公开(公告)号：US5776747A

公开(公告)日：1998-07-07

申请号：US447778

申请日：1995-05-23

Applicant: Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

Inventor： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC: A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12N11/02 ,  C12N11/04 ,  C12N11/06 ,  C12N11/08

CPC classification number: C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

Abstract: This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. A particular embodiment is directed to derivatizing or adsorbing polyethylene oxide-poly(dimethylsiloxane) copolymer (PEO-PDMS) onto a surface within the bioartificial organ to inhibit cellular attachment.

Abstract translation: 本发明涉及通过将细胞暴露于抑制细胞增殖，促进细胞分化或影响细胞附着于生物人造器官内的生长表面的处理来控制生物人造器官内的细胞分布的方法和组合物。 这样的处理包括（1）遗传操纵细胞，（2）将细胞暴露于增殖抑制化合物或分化诱导化合物，或除去细胞暴露于增殖刺激化合物或分化抑制化合物; 使细胞暴露于照射，和（3）用ECM分子修饰BAO的生长表面，影响细胞增殖或粘附的分子，或惰性支架或其组合。 这些处理可以组合使用。 一个具体实施方案涉及将聚环氧乙烷 - 聚（二甲基硅氧烷）共聚物（PEO-PDMS）衍生或吸附到生物人造器官内的表面上以抑制细胞附着。

公开(公告)号：USRE35653E

公开(公告)日：1997-11-04

申请号：US85504

申请日：1993-06-30

Applicant: Patrick Aebischer ,  Shelley R. Winn ,  Pierre M. Galletti

Inventor： Patrick Aebischer ,  Shelley R. Winn ,  Pierre M. Galletti

IPC: A61M37/00 ,  A61F2/02 ,  A61K9/00 ,  A61K9/22 ,  A61K9/48 ,  A61K9/50 ,  A61K9/52 ,  A61K35/12 ,  A61K35/22 ,  A61K35/30 ,  A61M31/00 ,  B01J13/02 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04

CPC classification number: A61K9/0092 ,  A61F2/022 ,  A61K35/22 ,  A61K35/30 ,  A61K9/0024 ,  A61K9/0085 ,  A61M31/002 ,  B01J13/02 ,  C12N11/04 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Methods and devices are disclosed for the delivery of a neurotransmitter from an implanted, neurotransmitter-secreting cell culture to a target region in a subject. The cell culture is maintained within a biocompatible, semipermeable membrane which permits the diffusion of the neurotransmitter therethrough while excluding viruses, antibodies, and other detrimental agents present in the external environment from gaining access. Implantable cell culture devices are disclosed, some of which may be retrieved from the subject, replaced or recharged with new, neurotransmitter-secreting cell cultures, and reimplanted.

Abstract translation: 公开了用于将神经递质从植入的神经递质分泌细胞培养物递送至受试者的靶区域的方法和装置。 细胞培养物保持在生物相容的半透膜中，其允许神经递质的扩散通过，同时排除存在于外部环境中的病毒，抗体和其它有害物质以获得通路。 公开了可植入细胞培养装置，其中一些可以从受试者中取出，用新的神经递质分泌细胞培养物替代或再充电并重新植入。

公开(公告)号：US5573528A

公开(公告)日：1996-11-12

申请号：US461301

申请日：1995-06-05

Applicant: Patrick Aebischer ,  Patrick A. Tresco

Inventor： Patrick Aebischer ,  Patrick A. Tresco

IPC: A61M31/00 ,  A61F2/02 ,  A61K9/00 ,  A61K9/22 ,  A61K31/195 ,  A61K35/12 ,  A61K35/39 ,  A61K35/54 ,  A61M37/00 ,  B01J13/02 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04

