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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。
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2.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。
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3.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。
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4.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。
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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.
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6.发明授权公开(公告)号：US07175828B2
公开(公告)日：2007-02-13
申请号：US10677076
申请日：2003-09-30
申请人： Mark A. Findeis , Malcolm L. Gefter , Gary F. Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
发明人： Mark A. Findeis , Malcolm L. Gefter , Gary F. Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. 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。
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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.
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8.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。
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公开(公告)号：US20060246521A1
公开(公告)日：2006-11-02
申请号：US11412869
申请日：2006-04-28
申请人： Jim Xuan , Joseph Chin
发明人： Jim Xuan , Joseph Chin
IPC分类号： G01N33/574 , C07H21/04 , C12P21/06 , C12N5/06 , C07K14/82
CPC分类号： G01N33/57434 , C07K14/82 , G01N33/5088
摘要： The present invention relates to a rodent serum marker for prostate cancer comprising b-microseminoprotein (PSP94) and diagnostic methods thereof. The present invention also relates to a recombinant sequence to raise a ligand of a specific binding affinity to a rodent serum marker for prostate cancer, which comprises the following amino acid sequence: (SEQ ID NO:1) MGGSHHHHHHGMASMTGGGGMGRNTRYDDDDKDRWGSWVCSIENREIFPN QMSDDCMDADGNKHFLNTPKKNCTWCSCDKTSITCCTNATPLSYDKDNCD VQFHPENCTYSVVDRKNPGKTCRVDSWTM.
摘要翻译： 本发明涉及包含b-microseminoprotein（PSP94）的前列腺癌的啮齿动物血清标志物及其诊断方法。 本发明还涉及一种用于产生对前列腺癌啮齿动物血清标志物具有特异性结合亲和力的配体的重组序列，其包含以下氨基酸序列：
（SEQ ID NO：1） TBODY VALIGN = “TOP”> MGGSHHHHHHGMASMTGGGGMGRNTRYDDDDKDRWGSWVCSIENREIFPN QMSDDCMDADGNKHFLNTPKKNCTWCSCDKTSITCCTNATPLSYDKDNCD VQFHPENCTYSVVDRKNPGKTCRVDSWTM。< / ENTRY> -
公开(公告)号：US20100268945A1
公开(公告)日：2010-10-21
申请号：US12825044
申请日：2010-06-28
申请人： Stephen Mereu , Matt Schnarr , Joseph Chin
发明人： Stephen Mereu , Matt Schnarr , Joseph Chin
IPC分类号： H04L29/06
CPC分类号： G06Q30/02 , G06Q30/04 , H04L63/0838
摘要： A secure communication module is provided for securing communication between a client application and a network service. The secure communication module comprises an authentication identifier provider for providing the client application a pool of authentication identifiers for use in subsequent communication with the network service, and an authentication identifier validator for checking the validity of an authentication identifiers from the pool of authentication identifiers sent with the subsequent communication.
摘要翻译： 提供了一种用于保护客户端应用程序和网络服务之间的通信的安全通信模块。 安全通信模块包括认证标识提供者，用于向客户端应用提供用于与网络服务的后续通信中使用的认证标识符池，以及认证标识符验证器，用于从发送的认证标识符池中检查认证标识符的有效性， 随后的沟通。
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