公开(公告)号：US08798980B2

公开(公告)日：2014-08-05

申请号：US13306774

申请日：2011-11-29

申请人： Thomas D. Schneider ,  Ilya Gennadiyevich Lyakhov

发明人： Thomas D. Schneider ,  Ilya Gennadiyevich Lyakhov

IPC分类号： G06F19/00 ,  G06G7/58 ,  C12M1/00 ,  C07K1/00 ,  B82B1/00 ,  B82B3/00 ,  B82Y30/00 ,  B82Y40/00 ,  C07K14/47 ,  H02N11/00

CPC分类号： C12M99/00 ,  B82B1/00 ,  B82B3/00 ,  B82Y30/00 ,  B82Y40/00 ,  C07K14/4716 ,  H02N11/006 ,  Y10S977/729 ,  Y10T29/4984 ,  Y10T156/10

摘要： A molecular motor in which multiple concentric cylinders (or nested cones) rotate around a common longitudinal axis. Opposing complementary surfaces of the cylinders or cones are coated with complementary motor protein pairs (such as actin and myosin). The actin and myosin interact with one another in the presence of ATP to rotate the cylinders or cones relative to one another, and this rotational energy is harnessed to produce work. The length of the cylinders can also be used to control the power generated by the motor. In another embodiment, the molecular motor includes at least two annular substrates wherein one annular substrate is coated with a first motor protein and the other annular substrate is coated with a second motor protein. The first and second motor proteins interact with each other to move the second annular relative to the first annular substrate.

摘要翻译： 一个分子马达，其中多个同心圆柱体（或嵌套圆锥体）围绕共同的纵向轴线旋转。 圆柱体或锥体的互补表面涂覆有互补的运动蛋白质对（如肌动蛋白和肌球蛋白）。 肌动蛋白和肌球蛋白在ATP存在下相互作用，以相对于彼此旋转圆柱体或锥体，并利用该旋转能量来产生作用。 气缸的长度也可用于控制电机产生的电力。 在另一个实施例中，分子马达包括至少两个环形基底，其中一个环形基底涂覆有第一运动蛋白，另一个环形基底涂覆有第二运动蛋白。 第一和第二运动蛋白相互作用以相对于第一环形基底移动第二环状物。

公开(公告)号：US07906626B2

公开(公告)日：2011-03-15

申请号：US11063350

申请日：2005-02-23

申请人： Victor Raso

发明人： Victor Raso

IPC分类号： C07K16/18 ,  A61K39/00 ,  A61K49/16

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 are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a β-amyloid epitope. Also disclosed are methods for inhibiting the formation of β-amyloid plaques in the brain of a human, or promoting the disaggregation of a preformed β-amyloid plaque. Such methods recite the administration of a bispecific antibody.

摘要翻译： 公开了包含赋予双特异性抗体跨越血脑屏障的能力的第一抗体结合特异性的双特异性抗体和赋予双特异性抗体结合于淀粉样蛋白表位的能力的第二抗体特异性。 还公开了抑制人脑中淀粉样斑块形成或促进预先形成的淀粉样斑块解聚的方法。 这种方法背诵了双特异性抗体的施用。

公开(公告)号：US20080127650A1

公开(公告)日：2008-06-05

申请号：US12011239

申请日：2008-01-24

申请人： Thomas D. Schneider ,  IIya Gennadiyevich Lyakhov

发明人： Thomas D. Schneider ,  IIya Gennadiyevich Lyakhov

IPC分类号： F03G7/00 ,  B29C65/00

CPC分类号： C12M99/00 ,  B82B1/00 ,  B82B3/00 ,  B82Y30/00 ,  B82Y40/00 ,  C07K14/4716 ,  H02N11/006 ,  Y10S977/729 ,  Y10T29/4984 ,  Y10T156/10

摘要： A molecular motor in which multiple concentric cylinders (or nested cones) rotate around a common longitudinal axis. Opposing complementary surfaces of the cylinders or cones are coated with complementary motor protein pairs (such as actin and myosin). The actin and myosin interact with one another in the presence of ATP to rotate the cylinders or cones relative to one another, and this rotational energy is harnessed to produce work. The concentration of ATP and the number of nested cylinders or cones can be used to control the rotational speed of the motor. The length of the cylinders can also be used to control the power generated by the motor. In another embodiment, the molecular motor includes at least two annular substrates wherein one annular substrate is coated with a first motor protein and the other annular substrate is coated with a second motor protein. The first and second motor proteins interact with each other to move the second annular relative to the first annular substrate.

