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41. 发明授权

US06867197B1 Method of targeting conjugate molecules to mitochondria 失效
标题翻译：将缀合物分子靶向线粒体的方法
公开(公告)号：US06867197B1
公开(公告)日：2005-03-15
申请号：US09448312
申请日：1999-11-23
申请人： Robert E. Davis , Soumitra S. Ghosh , John S. Kiely
发明人： Robert E. Davis , Soumitra S. Ghosh , John S. Kiely
IPC分类号： A61K38/00 , A61K48/00 , C07D219/08 , C07K14/47 , C12N9/02 , C12Q1/68
CPC分类号： C07D219/08 , A61K38/00 , A61K47/541 , A61K47/545 , C07K14/4711 , C07K14/4713 , C12N9/0053 , C12Q1/6806 , C12Q2527/101
摘要： The present invention relates to genetic mutations in mitochondrial cytochrome c oxidase genes that segregate with Alzheimer's disease (AD). The invention provides methods for detecting such mutations, as a diagnostic for Alzheimer's Disease, either before or after the onset of clinical symptoms. The invention further provides treatment of cytochrome c oxidase dysfunction.
摘要翻译：本发明涉及与阿尔茨海默氏病（AD）分离的线粒体细胞色素c氧化酶基因中的遗传突变。本发明提供了在临床症状发作之前或之后检测这种突变作为阿尔茨海默病诊断的方法。本发明进一步提供细胞色素c氧化酶功能障碍的治疗。

42. 发明授权

US06511966B2 Mitochondria protecting agents for treating mitochondria associated diseases 失效
公开(公告)号：US06511966B2
公开(公告)日：2003-01-28
申请号：US09933911
申请日：2001-08-20
申请人： Soumitra S. Ghosh , Scott W. Miller , Robert E. Davis , Walter H. Moos
发明人： Soumitra S. Ghosh , Scott W. Miller , Robert E. Davis , Walter H. Moos
IPC分类号： A01N4304
CPC分类号： A61K31/155 , A61K31/00 , A61K31/05 , A61K31/06 , A61K31/136 , C07C39/08 , C07C39/11 , C07C39/19 , C07C69/017 , C07C215/78 , C07C215/80 , C07C217/84 , C07C279/18 , C07D215/20 , C07D311/72
摘要： The present invention relates generally to mitochondria protecting agents for treating diseases in which mitochondrial dysfunction leads to tissue degeneration and, more specifically, to compounds, compositions and methods related to the same. The methods of this invention involve administration of a pharmaceutically effective amount of a mitochondria protecting agent to a warm-blooded animal in need thereof, and composition of this invention contain a mitochondria protecting agent in combination with a pharmaceutically acceptable carrier or diluent. Mitochondrial associated diseases which may be treated by the present invention include (but are not limited to) Alzheimer's Disease, diabetes mellitus. Parkinson's Disease, neuronal and cardiac ischemia. Huntington's disease and stroke.

43. 发明授权

US06489095B2 Diagnostic method based on quantification of extramitochondrial DNA 失效
公开(公告)号：US06489095B2
公开(公告)日：2002-12-03
申请号：US09098079
申请日：1998-06-15
申请人： Corinna Herrnstadt , Soumitra S. Ghosh , William Clevenger , Eoin D. Fahy , Robert E. Davis
发明人： Corinna Herrnstadt , Soumitra S. Ghosh , William Clevenger , Eoin D. Fahy , Robert E. Davis
IPC分类号： C12Q168
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/156 , C12Q2600/172
摘要： Compositions and methods based on quantification of extramitochondrial DNA (exmtDNA) sequences are provided that are useful for detecting the presence of or risk for having a disease associated with altered mitochondrial function, and for identifying agents suitable for treating such diseases. The exmtDNA sequences have strong homology to authentic mitochondrial DNA (mtDNA) sequences.

