公开(公告)号：US06476187B1

公开(公告)日：2002-11-05

申请号：US09353099

申请日：1999-07-14

申请人： Roger D. Cone ,  Wei Fan ,  Bruce A. Boston ,  Robert A. Kesterton ,  Dongsi Lu ,  Wenbiao Chen

发明人： Roger D. Cone ,  Wei Fan ,  Bruce A. Boston ,  Robert A. Kesterton ,  Dongsi Lu ,  Wenbiao Chen

IPC分类号： A61K3800

CPC分类号： C07K14/72 ,  A61K38/00 ,  C07K7/56 ,  C07K14/723 ,  C12Q1/6876 ,  C12Q1/6886 ,  C12Q1/6897 ,  C12Q2600/136 ,  G01N33/74 ,  G01N2333/68 ,  G01N2333/695 ,  G01N2333/72 ,  G01N2333/726 ,  G01N2500/00

摘要： The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian melanocortin receptors. The invention provides a panel of such transformed mammalian cells expressing melanocortin receptors for screening compounds for receptor agonist and antagonist activity. The invention also provides methods for using such panels of melanocortin receptor-expressing mammalian cells to specifically-detect and identify agonists and antagonists for each melanocortin receptor, as well as patterns of agonist and antagonist activity of said compounds for the class of melanocortin receptors. Such screening methods provide a means for identifying compounds with patterns of melanocortin agonist and antagonist activity which is associated with the capacity to influence or modify metabolism and behavior, particularly feeding behavior.

摘要翻译： 本发明提供包含编码哺乳动物黑皮质素受体的核酸的重组表达构建体和已经引入表达功能性哺乳动物黑皮质素受体的所述重组表达构建体的哺乳动物细胞。 本发明提供了一组这样的转化的哺乳动物细胞，其表达用于筛选受体激动剂和拮抗剂活性的化合物的黑皮质素受体。 本发明还提供了使用这样的黑皮质素受体表达哺乳动物细胞的这种面板来特异性检测和鉴定每种黑皮质素受体的激动剂和拮抗剂的方法，以及所述化合物对黑皮质素受体类型的激动剂和拮抗剂活性的模式。 这种筛选方法提供用于鉴定与影响或修饰代谢和行为，特别是进食行为的能力相关的黑皮质素激动剂和拮抗剂活性的化合物的方法。

公开(公告)号：US6100048A

公开(公告)日：2000-08-08

申请号：US706281

申请日：1996-09-04

申请人： Roger D. Cone ,  Wei Fan ,  Bruce A. Boston ,  Robert A. Kesterton ,  Dongsi Lu ,  Wenbiao Chen

发明人： Roger D. Cone ,  Wei Fan ,  Bruce A. Boston ,  Robert A. Kesterton ,  Dongsi Lu ,  Wenbiao Chen

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K45/00 ,  A61P3/04 ,  A61P43/00 ,  C07K7/54 ,  C07K7/56 ,  C07K14/72 ,  C12N5/10 ,  C12N15/12 ,  C12P21/02 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/74 ,  G01N33/566 ,  C07K14/71 ,  C12N15/10

CPC分类号： C07K14/72 ,  C07K14/723 ,  C07K7/56 ,  C12Q1/6876 ,  C12Q1/6886 ,  C12Q1/6897 ,  G01N33/74 ,  A61K38/00 ,  C12Q2600/136 ,  G01N2333/68 ,  G01N2333/695 ,  G01N2333/72 ,  G01N2333/726 ,  G01N2500/00

摘要： The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian melanocortin receptors. The invention provides a panel of such transformed mammalian cells expressing melanocortin receptors for screening compounds for receptor agonist and antagonist activity. The invention also provides methods for using such panels of melanocortin receptor-expressing mammalian cells to specifically detect and identify agonists and antagonists for each melanocortin receptor, as well as patterns of agonist and antagonist activity of said compounds for the class of melanocortin receptors. Such screening methods provide a means for identifying compounds with patterns of melanocortin agonist and antagonist activity which are associated with the capacity to influence or modify metabolism and behavior, particularly feeding behavior.