CPC classification number: A61F2/022 ,  A61K31/14 ,  A61K31/195 ,  A61K35/39 ,  A61K35/54 ,  A61K45/06 ,  A61K9/0024 ,  A61K9/0085 ,  A61K9/0092 ,  A61M31/002 ,  B01J13/02 ,  C12N11/04 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  C12N5/0676 ,  A61K2035/126 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Methods are disclosed for the alleviation of movement disorders via the implantation of static devices which focally release neuroinhibitory compounds to preselected brain areas. Pathological conditions to be treated by these methods include parkinsonian movement disorders, Huntington's chorea, and epileptiform seizure activity. In the treatment of parkinsonism, target areas implantation include the subthalamic nucleus, the globus pallidus internus, and the substantia nigra pars reticulata. In the treatment of epilepsy, implants may be placed in an epileptogenic focus area of neural over-activity. The devices may be polymeric implants that release neuroinhibitory compounds such as GABA, GABA agonists, GABA potentiators, action potential blockers and voltage dependent calcium channel blockers, and glutamate antagonists. Alternatively, the devices may contain living cells which secrete neuroinhibitory compounds.

公开(公告)号：US5487739A

公开(公告)日：1996-01-30

申请号：US459815

申请日：1995-06-02

Applicant: Patrick Aebischer ,  Moses Goddard ,  John G. Moldauer ,  Paul J. Mulhauser ,  Anne M. Rathbun ,  Paul R. Sanberg ,  Alfred V. Vasconcellos ,  Nicholas F. Warner

Inventor： Patrick Aebischer ,  Moses Goddard ,  John G. Moldauer ,  Paul J. Mulhauser ,  Anne M. Rathbun ,  Paul R. Sanberg ,  Alfred V. Vasconcellos ,  Nicholas F. Warner

IPC: A61F2/02 ,  A61K9/00 ,  A61K9/50 ,  A61K35/12 ,  A61K35/55 ,  A61M31/00 ,  A61M39/02 ,  B01J13/02 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04 ,  A61K9/22

CPC classification number: A61K9/0092 ,  A61F2/022 ,  A61K35/55 ,  A61K9/0024 ,  A61K9/0085 ,  A61M31/002 ,  A61M37/0069 ,  A61M39/0208 ,  B01J13/02 ,  C12N11/04 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  C12N5/0676 ,  A61K2035/126 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Implantable therapy systems are disclosed for the local and controlled delivery of a biologically active factor to the brain, spinal cord and other target regions of a subject suffering from a debilitating condition. The method of the invention involves surgically exposing an insertion site, generally located above a predetermined treatment site (12), in a patient. A cannula (20), having an obturator (30) or dilator (104) positioned therein, is inserted at the insertion site, defining a pathway to the treatment site. In some instances, the cannula can be inserted along the path of a guidewire (102) previously positioned at the treatment site. The cannula (20) is preferably a low friction polymeric material such as polytetrafluoroethylene. The cannula (20) generally has an open proximal end for receiving the obturator (30) or dilator (104), and an open distal end, preferably a tapered end, for delivery of neurologically active factors to the treatment site (12). The obturator (30) is then removed from the cannula (20), and a biocompatible tethered vehicle (40) containing a biologically active material is inserted into the cannula along the passageway. A pusher can be inserted within the cannula, behind the vehicle (40), to position the proximal end of the vehicle at the distal end of the cannula (20b). Once the vehicle (40) is positioned near the distal end of the cannula (20), the cannula is removed from the passageway, followed by the pusher, leaving the vehicle (40) positioned at the treatment site (12).

