公开(公告)号：US07247714B2

公开(公告)日：2007-07-24

申请号：US10271429

申请日：2002-10-16

申请人： Charles Kunsch ,  Signe E. Varner ,  Xilin Chen ,  Jayraz Luchoomun

发明人： Charles Kunsch ,  Signe E. Varner ,  Xilin Chen ,  Jayraz Luchoomun

IPC分类号： C07H21/04 ,  C07K1/00 ,  C12Q1/00 ,  C12Q1/68 ,  C12N1/20 ,  C12N15/00

CPC分类号： C07K14/4702

摘要： This invention is in the area of regulatory DNA sequences and their methods of use. Specifically, DNA sequences found in the regulatory region of cytoprotective genes are described that are termed cytoprotective response elements. DNA constructs also are provided that include cytoprotective response elements operably linked to heterologous protein coding sequence, as well as cells and non-human organisms that include the cytoprotective response elements optionally operably linked to a heterologous protein coding sequence, and a method for screening for a compound that increases mRNA or protein regulated by a cytoprotective response element. It has been discovered that the cytoprotective response elements mediate the coordinate activation of certain genes that protect cells from damaging effects of oxidative stress, and that they do so, for example during conditions of hemodynamic shear stress.

摘要翻译： 本发明在调节DNA序列及其使用方法领域。 具体来说，描述了在细胞保护基因的调节区中发现的称为细胞保护反应元件的DNA序列。 还提供了包括可操作地连接到异源蛋白质编码序列的细胞保护反应元件的DNA构建体，以及包括任选可操作地连接到异源蛋白质编码序列的细胞保护反应元件的细胞和非人生物，以及筛选 增加由细胞保护反应元件调节的mRNA或蛋白质的化合物。 已经发现，细胞保护反应元件介导某些保护细胞免受氧化应激影响的基因的配位活化，例如在血液动力学剪切应力的条件下。

公开(公告)号：US20110159073A1

公开(公告)日：2011-06-30

申请号：US12981038

申请日：2010-12-29

申请人： Eugene deJuan ,  Signe E. Varner ,  Laurie R. Lawin

发明人： Eugene deJuan ,  Signe E. Varner ,  Laurie R. Lawin

IPC分类号： A61F2/00

CPC分类号： A61K9/0051 ,  A61F9/0017 ,  A61L27/54 ,  A61L2300/41 ,  A61L2300/416 ,  A61L2300/43 ,  A61L2300/602 ,  A61L2430/16

摘要： Featured is a method for instilling one or more bioactive agents into ocular tissue within an eye of a patient for the treatment of an ocular condition, the method comprising concurrently using at least two of the following bioactive agent delivery methods (A)-(C): (A) implanting a sustained release delivery device comprising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more bioactive agents subretinally; and (C) instilling (e.g., injecting or delivering by ocular iontophoresis) one or more bioactive agents into the vitreous humor of the eye.

摘要翻译： 特征是一种将一种或多种生物活性剂滴入患者眼睛内用于治疗眼部病症的眼组织的方法，所述方法包括同时使用至少两种以下生物活性剂递送方法（A） - （C） （A）将包含一种或多种生物活性剂的持续释放递送装置植入眼睛的后部区域，使得其将一种或多种生物活性剂递送至眼睛的玻璃体液中; （B）将一种或多种生物活性剂灌注（例如注射或植入） 和（C）将眼睛离子电渗疗法中的一种或多种生物活性剂灌注（例如，注射或递送）到眼睛的玻璃体液中。

公开(公告)号：US08454582B2

公开(公告)日：2013-06-04

申请号：US12981038

申请日：2010-12-29

申请人： Eugene deJuan ,  Signe E. Varner ,  Laurie R. Lawin

发明人： Eugene deJuan ,  Signe E. Varner ,  Laurie R. Lawin

IPC分类号： A61K9/22 ,  A61M31/00

CPC分类号： A61K9/0051 ,  A61F9/0017 ,  A61L27/54 ,  A61L2300/41 ,  A61L2300/416 ,  A61L2300/43 ,  A61L2300/602 ,  A61L2430/16

摘要： Featured is a method for instilling one or more bioactive agents into ocular tissue within an eye of a patient for the treatment of an ocular condition, the method comprising concurrently using at least two of the following bioactive agent delivery methods (A)-(C): (A) implanting a sustained release delivery device comprising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more bioactive agents subretinally; and (C) instilling (e.g., injecting or delivering by ocular iontophoresis) one or more bioactive agents into the vitreous humor of the eye.

