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1. 发明申请

US20050203071A1 Use of carbon-2-modified-19-nor-vitamin d analogs to induce the formation of new bone 审中-公开
标题翻译：使用碳-2修饰的19-维生素d类似物诱导新骨的形成
公开(公告)号：US20050203071A1
公开(公告)日：2005-09-15
申请号：US10509065
申请日：2003-03-12
申请人： Hector Deluca , J. Pike , Nirupama Shevde
发明人： Hector Deluca , J. Pike , Nirupama Shevde
IPC分类号： A61C8/00 , A61F2/28 , A61K31/59 , A61K31/593 , A61P1/02 , A61P3/02 , A61P3/14 , A61P19/08
CPC分类号： A61K31/59 , A61K31/593
摘要： It has been discovered that the 2-carbon-modified derivatives of 1α,25-dihydroxyvitamin D3 specifically stimulate osteoblasts to form new bone. The ability of the 2-carbon-modified vitamin D analogs to stimulate new bone formation suggest that these compounds can be used where synthesis of new bone is required. Thus, these compounds can be used either systemically or locally to stimulate the growth of bone transplants, to increase the rate of fracture healing and thereby reduce the time required for the healing of fractures, the stimulation of bone growth when required for replacement surgery, and also for the growth of bone to implants or other devices required to maintain the skeleton or teeth in the proper positions.
摘要翻译：已经发现，1α，25-二羟基维生素D 3的2-碳改性衍生物特异地刺激成骨细胞形成新骨。 2碳改性维生素D类似物刺激新骨形成的能力表明，这些化合物可用于需要新骨合成的地方。因此，这些化合物可以全身或局部用于刺激骨移植物的生长，增加骨折愈合速率，从而减少骨折愈合所需的时间，替代手术时刺激骨骼生长，以及也用于将骨骼生长到将骨骼或牙齿保持在适当位置所需的植入物或其它装置中。

2. 发明申请

US20060008902A1 Method of forming mesenchymal stem cells from embryonic stem cells 有权
公开(公告)号：US20060008902A1
公开(公告)日：2006-01-12
申请号：US11123794
申请日：2005-05-06
申请人： J. Pike , Nirupama Shevde
发明人： J. Pike , Nirupama Shevde
IPC分类号： C12N5/08
CPC分类号： C12N5/0662 , C12N2500/38 , C12N2500/42 , C12N2501/30 , C12N2501/385 , C12N2501/39 , C12N2506/02
摘要： This invention relates to methods of producing a substantially homogenous population of mesenchymal stem cells derived from embryonic stem cells. Also, disclosed is a homogenous population of mesenchymal stem cells capable of further differentiating into a variety of specific cell types, characterized by various morphological factors and cell-specific markers. The compositions and methods described in this disclosure are useful for a variety of commercially important diagnostic, drug screening, and therapeutic applications.

3. 发明授权

US07259143B2 Method of extending the dose range of vitamin D compounds 有权
标题翻译：延长维生素D化合物剂量范围的方法
公开(公告)号：US07259143B2
公开(公告)日：2007-08-21
申请号：US10235244
申请日：2002-09-05
申请人： Hector F. DeLuca , John W. Pike , Nirupama Shevde , Lori A. Plum , Margaret Clagette-Dame
发明人： Hector F. DeLuca , John W. Pike , Nirupama Shevde , Lori A. Plum , Margaret Clagette-Dame
IPC分类号： A61K38/00 , A61K31/59
CPC分类号： A61K31/565 , A61K31/593 , A61K45/06 , A61K2300/00
摘要： Inhibitors of bone calcium resorption are administered to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating non-calcium related diseases such as cancer, psoriasis, and autoimmune disease without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-κB ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-κB gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene -19-nor-(20S)-1α,25-dihydroxyvitamin D3.
摘要翻译：施用骨钙吸收抑制剂以允许给予高剂量的维生素D化合物或模拟物，其目的是治疗非钙相关疾病如癌症，牛皮癣和自身免疫性疾病，而不会引起肾，心脏和主动脉。骨钙吸收抑制剂包括称为sRANK（可溶性RANK，由NF-κB基因表达的蛋白质）的双膦酸盐，OPG（骨保护素）或可溶性RANKL（NF-κB配体的受体活化剂）受体）和功能以阻止骨骼中钙的供应，从而防止高钙血症和软组织的钙化。因此，高剂量的1α，25-二羟基维生素D 3 N（1,25-（OH）2 N 3），其类似物，前药，或者模拟物可以以最小的风险使用于患者。具体地说，阿仑膦酸被显示阻断1,25-（OH）2 N 3 N 3及其非常有效的类似物2-亚甲基-19-二酮的骨钙动员活性，（20S）-1α，25-二羟基维生素D 3。

