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1. 发明授权

US09127088B2 Glucagon superfamily peptides exhibiting nuclear hormone receptor activity 有权
标题翻译：显示核激素受体活性的胰高血糖素超家族肽
公开(公告)号：US09127088B2
公开(公告)日：2015-09-08
申请号：US13697018
申请日：2011-05-10
申请人： Richard D. DiMarchi , Bin Yang , Brian Finan
发明人： Richard D. DiMarchi , Bin Yang , Brian Finan
IPC分类号： A61K38/26 , C07K14/62 , C07K14/72 , A61K47/48 , C07K14/605
CPC分类号： C07K14/721 , A61K38/26 , A61K47/55 , A61K47/554 , A61K47/64 , C07K14/605 , C07K14/72
摘要： Provided herein are glucagon superfamily peptides conjugated with NHR ligands that are capable of acting at a nuclear hormone receptor. Also provided herein are pharmaceutical compositions and kits of the conjugates of the invention. Further provided herein are methods of treating a disease, e.g., a metabolic disorder, such as diabetes and obesity, comprising administering the conjugates of the invention.
摘要翻译：本文提供了与能够作用于核激素受体的NHR配体缀合的胰高血糖素超家族肽。本文还提供了本发明的缀合物的药物组合物和试剂盒。本文还提供了治疗疾病，例如代谢紊乱（例如糖尿病和肥胖症）的方法，其包括施用本发明的缀合物。

2. 发明申请

US20130123178A1 GLUCAGON SUPERFAMILY PEPTIDES EXHIBITING NUCLEAR HORMONE RECEPTOR ACTIVITY 有权
标题翻译： GLUCAGON SUPERFAMILY PEPTIDES展示核激素受体活性
公开(公告)号：US20130123178A1
公开(公告)日：2013-05-16
申请号：US13697018
申请日：2011-05-10
申请人： Richard D. DiMarchi , Bin Yang , Brian Finan
发明人： Richard D. DiMarchi , Bin Yang , Brian Finan
IPC分类号： C07K14/72 , C07K14/605
CPC分类号： C07K14/721 , A61K38/26 , A61K47/55 , A61K47/554 , A61K47/64 , C07K14/605 , C07K14/72
摘要： Provided herein are glucagon superfamily peptides conjugated with NHR ligands that are capable of acting at a nuclear hormone receptor. Also provided herein are pharmaceutical compositions and kits of the conjugates of the invention. Further provided herein are methods of treating a disease, e.g., a metabolic disorder, such as diabetes and obesity, comprising administering the conjugates of the invention.
摘要翻译：本文提供了与能够作用于核激素受体的NHR配体缀合的胰高血糖素超家族肽。本文还提供了本发明的缀合物的药物组合物和试剂盒。本文还提供了治疗疾病，例如代谢紊乱（例如糖尿病和肥胖症）的方法，其包括施用本发明的缀合物。

3. 发明授权

US08729017B2 Glucagon/GLP-1 receptor co-agonists 有权
标题翻译：胰高血糖素/ GLP-1受体共激动剂
公开(公告)号：US08729017B2
公开(公告)日：2014-05-20
申请号：US13494480
申请日：2012-06-12
申请人： Richard D. DiMarchi , David L. Smiley , Bin Yang
发明人： Richard D. DiMarchi , David L. Smiley , Bin Yang
IPC分类号： A61K38/26 , A61P3/10 , C07K14/605
CPC分类号： C07K14/605 , A61K38/00 , A61K47/60 , C07K2319/00 , G01N33/74 , G01N2333/605 , G01N2800/042 , G01N2800/085 , G01N2800/2821 , G01N2800/2835
摘要： Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.
摘要翻译：本文提供了与天然胰高血糖素相比显示增强的GLP-1受体活性的肽和变体肽。

4. 发明授权

US08975223B2 Methods for treating metabolic disorders and obesity with a peptide comprising the amino acid sequence of SEQ ID No. 146 有权
标题翻译：用包含SEQ ID No.146的氨基酸序列的肽治疗代谢紊乱和肥胖症的方法
公开(公告)号：US08975223B2
公开(公告)日：2015-03-10
申请号：US13996937
申请日：2011-12-22
申请人： Louis Vignati , Richard D. DiMarchi
发明人： Louis Vignati , Richard D. DiMarchi
IPC分类号： A61K38/26 , A61P3/10 , A61K31/195 , A61K31/198 , A61K45/06
CPC分类号： A61K38/26 , A61K9/0019 , A61K31/195 , A61K31/198 , A61K38/17 , A61K45/06 , A61K47/60 , A61K2300/00
摘要： Methods are provided for administering an extended half-life GLP-1/GIP coagonist peptide to a patient in need thereof for reducing weight gain, inducing weight loss, treating hyperglycemia, reducing blood glucose levels, or normalizing blood glucose levels in said patient.
摘要翻译：提供了向有需要的患者施用延长的半衰期GLP-1 / GIP拮抗肽的方法，用于减轻体重增加，引起体重减轻，治疗高血糖，降低血糖水平或使所述患者的血糖水平正常化。