摘要翻译： 一个分子马达，其中多个同心圆筒（或嵌套圆锥体）围绕共同的纵向轴线旋转。 圆柱体或锥体的互补表面涂覆有互补的运动蛋白质对（如肌动蛋白和肌球蛋白）。 肌动蛋白和肌球蛋白在ATP存在下相互作用以相对于彼此旋转圆柱体或锥体，并且利用该旋转能量来产生作用。 ATP的浓度和嵌套圆柱体或锥体的数量可用于控制电机的转速。 气缸的长度也可用于控制电机产生的电力。 在另一个实施例中，分子马达包括至少两个环形基底，其中一个环形基底涂覆有第一运动蛋白，另一个环形基底涂覆有第二运动蛋白。 第一和第二运动蛋白相互作用以相对于第一环形基底移动第二环状物。

公开(公告)号：US20060228371A1

公开(公告)日：2006-10-12

申请号：US11324500

申请日：2006-01-03

申请人： Victor Raso

发明人： Victor Raso

IPC分类号： A61K39/00

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： An antibody and vectorized antibody, capable of crossing the blood brain barrier, which catalyze hydrolysis of β-amyloid at a predetermined amide linkage are described. The antibody preferentially binds a transition state analog which mimics the transition state adopted by β-amyloid during hydrolysis. Also described are methods for sequestering free β-amyloid in an animal's bloodstream or for reducing β-amyloid or for disaggregating or preventing the formation of amyloid plaques in an animal's brain by administering β-amyloid specific antibodies or by immunization with endogenous β-amyloid epitopes. Methods which utilize or generate antibodies which catalyze the hydrolysis of β-amyloid for reducing levels of circulating β-amyloid in an animal; which generate antibodies that catalyze hydrolysis of a polypeptide by immunization with an epitope having a statine analog which mimics the polypeptide's hydrolysis transition state; and which utilize reduced peptide bond analogs to mimic the polypeptide's hydrolysis transition state are also provided.

摘要翻译： 描述了能够穿过血脑屏障的抗体和载体化抗体，其催化预定酰胺键处的β-淀粉样蛋白的水解。 抗体优先结合模拟水解过程中β-淀粉样蛋白过渡态的过渡态类似物。 还描述了在动物血液中螯合游离β-淀粉样蛋白或减少β-淀粉样蛋白的方法，或通过施用β-淀粉样蛋白特异性抗体或通过用内源性β-淀粉样蛋白表位免疫来分解或预防动物脑中淀粉样蛋白斑的形成 。 利用或产生能够催化β-淀粉样蛋白水解以降低动物中循环β-淀粉样蛋白水平的抗体的方法; 其产生通过用模仿多肽水解转变状态的他汀类似物的表位进行免疫来催化多肽的水解的抗体; 并且还提供利用还原的肽键类似物来模拟多肽的水解过渡态。

公开(公告)号：US06872554B2

公开(公告)日：2005-03-29

申请号：US09992800

申请日：2001-11-06

申请人： Victor Raso

发明人： Victor Raso

IPC分类号： G01N33/53 ,  A61K38/00 ,  A61K39/395 ,  A61P25/28 ,  C07K16/18 ,  C12N9/00 ,  G01N33/577

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 are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a β-amyloid epitope. Also disclosed are methods for inhibiting the formation of β-amyloid plaques in the brain of a human, of promoting the disaggregation of a preformed β-amyloid plaque. Such methods recite the administration of a bispecific antibody.

