23L33/10 , A61K31/00 , A61K31/192 , A61K31/22 , A61K31/225 , A61K31/366 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/505 , A61K45/06 , A61K2300/00
摘要： The topical administration of statins for the treatment of bone disorders is disclosed.
摘要翻译：公开了用于治疗骨骼疾病的他汀类药物的局部给药。

30. 发明授权

US6008208A Compositions and methods for treating bone deficit conditions 失效
公开(公告)号：US6008208A
公开(公告)日：1999-12-28
申请号：US878868
申请日：1997-06-19
申请人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Scott M. Harris , Maria Kontoyianni , Gregory R. Mundy
发明人： Charles Petrie , Mark W. Orme , Nand Baindur , Kirk G. Robbins , Scott M. Harris , Maria Kontoyianni , Gregory R. Mundy
IPC分类号： A61K31/47 , A61K31/549 , A61K31/655 , A61K31/35 , A61K31/495
CPC分类号： A61K31/47 , A61K31/549 , A61K31/655
摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

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