公开(公告)号：EP1812062A2

公开(公告)日：2007-08-01

申请号：EP05820737.4

申请日：2005-10-21

申请人： Merck & Co., Inc. ,  Northwestern University

发明人： ACTON, Paul ,  AN, Zhiqiang ,  BETT, Andrew, J. ,  BREESE, Robert ,  DODSON, Elizabeth, Chen ,  KINNEY, Gene ,  KLEIN, William ,  LAMBERT, Mary, P. ,  LIANG, Xiaoping ,  SHUGHRUE, Paul ,  STROHL, William, R. ,  VIOLA, Kirsten, L. ,  CHANG, Lei

IPC分类号： A61K39/395

CPC分类号： G01N33/5058 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2800/2814 ,  G01N2800/2821

摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer’s Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer’s Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLs, and tauphosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.

摘要翻译： 本发明涉及差异识别Aβ衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可区分阿尔茨海默氏病和对照人脑提取物，并可用于检测ADDLs和诊断阿尔茨海默氏病的方法。 本发明的抗体还阻断ADDL与神经元的结合，ADDL的组装和tau磷酸化，并且可用于预防和治疗与淀粉样蛋白β1-42的可溶性寡聚体相关的疾病的方法。

公开(公告)号：EP1551447A2

公开(公告)日：2005-07-13

申请号：EP03757505.7

申请日：2003-06-11

申请人： NORTHWESTERN UNIVERSITY ,  UNIVERSITY OF SOUTHERN CALIFORNIA

发明人： KLEIN, William, L. ,  KRAFFT, Grant, A. ,  LAMBERT, Mary, P. ,  VIOLA, Kirsten, L. ,  CHROMY, Brett, A. ,  GONG, Yue, Song ,  CHANG, Lei ,  MORGAN, Todd, E. ,  ROZOFSKY, Irina ,  FINCH, Caleb, E.

IPC分类号： A61K39/00 ,  A61K39/395 ,  C07K16/00

CPC分类号： G01N33/6896 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/4711 ,  C07K16/18 ,  G01N2333/4709 ,  G01N2800/2821

摘要： The invention herein comprises antibodies that bind to amyloid beta-derived diffusible ligands (ADDLs). ADDLs comprise amyloid ß protein assembled into soluble, globular, non-fibrillar, oligomeric structures capable of activating specific cellular processes. The invention also comprises methods of using ADDL-specific antibodies for assaying the formation, presence, receptor protein binding and cellular activity of ADDLs, as well as using such antibodies to detect compounds that block the formation or activity of ADDLs, and methods of identifying such compounds. The invention further provides methods of using ADDL-specific antibodies in modulating ADDL formation and/or activity, inter alia in the treatment of learning and/or memory disorders.

公开(公告)号：EP1769002A1

公开(公告)日：2007-04-04

申请号：EP05788883.6

申请日：2005-07-05

申请人： Northwestern University

发明人： LAMBERT, Mary, P. ,  VELASCO, Pauline, T. ,  CHANG, Lei ,  VIOLA, Kirsten, L. ,  FERNANDEZ, Sara, J. ,  LACOR, Pascale, N. ,  KHUON, Daliya ,  GONG, Yuesong ,  KLEIN, William, L. ,  KRAFFT, Grant, A.

IPC分类号： C07K16/18 ,  G01N33/50 ,  G01N33/68

CPC分类号： C07K16/18 ,  C07K2317/76 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2800/2821

摘要： Disclosed herein are antibodies that bind with high specificity to soluble oligomers of amyloid β (Abeta) and methods utilizing such antibodies. The antibodies are able to distinguish between Alzheimer's Disease (AD) and control human brain extracts. The antibodies identify endogenous Abeta oligomers in AD brain slices and also bind to Abeta oligomers on cultured hippocampal cells. The antibodies neutralize endogenous Abeta oligomers and Abeta oligomers produced in solution.

