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1. 发明授权

US07507794B2 Isolated soluble corticotropin releasing factor receptor type 2 (sCRFR2) 有权
标题翻译：分离的可溶性促肾上腺皮质激素释放因子受体2型（sCRFR2）
公开(公告)号：US07507794B2
公开(公告)日：2009-03-24
申请号：US11350411
申请日：2006-02-08
申请人： Alon Chen , Marilyn Perrin , Wylie Vale
发明人： Alon Chen , Marilyn Perrin , Wylie Vale
IPC分类号： C07K1/00 , C07K14/00 , C07K17/00 , A01N37/18 , A61K38/00
CPC分类号： C07K14/47 , A61K38/1796 , C07K14/705
摘要： The present invention is directed to compositions and methods related to soluble G-protein coupled receptors (sGPCR). In ceratin aspects the invention includes compositions and methods related to a soluble corticotropin releasing factor receptor related protein, sCRFR2, as well as its effects on CRFR signaling and interaction between CRF family ligand and CRFR receptors, including but not limited to CRFR2, CRFR1 and functional or signaling capable variants thereof.
摘要翻译：本发明涉及与可溶性G蛋白偶联受体（sGPCR）相关的组合物和方法。在癌症方面，本发明包括与可溶性促肾上腺皮质激素释放因子受体相关蛋白sCRFR2相关的组合物和方法，以及其对CRFR信号传导和CRF家族配体与CRFR受体之间相互作用的影响，包括但不限于CRFR2，CRFR1和功能性或其信令能力变体。

2. 发明授权

US06692744B2 Betaglycan as an inhibin receptor and uses thereof 有权
公开(公告)号：US06692744B2
公开(公告)日：2004-02-17
申请号：US09738171
申请日：2000-12-15
申请人： Wylie Vale , Kathy A. Lewis , Peter C. Gray , Louise M. Bilezikjian , Amy L. Blount
发明人： Wylie Vale , Kathy A. Lewis , Peter C. Gray , Louise M. Bilezikjian , Amy L. Blount
IPC分类号： A61K39395
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/24 , C07K16/26 , G01N33/74 , G01N2500/00
摘要： Inhibins and activins are protein hormones that reciprocally modulate a diversity of regulatory pathways. Competitive binding experiments revealed that betaglycan, the type III TGF-&bgr; receptor, also functions as an inhibin receptor. Betaglycan augments the binding of inhibin to the ActRII activin receptor. By augmenting inhibin binding to ActRII, betaglycan effectively sequesters ActRII away from activin and thereby reduces activin signaling. In addition, the ActRII-betaglycan complex may generate novel signals distinct from those initiated by activin signaling via ActRII and ALK4. Betaglycan is produced in discrete nuclei of the rat brain and by specific cell types within the adult rat pituitary, testis, and ovary. The presence of betaglycan within inhibin-responsive tissues and cell types, together with the ability of this protoglycan to bind inhibin and to confer inhibin sensitivity, is consistent with a role of betaglycan as an inhibin-specific receptor mediating inhibin responses within various tissues.

3. 发明授权

US6147275A Corticotropin releasing factor receptor 1-deficient mice 失效
标题翻译：促肾上腺皮质激素释放因子受体1缺陷小鼠
公开(公告)号：US6147275A
公开(公告)日：2000-11-14
申请号：US281150
申请日：1999-03-30
申请人： Wylie Vale , Kuo-Fen Lee
发明人： Wylie Vale , Kuo-Fen Lee
IPC分类号： A01K67/027 , A61K31/56 , A61K31/573 , A61P11/00 , C07K2/00 , C07K14/72 , C12N15/00 , C12N15/09 , C12N15/85 , G01N33/15 , G01N33/50 , G01N33/53 , A01K62/027
CPC分类号： C12N15/8509 , A01K67/0276 , A61K31/573 , C07K14/723 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0356 , G01N2333/5751 , G01N2333/72
摘要： Signaling pathways dependent on members of the corticotropin releasing factor (CRF) gene family exert pleiotropic effects within both the brain and peripheral tissues. Two biochemically and pharmacologically distinct corticotropin releasing factor receptor subtypes (corticotropin releasing factor receptor-1 and corticotropin releasing factor receptor-2) have been described. To study the developmental and physiological role of the specific receptor subtypes, a strain of mice null for the corticotropin releasing factor receptor-1 gene has been generated. This genetically engineered strain of mice suggest that corticotropin releasing factor receptor-1 is obligatory both in development and function of the hypothalamic-pituitary-adrenal axis and in mediating behavioral changes associated with anxiety and locomotor activity rhythms.
摘要翻译：依赖于促肾上腺皮质激素释放因子（CRF）基因家族成员的信号通路在脑组织和外周组织中发挥多效作用。已经描述了两种生物化学和药理学上不同的促肾上腺皮质激素释放因子受体亚型（促皮质激素释放因子受体-1和促肾上腺皮质激素释放因子受体-2）。为了研究特异性受体亚型的发育和生理作用，已经产生了一种对促肾上腺皮质激素释放因子受体-1基因无效的小鼠。这种基因工程改造的小鼠表明，促肾上腺皮质激素释放因子受体-1在下丘脑 - 垂体 - 肾上腺轴的发育和功能以及介导与焦虑和运动活动节律相关的行为变化中是强制性的。

