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1. 发明授权

US07288523B2 Peptide binding the KLVFF-sequence of amyloid-β 失效
公开(公告)号：US07288523B2
公开(公告)日：2007-10-30
申请号：US10721774
申请日：2003-11-26
申请人： Christer Nordstedt , Jan Näslund , Johan Thyberg , Lars O. Tjernberg , Lars Terenius
发明人： Christer Nordstedt , Jan Näslund , Johan Thyberg , Lars O. Tjernberg , Lars Terenius
IPC分类号： A61K38/08
CPC分类号： C07K5/0821 , A61K38/00 , C07K5/0808 , C07K5/0815 , C07K5/0819 , C07K5/101 , C07K5/1019 , C07K5/1021 , C07K5/1024 , C07K14/4711 , G01N33/6896 , G01N2800/2821
摘要： The invention relates to compounds of formula (I) or (II), which are of interest especially for inhibition of polymerization of amyloid β peptide, as model substances for synthesis of amyloid β peptide-ligands, as tools for the identification of other organic compounds with similar functional properties and/or as ligands for detection of amyloid deposits using e.g., positron emission tomography (PET). Formula (II) is: R1-A′-Y′-Leu-X′-Z′-B′-R2 in which X′ means any group or amino acid imparting to the compound according to formula (I) the ability to bind to the KLVFF-sequence in amyloid β peptide, or two amino acids imparting the same ability, but with the proviso that one is not proline; Y′ means any amino acid; Z′ means any non-acidic amino acid; A′ means a direct bond or an α-amino acid bonded at the carboxyl terminal of the α-carboxy group or a di-, tri-, tetra- or pentapeptide bonded at the carboxyl terminal of the α-carboxy group; B′ means a direct bond or an α-amino acid bonded at the α-nitrogen or a di-, tri, tetra- or pentapeptide bonded at the α-nitrogen of the N-terminal α-amino acid; R1 is H or —CO—R3 bonded at the α-amino group of A′; R2 is H, —OR4 or NR5R6, all bonded to the α-carboxyl group of the α-carboxyterminal of B′; R3 and R4 are straight or branched carbon chain of 1-4 carbon atoms; R5 and R6 are independently H, alkyl, cycloalyl, aryl or substituted aryl or together are —(CH2)n— where n is 4-5; and R1 and R2 together can form a hydrocarbon ring or heterocyclic ring; all α-amino acids being either D- or L-isomers.

2. 发明授权

US06331440B1 Peptide binding the KLVFF-sequence of amyloid-&bgr; 失效
标题翻译：肽结合淀粉样蛋白-β的KLVFF序列
公开(公告)号：US06331440B1
公开(公告)日：2001-12-18
申请号：US09095106
申请日：1998-06-10
申请人： Christer Nordstedt , Jan Näslund , Johan Thyberg , Lars O. Tjernberg , Lars Terenius
发明人： Christer Nordstedt , Jan Näslund , Johan Thyberg , Lars O. Tjernberg , Lars Terenius
IPC分类号： G01N33566
CPC分类号： C07K5/0821 , A61K38/00 , C07K5/0808 , C07K5/0815 , C07K5/0819 , C07K5/101 , C07K5/1019 , C07K5/1021 , C07K5/1024 , C07K14/4711 , G01N33/6896 , G01N2800/2821
摘要： The invention relates to compounds of formula (I) or (II), which are of interest especially for inhibition of polymerization of amyloid &bgr; peptide, as model substances for synthesis of amyloid &bgr; peptide-ligands, as tools for the identification of other organic compounds with similar functional properties and/or as ligands for detection of amyloid deposits using e.g., positron emission tomography (PET). Formula (II) is: R1—A′—Y′—Leu—X′—Z′—B′—R2 in which X′ means any group or amino acid imparting to the compound according to formula (I) the ability to bind to the KLVFF-sequence in amyloid &bgr; peptide, or two amino acids imparting the same ability, but with the proviso that one is not proline; Y′ means any amino acid; Z′ means any non-acidic amino acid; A′ means a direct bond or an &agr;-amino acid bonded at the carboxyl terminal of the &agr;-carboxy group or a di-, tri-, tetra- or pentapeptide bonded at the carboxyl terminal of the &agr;-carboxy group; B′ means a direct bond or an &agr;-amino acid bonded at the &agr;-nitrogen or a di-, tri-, tetra- or pentapeptide bonded at the &agr;-nitrogen of the N-terminal &agr;-amino acid; R1 is H or —CO—R3 bonded at the &agr;-amino group of A′; R2 is H, —OR4 or NR5R6, all bonded to the &agr;-carboxyl group of the &agr;-carboxyterminal of B′; R3 and R4 are straight or branched carbon chain of 1-4 carbon atoms; R5 and R6 are independently H, alkyl, cycloalkyl, aryl or substituted aryl or together are —(CH2)n— where n is 4-5; and R1 and R2 together can form a hydrocarbon ring of heterocyclic ring; all &agr;-amino acids being either D- or L-isomers.
摘要翻译：本发明涉及式（I）或（II）的化合物，其特别用于抑制淀粉样蛋白β肽的聚合作为淀粉样蛋白β肽配体的合成的模型物质，作为鉴定其它有机化合物的工具具有类似的功能性质和/或用于使用例如正电子发射断层摄影（PET）检测淀粉样蛋白沉积物的配体。式（II）是：R1-A'-Y'-Leu-X'-Z'-B'-R2，其中X'表示赋予根据式（I）的化合物的任何基团或氨基酸，到淀粉样蛋白β肽中的KLVFF序列或赋予相同能力的两个氨基酸，但条件是一个不是脯氨酸; Y'表示任何氨基酸; Z'表示任何非酸性氨基酸; A'是指在α-羧基的羧基末端键合的直接键或α-氨基酸，或在α-羧基的羧基末端键合的二，三，四或五肽; B'是指在α-氮键合键或在N-末端α-氨基酸的α-氮键合的二 - ，三 - ，四 - 或五肽的直接键或α-氨基酸; R1是在A'的α-氨基键合的H或-CO-R3; R2是H，-OR4或NR5R6，均与B'的α-羧基末端的α-羧基键合; R3和R4是1-4个碳原子的直链或支链碳链; R 5和R 6独立地为H，烷基，环烷基，芳基或取代的芳基，或一起为 - （CH 2）n - ，其中n为4-5; R1和R2一起可以形成杂环的烃环; 所有α-氨基酸都是D-或L-异构体。