5. 发明授权

US08703701B2 Glucagon/GLP-1 receptor co-agonists 有权
标题翻译：胰高血糖素/ GLP-1受体共激动剂
公开(公告)号：US08703701B2
公开(公告)日：2014-04-22
申请号：US13515977
申请日：2010-12-09
申请人： Richard D. DiMarchi
发明人： Richard D. DiMarchi
IPC分类号： A61K38/26 , A61P3/10
CPC分类号： C07K14/605 , A61K38/00
摘要： Provided herein are glucagon analogs comprising a modified amino acid sequence of native human glucagon (SEQ ID NO: 2) that exhibit activity at the glucagon receptor, activity at the GLP-1 receptor, or activity at each of the glucagon receptor and the GLP-1 receptor. In some embodiments, the glucagon analog exhibits at least 100% or more of the activity of native glucagon at the glucagon receptor and/or at least 100% or more of the activity of native GLP-1 at the GLP-1 receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-1 receptor which is within 50-fold or less than the EC50 at the glucagon receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-1 receptor which is two- to ten-fold greater than the EC50 at the glucagon receptor. Related conjugates, dimers and multimers, and pharmaceutical compositions, and uses thereof, are further provided.
摘要翻译：本文提供的是包含显示胰高血糖素受体活性，GLP-1受体活性或每种胰高血糖素受体和GLP-1受体活性的天然人胰高血糖素（SEQ ID NO：2）的修饰氨基酸序列的胰高血糖素类似物， 1受体。在一些实施方案中，胰高血糖素类似物在胰高血糖素受体上表现出至少100％或更多的天然胰高血糖素的活性和/或天然GLP-1在GLP-1受体的至少100％或更多的活性。在一些实施方案中，胰高血糖素类似物在GLP-1受体处具有在胰高血糖素受体的50倍或更小的EC 50内的EC 50。在一些实施方案中，胰高血糖素类似物具有GLP-1受体的EC 50，其比胰高血糖素受体的EC50大2至10倍。还提供了相关的缀合物，二聚体和多聚体，以及药物组合物及其用途。

6. 发明申请

US20110245164A1 YL-BASED INSULIN-LIKE GROWTH FACTORS EXHIBITING HIGH ACTIVITY AT THE INSULIN RECEPTOR 审中-公开
标题翻译：基于YL的胰岛素样生长因子在胰岛素受体中展示高活性
公开(公告)号：US20110245164A1
公开(公告)日：2011-10-06
申请号：US13130960
申请日：2009-12-18
申请人： Richard D. DiMarchi , Shujiang Cheng , Binbin Kou , Jie Han
发明人： Richard D. DiMarchi , Shujiang Cheng , Binbin Kou , Jie Han
IPC分类号： A61K38/28 , C07K14/62 , A61K38/30 , A61P3/10 , C07K14/65
CPC分类号： C07K14/65 , A61K38/00
摘要： Insulin-like growth factor analogs are disclosed wherein substitution of the IGF native amino acids, at positions corresponding to positions B16 and B17 of native insulin, with tyrosine and leucine, respectively, increases potency of the resulting analog at the insulin receptor by tenfold. Also disclosed are prodrug and depot formulations of the IGF analogs, wherein the IGF analog has been modified by the linkage of a dipeptide to the analog through an amide bond linkage. The prodrug and depot formulations disclosed herein have extended half lives of at least 2 hours, 10 hours, and more typically greater than 2 are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.
摘要翻译：公开了胰岛素样生长因子类似物，其中分别用酪氨酸和亮氨酸取代天然胰岛素的位置B16和B17处的IGF天然氨基酸将胰岛素受体上得到的类似物的效力增加十倍。还公开了IGF类似物的前药和贮库制剂，其中IGF类似物已经通过二肽与类似物通过酰胺键连接而被修饰。本文公开的前药和贮库制剂具有至少2小时，10小时，更典型地大于2的半衰期在生理条件下通过由化学不稳定性驱动的非酶反应而转化为活性形式。

