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101. 发明申请

WO2019140021A1 COMBINATION THERAPY 审中-公开
公开(公告)号：WO2019140021A1
公开(公告)日：2019-07-18
申请号：PCT/US2019/012953
申请日：2019-01-10
申请人： ELI LILLY AND COMPANY
发明人： ALSINA-FERNANDEZ, Jorge , BROZINICK, Joseph, Thomas , COSKUN, Tamer
IPC分类号： A61K38/26 , A61K38/22 , A61P3/10
CPC分类号： A61K38/26 , A61K38/2228 , A61P3/10 , A61K2300/00
摘要： The disclosure describes a combination therapy for treating diabetes or chronic kidney disease by administering to an individual in need of such treatment an effective amount of a urocortin-2 compound (or a pharmaceutically acceptable salt thereof) with a glucagon-like peptide analog (or a pharmaceutically acceptable salt thereof), such as dulaglutide, and to methods of using the same to treat diabetes and chronic kidney disease.

102. 发明申请

WO2016061583A1 COMPOSITIONS AND METHODS FOR TREATING PITUITARY TUMORS 审中-公开
标题翻译：用于治疗原发性肿瘤的组合物和方法
公开(公告)号：WO2016061583A1
公开(公告)日：2016-04-21
申请号：PCT/US2015/056250
申请日：2015-10-19
申请人： UNIVERSITY OF VIRGINIA PATENT FOUNDATION
发明人： OLDFIELD, Edward H.
IPC分类号： A61K31/70 , A61K38/22 , A61P5/02 , A61P9/12
CPC分类号： A61K31/7004 , A61K9/0019 , A61K31/12 , A61K31/155 , A61K31/353 , A61K31/357 , A61K38/066 , A61K38/09 , A61K38/2228 , A61K38/25 , A61K38/28 , A61K45/06 , A61K2300/00
摘要： The present application discloses that pituitary tumor cells are sensitive to low concentrations of glucose and that methods of treating such tumors include methods to induce infarction that are designed to inhibit glucose uptake, reduce intracellular glucose levels, inhibit glucose utilization, or to reduce available glucose to the tumor or the tumor cells.
摘要翻译：本申请公开了垂体肿瘤细胞对低浓度葡萄糖敏感，并且治疗这种肿瘤的方法包括诱导梗塞的方法，其旨在抑制葡萄糖摄取，降低细胞内葡萄糖水平，抑制葡萄糖利用或降低可利用的葡萄糖肿瘤或肿瘤细胞。

103. 发明申请

WO2008157302A3 METHODS FOR TREATMENT AND PREVENTION OF TAUOPATHIES AND AMYLOID BETA AMYLOIDOSIS BY MODULATING CRF RECEPTOR SIGNALING 审中-公开
标题翻译：通过调节CRF受体信号治疗和预防TAUOPATHIES和AMYLOID BETA AMYLIDOSIS的方法
公开(公告)号：WO2008157302A3
公开(公告)日：2009-07-30
申请号：PCT/US2008066848
申请日：2008-06-13
申请人： RES DEV FOUNDATION , RISSMAN ROBERT A , LEE KUO-FEN , VALE WYLIE W , SAWCHENKO PAUL E
发明人： RISSMAN ROBERT A , LEE KUO-FEN , VALE WYLIE W , SAWCHENKO PAUL E
IPC分类号： A61K31/519 , A61K38/22 , A61K38/57 , A61K45/06 , A61P25/28 , G01N33/68
CPC分类号： A61K31/519 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0318 , A61K9/0019 , A61K38/2228 , A61K45/06 , G01N33/6896 , G01N2440/14 , G01N2500/00 , G01N2800/2814 , G01N2800/2821 , A61K2300/00
摘要： Methods for treating or preventing tauopathies and/or Aß amyloidosis by modulating CRF receptor signaling. Accumulation of hyperphosphorlyated tau protein in the CNS may be reduced by administration of CRF-Rl selective antagonists and/or CRF-R2 selective agonists. For example, in some aspects, methods for preventing the onset of Alzheimer's disease by administration of CRF-Rl selective antagonist are provided.
摘要翻译：通过调节CRF受体信号传导治疗或预防tau蛋白病和/或Aβ淀粉样变性的方法。通过施用CRF-R1选择性拮抗剂和/或CRF-R2选择性激动剂可以减少CNS中超磷酸化tau蛋白的积累。例如，在一些方面，提供了通过施用CRF-R1选择性拮抗剂来预防阿尔茨海默病发作的方法。