4. 发明申请

US20080249068A1 Method of Extending the Dose Range of Vitamin D Compounds 审中-公开
标题翻译：延长维生素D剂量范围的方法
公开(公告)号：US20080249068A1
公开(公告)日：2008-10-09
申请号：US11842752
申请日：2007-08-21
申请人： Hector F. DeLuca , John W. Pike , Nirupama Shevde , Lori A. Plum , Margaret Clagett-Dame
发明人： Hector F. DeLuca , John W. Pike , Nirupama Shevde , Lori A. Plum , Margaret Clagett-Dame
IPC分类号： A61K31/66 , A61K31/59 , A61P19/08
CPC分类号： A61K45/06 , A61K31/565 , A61K31/593 , A61K2300/00
摘要： Inhibitors of bone calcium resorption are administered, and calcium intake in the subject's diet is restricted, to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating diseases such as metabolic bone diseases, hyperparathyroidism, cancer, psoriasis, and autoimmune diseases without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-κB ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-κB gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized to treat the target disease with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3, as long as the subject being treated is on a low calcium diet.
摘要翻译：施用骨钙吸收的抑制剂，受限饮食中的钙摄入受到限制，以允许给予高剂量的维生素D化合物或模拟物，其目的是治疗诸如代谢性骨疾病，甲状旁腺功能亢进，癌症，牛皮癣和自身免疫性疾病，无肾脏，心脏和主动脉钙化的危险。骨钙吸收抑制剂包括称为sRANK（可溶性RANK，由NF-κB基因表达的蛋白质）的双膦酸盐，OPG（骨保护素）或可溶性RANKL（NF-κB配体的受体活化剂）受体）和功能以阻止骨骼中钙的供应，从而防止高钙血症和软组织的钙化。因此，高剂量的1α，25-二羟基维生素D 3 N（1,25-（OH）2 N 3），其类似物，前药，或模拟物可用于以最小的患者风险来治疗目标疾病。具体地说，阿仑膦酸被显示阻断1,25-（OH）2 N 3 N 3和其非常有效的类似物2-亚甲基-19- （20S）-1α，25-二羟基维生素D 3 N，只要被治疗的受试者处于低钙饮食即可。

5. 发明申请

US20070117182A1 Nucleic acids conferring transcriptional responsiveness on the RANKL gene promoter and uses thereof 审中-公开
标题翻译：赋予RANKL基因启动子转录反应性的核酸及其用途
公开(公告)号：US20070117182A1
公开(公告)日：2007-05-24
申请号：US11283599
申请日：2005-11-18
申请人： John Pike , Nirupama Shevde
发明人： John Pike , Nirupama Shevde
IPC分类号： C12P21/06 , C07K14/705 , C12N9/64 , C07H21/04 , C12N5/06
CPC分类号： C07K14/4703 , C07K14/705
摘要： The present invention provides isolated nucleic acids containing functional polynucleotide sequences from the upstream region of the RANKL gene useful in conferring transcriptional responsiveness (e.g., vitamin D3 receptor complex responsiveness) on associated promoters and methods of using same to identify chemical entities capable of affecting transcriptional activity of the RANKL gene.
摘要翻译：本发明提供了分离的核酸，其含有来自RANKL基因的上游区域的功能性多核苷酸序列，其可用于赋予相关启动子的转录反应性（例如维生素D 3受体复合物应答性）及其使用方法鉴定能够影响RANKL基因转录活性的化学实体。

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