44. 发明授权

US06280981B1 Compositions and methods for assaying subcellular conditions and processes using energy transfer 失效
标题翻译：使用能量转移分析亚细胞条件和过程的组合物和方法
公开(公告)号：US06280981B1
公开(公告)日：2001-08-28
申请号：US09514569
申请日：2000-02-23
申请人： James A. Dykens , Gönül Veliçelebi , Soumitra S. Ghosh
发明人： James A. Dykens , Gönül Veliçelebi , Soumitra S. Ghosh
IPC分类号： C12P1314
CPC分类号： G01N33/582 , G01N33/5005 , G01N33/5079 , G01N33/542 , G01N2500/00
摘要： The invention is provides compositions and methods for monitoring subcellular compartments such as organelles by energy transfer techniques that do not require specific intermolecular affinity binding events between energy transfer donor and energy transfer acceptor molecules. Provided are methods for assaying cellular membrane potential, including mitochondrial membrane potential, by energy transfer methodologies including fluorescence resonance energy transfer (FRET). Diagnostic and drug screening assays are also provided.
摘要翻译：本发明提供了通过能量转移技术监测亚细胞隔室例如细胞器的组合物和方法，其不需要能量转移供体和能量转移受体分子之间的特异性分子间亲和力结合事件。提供了通过能量转移方法（包括荧光共振能量转移（FRET））来测定细胞膜电位的方法，包括线粒体膜电位。还提供诊断和药物筛选测定。

45. 发明授权

US09382304B2 Engineered polypeptides having enhanced duration of action with reduced immunogenicity 有权
标题翻译：具有增强的作用持续时间并具有降低的免疫原性的工程化多肽
公开(公告)号：US09382304B2
公开(公告)日：2016-07-05
申请号：US14129815
申请日：2012-07-03
申请人： Mary Erickson , David C. Litzinger , Soumitra S. Ghosh , Zijian Guo , Manoj P. Samant , Abhinandini Sharma , Lala Mamedova , Esther Odile Levy , Caroline Ekblad
发明人： Mary Erickson , David C. Litzinger , Soumitra S. Ghosh , Zijian Guo , Manoj P. Samant , Abhinandini Sharma , Lala Mamedova , Esther Odile Levy , Caroline Ekblad
IPC分类号： C07K14/605 , A61K47/48 , C12N15/62
CPC分类号： C07K14/605 , A61K47/65 , C07K2319/21 , C07K2319/31 , C07K2319/50 , C07K2319/70
摘要： Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration, and reduced immunogenicity. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, Short Bowel Syndrome, Parkinson's disease, and cardiovascular disease.
摘要翻译：提供化合物尤其具有良好的作用持续时间，高效力和/或方便的给药方案，包括口服给药和降低的免疫原性。所述化合物是结合一种或多种生物活性多肽的白蛋白结合结构域的工程多肽。还提供了治疗疾病和病症的药物组合物和方法，包括肥胖和超重，糖尿病，血脂异常，高脂血症，阿尔茨海默病，脂肪肝疾病，短肠综合症，帕金森病和心血管疾病。

46. 发明授权

US09217022B2 GLP-1 receptor agonist compounds having stabilized regions 有权
标题翻译：具有稳定区域的GLP-1受体激动剂化合物
公开(公告)号：US09217022B2
公开(公告)日：2015-12-22
申请号：US13812445
申请日：2011-07-27
申请人： Josue Alfaro-Lopez , Abhinandini Sharma , Christopher J. Soares , Eugene Coats , Soumitra S. Ghosh
发明人： Josue Alfaro-Lopez , Abhinandini Sharma , Christopher J. Soares , Eugene Coats , Soumitra S. Ghosh
IPC分类号： C07K14/605 , A61K38/00
CPC分类号： C07K14/605 , A61K38/00 , Y02E50/343
摘要： The disclosure provides GLP-1 receptor agonist compounds having stabilized regions corresponding to alpha-helical regions of the natural peptide compounds. The disclosure also provides benzamide-containing exendin-4 analogs and alkene-constrained exendin-4 analogs, both of which have stabilized regions corresponding to alpha-helical regions of exendin-4.
摘要翻译：本公开提供了具有对应于天然肽化合物的α-螺旋区域的稳定区域的GLP-1受体激动剂化合物。本公开还提供含有苯甲酰胺的毒蜥外泌肽-4类似物和烯烃受限的毒蜥外泌肽-4类似物，两者都具有对应于毒蜥外泌肽-4的α-螺旋区域的稳定区域。