摘要翻译： 本发明提供包含编码哺乳动物黑皮质素受体的核酸的重组表达构建体和已经引入表达功能性哺乳动物黑皮质素受体的所述重组表达构建体的哺乳动物细胞。 本发明提供了一组这样的转化的哺乳动物细胞，其表达用于筛选受体激动剂和拮抗剂活性的化合物的黑皮质素受体。 本发明还提供了使用这样的黑皮质素受体表达哺乳动物细胞的这种面板专门检测和鉴定每种黑皮质素受体的激动剂和拮抗剂的方法，以及所述化合物对黑皮质素受体类型的激动剂和拮抗剂活性的模式。 这种筛选方法提供了鉴定与影响或改变代谢和行为，特别是进食行为的能力有关的黑皮质素激动剂和拮抗剂活性的化合物的方法。

公开(公告)号：US06278038B1

公开(公告)日：2001-08-21

申请号：US09097231

申请日：1998-06-12

申请人： Roger D. Cone ,  Wenbiao Chen ,  Malcolm J. Low

发明人： Roger D. Cone ,  Wenbiao Chen ,  Malcolm J. Low

IPC分类号： A01K6700

CPC分类号： C12Q1/6897 ,  A01K2217/075 ,  A61K38/00 ,  C07K7/56 ,  C07K14/4711 ,  C07K14/723 ,  C12Q1/6876 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/74 ,  G01N2333/68 ,  G01N2333/695 ,  G01N2333/72 ,  G01N2333/726 ,  G01N2500/00

摘要： This invention provides methods and reagents for developing naturally-occurring and synthetic agonists and antagonists specific for a mammalian melanocortin receptor, and the use of such agonists and antagonists for treatment and alleviation of dysfunction and disease. The invention specifically provides reagents and methods for developing naturally-occurring and synthetic agonists and antagonists specific for a mammalian melanocortin receptor termed MC5-R. The naturally-occurring and synthetic agonists and antagonists specific for the MC5-R receptor are provided by the invention for the treatment, control, amelioration and alleviation of diseases, and dysfunctional and abnormal states related to thermoregulatory disorders, as well as other diseases relating to exocrine gland disorders, including lacrimal gland dysfunction and sebaceous gland disorders including acne and other skin problems. Also provided by the invention are nucleic acids, constructs, vectors and methods for producing an animal bearing a genetically-disrupted endogenous MC5-R melanocortin receptor, in both the heterozygous and homozygous condition, preferably a rodent and most preferably a mouse. Rodents bearing genetically disrupted MC5-R genes homozygously, termed “gene knockout”rodents in the art, are also advantageously provided.

摘要翻译： 本发明提供用于开发天然存在的和合成的哺乳动物黑皮质素受体特异的激动剂和拮抗剂的方法和试剂，以及这些激动剂和拮抗剂用于治疗和减轻功能障碍和疾病的用途。 本发明特别提供了用于开发天然存在的和合成的激动剂和特异于哺乳动物黑皮质素受体MC5-R的拮抗剂的试剂和方法。 本发明提供了针对MC5-R受体特异性的天然存在和合成的激动剂和拮抗剂，用于治疗，控制，改善和缓解疾病，以及与体温调节性疾病有关的功能障碍和异常状态以及与 外分泌腺疾病，包括泪腺功能障碍和皮脂腺疾病，包括痤疮和其他皮肤问题。 本发明还提供了在杂合和纯合条件下产生具有遗传破坏的内源性MC5-R黑皮质素受体的动物的核酸，构建体，载体和方法，优选啮齿动物，最优选小鼠。 也有利地提供了在本领域中遗传上破坏的基因破坏的MC5-R基因，称为“基因敲除”啮齿动物。

公开(公告)号：US5532347A

公开(公告)日：1996-07-02

申请号：US866979

申请日：1992-04-10

申请人： Roger D. Cone ,  Kathleen G. Mountjoy

发明人： Roger D. Cone ,  Kathleen G. Mountjoy

IPC分类号： G01N33/53 ,  A61K39/395 ,  C07H21/04 ,  C07K14/705 ,  C07K14/72 ,  C07K16/00 ,  C07K16/28 ,  C07K19/00 ,  C12N5/00 ,  C12N5/10 ,  C12N15/02 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/02 ,  C12Q1/68 ,  C12R1/91 ,  G01N33/74 ,  C12N15/63