3. 发明申请

US20120027755A1 PREVENTION AND TREATMENT OF ALZHEIMER'S DISEASE 有权
标题翻译：预防和治疗阿尔茨海默病
公开(公告)号：US20120027755A1
公开(公告)日：2012-02-02
申请号：US13218592
申请日：2011-08-26
申请人： Lars Lannfelt , Camilla Nilsberth , Anita Campbell , Jan Näslund
发明人： Lars Lannfelt , Camilla Nilsberth , Anita Campbell , Jan Näslund
IPC分类号： A61K39/395 , A61P25/28 , C07K16/00
CPC分类号： C07K14/4711 , A61K38/00 , A61K2039/505
摘要： The invention relates to a purified antibody or fragment thereof that specifically binds an Aβ protofibril. The invention further relates to a composition that includes such antibodies. The invention also relates to using such antibodies and compositions for treating a patient having of suspected of having Alzheimer's disease.
摘要翻译：本发明涉及特异性结合A和Bgr的纯化抗体或其片段; 原纤维本发明还涉及包含这种抗体的组合物。本发明还涉及使用这样的抗体和组合物来治疗怀疑患有阿尔茨海默病的患者。

4. 发明授权

US07179463B2 Treatment of alzheimer's disease 有权
标题翻译：治疗阿尔茨海默病
公开(公告)号：US07179463B2
公开(公告)日：2007-02-20
申请号：US09899815
申请日：2001-07-09
申请人： Lars Lannfelt , Camilla Nilsberth , Anita Westlind-Danielsson , Jan Näslund
发明人： Lars Lannfelt , Camilla Nilsberth , Anita Westlind-Danielsson , Jan Näslund
IPC分类号： A61K39/395 , A61K39/40 , A61K39/42 , A01N37/18 , C07K16/00
CPC分类号： C07K14/4711 , A61K38/00 , A61K2039/505
摘要： A method for the treatment of Alzheimer's disease in a subject having or suspected of having Alzheimer's disease by administering to the subject a therapeutically effective amount of an antibody wherein the antibody is raised against a protofibril that contains an Aβ-Arc peptide.
摘要翻译：一种通过向受试者施用治疗有效量的抗体，其中所述抗体针对含有Abeta-Arc肽的原纤维起立，用于治疗患有或怀疑患有阿尔茨海默病的受试者中的阿尔茨海默氏病的方法。

5. 发明授权

US08409575B2 Antibodies specific for amyloid beta protofibril 有权
标题翻译：对淀粉样蛋白β原纤维特异的抗体
公开(公告)号：US08409575B2
公开(公告)日：2013-04-02
申请号：US13218592
申请日：2011-08-26
申请人： Lars Lannfelt , Camilla Nilsberth , Anita Campbell , Jan Näslund
发明人： Lars Lannfelt , Camilla Nilsberth , Anita Campbell , Jan Näslund
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K14/4711 , A61K38/00 , A61K2039/505
摘要： The invention relates to a purified antibody or fragment thereof that specifically binds an Aβ protofibril. The invention further relates to a composition that includes such antibodies. The invention also relates to using such antibodies and compositions for treating a patient having of suspected of having Alzheimer's disease.
摘要翻译：本发明涉及特异性结合A和Bgr的纯化抗体或其片段; 原纤维本发明还涉及包含这种抗体的组合物。本发明还涉及使用这样的抗体和组合物来治疗怀疑患有阿尔茨海默病的患者。

6. 发明授权

US07700719B2 Arctic β amyloid protofibril 有权
标题翻译：北极和北极淀粉样蛋白原纤维
公开(公告)号：US07700719B2
公开(公告)日：2010-04-20
申请号：US11654508
申请日：2007-01-18
申请人： Lars Lannfelt , Camilla Nilsberth , Anita Campbell , Jan Näslund
发明人： Lars Lannfelt , Camilla Nilsberth , Anita Campbell , Jan Näslund
IPC分类号： A61K38/00 , A61K39/00 , A61K39/38 , C07K16/00 , C07K17/00 , C07K5/00
CPC分类号： C07K14/4711 , A61K38/00 , A61K2039/505
摘要： The present invention relates to prevention and treatment of Alzheimer's disease (AD). More specifically, the invention relates to use of a non-wild type protofibril or compound(s) with protofibril forming activity for active immunisation in the purpose of treating or preventing AD. The invention further relates to a peptide, Aβ-Arc, with high protofibril forming activity as well as several applications thereof, such as antibodies against said peptide for passive immunisation against AD.
摘要翻译：本发明涉及阿尔茨海默氏病（AD）的预防和治疗。更具体地，本发明涉及用于治疗或预防AD的目的的用于主动免疫的原始原纤维形成活性的非野生型原纤维或化合物的用途。本发明进一步涉及具有高原纤维形成活性的肽，其具有高的原纤维形成活性以及其几种应用，例如针对所述肽的针对AD的被动免疫的抗体。

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