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1. 发明申请

US20050208045A1 Cripto antagonism of activin and TGF-b signaling 有权
标题翻译：激活素和TGF-b信号传导的Cripto拮抗作用
公开(公告)号：US20050208045A1
公开(公告)日：2005-09-22
申请号：US10940431
申请日：2004-09-14
申请人： Wylie Vale , Craig Harrison , Peter Gray
发明人： Wylie Vale , Craig Harrison , Peter Gray
IPC分类号： A61K39/395 , C07D20060101 , C07K14/47 , C07K14/71 , C07K14/82 , C07K16/22
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。该复合物阻止了功能性激活素/ TGF-b.型II型I复合体的形成，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。

2. 发明申请

US20060008846A1 Antagonism of TGF-beta superfamily receptor signaling 有权
标题翻译： TGF-β超家族受体信号传导的拮抗作用
公开(公告)号：US20060008846A1
公开(公告)日：2006-01-12
申请号：US11115877
申请日：2005-04-27
申请人： Wylie Vale , Craig Harrison , Peter Gray , Wolfgang Fischer , Senyon Choe
发明人： Wylie Vale , Craig Harrison , Peter Gray , Wolfgang Fischer , Senyon Choe
IPC分类号： A61K38/18 , G01N33/53
CPC分类号： G01N33/5005 , A61K38/00 , C07K14/495 , G01N33/566 , G01N33/574 , G01N2500/00
摘要： Members of the TGF-β superfamily control many physiologic and pathophysiologic processes in multiple tissues and signal via type II and type I receptor serine kinases. Type II activin receptors are promiscuous and known to bind 12 TGF-β ligands including activins, myostatin, BMPs and nodal. Methods are described for the screening and identification of antagonist for TGF-β superfamily members, in particular activin-A antagonist.
摘要翻译： TGF-β超家族的成员控制多个组织中的许多生理和病理生理过程，并通过II型和I型受体丝氨酸激酶信号。 II型激活素受体是混杂的，已知结合12种TGF-β配体，包括激活素，肌生成抑制素，BMP和结节。描述了筛选和鉴定TGF-β超家族成员，特别是激活素-A拮抗剂的拮抗剂的方法。

3. 发明授权

US07575751B2 Activin-A mutants 有权
标题翻译：活化素-A突变体
公开(公告)号：US07575751B2
公开(公告)日：2009-08-18
申请号：US11115877
申请日：2005-04-27
申请人： Wylie Vale , Craig Harrison , Peter Gray , Wolfgang Fischer , Senyon Choe
发明人： Wylie Vale , Craig Harrison , Peter Gray , Wolfgang Fischer , Senyon Choe
IPC分类号： A61K39/00 , C07K14/00
CPC分类号： G01N33/5005 , A61K38/00 , C07K14/495 , G01N33/566 , G01N33/574 , G01N2500/00
摘要： Members of the TGF-β superfamily control many physiologic and pathophysiologic processes in multiple tissues and signal via type II and type I receptor serine kinases. Type II activin receptors are promiscuous and known to bind 12 TGF-β ligands including activins, myostatin, BMPs and nodal. Methods are described for the screening and identification of antagonist for TGF-β superfamily members, in particular activin-A antagonist.
摘要翻译： TGF-β超家族的成员控制多个组织中的许多生理和病理生理过程，并通过II型和I型受体丝氨酸激酶信号。 II型激活素受体是混杂的，已知结合12种TGF-β配体，包括激活素，肌生成抑制素，BMP和结节。描述了筛选和鉴定TGF-β超家族成员，特别是激活素-A拮抗剂的拮抗剂的方法。

4. 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。

5. 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.