4. 发明申请

US20120088287A1 CRIPTO ANTAGONISM OF ACTIVIN AND TGF-B SIGNALING 审中-公开
公开(公告)号：US20120088287A1
公开(公告)日：2012-04-12
申请号：US13276918
申请日：2011-10-19
申请人： Wylie Vale , Craig A. Harrison , Peter C. Gray
发明人： Wylie Vale , Craig A. Harrison , Peter C. Gray
IPC分类号： C12N5/09 , C12N5/071 , C12N9/12
CPC分类号： C07K16/22 , C07K14/47 , C07K14/475 , C07K14/71 , C07K14/82
摘要： Cripto, a developmental oncoprotein, antagonizes activin and TGF-b signaling by forming a complex with activin and TGF-b and their type II receptors. This complex precludes the formation of a functional activin/TGF-b•type II•type I complex, thereby blocking the signaling of activin and TGF-b. Cripto may be generally capable of blocking antiproliferative Smad2/3 signals and provides a novel mechanism of oncogenic action with multiple therapeutic implications. Inhibiting the formation of Cripto and activin/TGF-b complex may enhance antiproliferative effects of activin and TGF-b.

5. 发明申请

US20110009319A1 CRIPTO ANTAGONISM OF ACTIVIN AND TGF-B SIGNALING 审中-公开
标题翻译：激活和TGF-B信号的激活拮抗剂
公开(公告)号：US20110009319A1
公开(公告)日：2011-01-13
申请号：US12887272
申请日：2010-09-21
申请人： Wylie Vale , Craig A. Harrison , Peter C. Gray
发明人： Wylie Vale , Craig A. Harrison , Peter C. Gray
IPC分类号： A61K38/18 , A61P15/16
CPC分类号： C07K16/22 , C07K14/47 , C07K14/475 , C07K14/71 , C07K14/82
摘要： Cripto, a developmental oncoprotein, antagonizes activin and TGF-b signaling by forming a complex with activin and TGF-b and their type II receptors. This complex precludes the formation of a functional activin/TGF-b•type II•type I complex, thereby blocking the signaling of activin and TGF-b. Cripto may be generally capable of blocking antiproliferative Smad2/3 signals and provides a novel mechanism of oncogenic action with multiple therapeutic implications. Inhibiting the formation of Cripto and activin/TGF-b complex may enhance antiproliferative effects of activin and TGF-b.
摘要翻译： Cripto是发育中的癌蛋白，通过与激活素和TGF-b及其II型受体形成复合物来拮抗激活素和TGF-b信号传导。该复合物排除功能性激活素/ TGF-b·II型I型复合物的形成，从而阻断激活素和TGF-b的信号传导。 Cripto通常能够阻断抗增殖性Smad2 / 3信号并提供具有多种治疗意义的致癌作用的新机制。抑制Cripto和激活素/ TGF-b复合物的形成可增强激活素和TGF-b的抗增殖作用。