104. 发明申请

WO02074326A2 UROCORTIN-III AND USES THEREOF 审中-公开
标题翻译： UROCORTIN-III及其用途
公开(公告)号：WO02074326A2
公开(公告)日：2002-09-26
申请号：PCT/US0209115
申请日：2002-03-15
申请人： RES DEV FOUNDATION
发明人： VALE WYLIE W JR , RIVIER JEAN E , KUNITAKE KOICHI S , LEWIS KATHY A , PERRIN MARILYN H , GULYAS JOZSEF
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61P1/00 , A61P3/08 , A61P3/10 , A61P9/00 , A61P9/10 , A61P25/06 , A61P25/22 , A61P29/00 , A61P43/00 , C07H21/04 , C07K14/00 , C07K14/47 , C07K14/575 , C07K16/00 , C07K16/18 , C12P21/08 , C12Q1/02 , A61K38/12 , C07D239/02 , C07K2/00 , C07K4/00 , C07K5/00 , C07K7/00 , C07K17/00
CPC分类号： A61K38/2228 , A61K38/00 , C07K14/57509 , C07K14/695
摘要： A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2 alpha or beta . Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.
摘要翻译：对公共人类基因组数据库的搜索鉴定了人EST，GenBank登录号AW293249，其与已知的河豚鱼皮肽序列具有高度同源性。全长序列从人类基因组DNA扩增并测序。新序列与人尿皮蛋白I和尿皮蛋白II的序列同源性比较显示该序列编码新的人尿皮质素，其被命名为尿皮质素III（UcnIII）。尽管urocortin III对CRF-R1或CRF-R2没有高亲和力，但对CRF-R2的亲和力大于对CRF-R1的亲和力。 Urocortin III能够在表达CRF-R2α或β的细胞中刺激环AMP产生。因此，亲和力足够高，使得urocortin III可以充当CRF-R2的天然激动剂。然而，urocortin III也可能是尚未被鉴定的受体的更强的激动剂。

105. 发明申请

WO1991004479A1 EVALUATIVE MEANS FOR DETECTING INFLAMMATORY REACTIVITY AND FOR PREDICTING RESPONSE TO STRESS 审中-公开
标题翻译：用于检测炎症反应性和预测应激反应的评价手段
公开(公告)号：WO1991004479A1
公开(公告)日：1991-04-04
申请号：PCT/US1990005457
申请日：1990-09-25
申请人： THE UNITED STATES OF AMERICA, represented by THE ...
发明人： THE UNITED STATES OF AMERICA, represented by THE ... , STERNBERG, Esther, M. , WILDER, Ronald, L. , CHROUSOS, George, P. , GOLD, Philip, W.
IPC分类号： G01N01/00
CPC分类号： G01N33/5091 , A61K38/11 , A61K38/2006 , A61K38/2228 , A61K38/31 , G01N2800/102
摘要： The present invention relates to a diagnostic test for testing susceptibility of individuals to inflammatory diseases such as rheumatoid arthritis and to means to evaluate potential treatment of arthritis with therapeutic agents directed at the central nervous system (CNS), designed to by-pass the CNS defect. The invention also provides means for evaluating and predicting response to stress in individuals. A counter-regulatory feedback loop exists between the immune and central nervous systems, in which the immune or pro-inflammatory mediators stimulate corticotropin-releasing hormone (CRH) activation of the hypothalamic-pituitary-adrenal (HPA) axis hormonal cascade. The resultant increase in plasma glucocorticoids serves to restrain and limit the intensity of the inflammatory-immune response, through the potent immunosuppressive/anti-inflammatory actions of the glucocorticoids.
摘要翻译：本发明涉及用于测试个体对炎性疾病如类风湿性关节炎的易感性的诊断试验，以及用于评估针对中枢神经系统（CNS）的治疗剂对关节炎的潜在治疗的手段的设计，以设计用于旁路CNS缺陷。本发明还提供了评估和预测个体压力反应的方法。在免疫和中枢神经系统之间存在反调节反馈回路，其中免疫或促炎介质刺激下丘脑 - 垂体 - 肾上腺（HPA）轴激素级联的促肾上腺皮质激素释放激素（CRH）激活。血浆糖皮质激素的产生增加通过糖皮质激素的有效的免疫抑制/抗炎作用来抑制和限制炎症免疫反应的强度。