公开(公告)号：EP1755644A2

公开(公告)日：2007-02-28

申请号：EP05779925.6

申请日：2005-05-16

申请人： Northwestern University

发明人： LACOR, Pascale N. ,  VIOLA, Kirsten, L. ,  LAMBERT, Mary, P. ,  GONG, Yuesong ,  CHANG, Lei ,  VELASCO, Pauline, T. ,  BIGIO, Eileen, H. ,  BUNIEL, Maria, C. ,  FERNANDEZ, Sara J. ,  JERECIC, Jasna ,  CATALANO, Susan ,  PRAY, Todd ,  LOWE, Ray ,  KRAFFT, Grant, A. ,  KLEIN, William, L.

IPC分类号： A61K38/17 ,  C07K14/705

CPC分类号： C07K14/4711 ,  A61K31/495 ,  A61K38/00 ,  G01N33/5058 ,  G01N2800/2821

摘要： Disclosed and claimed herein are compositions comprising ADDL receptors, related compositions, and related methods. ADDL receptors are typically, but perhaps not exclusively, localized at the post-synaptic density (PSD) of neuronal cells. Related compositions include, but are not limited to, compounds that affect, positively or negatively, ADDL binding to neuronal cells, either via one or more receptors localized at the post-synaptic density (PSD) or otherwise. Related methods include, but are not limited to, procedures to screen for compounds that affect, either positively or negatively, ADDL binding to neuronal cells, either via one or more receptors localized at the post-synaptic density (PSD) or otherwise. Other related methods include, but are not limited to, prevention and treatment of ADDL-related diseases, such as Alzheimer’s disease, mild cognitive impairment, Down’s syndrome, and the like, using compositions that inhibit, block, or otherwise interfere with ADDL binding to one or more receptors localized at the post-synaptic density of neuronal cells.

摘要翻译： 本文公开并要求保护的是包含ADDL受体的组合物，相关组合物和相关方法。 ADDL受体通常但可能不是唯一地定位于神经元细胞的突触后密度（PSD）。 相关组合物包括但不限于通过定位于突触后密度（PSD）或其他位置的一个或多个受体，正向或负向影响ADDL与神经元细胞的结合的化合物。 相关方法包括但不限于筛选通过定位于突触后密度（PSD）的一种或多种受体或其他方式影响（正向或负向）ADDL与神经元细胞的结合的化合物的程序。 其他相关方法包括但不限于预防和治疗与ADDL相关的疾病，例如阿尔茨海默病，轻度认知障碍，唐氏综合征等，使用抑制，阻断或以其他方式干扰ADDL结合的组合物 一个或多个受体位于神经元细胞的突触后密度处。

公开(公告)号：EP1545582A2

公开(公告)日：2005-06-29

申请号：EP03773066.0

申请日：2003-10-01

申请人： NORTHWESTERN UNIVERSITY

发明人： KLEIN, William ,  KRAFFT, Grant, A. ,  CHANG, Lei ,  GONG, Yuesong ,  VIOLA, Kirsten ,  LAMBERT, Mary ,  CHROMY, Brett ,  SUMMA, David

IPC分类号： A61K38/16 ,  A61K39/00 ,  C12P21/08 ,  C07K14/00 ,  C07K14/575 ,  C07K16/00

CPC分类号： G01N33/6896 ,  C07K16/18

摘要： The invention herein comprises amyloid beta-derived diffusible ligands (ADDLs), compositions comprising ADDLs, ADDL-surrogates, ADDL-binding molecules, and methods of using any of the foregoing compounds and compositions. ADDLs comprise amyloid β protein assembled into soluble, globular, non-fibrillar, oligomeric structures capable of activating specific cellular processes. The invention also comprises methods of generating ADDL-specific antibodies and methods of using ADDL-specific antibodies for assaying the formation, presence, receptor protein binding and cellular activity of ADDLs, as well as using such antibodies to detect compounds that block the formation or activity of ADDLs, and methods of identifying such compounds. The invention further provides methods of using ADDL-specifc antibodies in modulating ADDL formation and/or activity, inter alia in the treatment of learning and/or memory disorders.