公开(公告)号：US07358225B2

公开(公告)日：2008-04-15

申请号：US10649193

申请日：2003-08-26

申请人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

发明人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

IPC分类号： C07K14/435 ,  C07K14/72 ,  C07K14/705 ,  A61K38/00 ,  A61K38/17

CPC分类号： C07K14/72 ,  A61K38/00 ,  C07K14/723

摘要： In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of £ 10 nM of CRF occupy 350% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

摘要翻译： 根据本发明，提供了新颖的G蛋白偶联受体蛋白（CRF-R），其特征在于对促肾上腺皮质激素释放因子（CRF）具有足够的结合亲和力，使得CRF 10nM的浓度占据了3 所述受体蛋白的结合位点的50％。 还公开了编码这种受体的核酸序列，使用其的测定法，以及由其衍生的抗体。 本发明CRF-Rs可以以各种方式使用，例如在生物测定中用于生产抗体，在含有这种蛋白质和/或抗体的治疗组合物中。

公开(公告)号：US06482608B1

公开(公告)日：2002-11-19

申请号：US09580734

申请日：2000-05-26

申请人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

发明人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

IPC分类号： C12N510

CPC分类号： C07K14/72 ,  A61K38/00 ,  C07K14/723

摘要： In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of 10 nM of CRF occupy 50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

摘要翻译： 根据本发明，提供了新型G蛋白偶联受体蛋白（CRF-R），其特征在于对促皮质激素释放因子（CRF）具有足够的结合亲和力，使得10nM CRF的浓度占结合物的50％ 所述受体蛋白的位点。 还公开了编码这种受体的核酸序列，使用其的测定法，以及由其衍生的抗体。 本发明CRF-Rs可以以各种方式使用，例如在生物测定中用于生产抗体，在含有这种蛋白质和/或抗体的治疗组合物中。

公开(公告)号：US5728545A

公开(公告)日：1998-03-17

申请号：US110286

申请日：1993-08-23

申请人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson

发明人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson

IPC分类号： G01N33/53 ,  C07K14/72 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/68 ,  C12R1/91 ,  G01N33/566 ,  C07H21/04 ,  C12N15/11

CPC分类号： C07K14/72

摘要： In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of .ltoreq.10 nM of CRF occupy .gtoreq.50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. The invention CRF-R can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

摘要翻译： 根据本发明，提供了新颖的G蛋白偶联受体蛋白（CRF-R），其特征在于对促肾上腺皮质激素释放因子（CRF）具有足够的结合亲和力，使得CRF的<10nM浓度占据> =所述受体蛋白的结合位点的50％。 还公开了编码这种受体的核酸序列，使用其的测定法，以及由其衍生的抗体。 本发明CRF-R可以以各种方式使用，例如在生物测定中用于制备其抗体，在含有这种蛋白质和/或抗体的治疗组合物中。

公开(公告)号：US06638905B2

公开(公告)日：2003-10-28

申请号：US09191724

申请日：1998-11-12

申请人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

发明人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

IPC分类号： A61K3817

CPC分类号： C07K14/72 ,  A61K38/00 ,  C07K14/723

摘要： In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of 10 nM of CRF occupy 50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

摘要翻译： 根据本发明，提供了新型G蛋白偶联受体蛋白（CRF-R），其特征在于对促皮质激素释放因子（CRF）具有足够的结合亲和力，使得10nM CRF的浓度占结合物的50％ 所述受体蛋白的位点。 还公开了编码这种受体的核酸序列，使用其的测定法，以及由其衍生的抗体。 本发明CRF-Rs可以以各种方式使用，例如在生物测定中用于生产抗体，在含有这种蛋白质和/或抗体的治疗组合物中。

公开(公告)号：US06399315B1

公开(公告)日：2002-06-04

申请号：US08482746

申请日：1995-06-07

申请人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

发明人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

IPC分类号： G01N3353

CPC分类号： C07K14/723 ,  A61K38/00 ,  C07K14/72

摘要： In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of ≦10 nM of CRF occupy ≧50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

摘要翻译： 根据本发明，提供了新颖的G蛋白偶联受体蛋白（CRF-R），其特征在于对促皮质激素释放因子（CRF）具有足够的结合亲和力，使得CRF的<= 10nM的浓度占据≥50 所述受体蛋白的结合位点的百分比。 还公开了编码这种受体的核酸序列，使用其的测定法，以及由其衍生的抗体。 本发明CRF-Rs可以以各种方式使用，例如在生物测定中用于生产抗体，在含有这种蛋白质和/或抗体的治疗组合物中。

公开(公告)号：US06495343B1

公开(公告)日：2002-12-17

申请号：US08374009

申请日：1995-01-17

申请人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

发明人： Marilyn H. Perrin ,  Ruoping Chen ,  Kathy A. Lewis ,  Wylie W. Vale, Jr. ,  Cynthia J. Donaldson ,  Paul Sawchenko

IPC分类号： C12P2102

CPC分类号： C07K14/723 ,  A61K38/00 ,  C07K14/72

摘要： In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of ≦10 nM of CRF occupy ≧50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

摘要翻译： 根据本发明，提供了新颖的G蛋白偶联受体蛋白（CRF-R），其特征在于对促皮质激素释放因子（CRF）具有足够的结合亲和力，使得CRF的<= 10nM的浓度占据≥50 所述受体蛋白的结合位点的百分比。 还公开了编码这种受体的核酸序列，使用它们的测定法，以及由其衍生的抗体。 本发明CRF-Rs可以以各种方式使用，例如在生物测定中用于生产抗体，在含有这种蛋白质和/或抗体的治疗组合物中。