47. 发明申请

US20140256621A1 ENGINEERED POYPEPTIDES HAVING ENHANCED DURATION OF ACTION AND REDUCED IMMUNOGENICITY 审中-公开
标题翻译：具有增强作用持续时间和降低免疫原性的工程应用
公开(公告)号：US20140256621A1
公开(公告)日：2014-09-11
申请号：US14129793
申请日：2012-07-03
申请人： Mary Erickson , David C. Litzinger , Soumitra S. Ghosh , Zijian Guo , Caroline Ekbland , Jonathan David Roth
发明人： Mary Erickson , David C. Litzinger , Soumitra S. Ghosh , Zijian Guo , Caroline Ekbland , Jonathan David Roth
IPC分类号： C07K14/575 , C07K14/315
CPC分类号： C07K14/5759 , A61K38/00 , A61K38/22 , A61K38/2264 , C07K14/315 , C07K14/575 , C07K2319/31 , C07K2319/70
摘要： Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.
摘要翻译：提供化合物尤其具有良好的作用持续时间，高效力和/或方便的给药方案，包括每周给药一次。所述化合物是结合一种或多种生物活性多肽的白蛋白结合结构域的工程多肽。还提供了包括脂肪营养不良，血脂异常，高脂血症，超重，肥胖，下丘脑闭经，阿尔茨海默病，瘦素缺乏症，脂肪肝疾病或糖尿病（包括I型和II型）的疾病和病症的药物组合物和治疗方法。可以通过本文所述的化合物和方法治疗的其它疾病和病症包括非酒精性脂肪性肝炎（NASH）和非酒精性脂肪性肝病（NAFLD），代谢综合征X和亨廷顿氏病。

48. 发明申请

US20140235535A1 ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION WITH REDUCED IMMUNOGENICITY 有权
标题翻译：具有减少免疫原性的增强作用时间的工程多糖
公开(公告)号：US20140235535A1
公开(公告)日：2014-08-21
申请号：US14129815
申请日：2012-07-03
申请人： Mary Erickson , David C. Litzinger , Soumitra S. Ghosh , Zijian Guo , Manoj P. Samant , Abhinandini Sharma , Lala Mamedova , Esther Odile Levy , Caroline Ekblad
发明人： Mary Erickson , David C. Litzinger , Soumitra S. Ghosh , Zijian Guo , Manoj P. Samant , Abhinandini Sharma , Lala Mamedova , Esther Odile Levy , Caroline Ekblad
IPC分类号： C07K14/605
CPC分类号： C07K14/605 , A61K47/65 , C07K2319/21 , C07K2319/31 , C07K2319/50 , C07K2319/70
摘要： Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration, and reduced immunogenicity. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, Short Bowel Syndrome, Parkinson's disease, and cardiovascular disease.
摘要翻译：提供化合物尤其具有良好的作用持续时间，高效力和/或方便的给药方案，包括口服给药和降低的免疫原性。所述化合物是结合一种或多种生物活性多肽的白蛋白结合结构域的工程多肽。还提供了治疗疾病和病症的药物组合物和方法，包括肥胖和超重，糖尿病，血脂异常，高脂血症，阿尔茨海默病，脂肪肝疾病，短肠综合症，帕金森病和心血管疾病。