CPC分类号： G01N33/74 ,  C07K14/72 ,  C12Q1/6886 ,  C12Q2600/136 ,  G01N2333/726

摘要： The present invention relates to a mammalian melanocyte stimulating hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian melanocyte stimulating hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian melanocyte stimulating hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian melanocyte stimulating hormone receptor. The invention also provides methods for screening MSH.sup.R agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the MSH.sup.R receptor gene. The invention specifically provides human and mouse MSH.sup.R genes.

摘要翻译： 本发明涉及哺乳动物黑素细胞刺激激素受体。 本发明涉及哺乳动物黑素细胞刺激激素受体的分离，表征和药理学应用，该受体是相应于该受体的基因，能够在转化的真核细胞培养物中表达哺乳动物黑素细胞刺激激素受体的重组真核表达构建体， 转化的真核细胞合成哺乳动物黑素细胞刺激激素受体。 本发明还提供了使用由包含MSHR受体基因的重组真核表达构建体转化的真核细胞培养物的受体制备体外筛选MSHR激动剂和拮抗剂的方法。 本发明特别提供人和小鼠MSHR基因。

公开(公告)号：US06392027B1

公开(公告)日：2002-05-21

申请号：US09542122

申请日：2000-04-04

申请人： Roger D. Cone ,  Kathleen G. Mountjoy

发明人： Roger D. Cone ,  Kathleen G. Mountjoy

IPC分类号： C07H2104

CPC分类号： G01N33/566 ,  C07K14/723 ,  C12Q1/6876 ,  C12Q2600/158 ,  G01N33/74 ,  G01N2333/695 ,  G01N2333/72 ,  G01N2333/726 ,  G01N2500/00

摘要： The present invention relates to a mammalian adrenocorticotropic hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian adrenocorticotropic hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian adrenocorticotropic hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian adrenocorticotropic hormone receptor. The invention also provides methods for screening ACTHR agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the ACTHR receptor gene. The invention specifically provides human and bovine ACTHR genes.

摘要翻译： 本发明涉及哺乳动物促肾上腺皮质激素受体。 本发明涉及哺乳动物促肾上腺皮质激素受体的分离，表征和药理学应用，该受体是相应于该受体的基因，能够在转化的真核细胞和转化真核生物培养物中表达哺乳动物促肾上腺皮质激素受体的重组真核表达构建体 合成哺乳动物促肾上腺皮质激素受体的细胞。 本发明还提供了使用由包含ACTHR受体基因的重组真核表达构建体转化的真核细胞的这种培养物的受体制备体外筛选ACTHR激动剂和拮抗剂的方法。 本发明特别提供人和牛ACTHR基因。

公开(公告)号：US5280112A

公开(公告)日：1994-01-18

申请号：US866560

申请日：1992-04-10

申请人： Roger D. Cone ,  Kathleen G. Mountjoy

发明人： Roger D. Cone ,  Kathleen G. Mountjoy

IPC分类号： C07H21/04 ,  C07K14/72 ,  C12N5/06 ,  C12N15/12 ,  C12P21/08 ,  C12Q1/68 ,  G01N33/566 ,  G01N33/567 ,  G01N33/74 ,  C07H15/12 ,  A61K37/24 ,  A61K37/38 ,  C12Q1/00

CPC分类号： G01N33/566 ,  C07K14/723 ,  C12Q1/6876 ,  G01N33/74 ,  C12Q2600/158 ,  G01N2333/695 ,  G01N2333/72 ,  G01N2333/726 ,  G01N2500/00

摘要： The present invention relates to a mammalian adrenocorticotropic hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian adrenocorticotropic hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian adrenocorticotropic hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian adrenocorticotropic hormone receptor. The invention also provides methods for screening ACTH.sup.R agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the ACTH.sup.R receptor gene. The invention specifically provides human and bovine ACTH.sup.R genes.

