-
公开(公告)号：US20070248996A1
公开(公告)日：2007-10-25
申请号：US11600290
申请日：2006-11-14
申请人： Mark Findeis , Malcolm Gefter , Gary Musso , Ethan Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher Arico-Muendel , Kathryn Phillips , Neil Hayward
发明人： Mark Findeis , Malcolm Gefter , Gary Musso , Ethan Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher Arico-Muendel , Kathryn Phillips , Neil Hayward
CPC分类号： C07K5/101 , A61K38/00 , C07K5/1027 , C07K7/06 , C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： Compounds that modulate natural β amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a β amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a β amyloid peptide, preferably a retro-inverso isomer of Aβ17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
-
2.发明申请公开(公告)号：US20060014696A1
公开(公告)日：2006-01-19
申请号：US10677076
申请日：2003-09-30
申请人： Mark Findeis , Malcolm Gefter , Gary Musso , Ethan Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher Arico-Muendel , Kathryn Phillips , Neil Hayward
发明人： Mark Findeis , Malcolm Gefter , Gary Musso , Ethan Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher Arico-Muendel , Kathryn Phillips , Neil Hayward
CPC分类号： C07K5/101 , A61K38/00 , C07K5/1027 , C07K7/06 , C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： Compounds that modulate natural β amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a β amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a β amyloid peptide, preferably a retro-inverso isomer of Aβ17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
摘要翻译： 提供调节天然β淀粉样肽聚集的化合物。 本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。 优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。 在特别优选的实施方案中，肽是β淀粉样肽的逆反异构体，优选Abeta 17-21的逆反异构体。 在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。 优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。 优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。
-
3.发明授权
公开(公告)号：US5985242A
公开(公告)日：1999-11-16
申请号：US920162
申请日：1997-08-27
申请人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
发明人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
CPC分类号： C07K14/4711 , A61K38/00
摘要： Compounds that modulate natural .beta. amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a .beta. amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a .beta. amyloid peptide, preferably a retro-inverso isomer of A.beta..sub.17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
摘要翻译： 提供调节天然β淀粉样肽聚集的化合物。 本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。 优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。 在特别优选的实施方案中，肽是β淀粉样蛋白肽的逆反异构体，优选Aβ17-21的逆反式异构体。 在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。 优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。 优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。
-
4.发明授权公开(公告)号：US06689752B2
公开(公告)日：2004-02-10
申请号：US09895443
申请日：2001-06-29
申请人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
发明人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
IPC分类号： A61K3807
CPC分类号： C07K5/101 , A61K38/00 , C07K5/1027 , C07K7/06 , C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
摘要翻译： 提供调节天然β淀粉样肽聚集的化合物。 本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。 优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。 在特别优选的实施方案中，肽是β淀粉样肽的逆反异构体，优选Abeta17-21的逆反异构体。 在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。 优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。 优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。
-
5.发明授权公开(公告)号：US06277826B1
公开(公告)日：2001-08-21
申请号：US09356931
申请日：1999-07-19
申请人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
发明人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
IPC分类号： A61K3806
CPC分类号： C07K5/101 , A61K38/00 , C07K5/1027 , C07K7/06 , C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
摘要翻译： 提供调节天然β淀粉样肽聚集的化合物。 本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。 优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。 在特别优选的实施方案中，肽是β淀粉样肽的逆反异构体，优选Abeta17-21的逆反异构体。 在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。 优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。 优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。
-
公开(公告)号：US06303567B1
公开(公告)日：2001-10-16
申请号：US08703675
申请日：1996-08-27