摘要翻译： 特征是一种将一种或多种生物活性剂滴入患者眼睛内用于治疗眼部病症的眼组织的方法，所述方法包括同时使用至少两种以下生物活性剂递送方法（A） - （C） （A）将包含一种或多种生物活性剂的持续释放递送装置植入眼睛的后部区域，使得其将一种或多种生物活性剂递送至眼睛的玻璃体液中; （B）将一种或多种生物活性剂灌注（例如注射或植入） 和（C）将眼睛离子电渗疗法中的一种或多种生物活性剂灌注（例如，注射或递送）到眼睛的玻璃体液中。

公开(公告)号：US08034369B2

公开(公告)日：2011-10-11

申请号：US11225301

申请日：2005-09-12

申请人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

发明人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

IPC分类号： A61F2/00

CPC分类号： A61K31/58 ,  A61F2310/00353 ,  A61K9/0051

摘要： The invention provides a controlled release bioactive agent delivery device for treatment of an eye that includes a body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension, and a polymeric coated composition in contact with a surface of the body member, the polymeric coated composition including a first polymer, a second polymer, and a bioactive agent. The first polymer and the second polymer are hydrophobic, and the body member has a length such that, upon placement of the device at an implantation site within a posterior segment of an eye, the device does not enter a central visual field of the eye. The invention also provides methods method of delivering bioactive agent to a posterior region of an eye.

摘要翻译： 本发明提供一种用于治疗眼睛的控制释放生物活性剂递送装置，其包括具有延伸方向的本体构件，沿着延伸方向的纵向轴线，以及近端和远端，其中至少一部分 身体构件偏离延伸方向，以及与本体构件的表面接触的聚合物涂覆的组合物，聚合物涂覆的组合物包括第一聚合物，第二聚合物和生物活性剂。 第一聚合物和第二聚合物是疏水性的，并且本体构件具有这样的长度，使得当将该装置放置在眼睛后部的植入部位时，该装置不进入眼睛的中心视野。 本发明还提供了将生物活性剂递送到眼后部区域的方法。

公开(公告)号：US08003124B2

公开(公告)日：2011-08-23

申请号：US11399945

申请日：2006-04-07

申请人： Signe E. Varner ,  Nathan Robert Fox Beeley ,  Eugene de Juan

发明人： Signe E. Varner ,  Nathan Robert Fox Beeley ,  Eugene de Juan

IPC分类号： A61F2/00

CPC分类号： A61F9/0017 ,  A61K9/0051 ,  A61L27/44 ,  A61L27/54 ,  A61L2300/252 ,  A61L2300/406 ,  A61L2300/41 ,  A61L2300/416 ,  A61L2300/604 ,  A61L2300/606 ,  A61L2430/16

摘要： The invention relates to sustained release implants and to methods for treating eyes, particularly the eyes of mammals having eye disorders or diseases. By using the implants and methods described herein, the delivery of the one or more bioactive agents can be localized at a desired treatment site, particularly the choroid and the retina.

