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公开(公告)号：US20020102261A1
公开(公告)日：2002-08-01
申请号：US09992800
申请日：2001-11-06
发明人： Victor Raso
IPC分类号： A61K039/395 , C12N009/00 , C07K016/40
CPC分类号： C07K16/18 , A61K38/00 , A61K39/0007 , A61K39/3955 , C07K2317/34 , C12N9/0002 , Y10S977/729 , Y10S977/896 , Y10S977/915 , Y10S977/918
摘要： The present invention provides an antibody which catalyzes hydrolysis of null-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural null-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural null-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of null-amyloid. The present invention also provides a vectorized antibody which is characterized by the ability to cross the blood brain barrier and is also characterized by the ability to catalyze the hydrolysis of null-amyloid at a predetermined amide linkage. The vectorized antibody can take the form of a bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a transition state adopted by null-amyloid during hydrolysis. The present invention also provides a method for sequestering free null-amyloid in the bloodstream of an animal by intravenously administering antibodies specific for null-amyloid to the animal in an amount sufficient to increase retention of null-amyloid in the circulation. In addition, the present invention provides a method for sequestering free null-amyloid in the bloodstream of an animal by immunizing an animal with an antigen comprised of an epitope which is present on null-amyloid endogenous to the animal under conditions appropriate for the generation of antibodies which bind endogenous null-amyloid. Therapeutic applications of these methods include treating patients diagnosed with, or at risk for Alzheimer's disease. Methods for reducing levels of null-amyloid in the brain of an animal, by intravenously administering antibodies specific for endogenous null-amyloid to the animal, or by immunizing the animal with an antigen comprised of an epitope which is present on endogenous null-amyloid are also provided. In one embodiment, the antigen used to generate the antibodies is a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage. Similar methods which utilize or generate antibodies which catalyze the hydrolysis of null-amyloid for reducing levels of circulating null-amyloid in an animal, and also for preventing the formation of amyloid plaques in the brain of an animal, and also for disaggregating amyloid plaques present in the brain of an animal, are also provided. Also provided is a method for generating antibodies which catalyze hydrolysis of a protein or polypeptide by immunizing an animal with an antigen comprised of an epitope which has a statine analog which mimics the conformation of a predetermined hydrolysis transition state of the polypeptide. A similar method, which utilizes reduced peptide bond analogs to mimic the conformation of a hydrolysis transition state of a polypeptide, is also provided.
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公开(公告)号：US20160039915A1
公开(公告)日：2016-02-11
申请号：US14688449
申请日：2015-04-16
发明人： Victor Raso
IPC分类号： C07K16/18
CPC分类号： C07K16/18 , A61K38/00 , A61K39/0007 , A61K39/3955 , C07K2317/34 , C12N9/0002 , Y10S977/729 , Y10S977/896 , Y10S977/915 , Y10S977/918
摘要： Disclosed herein are compositions and methods useful for controlling β-amyloid levels. In particular, the instant invention relates to an antibody that catalyzes hydrolysis of β-amyloid at a predetermined amide linkage are provided. The present invention also provides a vectorized antibody that is capable of crossing the blood brain barrier and is also capable of catalyzing the hydrolysis of β-amyloid at a predetermined amide linkage. Also provided are methods for modulating β-amyloid levels in vivo using antibodies that bind to β-amyloid. These compositions and methods have therapeutic applications, including the treatment of Alzheimer's disease.