106. 发明申请

US20190250173A1 METHODS FOR DETERMINING WHETHER A PATIENT IS LIKELY TO BENEFIT FROM TREATMENT WITH A THERAPEUTIC FORMULATION 审中-公开
公开(公告)号：US20190250173A1
公开(公告)日：2019-08-15
申请号：US16340674
申请日：2017-10-10
申请人： Iconic Intellectual Property Limited
发明人： Deirdre Patricia McIntosh , Syed Ebadat Haq
IPC分类号： G01N33/74 , A61K38/22 , G01N33/564 , A61P25/00
CPC分类号： G01N33/74 , A61K38/2228 , A61K38/33 , A61P25/00 , G01N33/564 , G01N33/6893 , G01N33/6896 , G01N2333/5751 , G01N2333/665 , G01N2800/52
摘要： The present invention relates to a method for determining whether a patient is likely to benefit from treatment with a therapeutic formulation, the method comprising the steps of: (a) determining the concentration of corticotropin releasing hormone (CRH) in a sample from a patient prior to administration of the therapeutic formulation; (b) determining the concentration of CRH in a sample from a patient subsequent to administration of the therapeutic formulation; and (c) comparing the concentration of CRH pre-administration with the concentration of CRH subsequent to administration; wherein an increase in patient CRH concentration subsequent to administration indicates that the patient is likely to benefit from treatment with the therapeutic formulation and wherein no increase or a decrease in patient CRH concentration subsequent to administration indicates that the patient is unlikely to benefit from treatment with the therapeutic formulation. The patient may have multiple sclerosis or systemic sclerosis. The therapeutic formulation may be derived from an ungulate such as a goat and may contain CRH, CRH-binding protein, pro-opiomelanocortin (POMC) and alpha-2 macroglobulin. Also provided are methods of treating a patient with a disorder such as multiple sclerosis or systemic sclerosis.

107. 发明申请

US20170105964A1 METHODS AND COMPOSITIONS FOR THE MODULATION OF BETA-ENDORPHIN LEVELS 审中-公开
公开(公告)号：US20170105964A1
公开(公告)日：2017-04-20
申请号：US15318245
申请日：2015-06-18
申请人： The General Hospital Corporation
发明人： David E. Fisher , Kathleen Robinson , Gillian Fell , Rosa Veguilla
IPC分类号： A61K31/352 , A61K9/00 , A61K31/4015
CPC分类号： A61K31/352 , A61K9/0014 , A61K31/137 , A61K31/167 , A61K31/222 , A61K31/4015 , A61K31/444 , A61K31/4709 , A61K31/522 , A61K31/5575 , A61K31/573 , A61K38/043 , A61K38/046 , A61K38/164 , A61K38/2228 , A61K38/2271 , A61K38/29 , A61K38/33 , A61N5/0616 , A61N2005/0661 , Y02A50/471
摘要： Methods and compositions for treatment of pain, mood, or for the treatment of opiate withdrawal symptoms with the modulation of systemic beta-endorphin levels by the topical administration of cAMP elevating agents and/or dermal exposure to ultraviolet (UV) irradiation.