公开(公告)号：US06214797B1

公开(公告)日：2001-04-10

申请号：US08981189

申请日：1997-12-10

申请人： Wylie W. Vale, Jr. ,  Joan Vaughan ,  Cynthia J. Donaldson ,  Kathy A. Lewis ,  Paul Sawchenko ,  Jean E. F. Rivier ,  Marilyn H. Perrin

发明人： Wylie W. Vale, Jr. ,  Joan Vaughan ,  Cynthia J. Donaldson ,  Kathy A. Lewis ,  Paul Sawchenko ,  Jean E. F. Rivier ,  Marilyn H. Perrin

IPC分类号： A61K3817

CPC分类号： C07K14/57509 ,  A61K38/00

摘要： Urocortin (Ucn) is a native mammalian peptide generally related to Urotensin I and Corticotropin Releasing Factor (CRF). Human Ucn has the formula: Asp-Asn-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Thr-Leu-Leu-Glu-Leu-Ala-Arg-Thr-Gln-Ser-Gln-Arg-Glu-Arg-Ala-Glu-Gln-Asn-Arg-Ile-Ile-Phe-Asp-Ser-Val-NH2 (SEQ ID NO:15). Rat-derived Ucn is identical but for 2 substitutions, Asp2 for Asn2 and Pro4 for Ser4. Ucn or analogs thereof or pharmaceutically acceptable salts can be administered to humans and other mammals to achieve substantial elevation of ACTH, &bgr;-endorphin, &bgr;-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone. They can also be used to lower blood pressure over an extended period of time, as stimulants to elevate mood and to improve memory and learning performance, as well as diagnostically. Shortened fragments may be administered to release endogenous CRF and/or Ucn in the brain and peripherally. Ucn antagonists can be used to block the action of Ucn and/or CRF, as can antibodies to Ucn. Labelled Ucn agonists and antagonists can be used in drug screening assays along with CRF receptors; they may also be used diagnostically along with Ucn antibodies.

摘要翻译： Urocortin（Ucn）是通常与促进素I和促皮质素释放因子（CRF）相关的天然哺乳动物肽。 人Ucn具有下式：Asp-Asn-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Thr-Leu-Leu-Glu-Leu-Ala-Arg- Thr-Gln-Ser-Gln-Arg-Glu-Arg-Ala-Glu-Gln-Asn-Arg-Ile-Ile-Phe-Asp-Ser-Val-NH2（SEQ ID NO：15）。 大鼠衍生的Ucn是相同的，但是对于2个取代，As 2的Asp 2和Ser 4的Pro 4。 可以将Ucn或其类似物或药学上可接受的盐施用于人和其它哺乳动物，以实现ACTH，β-内啡肽，β-促脂解素，前 - 肌内注射皮质酮基因和皮质酮的其它产物的显着升高。 它们也可用于在较长时间内降低血压，作为兴奋剂提高心情，提高记忆力和学习表现以及诊断。 可以施用缩短的片段以释放脑中和外周的内源性CRF和/或Ucn。 Ucn拮抗剂可用于阻断Ucn和/或CRF的作用，以及Ucn的抗体。 标记的Uc激动剂和拮抗剂可与CRF受体一起用于药物筛选测定; 它们也可以与Ucn抗体一起在诊断上使用。

公开(公告)号：US06838274B2

公开(公告)日：2005-01-04

申请号：US09919473

申请日：2001-07-31

申请人： Wylie W. Vale, Jr. ,  Teresa M. Reyes ,  Paul E. Sawchenko ,  Jean E. Rivier ,  Kathy A. Lewis ,  John B. Hogenesch ,  Joan M. Vaughan ,  Marilyn H. Perrin

发明人： Wylie W. Vale, Jr. ,  Teresa M. Reyes ,  Paul E. Sawchenko ,  Jean E. Rivier ,  Kathy A. Lewis ,  John B. Hogenesch ,  Joan M. Vaughan ,  Marilyn H. Perrin

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/22 ,  A61K39/00 ,  A61P3/00 ,  A61P5/06 ,  A61P9/04 ,  A61P9/10 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P29/00 ,  C07K14/435 ,  C07K14/52 ,  C07K14/575 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12N15/12 ,  C12N15/16 ,  C12P21/08 ,  C12R1/19 ,  C12N15/63

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-pituituary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn II. 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。 这些肽在基础和应激条件下参与下丘脑 - 垂体 - 肾上腺轴的调节，表明URP和Ucn II具有类似的作用。 合成的Ucn-II和URP肽以比CRF-R1 Ucn II更高的亲和力结合，并且人URP似乎参与体温和食欲的调节，并且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。

公开(公告)号：US20120270792A1

公开(公告)日：2012-10-25

申请号：US13328821

申请日：2011-12-16

申请人： Wylie W. Vale, JR. ,  Kathy A. Lewis ,  Marilyn H. Perrin ,  Koichi S. Kunitake ,  Jean E. Rivier ,  Jozsef Gulyas

发明人： Wylie W. Vale, JR. ,  Kathy A. Lewis ,  Marilyn H. Perrin ,  Koichi S. Kunitake ,  Jean E. Rivier ,  Jozsef Gulyas

IPC分类号： A61K38/02 ,  A61P9/00

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。

公开(公告)号：US08084413B2

公开(公告)日：2011-12-27

申请号：US12266430

申请日：2008-11-06

申请人： Wylie W. Vale, Jr. ,  Kathy A. Lewis ,  Marilyn H. Perrin ,  Koichi S. Kunitake ,  Jean E. Rivier ,  Jozsef Gulyas

发明人： Wylie W. Vale, Jr. ,  Kathy A. Lewis ,  Marilyn H. Perrin ,  Koichi S. Kunitake ,  Jean E. Rivier ,  Jozsef Gulyas

IPC分类号： C07K14/00

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。