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1.发明授权
公开(公告)号：US5422341A
公开(公告)日：1995-06-06
申请号：US103490
申请日：1993-08-06
申请人： Mark J. Macielag , Ramalinga Dharanipragada , James R. Florance , Mary S. Marvin , Alphonse Galdes
发明人： Mark J. Macielag , Ramalinga Dharanipragada , James R. Florance , Mary S. Marvin , Alphonse Galdes
IPC分类号： C07K7/04 , A61K38/00 , A61P3/00 , A61P3/02 , C07K14/575 , C07K14/63 , C07K5/00 , C07K7/00 , C07K17/00
摘要： This invention pertains to polypeptides, other than motilin, having gastrointestinal motor stimulating activity and represented by the formula: ##STR1## wherein A and D are lipophilic aliphatic or alicyclic amino acids; B is L-proline or L-alanine; E is an aromatic, lipophilic aliphatic, or alicyclic amino acid; F is an aromatic or heteroaromatic amino acid; G is glycine or D-alanine; H is L-glutamic acid or L-glutamine; I is L-glutamine, L-glutamic acid, or L-alanine; J is a direct bond or is selected from, inter alia Z, Z-Leu, Z-Leu-Gln, Z-Leu-Gln-Glu (SEQ ID NO:2) or Z-Leu-Gln-Glu-Lys (SEQ ID NO:3), wherein Z is, inter alia, arginine, D-arginine, D-homoarginine, or D-lysine, and further wherein the amino acids represented by A, D, E and F are L-stereoisomers; R.sub.1 is lower-alkyl or allyl; R.sub.2 is hydrogen, lower-alkyl, propargyl, or allyl; R.sub.3 is hydrogen, lower-alkyl, and allyl; R.sub.4 is lower-alkyl, cycloalkyl, heteroaryl, unsubstituted aryl, and aryl substituted by halogen, hydroxy, or lower-alkoxy; R.sub.5 is --CH.sub.2 CONH.sub.2, aminoalkyl, or guanidinoalkyl; R.sub.6 is --COOH or --CONH.sub.2 ; and m is 0 or 1, and the asymmetric carbon represented by * may be D or L configuration, with certain specified provisos.
摘要翻译： 本发明涉及具有胃肠运动刺激活性并由下式表示的除胃动素以外的多肽：其中A和D是亲脂性脂族或脂环族氨基酸; B是L-脯氨酸或L-丙氨酸; E是芳族，亲脂性脂族或脂环族氨基酸; F是芳族或杂芳族氨基酸; G是甘氨酸或D-丙氨酸; H是L-谷氨酸或L-谷氨酰胺; 我是L-谷氨酰胺，L-谷氨酸或L-丙氨酸; J是直接键或选自Z，Z-Leu，Z-Leu-Gln，Z-Leu-Gln-Glu（SEQ ID NO：2）或Z-Leu-Gln-Glu-Lys（SEQ 其中Z特别是精氨酸，D-精氨酸，D-高精氨酸或D-赖氨酸，其中由A，D，E和F表示的氨基酸是L-立体异构体; R1是低级烷基或烯丙基; R2是氢，低级烷基，炔丙基或烯丙基; R3是氢，低级烷基和烯丙基; R4是低级烷基，环烷基，杂芳基，未取代的芳基和被卤素，羟基或低级烷氧基取代的芳基; R5是-CH2CONH2，氨基烷基或胍基烷基; R6是-COOH或-CONH 2; 并且m为0或1，并且由*表示的不对称碳可以是D或L构型，具有特定的条件。
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公开(公告)号：US20050119181A1
公开(公告)日：2005-06-02
申请号：US10956724
申请日：2004-10-01
申请人： R. Pepinsky , Alphonse Galdes , Ellen Garber , Darren Baker , Jeffery Porter , Frederick Taylor , Kevin Williams , Russell Petter , Kathryn Strauch , Paul Weinreb , Dingyi Wen , Chenhui Zeng
发明人： R. Pepinsky , Alphonse Galdes , Ellen Garber , Darren Baker , Jeffery Porter , Frederick Taylor , Kevin Williams , Russell Petter , Kathryn Strauch , Paul Weinreb , Dingyi Wen , Chenhui Zeng
CPC分类号： C07K14/46 , A61K38/1709 , C07K2319/00
摘要： Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.