申请人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
发明人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
IPC分类号： A61K3806
CPC分类号： C07K14/4711 , A61K38/00
摘要： Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
-
公开(公告)号：US5854204A
公开(公告)日：1998-12-29
申请号：US612785
申请日：1996-03-14
申请人： Mark A. Findeis , Howard Benjamin , Marc B. Garnick , Malcolm L. Gefter , Arvind Hundal , Laura Kasman , Gary Musso , Ethan R. Signer , James Wakefield , Michael Reed , Susan Molineaux , William Kubasek , Joseph Chin , Jung-Ja Lee , Michael Kelley
发明人： Mark A. Findeis , Howard Benjamin , Marc B. Garnick , Malcolm L. Gefter , Arvind Hundal , Laura Kasman , Gary Musso , Ethan R. Signer , James Wakefield , Michael Reed , Susan Molineaux , William Kubasek , Joseph Chin , Jung-Ja Lee , Michael Kelley
IPC分类号： A61K39/02 , A61K31/00 , A61K38/00 , A61K51/00 , A61P25/00 , C07K7/06 , C07K14/47 , C07K14/435 , C07K7/08
CPC分类号： C07K14/4711 , A61K38/00
摘要： Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural .beta. amyloid peptides (.beta.-AP). In a preferred embodiment, the .beta. amyloid modulator compounds of the invention are comprised of an A.beta. aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural .beta. amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural .beta.-AP aggregation when the natural .beta.-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
摘要翻译： 公开了调节淀粉样蛋白形成蛋白或肽聚集的化合物。 本发明的调节剂可以促进淀粉样蛋白聚集，更优选可以抑制天然淀粉样蛋白聚集。 在优选的实施方案中，化合物调节天然β淀粉样蛋白肽（β-AP）的聚集。 在优选的实施方案中，本发明的β淀粉样蛋白调节剂化合物由Aβ聚集核心结构域和与其偶联的修饰基团组成，使得当与肽接触时，该化合物改变聚集或抑制天然β淀粉样肽的神经毒性。 此外，当天然β-APs相对于调节剂摩尔过量时，调节剂能够改变天然的β-AP聚集。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。
-
公开(公告)号：US20080032896A1
公开(公告)日：2008-02-07
申请号：US11704580
申请日：2007-02-09
申请人： Howard Benjamin , Mark Findeis , Malcolm Gefter , Gary Musso , Ethan Signer
发明人： Howard Benjamin , Mark Findeis , Malcolm Gefter , Gary Musso , Ethan Signer
CPC分类号： C07K1/047
摘要： Methods for identifying a compound that binds to a target are described. In general, the methods involve forming a first library comprising a multiplicity of peptides, identifying one or more peptides that bind to the target and determining a peptide motif therefrom, forming a second library comprising a multiplicity of compounds designed based on the peptide motif, selecting from the second library at least one compound that binds to the target, and determining the structure or structures of the at least one compound that binds to the target. Libraries of compounds based on a peptide motif and compounds identified by the methods of the invention are also disclosed.
摘要翻译： 描述了用于鉴定与靶标结合的化合物的方法。 通常，所述方法包括形成包含多个肽的第一文库，鉴定结合靶标的一种或多种肽，并从其中确定肽基序，形成包含基于肽基序设计的多种化合物的第二文库，选择 来自第二文库的至少一种与靶标结合的化合物，以及确定结合靶标的至少一种化合物的结构或结构。 还公开了基于肽基序的化合物和通过本发明的方法鉴定的化合物的文库。
-
公开(公告)号：US20070185032A1
公开(公告)日：2007-08-09
申请号：US11265520
申请日：2005-11-02
摘要： Sustained delivery formulations comprising a water-insoluble complex of a peptidic compound (e.g., a peptide, polypeptide, protein, peptidomimetic or the like) and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptidic compound in a small volume and for delivery of a pharmaceutically active peptidic compound for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptidic compound of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.
-
公开(公告)号：US20070185033A1
公开(公告)日：2007-08-09
申请号：US11205270
申请日：2005-08-15
CPC分类号： A61K9/146 , A61K9/0019 , A61K38/09
摘要： Sustained delivery formulations comprising a water-insoluble complex of a peptidic compound (e.g., a peptide, polypeptide, protein, peptidomimetic or the like) and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptidic compound in a small volume and for delivery of a pharmaceutically active peptidic compound for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptidic compound of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.
摘要翻译： 公开了包含肽化合物（例如肽，多肽，蛋白质，拟肽等）和载体大分子的水不溶性络合物的持续递送制剂。 本发明的制剂允许在施用复合物之后将较高体积的肽化合物加载至少量的药物活性肽化合物延长的时期，例如一个月。 本发明的络合物可以研磨或粉碎成细粉末。 以粉末形式，络合物形成稳定的水性悬浮液和分散体，适于注射。 在优选的实施方案中，复合物的肽化合物是LHRH类似物，优选LHRH拮抗剂，载体大分子是阴离子聚合物，优选羧甲基纤维素。 还公开了制备本发明复合物的方法，以及使用含LHRH类似物的复合物治疗可用LHRH类似物治疗的病症的方法。
-
-
-
-
-
-
-
-
-
搜索结果
23 条记录 (耗时 0.047 秒)