Abstract translation: 公开了植入式治疗系统，用于将局部和受控制的生物活性因子递送至患有衰弱病症的受试者的脑，脊髓和其他目标区域。 本发明的方法涉及通常在患者体内暴露通常位于预定治疗部位（12）上方的插入部位。 具有定位在其中的闭塞器（30）或扩张器（104）的插管（20）插入插入位置，从而限定到治疗部位的通路。 在一些情况下，套管可以沿着预先位于治疗部位的导丝（102）的路径插入。 插管（20）优选为低摩擦聚合材料，例如聚四氟乙烯。 插管（20）通常具有用于接收封闭器（30）或扩张器（104）的开放近端，以及用于将神经活性因子递送至治疗部位（12）的开口远端，优选地为锥形末端。 然后将塞子（30）从插管（20）中取出，并且将包含生物活性物质的生物相容性系留载体（40）沿通道插入插管中。 推动器可以插入插管内，在车辆（40）后面，以将车辆的近端定位在套管（20b）的远端。 一旦车辆（40）定位在套管（20）的远端附近，则套管从通道中移除，随后是推动器，使车辆（40）位于治疗部位（12）处。

公开(公告)号：US5474547A

公开(公告)日：1995-12-12

申请号：US168858

申请日：1993-12-16

Applicant: Patrick Aebischer ,  Patrick A. Tresco

Inventor： Patrick Aebischer ,  Patrick A. Tresco

IPC: A61M31/00 ,  A61F2/02 ,  A61K9/00 ,  A61K9/22 ,  A61K31/195 ,  A61K35/12 ,  A61K35/39 ,  A61K35/54 ,  A61M37/00 ,  B01J13/02 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04

CPC classification number: A61F2/022 ,  A61K31/14 ,  A61K31/195 ,  A61K35/39 ,  A61K35/54 ,  A61K45/06 ,  A61K9/0024 ,  A61K9/0085 ,  A61K9/0092 ,  A61M31/002 ,  B01J13/02 ,  C12N11/04 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  C12N5/0676 ,  A61K2035/126 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Methods are disclosed for the alleviation of movement disorders via the implantation of static devices which focally release neuroinhibitory compounds to preselected brain areas. Pathological conditions to be treated by these methods include parkinsonian movement disorders, Huntington's chorea, and epileptiform seizure activity. In the treatment of parkinsonism, target areas implantation include the subthalamic nucleus, the globus pallidus internus, and the substantia nigra pars reticulata. In the treatment of epilepsy, implants may be placed in an epileptogenic focus area of neural over-activity. The devices may be polymeric implants that release neuroinhibitory compounds such as GABA, GABA agonists, GABA potentiators, action potential blockers and voltage dependent calcium channel blockers, and glutamate antagonists. Alternatively, the devices may contain living cells which secrete neuroinhibitory compounds.

Abstract translation: 公开了通过植入将脑神经抑制化合物向预选脑区域释放的静态装置来减轻运动障碍的方法。 通过这些方法治疗的病理状况包括帕金森病运动障碍，亨廷顿舞蹈病和癫痫发作活动。 在治疗帕金森综合征时，目标区域植入包括丘脑底核，苍白球和黑质黑质。 在癫痫治疗中，植入物可能被置于神经过度活动的癫痫发生重点领域。 该装置可以是释放神经抑制性化合物如GABA，GABA激动剂，GABA增效剂，动作电位阻断剂和电压依赖性钙通道阻滞剂以及谷氨酸拮抗剂的聚合物植入物。 或者，装置可以含有分泌神经抑制性化合物的活细胞。

公开(公告)号：US5106627A

公开(公告)日：1992-04-21

申请号：US613109

申请日：1990-11-14

Applicant: Patrick Aebischer ,  Shelley R. Winn

Inventor： Patrick Aebischer ,  Shelley R. Winn

IPC: A61F2/02 ,  A61K9/00 ,  A61K9/22 ,  A61K35/12 ,  A61K35/30 ,  A61M31/00 ,  B01J13/02 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04

CPC classification number: A61K9/0092 ,  A61F2/022 ,  A61K35/12 ,  A61K35/30 ,  A61K38/1825 ,  A61K9/0024 ,  A61K9/0085 ,  A61M31/002 ,  B01J13/02 ,  C12N11/04 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  C12N5/0676 ,  A61K2035/126 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Neurological therapy devices are disclosed for the local and controlled delivery of a neurotransmitter to the brain of a subject suffering from neurotransmitter deficiency or dysfunction. In one embodiment the device includes a biocompatible, implantable, and retrievable polymeric insert including a source of neurotransmitter embedded therein. In another embodiment, the device includes a retrievable source of neurotransmitter including at least one neurotransmitter-secreting cell encapsulated within a semipermeable membrane allowing the diffusion therethrough of the neurotransmitter, and further includes a source of growth factor in close proximity to the neurotransmitter-secreting cells.