6. 发明申请

US20100135904A1 COMPOSITIONS AND METHODS FOR THE INHIBITION OF CRIPTO / GRP78 COMPLEX FORMATION AND SIGNALING 审中-公开
标题翻译：用于抑制CRIPTO / GRP78复合形成和信号的组合物和方法
公开(公告)号：US20100135904A1
公开(公告)日：2010-06-03
申请号：US12615033
申请日：2009-11-09
申请人： Peter C. Gray , Gidi Shani , Jonathan A. Kelber , Wylie Vale
发明人： Peter C. Gray , Gidi Shani , Jonathan A. Kelber , Wylie Vale
IPC分类号： A61K39/395 , A61K51/10 , A61K33/24 , A61P35/00 , G01N33/53 , A61K31/7088 , C07K16/00 , A61K38/16
CPC分类号： C12N15/113 , A61K2039/505 , C07K16/28 , C07K2317/34 , C07K2317/73 , C07K2317/75 , C07K2317/76 , C12N2310/14 , C12N2310/531
摘要： The present invention provides methods compositions and methods for treating a hyperproliferative disease comprising disrupting Cripto/GRP78 complex formation in a hyperproliferative cell. In certain embodiments, an antibody and/or siRNA may be used to inhibit Cripto/GRP78 binding, optionally coupled with other cancer therapies. Also provided are methods for identifying therapeutic compounds which can selectively inhibit Cripto/GRP78 binding.
摘要翻译：本发明提供了用于治疗过度增殖性疾病的组合物和方法，其包括在过度增殖细胞中破坏Cripto / GRP78复合物形成。在某些实施方案中，可以使用抗体和/或siRNA来抑制Cripto / GRP78结合，任选与其它癌症疗法联合。还提供了用于鉴定可选择性抑制Cripto / GRP78结合的治疗化合物的方法。

7. 发明申请

US20090117649A1 ISOLATED SOLUBLE CORTICOTROPIN RELEASING FACTOR RECEPTOR TYPE 2 (SCRFR2) 有权
标题翻译：分离型可溶性抗真菌素释放因子受体2型（SCRFR2）
公开(公告)号：US20090117649A1
公开(公告)日：2009-05-07
申请号：US12236806
申请日：2008-09-24
申请人： ALON CHEN , MARILYN PERRIN , WYLIE VALE
发明人： ALON CHEN , MARILYN PERRIN , WYLIE VALE
IPC分类号： C12N15/00 , C12N15/11
CPC分类号： C07K14/47 , A61K38/1796 , C07K14/705
摘要： The present invention is directed to compositions and methods related to soluble G-protein coupled receptors (sGPCR). In certain aspects the invention includes compositions and methods related to a soluble corticotropin releasing factor receptor related protein, sCRFR2, as well as its effects on CRFR signaling and interaction between CRF family ligand and CRFR receptors, including but not limited to CRFR2, CRFR1 and functional or signaling capable variants thereof.
摘要翻译：本发明涉及与可溶性G蛋白偶联受体（sGPCR）相关的组合物和方法。在某些方面，本发明包括与可溶性促肾上腺皮质激素释放因子受体相关蛋白sCRFR2相关的组合物和方法，以及其对CRFR信号传导和CRF家族配体与CRFR受体之间相互作用的影响，包括但不限于CRFR2，CRFR1和功能性或其信令能力变体。

8. 发明授权

US07455839B2 Method of inhibiting the formation of inhibin/betaglycan complexes with an anti-betaglycan antibody 失效
标题翻译：抑制与抗β-糖苷聚糖抗体形成抑制素/糖浆蛋白复合物的方法
公开(公告)号：US07455839B2
公开(公告)日：2008-11-25
申请号：US10696717
申请日：2003-10-29
申请人： Wylie Vale , Kathy A. Lewis , Peter C. Gray , Louise M. Bilezikjian , Amy L. Blount
发明人： Wylie Vale , Kathy A. Lewis , Peter C. Gray , Louise M. Bilezikjian , Amy L. Blount
IPC分类号： A61K39/395 , C07K16/00 , C12P21/08
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/24 , C07K16/26 , G01N33/74 , G01N2500/00
摘要： Inhibins and activins are protein hormones that reciprocally modulate a diversity of regulatory pathways. Competitive binding experiments revealed that betaglycan, the type III TGF-β receptor, also functions as an inhibin receptor. Betaglycan augments the binding of inhibin to the ActRII activin receptor. By augmenting inhibin binding to ActRII, betaglycan effectively sequesters ActRII away from activin and thereby reduces activin signaling. In addition, the ActRII-betaglycan complex may generate novel signals distinct from those initiated by activin signaling via ActRII and ALK4. Betaglycan is produced in discrete nuclei of the rat brain and by specific cell types within the adult rat pituitary, testis, and ovary. The presence of betaglycan within inhibin-responsive tissues and cell types, together with the ability of this protoglycan to bind inhibin and to confer inhibin sensitivity, is consistent with a role of betaglycan as an inhibin-specific receptor mediating inhibin responses within various tissues.
摘要翻译：抑制素和激活素是相互调节多种调节途径的蛋白质激素。竞争性结合实验显示，β糖蛋白聚糖，III型TGF-β受体也起抑制素受体的作用。 Betaglycan可增强抑制素与ActRII激活素受体的结合。通过增加与ActRII的抑制素结合，betaglycan可以有效地将ActRII螯合起激活素，从而减少激活素信号。此外，ActRII-betaglycan复合物可以产生与通过ActRII和ALK4的激活素信号发起的新信号不同的新信号。雌激素在大鼠脑的离散细胞核和成年大鼠垂体，睾丸和卵巢中的特定细胞类型产生。抑制素反应性组织和细胞类型中存在的betaglycan，以及该原始糖蛋白结合抑制素并赋予抑制素敏感性的能力与betaglycan作为介导各种组织内的抑制素反应的抑制素特异性受体的作用一致。