摘要翻译： 本发明涉及哺乳动物促肾上腺皮质激素受体。 本发明涉及哺乳动物促肾上腺皮质激素受体的分离，表征和药理学应用，该受体是相应于该受体的基因，能够在转化的真核细胞和转化真核生物培养物中表达哺乳动物促肾上腺皮质激素受体的重组真核表达构建体 合成哺乳动物促肾上腺皮质激素受体的细胞。 本发明还提供了使用由含有ACTHR受体基因的重组真核表达构建体转化的真核细胞培养物的受体制备体外筛选ACTHR激动剂和拮抗剂的方法。 本发明特别提供人和牛ACTHR基因。

公开(公告)号：US06268221B1

公开(公告)日：2001-07-31

申请号：US09201746

申请日：1998-12-01

申请人： Roger D. Cone ,  Kathleen G. Mountjoy

发明人： Roger D. Cone ,  Kathleen G. Mountjoy

IPC分类号： G01N33566

CPC分类号： G01N33/74 ,  C07K14/72 ,  C12Q1/6886 ,  C12Q2600/136 ,  G01N2333/726

摘要： The present invention relates to a mammalian melanocyte stimulating hormone receptor (MSH-R). The invention is directed toward the isolation, characterization and pharmacological use of a mammalian melanocyte stimulating hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian melanocyte stimulating hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian melanocyte stimulating hormone receptor. The invention also provide methods for screening MSH-R agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the MSH-R receptor gene. The invention specifically provides human and mouse MSH-R genes.

摘要翻译： 本发明涉及哺乳动物黑素细胞激素受体（MSH-R）。 本发明涉及哺乳动物黑素细胞刺激激素受体的分离，表征和药理学应用，该受体是相应于该受体的基因，能够在转化的真核细胞和这种培养物的培养物中表达哺乳动物黑素细胞刺激激素受体的重组真核表达构建体 的转化真核细胞，合成哺乳动物黑素细胞刺激激素受体。 本发明还提供了使用由包含MSH-R受体基因的重组真核表达构建体转化的真核细胞的这种培养物的受体制备体外筛选MSH-R激动剂和拮抗剂的方法。 本发明特别提供人和小鼠MSH-R基因。

公开(公告)号：US5837521A

公开(公告)日：1998-11-17

申请号：US44812

申请日：1993-04-08

申请人： Roger D. Cone ,  Linda Roselli-Rehfuss ,  Kathleen G. Mountjoy ,  Linda S. Robbins

发明人： Roger D. Cone ,  Linda Roselli-Rehfuss ,  Kathleen G. Mountjoy ,  Linda S. Robbins

IPC分类号： C07K14/72 ,  C12N15/12 ,  G01N33/74 ,  C07H21/04

CPC分类号： G01N33/74 ,  C07K14/723

摘要： The present invention relates to a mammalian melanocortin receptor. The invention is directed toward the isolation, characterization and pharmacological use of a mammalian melanocortin receptor (MC3-R). The invention specifically provides a particular melanocortin receptor, termed MC3-R, isolated as a complementary DNA copy of mRNA corresponding to the gene for this receptor in rats. Also provided is a eukaryotic recombinant expression construct capable of expressing a mammalian melanocortin receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize a mammalian melanocortin receptor. The invention also provides methods for screening in vitro agonists and antagonists of such a melanocortin receptor using preparations of receptor protein from such cultures of eukaryotic cells transformed with a recombinant expression construct.