Abstract translation: 公开了用于局部和控制递送神经递质给患有神经递质缺乏或功能障碍的受试者脑部的神经治疗装置。 在一个实施方案中，该装置包括生物相容的，可植入的和可回收的聚合物插入物，其包含嵌入其中的神经递质源。 在另一个实施方案中，该装置包括可回收的神经递质来源，其包括至少一种包封在半透膜内的神经递质分泌细胞，其允许神经递质的扩散，并且还包括紧邻神经递质分泌细胞的生长因子源 。

公开(公告)号：US4892538A

公开(公告)日：1990-01-09

申请号：US121626

申请日：1987-11-17

Applicant: Patrick Aebischer ,  Shelley R. Winn ,  Pierre M. Galletti

Inventor： Patrick Aebischer ,  Shelley R. Winn ,  Pierre M. Galletti

IPC: A61M37/00 ,  A61F2/02 ,  A61K9/00 ,  A61K9/22 ,  A61K9/48 ,  A61K9/50 ,  A61K9/52 ,  A61K35/12 ,  A61K35/22 ,  A61K35/30 ,  A61M31/00 ,  B01J13/02 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04

CPC classification number: A61K9/0092 ,  A61F2/022 ,  A61K35/22 ,  A61K35/30 ,  A61K9/0024 ,  A61K9/0085 ,  A61M31/002 ,  B01J13/02 ,  C12N11/04 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Methods and devices are disclosed for the delivery of a neurotransmitter from an implanted, neurotransmitter-secreting cell culture to a target region in a subject. The cell culture is maintained within a biocompatible, semipermeable membrane which permits the diffusion of the neurotransmitter therethrough while excluding viruses, antibodies, and other detrimental agents present in the external environment from gaining access. Implantable cell culture devices are disclosed, some of which may be retrieved from the subject, replaced or recharged with new, neurotransmitter-secreting cell cultures, and reimplanted.

Abstract translation: 公开了用于将神经递质从植入的神经递质分泌细胞培养物递送至受试者的靶区域的方法和装置。 细胞培养物保持在生物相容的半透膜中，其允许神经递质的扩散通过，同时排除存在于外部环境中的病毒，抗体和其它有害物质以获得通路。 公开了可植入细胞培养装置，其中一些可以从受试者中取出，用新的神经递质分泌细胞培养物替代或再充电并重新植入。

公开(公告)号：US08329654B2

公开(公告)日：2012-12-11

申请号：US12717305

申请日：2010-03-04

Applicant: Nicole Deglon ,  Patrick Aebischer ,  Jean-Charles Bensadoun

Inventor： Nicole Deglon ,  Patrick Aebischer ,  Jean-Charles Bensadoun

IPC: A61K38/00 ,  A61K38/16

CPC classification number: A61K38/204 ,  A61K48/00

Abstract: The invention relates to the use of an IL-6R/IL-6 chimera, a mutein, isoform, fused protein, functional derivative, active fraction or circularly permutated derivative or a salt thereof, for the manufacture of a medicament for the treatment and/or prevention of Huntington's disease.