9. 发明申请

US20070191592A1 Urocortin proteins and uses thereof 有权
标题翻译：尿皮质蛋白及其用途
公开(公告)号：US20070191592A1
公开(公告)日：2007-08-16
申请号：US11784317
申请日：2007-04-05
申请人： Wylie Vale , Teresa Reyes , Paul Sawchenko , Jean Rivier , Kathy Lewis , John Hogenesch , Joan Vaughan , Marilyn Perrin
发明人： Wylie Vale , Teresa Reyes , Paul Sawchenko , Jean Rivier , Kathy Lewis , John Hogenesch , Joan Vaughan , Marilyn Perrin
IPC分类号： C07K14/705 , A61K38/17 , C07H21/04 , C12P21/06 , C12N1/21 , C12N5/06 , C07K16/28
CPC分类号： C07K14/57509 , A61K38/00 , A61K39/00
摘要： A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse CDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn IL Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.
摘要翻译：鉴定出与CRF神经肽家族具有显着序列同源性的人尿皮质素相关肽。从编码本文称为尿皮质素II的预测的38个氨基酸的肽蛋白质的全脑poly（A +）RNA中分离出小鼠cDNA。人URP和小鼠Ucn II都与其他已知的哺乳动物家族成员CRF和尿皮质素（Ucn）结构相关。这些肽在基底和应激条件下参与下丘脑 - 垂体 - 肾上腺轴的调节，这表明URP和Ucn IL的相似作用合成的Ucn-II和URP肽与CRF-R2的亲和力高于CRF-R1 Ucn II和人类URP似乎参与了体温和食欲的调节，可能在其他压力相关现象中起作用。这些发现将Ucn II和人类URP鉴定为CRF家族的新成员，它们集中表达并结合CRF-R2。

10. 发明申请

US20060069516A1 Structure-based modulators of B1 G-protein coupled receptors 有权
标题翻译： B1 G蛋白偶联受体的基于结构的调节剂
公开(公告)号：US20060069516A1
公开(公告)日：2006-03-30
申请号：US11199821
申请日：2005-08-09
申请人： Grace Royappa , Marilyn Perrin , Jean Rivier , Wylie Vale , Roland Riek
发明人： Grace Royappa , Marilyn Perrin , Jean Rivier , Wylie Vale , Roland Riek
IPC分类号： G06F19/00
CPC分类号： C07K14/723 , C07K2299/00 , G01N2333/726 , G06F19/16 , G06F19/18
摘要： The present invention relates to a method for identifying modulators of B1 G-protein coupled receptors. The present invention also relates to a method for identifying an antagonist or agonist of the corticotropin-releasing factor receptor 2 (CRFR2). The present invention also relates to a method for improving antagonists or agonists of CRFR2. The present invention also relates to the three-dimensional structure of CRFR2 as representative of the B1 GPCR subfamily and its use as a basis for rational drug design of antagonist or agonists of B1 GPCRs.
摘要翻译：本发明涉及用于鉴定B1G-蛋白偶联受体调节剂的方法。本发明还涉及用于鉴定促肾上腺皮质激素释放因子受体2（CRFR2）的拮抗剂或激动剂的方法。本发明还涉及一种改善CRFR2拮抗剂或激动剂的方法。本发明还涉及作为B1GPCR亚族的代表性的CRFR2的三维结构及其作为B1GPCR的拮抗剂或激动剂的合理药物设计的基础的用途。

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