摘要翻译： 公开了包含赋予双特异性抗体跨越血脑屏障的能力的第一抗体结合特异性的双特异性抗体，以及赋予双特异性抗体结合β-淀粉样蛋白表位的能力的第二抗体特异性。 还公开了抑制人脑中β-淀粉样蛋白斑形成的方法，促进预先形成的β-淀粉样蛋白斑块的解聚。 这种方法背诵了双特异性抗体的施用。

公开(公告)号：US20040018543A1

公开(公告)日：2004-01-29

申请号：US10618586

申请日：2003-07-15

申请人： COMMISSARIAT A L'ENERGIE ATOMIQUE

发明人： Fabrice Balavoine ,  Charles Miokowski ,  Patrick Schultz ,  Cyrille Richard

IPC分类号： B05D003/00 ,  C12Q001/68 ,  G01N033/53 ,  C12N009/00

CPC分类号： C07D495/04 ,  B82Y30/00 ,  C07C233/40 ,  C07C235/20 ,  C07C2603/24 ,  C07C2603/54 ,  C07F1/005 ,  C07F15/045 ,  C30B7/00 ,  C30B29/58 ,  G01N33/54353 ,  G01N33/54373 ,  G01N33/551 ,  Y10S977/729 ,  Y10S977/742 ,  Y10S977/746 ,  Y10S977/747 ,  Y10S977/793 ,  Y10S977/842 ,  Y10S977/848 ,  Y10S977/894 ,  Y10S977/896 ,  Y10S977/898 ,  Y10S977/92

摘要： Method for the attachment and/or crystallization of macromolecules, chemical reagents used in the said method, products obtained as well as applications of the said products in the field of materials and of structural biology, in particular as biosensors or as biomaterials. The said method comprises essentially the incubation, without stirring, for at least 15 minutes, of a biological macromolecule in solution with nanotubes of carbon closed at their ends, under suitable temperature and pH conditions.

摘要翻译： 用于大分子的附着和/或结晶的方法，所述方法中使用的化学试剂，所获得的产物以及所述产品在材料和结构生物学领域的应用，特别是作为生物传感器或作为生物材料。 所述方法基本上包括在合适的温度和pH条件下，在其末端封闭碳纳米管的情况下，不搅拌至少15分钟孵育溶液中的生物大分子。

公开(公告)号：US20030235897A1

公开(公告)日：2003-12-25

申请号：US10385065

申请日：2003-03-10

申请人： Boston Biomedical Research Institute

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.

公开(公告)号：US5718915A

公开(公告)日：1998-02-17

申请号：US424874

申请日：1995-04-19

申请人： Jorma Virtanen ,  Sinikka Virtanen

发明人： Jorma Virtanen ,  Sinikka Virtanen

IPC分类号： G01N33/531 ,  A61K9/127 ,  A61K31/70 ,  A61K38/00 ,  A61K38/46 ,  A61K47/48 ,  A61P9/10 ,  A61P31/12 ,  C07H21/00 ,  C07K14/73 ,  C07K16/00 ,  C07K16/10 ,  C07K17/00 ,  C07K19/00 ,  C12N15/09 ,  C12N15/88 ,  C12Q1/68 ,  G01N33/535 ,  C12N7/04 ,  C12N11/00

CPC分类号： C07K16/1063 ,  A61K47/48169 ,  A61K47/48369 ,  A61K47/484 ,  A61K47/48523 ,  A61K9/1271 ,  C07K19/00 ,  C12N15/88 ,  C12Q1/68 ,  G01N33/535 ,  A61K38/00 ,  C07K2319/00 ,  Y10S977/728 ,  Y10S977/729 ,  Y10S977/754 ,  Y10S977/882 ,  Y10S977/898 ,  Y10S977/907