6. 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。

7. 发明授权

US08258279B2 Isolated nucleic acids encoding soluble corticotropin releasing factor receptor type 2 (sCRFR2) polypeptides 有权
标题翻译：编码可溶性促肾上腺皮质激素释放因子受体2型（sCRFR2）多肽的分离核酸
公开(公告)号：US08258279B2
公开(公告)日：2012-09-04
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： C07H21/04 , C12N15/00
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 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

US07820620B2 Cripto antagonism of activin and TGF-b signaling 有权
标题翻译：激活素和TGF-b信号传导的Cripto拮抗作用
公开(公告)号：US07820620B2
公开(公告)日：2010-10-26
申请号：US10940431
申请日：2004-09-14
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
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。

9. 发明授权

US07488865B2 Urocortin-deficient mice and uses thereof 有权
标题翻译：尿细胞坏死小鼠及其用途
公开(公告)号：US07488865B2
公开(公告)日：2009-02-10
申请号：US10440636
申请日：2003-05-19
申请人： Kuo-Fen Lee , Wylie Vale , Chien Li , Lingyun Zhao , Douglas E. Vetter
发明人： Kuo-Fen Lee , Wylie Vale , Chien Li , Lingyun Zhao , Douglas E. Vetter
IPC分类号： A01K67/00 , A01K67/027 , A01K67/033
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0356
摘要： The present invention provides transgenic mice deficient in urocortin. Urocortin null mutant mice are hypersensitive to stress and display heightened anxiety-like behaviors in the elevated plus maze and open field tests. These mice also demonstrate physiological alterations in auditory thresholds and distortion product otoacoustic emissions. These results indicate that urocortin plays a modulatory role in anxiety-related behaviors and in contributing to the establishment of auditory thresholds. Such urocortin deficient mutant mice can provide useful models in the study of anxiety pathology and hearing physiology at the biochemical and molecular levels.
摘要翻译：本发明提供了缺乏尿皮质素的转基因小鼠。 Urocortin null突变小鼠对高压加迷宫和开放野外试验的应激过敏和显示焦虑状态升高。这些小鼠也表现出听觉阈值和失真产物耳声发射的生理改变。这些结果表明，尿皮质素在焦虑相关行为中发挥调节作用，并有助于建立听觉阈值。这种尿皮质素缺陷型突变体小鼠可以在生化和分子水平的焦虑病理学和听觉生理学研究中提供有用的模型。

10. 发明申请

US20050186593A1 Cloning and recombinant production of CRF receptor(s) 审中-公开
标题翻译： CRF受体的克隆和重组产生
公开(公告)号：US20050186593A1
公开(公告)日：2005-08-25
申请号：US11007077
申请日：2004-12-07
申请人： Lawrence Mathews , Wylie Vale , Kunihiro Tsuchida
发明人： Lawrence Mathews , Wylie Vale , Kunihiro Tsuchida
IPC分类号： A61K38/00 , C07K14/71 , C12Q1/68 , C07H21/04 , C07K14/705
CPC分类号： C07K14/71 , A61K38/00 , C07K2319/00
摘要： In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein: an extracellular, ligand-binding domain, a hydrophobic, trans-membrane domain, and an intracellular, receptor domain having serine kinase-like activity. The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-β superfamily of polypeptide growth factors such that concentrations of ≦10 nM of said polypeptide growth factor occupy ≦50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-β, and other non-activin-like proteins. DNA sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed.
摘要翻译：根据本发明，提供了新的受体蛋白，其特征在于具有以下结构域，从所述蛋白质的N-末端读取：细胞外，配体结合结构域，疏水性，跨膜结构域和细胞内，具有丝氨酸激酶样活性的受体结构域。本发明受体任选地还包含在其氨基末端的第二疏水结构域。本发明受体蛋白的进一步特征在于对多肽生长因子的活化素/ TGF-β超家族的至少一个成员具有足够的结合亲和力，使得所述多肽生长因子的<= 10nM的浓度占结合物的<50％所述受体蛋白的位点。本发明目前优选的受体超家族成员特异性结合激活素，优于抑制素，转化生长因子-β和其他非激活素样蛋白。还公开了编码这种受体的DNA序列，使用其的测定法，以及由其衍生的抗体。

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