7. 发明申请

US20110190200A1 GLUCAGON ANALOGS EXHIBITING ENHANCED SOLUBILITY AND STABILITY IN PHYSIOLOGICAL pH BUFFERS 有权
标题翻译： GLUCAGON ANALOGS展示增强的生理pH缓冲液中的溶解性和稳定性
公开(公告)号：US20110190200A1
公开(公告)日：2011-08-04
申请号：US12999284
申请日：2009-06-16
申请人： Richard D. DiMarchi , David L. Smiley , Maria Dimarchi , Joseph Chabenne , Jonathan Day
发明人： Richard D. DiMarchi , David L. Smiley , Maria Dimarchi , Joseph Chabenne , Jonathan Day
IPC分类号： A61K38/26 , C07K14/605 , A61P3/08
CPC分类号： C07K14/605 , A61K38/00
摘要： Modified glucagon peptides are disclosed having improved solubility and/or half-life while retaining glucagon agonist activity. The glycogen peptides have been modified by substitution of native amino acids with, and/or addition of, charged amino acids to the carboxy terminus of the peptide. The modified glucagon agonists can be further modified by pegylation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, or both to further enhance the solubility of the glucagon agonist analogs.
摘要翻译：公开了具有改善的溶解度和/或半衰期同时保留胰高血糖素激动剂活性的改良的胰高血糖素肽。糖原肽已经通过用带氨基酸的氨基酸取代天然氨基酸和/或添加到肽的羧基末端而被修饰。修饰的胰高血糖素激动剂可以通过聚乙二醇化，或加入选自SEQ ID NO：20，SEQ ID NO：21，SEQ ID NO：23或两者的羧基末端肽进一步修饰，以进一步增强溶解度的胰高血糖素激动剂类似物。

8. 发明授权

US07939496B2 Modified human growth horomone polypeptides and their uses 有权
标题翻译：改良人类生长horomone多肽及其用途
公开(公告)号：US07939496B2
公开(公告)日：2011-05-10
申请号：US11316534
申请日：2005-12-21
申请人： Ho Sung Cho , Thomas O. Daniel , Richard D. DiMarchi , Anna-Maria Hays , Troy E. Wilson , Bee-Cheng Sim , David C. Litzinger
发明人： Ho Sung Cho , Thomas O. Daniel , Richard D. DiMarchi , Anna-Maria Hays , Troy E. Wilson , Bee-Cheng Sim , David C. Litzinger
IPC分类号： A61K38/27 , C07K14/61
CPC分类号： A61K38/27 , A61K9/0019 , A61K9/19 , A61K47/02 , A61K47/183 , A61K47/26 , C07K14/61 , C08G65/33396
摘要： Modified growth hormone polypeptide and uses thereof are provided.
摘要翻译：提供了改良的生长激素多肽及其用途。

9. 发明授权

US5622932A IGF-1 superagonists 失效
标题翻译： IGF-1激素
公开(公告)号：US5622932A
公开(公告)日：1997-04-22
申请号：US435252
申请日：1995-05-05
申请人： Richard D. DiMarchi , Li Fan , Harlan B. Long
发明人： Richard D. DiMarchi , Li Fan , Harlan B. Long
IPC分类号： A61K38/27 , A61K38/00 , A61P43/00 , C07K14/575 , C07K14/65
CPC分类号： C07K14/65 , A61K38/00
摘要： The instant invention provides two-chain IGF-1 superagonists which are derivatives of the naturally occurring single-chain IGF-1 having an abbreviated C domain. The invention also provides synthetic and semi-synthetic DNA sequences, recombinant DNA vectors and transformed host cells useful in the recombinant production of these analogs. The invention also provides pharmaceutical formulations comprising these IGF-1 analogs. The invention also provides methods of using these analogs in a variety of therapeutic applications. The instant invention provides IGF-1 analogs of the formula:BC.sup.n,A (1)wherein:B is the B domain of IGF-1 or a functional analog thereof,C is the C domain of IGF-1 or a functional analog thereof,n is the number of amino acids in the C domain and is from about 6 to about 12, andA is the A domain of IGF-1 or a functional analog thereof.
摘要翻译：本发明提供了作为具有缩写C结构域的天然存在的单链IGF-1的衍生物的双链IGF-1超激动剂。本发明还提供用于重组生产这些类似物的合成和半合成DNA序列，重组DNA载体和转化的宿主细胞。本发明还提供了包含这些IGF-1类似物的药物制剂。本发明还提供了在各种治疗应用中使用这些类似物的方法。本发明提供下式的IGF-1类似物：BCn，A（1）其中：B是IGF-1的B结构域或其功能类似物，C是IGF-1的C结构域或其功能类似物， n是C结构域中氨基酸的数目，为约6至约12，A为IGF-1的A结构域或其功能类似物。

10. 发明授权

US5594104A Anti-obesity proteins 失效
公开(公告)号：US5594104A
公开(公告)日：1997-01-14
申请号：US384492
申请日：1995-02-06
申请人： Margret B. Basinski , Richard D. DiMarchi , David B. Flora , William F. Heath, Jr. , James A. Hoffmann , Brigitte E. Schoner , James E. Shields , David L. Smiley
发明人： Margret B. Basinski , Richard D. DiMarchi , David B. Flora , William F. Heath, Jr. , James A. Hoffmann , Brigitte E. Schoner , James E. Shields , David L. Smiley
IPC分类号： A61K38/00 , C07K14/575 , C07K7/00 , C07K7/10
CPC分类号： C07K14/5759 , A61K38/00
摘要： The present invention provides anti-obesity proteins, which when administered to a patient regulate fat tissue. Accordingly, such agents allow patients to overcome their obesity handicap and live normal lives with much reduced risk for type II diabetes, cardiovascular disease and cancer.

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