摘要翻译： 本发明涉及持续释放植入物和用于治疗眼睛，特别是具有眼睛疾病或疾病的哺乳动物的眼睛的方法。 通过使用本文所述的植入物和方法，一种或多种生物活性剂的递送可以定位在期望的治疗部位，特别是脉络膜和视网膜。

公开(公告)号：US08021680B2

公开(公告)日：2011-09-20

申请号：US10835530

申请日：2004-04-29

申请人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

发明人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

IPC分类号： A61F2/00

CPC分类号： A61K31/58 ,  A61F2310/00353 ,  A61K9/0051

摘要： The invention provides a controlled release bioactive agent delivery device that includes a body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension, and a polymeric coated composition in contact with the body member, the polymeric coated composition including a first polymer, a second polymer, and a bioactive agent, wherein the first polymer comprises polyalkyl(meth)acrylate, aromatic poly(meth)acrylate, or a combination of polyalkyl(meth)acrylate and aromatic poly(meth)acrylate, and wherein the second polymer comprises poly(ethylene-co-vinyl acetate). The invention also provides methods of delivering a bioactive agent to a patient in a controlled release manner, as well as methods of making a controlled release bioactive agent delivery device.

摘要翻译： 本发明提供一种控制释放的生物活性剂递送装置，其包括具有延伸方向的本体构件，沿着延伸方向的纵向轴线，以及近端和远端，其中，身体构件的至少一部分偏离 所述聚合物涂覆组合物包括第一聚合物，第二聚合物和生物活性剂，其中所述第一聚合物包含（甲基）丙烯酸烷基酯，（甲基）丙烯酸烷基酯，芳族聚（甲基）丙烯酸酯， ）丙烯酸酯或聚（甲基）丙烯酸烷基酯和芳族聚（甲基）丙烯酸酯的组合，其中第二聚合物包括聚（乙烯 - 共 - 乙酸乙烯酯）。 本发明还提供了以受控释放方式将生物活性剂递送到患者的方法，以及制备受控释放的生物活性剂递送装置的方法。

公开(公告)号：US07976862B2

公开(公告)日：2011-07-12

申请号：US11203879

申请日：2005-08-15

申请人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

发明人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

IPC分类号： A61F2/00

CPC分类号： A61K31/58 ,  A61F2310/00353 ,  A61K9/0051

摘要： The invention provides implantable sustained release bioactive agent delivery devices that include a body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension; and a polymeric coated composition in contact with a surface of the body member, the polymeric coated composition including a first polymer, a second polymer, and a bioactive agent. The polymeric coated composition is formulated to provide controlled release of bioactive agent over time when introduced into physiological conditions. Methods of preparing implantable devices configured and formulated to provide controlled release of bioactive agent are also provided.

摘要翻译： 本发明提供了可植入的缓释生物活性剂递送装置，其包括具有延伸方向的本体构件，沿着延伸方向的纵向轴线，以及近端和远端，其中，身体构件的至少一部分偏离 延伸方向; 以及与本体构件的表面接触的聚合物涂覆的组合物，所述聚合物涂覆的组合物包含第一聚合物，第二聚合物和生物活性剂。 配制聚合物涂覆的组合物以在引入生理条件时随时间提供生物活性剂的受控释放。 还提供了配制和配制以提供生物活性剂的受控释放的可植入装置的制备方法。

公开(公告)号：US07824704B2

公开(公告)日：2010-11-02

申请号：US11203981

申请日：2005-08-15

申请人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

发明人： Aron B. Anderson ,  Laurie R. Lawin ,  Byron C. Shen ,  Eugene de Juan ,  Signe E. Varner ,  Ralph A. Chappa

IPC分类号： A61F2/00

CPC分类号： A61K31/58 ,  A61F2310/00353 ,  A61K9/0051

摘要： The invention provides retrievable devices for sustained delivery of bioactive agent to a site within a patient, the devices including a body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension; a cap at the proximal end of the body member; and a polymeric coated composition in contact with a surface of the body member, the polymeric coated composition including a first polymer, a second polymer, and a bioactive agent.

摘要翻译： 本发明提供了用于将生物活性剂持续递送到患者内的部位的可回收装置，所述装置包括具有延伸方向的本体构件，沿着延伸方向的纵向轴线，以及近端和远端，其中， 身体构件的至少一部分偏离延伸方向; 在主体构件的近端处的帽; 以及与本体构件的表面接触的聚合物涂覆的组合物，所述聚合物涂覆的组合物包含第一聚合物，第二聚合物和生物活性剂。