108. 发明授权

US09572866B2 Urocortin 2 analogs and uses thereof 有权
标题翻译：尿皮质素2类似物及其用途
公开(公告)号：US09572866B2
公开(公告)日：2017-02-21
申请号：US14802812
申请日：2015-07-17
申请人： Research Development Foundation , Research Development Foundation
发明人： Wylie W. Vale, Jr. , Joan M. Vaughan , Cindy Donaldson , Wolfgang Fischer , Jean E. F. Rivier
IPC分类号： C07K14/47 , A61K38/22 , C07K14/575
CPC分类号： A61K38/2228 , C07K14/4705 , C07K14/57509 , Y10T428/13
摘要： Disclosed are polypeptides that are analogs of urocortin 2 that have pharmacological activity similar to urocortin 2 but have improved water solubility compared to urocortin 2, and pharmaceutical compositions of the polypeptides of the present invention. Also disclosed are polynucleotides encoding the polypeptides, and methods of treating pathophysiological states employing pharmaceutical compositions of the polypeptides and polynucleotides of the present invention. In addition, disclosed are vectors and host cells that include a nucleic acid encoding a polypeptide of the present invention, and kits that include pharmaceutical compositions of the present invention.
摘要翻译：公开的是具有类似于尿皮质素2但具有与尿皮质素2相比具有改善的水溶性的药理学活性的尿皮质素2的类似物的多肽和本发明的多肽的药物组合物。还公开了编码多肽的多核苷酸，以及使用本发明的多肽和多核苷酸的药物组合物治疗病理生理状态的方法。此外，所公开的是包含编码本发明多肽的核酸的载体和宿主细胞，以及包括本发明的药物组合物的试剂盒。

109. 发明申请

US20160375102A1 UROCORTIN-III AND USES THEREOF 审中-公开
标题翻译：胭脂红III及其用途
公开(公告)号：US20160375102A1
公开(公告)日：2016-12-29
申请号：US15206083
申请日：2016-07-08
申请人： Research Development Foundation
发明人： Wylie W. VALE, JR. , Kathy A. LEWIS , Marilyn H. PERRIN , Koichi KUNITAKE , Jean E. F. RIVIER , Jozsef GULYAS
IPC分类号： A61K38/22
CPC分类号： A61K38/2228 , A61K38/00 , C07K14/57509 , C07K14/695
摘要： A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2α or β. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to b e identified receptor.
摘要翻译：公众人类基因组数据库的搜索确定了人类EST，GenBank登录号AW293249，其与已知的河豚urocortin序列具有高同源性。从人类基因组DNA扩增全长序列并进行测序。新序列与人尿皮质素I和尿皮质素II的序列同源性比较显示，该序列编码了一种新的人类urocortin，其命名为urocortin III（UcnIII）。虽然urocortin III对CRF-R1或CRF-R2没有高亲和力，但CRF-R2的亲和力大于对CRF-R1的亲和力。 Urocortin III能够激活表达CRF-R2α或β的细胞中的环AMP产生。因此，亲和力足够高，使得尿皮质素III可以作为CRF-R2的天然激动剂。然而，尿细胞素III也可能是尚未被鉴定的受体的更强的激动剂。

110. 发明授权

US09388229B2 Urocortin-III and uses thereof 有权
标题翻译： Urocortin-III及其用途
公开(公告)号：US09388229B2
公开(公告)日：2016-07-12
申请号：US14179543
申请日：2014-02-12
申请人： Research Development Foundation
发明人： Wylie W. Vale, Jr. , Kathy A. Lewis , Marilyn H. Perrin , Koichi Kunitake , Jean E. F. Rivier , Jozsef Gulyas
IPC分类号： C07K14/00 , C07K14/695 , C07K14/575 , A61K38/00
CPC分类号： A61K38/2228 , A61K38/00 , C07K14/57509 , C07K14/695
摘要： A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2α or β. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.
摘要翻译：公众人类基因组数据库的搜索确定了人类EST，GenBank登录号AW293249，其与已知的河豚urocortin序列具有高同源性。从人类基因组DNA扩增全长序列并进行测序。新序列与人尿皮质素I和尿皮质素II的序列同源性比较显示，该序列编码了一种新的人类urocortin，其命名为urocortin III（UcnIII）。虽然urocortin III对CRF-R1或CRF-R2没有高亲和力，但CRF-R2的亲和力大于对CRF-R1的亲和力。 Urocortin III能够刺激表达CRF-R2α或bgr的细胞中的环AMP产生。因此，亲和力足够高，使得尿皮质素III可以作为CRF-R2的天然激动剂。然而，urocortin III也可能是未被鉴定的受体的更强的激动剂。

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