摘要翻译： 本发明涉及哺乳动物黑皮质素受体。 本发明涉及哺乳动物黑皮质素受体（MC3-R）的分离，表征和药理学应用。 本发明特别提供了一种称为MC3-R的特异性黑皮质素受体，其被分离为相应于大鼠该受体基因的mRNA的互补DNA拷贝。 还提供了能够在转化的真核细胞和合成哺乳动物黑皮质素受体的转化真核细胞的这种培养物中表达哺乳动物黑皮质素受体的真核重组表达构建体。 本发明还提供了使用来自用重组表达构建体转化的真核细胞的这种培养物的受体蛋白质的制备物筛选这种黑皮质素受体的体外激动剂和拮抗剂的方法。

公开(公告)号：US6046011A

公开(公告)日：2000-04-04

申请号：US105298

申请日：1998-06-26

申请人： Roger D. Cone ,  Kathleen G. Mountjoy

发明人： Roger D. Cone ,  Kathleen G. Mountjoy

IPC分类号： C07H21/04 ,  C07K14/72 ,  C12N5/06 ,  C12N15/12 ,  C12P21/08 ,  C12Q1/68 ,  G01N33/566 ,  G01N33/567 ,  G01N33/74

CPC分类号： G01N33/566 ,  C07K14/723 ,  C12Q1/6876 ,  G01N33/74 ,  C12Q2600/158 ,  G01N2333/695 ,  G01N2333/72 ,  G01N2333/726 ,  G01N2500/00

摘要： The present invention relates to a mammalian adrenocorticotropic hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian adreocorticotropic hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian adrenocorticotropic hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian adrenocorticotropic hormone receptor. The invention also provides methods for screening ACTH-R agonists and antagonists in vitro using prerations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the ACTH-R receptor gene. The invention specifically provides human and bovine ACTH-R genes.

摘要翻译： 本发明涉及哺乳动物促肾上腺皮质激素受体。 本发明涉及哺乳动物促肾上腺皮质激素受体的分离，表征和药理学应用，该受体是相应于该受体的基因，能够在转化真核细胞的培养物中表达哺乳动物促肾上腺皮质激素受体的重组真核表达构建体和转化的真核生物 合成哺乳动物促肾上腺皮质激素受体的细胞。 本发明还提供了使用由包含ACTH-R受体基因的重组真核表达构建体转化的真核细胞的这种培养物的受体的预测体外筛选ACTH-R激动剂和拮抗剂的方法。 本发明特别提供人和牛ACTH-R基因。

公开(公告)号：US5994087A

公开(公告)日：1999-11-30

申请号：US475637

申请日：1995-06-07

申请人： Roger D. Cone ,  Linda Roselli-Rehfuss ,  Kathleen G. Mountjoy ,  Linda S. Robbins

发明人： Roger D. Cone ,  Linda Roselli-Rehfuss ,  Kathleen G. Mountjoy ,  Linda S. Robbins

IPC分类号： C07K14/72 ,  C12N15/12 ,  G01N33/74 ,  G01N33/567 ,  G01N33/48 ,  G01N33/53 ,  G01N33/574

CPC分类号： G01N33/74 ,  C07K14/723

摘要： The present invention relates to a mammalian melanocortin receptor. The invention is directed toward the isolation, characterization and pharmacological use of a mammalian melanocortin receptor (MC3-R). The invention specifically provides a particular melanocortin receptor, termed MC3-R, isolated as a complementary DNA copy of mRNA corresponding to the gene for this receptor in rats. Also provided is a eukaryotic recombinant expression construct capable of expressing a mammalian melanocortin receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize a mammalian melanocortin receptor. The invention also provides methods for screening in vitro agonists and antagonists of such a melanocortin receptor using preparations of receptor protein from such cultures of eukaryotic cells transformed with a recombinant expression construct.

摘要翻译： 本发明涉及哺乳动物黑皮质素受体。 本发明涉及哺乳动物黑皮质素受体（MC3-R）的分离，表征和药理学应用。 本发明特别提供了一种称为MC3-R的特异性黑皮质素受体，其被分离为相应于大鼠该受体基因的mRNA的互补DNA拷贝。 还提供了能够在转化的真核细胞和合成哺乳动物黑皮质素受体的转化真核细胞的这种培养物中表达哺乳动物黑皮质素受体的真核重组表达构建体。 本发明还提供了使用来自用重组表达构建体转化的真核细胞的这种培养物的受体蛋白质的制备物筛选这种黑皮质素受体的体外激动剂和拮抗剂的方法。