49. 发明授权

US08697647B2 Hybrid polypeptides with selectable properties 有权
标题翻译：具有可选性质的杂交多肽
公开(公告)号：US08697647B2
公开(公告)日：2014-04-15
申请号：US13323608
申请日：2011-12-12
申请人： Odile Esther Levy , Michael R. Hanley , Carolyn M. Jodka , Diana Y. Lewis , Christopher J. Soares , Soumitra S. Ghosh , Lawrence J. D'Souza , David G. Parkes , Christine M. Mack
发明人： Odile Esther Levy , Michael R. Hanley , Carolyn M. Jodka , Diana Y. Lewis , Christopher J. Soares , Soumitra S. Ghosh , Lawrence J. D'Souza , David G. Parkes , Christine M. Mack
IPC分类号： A61K38/00 , A61K38/26
CPC分类号： C07K14/605 , A61K9/0019 , A61K9/19 , A61K38/00 , C07K5/1013 , C07K5/1024 , C07K14/575 , C07K14/58
摘要： The present invention relates generally to novel, selectable hybrid polypeptides useful as agents for the treatment and prevention of metabolic diseases and disorders which can be alleviated by control plasma glucose levels, insulin levels, and/or insulin secretion, such as diabetes and diabetes-related conditions. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.
摘要翻译：本发明一般涉及可用作治疗和预防代谢性疾病和病症的新颖的可选择的杂交多肽，其可通过控制血浆葡萄糖水平，胰岛素水平和/或胰岛素分泌而减轻，所述胰岛素分泌如糖尿病和糖尿病相关条件。这些病症和障碍包括但不限于高血压，血脂异常，心血管疾病，进食障碍，胰岛素抵抗，肥胖症和任何类型的糖尿病，包括1型，2型和妊娠糖尿病。

50. 发明申请

US20120046222A1 N-TERMINUS CONFORMATIONALLY CONSTRAINED GLP-1 RECEPTOR AGONIST COMPOUNDS 有权
标题翻译： N-TERMINUS一致约束GLP-1受体激动剂化合物
公开(公告)号：US20120046222A1
公开(公告)日：2012-02-23
申请号：US13260702
申请日：2010-03-26
申请人： Josue Alfaro-Lopez , Abhinandini Sharma , Soumitra S. Ghosh
发明人： Josue Alfaro-Lopez , Abhinandini Sharma , Soumitra S. Ghosh
IPC分类号： A61K38/17 , A61P3/10 , A61K38/26 , A61P3/04 , C07K14/605 , C07K14/435
CPC分类号： C07K14/605 , A61K38/00 , C07K14/46
摘要： The disclosure provides N-terminus conformationally constrained compounds, which may comprise peptide mimetics and/or amino acid substitutions, which may be used in peptides, such as GLP-1 receptor agonist compounds, to induce a β-turn secondary structure at the N-terminus. The N-terminus conformationally constrained compounds may be used for research purposes; to produce GLP-1 receptor agonist compounds having improved GLP-1 receptor binding activity, enzymatic stability, or in vivo glucose lowering activity; and to develop GLP-1 receptor agonist compounds which have fewer amino acid residues. The disclosure also provides GLP-1 receptor agonist compounds, such as exendins, exendin analogs, GLP-1 (7-37), GLP-1 (7-37) analogs, comprising the N-terminus conformationally constrained compounds. The compounds are useful for treating various diseases, such as diabetes and obesity. The disclosure also provides methods for chemically synthesizing the N-terminus conformationally constrained compounds.
摘要翻译：本公开提供了N末端构象约束的化合物，其可以包含肽模拟物和/或氨基酸取代，其可以用于肽，例如GLP-1受体激动剂化合物，以诱导N末端的二级结构 -terminus。 N末端构象约束化合物可用于研究目的; 以产生具有改善的GLP-1受体结合活性，酶稳定性或体内葡萄糖降低活性的GLP-1受体激动剂化合物; 并开发具有较少氨基酸残基的GLP-1受体激动剂化合物。本公开还提供了GLP-1受体激动剂化合物，例如包含N末端构象约束的化合物的毒蜥外泌肽，毒蜥外泌肽类似物，GLP-1（7-37），GLP-1（7-37）类似物。该化合物可用于治疗各种疾病，如糖尿病和肥胖症。本公开还提供了化学合成N末端构象约束化合物的方法。

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