摘要翻译： 本文公开了可用于控制和淀粉样蛋白水平的组合物和方法。 特别地，本发明涉及以预定的酰胺键催化水解淀粉样蛋白的抗体。 本发明还提供能够穿过血脑屏障的载体化抗体，并且还能够以预定的酰胺键催化β-淀粉样蛋白的水解。 还提供了使用与β-淀粉样蛋白结合的抗体在体内调节和淀粉样蛋白水平的方法。 这些组合物和方法具有治疗应用，包括治疗阿尔茨海默氏病。
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公开(公告)号：US20020136718A1
公开(公告)日：2002-09-26
申请号：US09992994
申请日：2001-11-06
发明人： Victor Raso
IPC分类号： A61K039/395 , G01N033/53 , G01N033/537 , G01N033/543 , C12N009/00
CPC分类号： C07K16/18 , A61K38/00 , A61K39/0007 , A61K39/3955 , C07K2317/34 , C12N9/0002 , Y10S977/729 , Y10S977/896 , Y10S977/915 , Y10S977/918
摘要： The present invention provides an antibody which catalyzes hydrolysis of null-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural null-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural null-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of null-amyloid. The present invention also provides a vectorized antibody which is characterized by the ability to cross the blood brain barrier and is also characterized by the ability to catalyze the hydrolysis of null-amyloid at a predetermined amide linkage. The vectorized antibody can take the form of a bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a transition state adopted by null-amyloid during hydrolysis. The present invention also provides a method for sequestering free null-amyloid in the bloodstream of an animal by intravenously administering antibodies specific for null-amyloid to the animal in an amount sufficient to increase retention of null-amyloid in the circulation. In addition, the present invention provides a method for sequestering free null-amyloid in the bloodstream of an animal by immunizing an animal with an antigen comprised of an epitope which is present on null-amyloid endogenous to the animal under conditions appropriate for the generation of antibodies which bind endogenous null-amyloid. Therapeutic applications of these methods include treating patients diagnosed with, or at risk for Alzheimer's disease. Methods for reducing levels of null-amyloid in the brain of an animal, by intravenously administering antibodies specific for endogenous null-amyloid to the animal, or by immunizing the animal with an antigen comprised of an epitope which is present on endogenous null-amyloid are also provided. In one embodiment, the antigen used to generate the antibodies is a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage. Similar methods which utilize or generate antibodies which catalyze the hydrolysis of null-amyloid for reducing levels of circulating null-amyloid in an animal, and also for preventing the formation of amyloid plaques in the brain of an animal, and also for disaggregating amyloid plaques present in the brain of an animal, are also provided. Also provided is a method for generating antibodies which catalyze hydrolysis of a protein or polypeptide by immunizing an animal with an antigen comprised of an epitope which has a statine analog which mimics the conformation of a predetermined hydrolysis transition state of the polypeptide. A similar method, which utilizes reduced peptide bond analogs to mimic the conformation of a hydrolysis transition state of a polypeptide, is also provided.
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公开(公告)号：US20030235897A1
公开(公告)日：2003-12-25
申请号：US10385065
申请日：2003-03-10
发明人： Victor Raso
IPC分类号： C07K016/00 , C12N009/00 , G01N033/53 , G01N033/537 , G01N033/543
CPC分类号： C07K16/18 , A61K38/00 , A61K39/0007 , A61K39/3955 , C07K2317/34 , C12N9/0002 , Y10S977/729 , Y10S977/896 , Y10S977/915 , Y10S977/918
摘要： The present invention provides an antibody which catalyzes hydrolysis of null-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural null-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural null-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of null-amyloid. The present invention also provides a vectorized antibody which is characterized by the ability to cross the blood brain barrier and is also characterized by the ability to catalyze the hydrolysis of null-amyloid at a predetermined amide linkage. The vectorized antibody can take the form of a bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a transition state adopted by null-amyloid during hydrolysis. The present invention also provides a method for sequestering free null-amyloid in the bloodstream of an animal by intravenously administering antibodies specific for null-amyloid to the animal in an amount sufficient to increase retention of null-amyloid in the circulation. In addition, the present invention provides a method for sequestering free null-amyloid in the bloodstream of an animal by immunizing an animal with an antigen comprised of an epitope which is present on null-amyloid endogenous to the animal under conditions appropriate for the generation of antibodies which bind endogenous null-amyloid. Therapeutic applications of these methods include treating patients diagnosed with, or at risk for Alzheimer's disease. Methods for reducing levels of null-amyloid in the brain of an animal, by intravenously administering antibodies specific for endogenous null-amyloid to the animal, or by immunizing the animal with an antigen comprised of an epitope which is present on endogenous null-amyloid are also provided. In one embodiment, the antigen used to generate the antibodies is a transition state analog which mimics the transition state adopted by null-amyloid during hydrolysis at a predetermined amide linkage. Similar methods which utilize or generate antibodies which catalyze the hydrolysis of null-amyloid for reducing levels of circulating null-amyloid in an animal, and also for preventing the formation of amyloid plaques in the brain of an animal, and also for disaggregating amyloid plaques present in the brain of an animal, are also provided. Also provided is a method for generating antibodies which catalyze hydrolysis of a protein or polypeptide by immunizing an animal with an antigen comprised of an epitope which has a statine analog which mimics the conformation of a predetermined hydrolysis transition state of the polypeptide. A similar method, which utilizes reduced peptide bond analogs to mimic the conformation of a hydrolysis transition state of a polypeptide, is also provided.
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