摘要： Complexes are prepared containing two or more different effector molecules joined to each other by a joining component. At least one of the effector molecules can bind to a target molecule and at least one of the other effector molecules has therapeutic properties. The joining component can be liposomes, proteins and organic polymers including dendrimer polymers, and can be of sufficient length and/or flexibility to permit the therapeutic effector molecule to interact with a target at the same time as the binding molecules. An antiviral liposome is prepared by coupling to a liposome outer surface a hydrolytic enzyme capable of digesting a viral component and a target-binding moiety which may be a polypeptide, glycoprotein or glycoprotein fragment having specificity for viruses such as HIV-1, influenza virus and hepatitis virus. The hydrolytic enzyme may be a glycosidase, phospholipase, lipase, cholesterol esterase, nuclease or protease. A second hydrolytic enzyme and target-binding moiety may also be present, and albumin may be coupled to the liposome surface. Within the liposome may be an internal hydrolytic enzyme capable of digesting a viral component.

摘要翻译： 制备的复合物含有通过接合组分彼此连接的两个或更多个不同的效应分子。 至少一个效应分子可以结合靶分子，并且至少一个其它效应分子具有治疗性质。 连接组分可以是脂质体，蛋白质和包括树状聚合物聚合物的有机聚合物，并且可以具有足够的长度和/或柔性，以允许治疗效应分子与结合分子同时与靶相互作用。 通过将脂质体外表面与能够消化病毒组分的水解酶和靶结合部分（其可以是具有对HIV-1，流感病毒等病毒具有特异性的多肽，糖蛋白或糖蛋白片段）进行偶联来制备抗病毒脂质体， 肝炎病毒。 水解酶可以是糖苷酶，磷脂酶，脂肪酶，胆固醇酯酶，核酸酶或蛋白酶。 也可以存在第二水解酶和​​靶结合部分，并且白蛋白可以偶联到脂质体表面。 在脂质体内可以是能够消化病毒成分的内部水解酶。

公开(公告)号：US20140086937A1

公开(公告)日：2014-03-27

申请号：US13860966

申请日：2013-04-11

申请人： Victor Raso

发明人： Victor Raso

IPC分类号： A61K39/395

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。

公开(公告)号：US08086432B2

公开(公告)日：2011-12-27

申请号：US12011239

申请日：2008-01-24

申请人： Thomas D. Schneider ,  Ilya Gennadiyevich Lyakhov

发明人： Thomas D. Schneider ,  Ilya Gennadiyevich Lyakhov

IPC分类号： G06G7/58

CPC分类号： C12M99/00 ,  B82B1/00 ,  B82B3/00 ,  B82Y30/00 ,  B82Y40/00 ,  C07K14/4716 ,  H02N11/006 ,  Y10S977/729 ,  Y10T29/4984 ,  Y10T156/10

摘要： A molecular motor in which multiple concentric cylinders (or nested cones) rotate around a common longitudinal axis. Opposing complementary surfaces of the cylinders or cones are coated with complementary motor protein pairs (such as actin and myosin). The actin and myosin interact with one another in the presence of ATP to rotate the cylinders or cones relative to one another, and this rotational energy is harnessed to produce work. The concentration of ATP and the number of nested cylinders or cones can be used to control the rotational speed of the motor. The length of the cylinders can also be used to control the power generated by the motor. In another embodiment, the molecular motor includes at least two annular substrates wherein one annular substrate is coated with a first motor protein and the other annular substrate is coated with a second motor protein. The first and second motor proteins interact with each other to move the second annular relative to the first annular substrate.

摘要翻译： 一个分子马达，其中多个同心圆柱体（或嵌套圆锥体）围绕共同的纵向轴线旋转。 圆柱体或锥体的互补表面涂覆有互补的运动蛋白质对（如肌动蛋白和肌球蛋白）。 肌动蛋白和肌球蛋白在ATP存在下相互作用以相对于彼此旋转圆柱体或锥体，并且利用该旋转能量来产生作用。 ATP的浓度和嵌套圆柱体或锥体的数量可用于控制电机的转速。 气缸的长度也可用于控制电机产生的电力。 在另一个实施例中，分子马达包括至少两个环形基底，其中一个环形基底涂覆有第一运动蛋白，另一个环形基底涂覆有第二运动蛋白。 第一和第二运动蛋白相互作用以相对于第一环形基底移动第二环状物。