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3.发明申请Methods and compositions for treating disorders involving excitotoxicity 审中-公开用于治疗涉及兴奋性毒性的疾病的方法和组合物公开(公告)号：US20070254364A1
公开(公告)日：2007-11-01
申请号：US11725144
申请日：2007-03-16
CPC分类号： A61K38/17 , A61K38/1709
摘要： It is shown here that hedgehog polypeptides possess novel activities beyond phenotype specification. Using cultures derived from the embryonic day 14.5 (E14.5) rat ventral mesencephalon, we show that hedgehog is also trophic for dopaminergic neurons and other neurons which are sensitive to exotoxicity.
摘要翻译： 这里显示，刺猬多肽具有超出表型规范的新活性。 使用来自胚胎第14.5天（E14.5）大鼠腹侧中脑的培养物，我们显示刺猬也对多巴胺能神经元和其他对外毒素敏感的神经元营养不良。
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4.发明授权公开(公告)号：US06884770B1
公开(公告)日：2005-04-26
申请号：US09569386
申请日：2000-05-11
IPC分类号： A61K31/00 , A61K31/472 , A61K31/496 , A61K31/553 , A61K38/00 , A61K38/17 , A61K48/00 , C07K1/00 , C07H21/04 , C12N1/20 , C12P21/06 , G01N33/567
CPC分类号： A61K31/7076 , A61K31/00 , A61K31/472 , A61K31/496 , A61K31/553 , A61K38/1709 , A61K48/00
摘要： The present application is directed to the discovery that hedgehog gene products are able to protect peripheral nerve cells under conditions which otherwise result in peripheral neuropathy. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, or other molecules which regulate patched or smoothened signalling, and their uses as protective agents against both acquired and hereditary neuropathies. As used herein, “peripheral neuropathy” refers to a disorder affecting a segment of the peripheral nervous system. For instance, the method of the present invention can be used as part of a treatment program in the management of neuropathies associated with systemic disease, e.g., viral infections, diabetes, inflamation; as well as genetically acquired (hereditary) neuropathies, e.g., Charcot-Marie-Tooth disease; and neuropathies caused by a toxic agent, e.g., a chemotherapeutic agent such as vincristine.
摘要翻译： 本申请旨在发现刺猬蛋白基因产物能够在否则导致周围神经病变的条件下保护外周神经细胞。 本发明的某些方面涉及刺猬蛋白多肽或调节修补或平滑信号传导的其它分子及其作为对获得性和遗传性神经病的保护剂的用途的制备。 如本文所用，“周围神经病”是指影响周围神经系统的一部分的病症。 例如，本发明的方法可用作治疗与全身疾病相关的神经病的治疗方案的一部分，例如病毒感染，糖尿病，炎症; 以及遗传获得（遗传性）神经病，例如Charcot-Marie-Tooth疾病; 以及由毒性剂例如长春新碱等化学治疗剂引起的神经病变。
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公开(公告)号：US20090054632A1
公开(公告)日：2009-02-26
申请号：US11894745
申请日：2007-08-20
申请人： R. Blake Pepinsky , Alphonse Galdes , Ellen A. Garber , Darren P. Baker , Jeffery A. Porter , Frederick R. Taylor , Kevin P. Williams , Russell C. Petter , Kathryn Strauch , Paul H. Weinreb , Dingyi Wen , Chenhui Zeng
发明人： R. Blake Pepinsky , Alphonse Galdes , Ellen A. Garber , Darren P. Baker , Jeffery A. Porter , Frederick R. Taylor , Kevin P. Williams , Russell C. Petter , Kathryn Strauch , Paul H. Weinreb , Dingyi Wen , Chenhui Zeng
CPC分类号： C07K14/46 , A61K38/1709 , C07K2319/00
摘要： Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.
摘要翻译： 描述了疏水性修饰的蛋白质及其制备方法。 疏水部分连接到蛋白质的表面氨基酸残基。 疏水部分可以是脂质或肽。 或者，蛋白质可以通过向蛋白质附加疏水结构的各种化学反应衍生化。 优选的蛋白质是哺乳动物来源的，并且选自Sonic，Indian和Desert hedgehog。 疏水部分用作方便的系链，其可以连接囊泡，例如细胞膜，脂质体或胶束。
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6.发明申请Methods and compositions for treating disorders involving excitotoxicity 审中-公开用于治疗涉及兴奋性毒性的疾病的方法和组合物公开(公告)号：US20080221037A1
公开(公告)日：2008-09-11
申请号：US12082946
申请日：2008-04-14
CPC分类号： A61K38/17 , A61K38/1709
摘要： It is shown here that hedgehog polypeptides possess novel activities beyond phenotype specification. Using cultures derived from the embryonic day 14.5 (E14.5) rat ventral mesencephalon, we show that hedgehog is also trophic for dopaminergic neurons and other neurons which are sensitive to exotoxicity.
摘要翻译： 这里显示，刺猬多肽具有超出表型规范的新活性。 使用来自胚胎第14.5天（E14.5）大鼠腹侧中脑的培养物，我们显示刺猬也对多巴胺能神经元和其他对外毒素敏感的神经元营养不良。
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公开(公告)号：US06897297B1
公开(公告)日：2005-05-24
申请号：US09579680
申请日：2000-05-26
申请人： R. Blake Pepinsky , Chenhui Zeng , Darren P. Baker , Dingyi Wen , Kevin P. Williams , Ellen A. Garber , Kathryn L. Strauch , Frederick R. Taylor , Paul H. Weinreb , Russell C. Petter , Alphonse Galdes , Jeffrey Porter
发明人： R. Blake Pepinsky , Chenhui Zeng , Darren P. Baker , Dingyi Wen , Kevin P. Williams , Ellen A. Garber , Kathryn L. Strauch , Frederick R. Taylor , Paul H. Weinreb , Russell C. Petter , Alphonse Galdes , Jeffrey Porter
IPC分类号： A61K38/00 , A61K38/17 , C07K14/46 , C07K14/435 , C07K1/107
CPC分类号： C07K14/46 , A61K38/1709 , C07K2319/00
摘要： Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.
摘要翻译： 描述了疏水性修饰的蛋白质及其制备方法。 疏水部分连接到蛋白质的表面氨基酸残基。 疏水部分可以是脂质或肽。 或者，蛋白质可以通过向蛋白质附加疏水结构的各种化学反应衍生化。 优选的蛋白质是哺乳动物来源的，并且选自Sonic，Indian和Desert hedgehog。 疏水部分用作方便的系链，其可以连接囊泡，例如细胞膜，脂质体或胶束。
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公开(公告)号：US06444793B1
公开(公告)日：2002-09-03
申请号：US09325256
申请日：1999-06-03
申请人： R. Blake Pepinsky , Darren P. Baker , Dingyi Wen , Kevin P. Williams , Ellen A. Garber , Frederick R. Taylor , Alphonse Galdes , Jeffrey Porter
发明人： R. Blake Pepinsky , Darren P. Baker , Dingyi Wen , Kevin P. Williams , Ellen A. Garber , Frederick R. Taylor , Alphonse Galdes , Jeffrey Porter
IPC分类号： C07K14435
CPC分类号： A61K38/1709 , C07K1/1077 , C07K14/46 , C07K2319/00
摘要： Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.
摘要翻译： 描述了疏水性修饰的蛋白质及其制备方法。 疏水部分连接到蛋白质的表面氨基酸残基。 疏水部分可以是脂质或肽。 或者，蛋白质可以通过向蛋白质附加疏水结构的各种化学反应衍生化。 优选的蛋白质是哺乳动物来源的，并且选自Sonic，Indian和Desert hedgehog。 疏水部分用作方便的系链，其可以连接囊泡，例如细胞膜，脂质体或胶束。
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