Abstract translation: 本发明涉及IL-6R / IL-6嵌合体，突变蛋白，同种型，融合蛋白，功能衍生物，活性级分或环状置换衍生物或其盐在制备用于治疗和/ 或预防亨廷顿氏病。

公开(公告)号：US20100166703A1

公开(公告)日：2010-07-01

申请号：US12717305

申请日：2010-03-04

Applicant: NICOLE DEGLON ,  PATRICK AEBISCHER ,  JEAN-CHARLES BENSADOUN

Inventor： NICOLE DEGLON ,  PATRICK AEBISCHER ,  JEAN-CHARLES BENSADOUN

IPC: A61K38/20 ,  A61K35/12 ,  A61K31/7088

CPC classification number: A61K38/204 ,  A61K48/00

Abstract: The invention relates to the use of an IL-6R/IL-6 chimera, a mutein, isoform, fused protein, functional derivative, active fraction or circularly permutated derivative or a salt thereof, for the manufacture of a medicament for the treatment and/or prevention of Huntington's disease.

Abstract translation: 本发明涉及IL-6R / IL-6嵌合体，突变蛋白，同种型，融合蛋白，功能衍生物，活性级分或环状置换衍生物或其盐在制备用于治疗和/ 或预防亨廷顿氏病。

公开(公告)号：US06960351B2

公开(公告)日：2005-11-01

申请号：US10624081

申请日：2003-07-21

Applicant: Keith E. Dionne ,  Dwaine F. Emerich ,  Diane Hoffman ,  Paul R. Sanberg ,  Lisa Christenson ,  Orion D. Hegre ,  David W. Scharp ,  Paul E. Lacy ,  Patrick Aebischer ,  Alfred V. Vasconcellos ,  Michael J. Lysaght ,  Frank T. Gentile

Inventor： Keith E. Dionne ,  Dwaine F. Emerich ,  Diane Hoffman ,  Paul R. Sanberg ,  Lisa Christenson ,  Orion D. Hegre ,  David W. Scharp ,  Paul E. Lacy ,  Patrick Aebischer ,  Alfred V. Vasconcellos ,  Michael J. Lysaght ,  Frank T. Gentile

IPC: A61F2/02 ,  A61K9/00 ,  A61K9/48 ,  A61K9/50 ,  A61K35/12 ,  A61K35/30 ,  A61K35/39 ,  A61K38/18 ,  A61K39/395 ,  A61K47/36 ,  A61K48/00 ,  A61L27/00 ,  C12N5/00 ,  C12N5/071 ,  C12N5/077 ,  A61F13/00 ,  A61F2/00 ,  A61F9/14 ,  A61F9/16 ,  A61F9/22

CPC classification number: A61K9/0092 ,  A61K9/0024 ,  A61K9/4816 ,  A61K35/12 ,  A61K35/30 ,  A61K35/39 ,  A61K38/185 ,  A61K48/00 ,  A61K2035/126 ,  A61K2035/128 ,  C12N5/0012 ,  C12N5/0062 ,  C12N5/0614 ,  C12N5/0656 ,  C12N5/0677 ,  C12N2510/02 ,  Y10S514/814 ,  Y10S514/866

Abstract: An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process. A method for isolating cells within a biocompatible, immunoisolatory implantable vehicle, which protects the isolated cells from attack by the immune system of an individual in whom the vehicle is implanted. A method of providing a needed biological product or metabolic function to an individual, comprising implanting into the individual an immunoisolatory vehicle containing isolated cells which produce the product or provide the metabolic function.

Abstract translation: 用于植入到产生所需产品或提供所需代谢功能的细胞个体中的免疫分析载体。 载体由含有分离的细胞和足以维持细胞的材料的核心区域组成，以及不含分离细胞的选择性选择性生物相容的外周区域，所述细胞免疫分离核心，但提供分泌产物或代谢功能的递送， 个人 该载体特别适合于从朗格汉斯的免疫隔离胰岛递送胰岛素，并且还可有利地用于递送高分子量产物，例如大于IgG的产物。 在共挤出方法的第一实施方案中和在逐步方法的第二实施方案中制备生物相容的免疫隔离可植入载体的方法。 一种用于分离生物相容的免疫隔离可植入载体中的细胞的方法，其保护分离的细胞免受被植入其中的个体的免疫系统的攻击。 向个体提供所需的生物制品或代谢功能的方法，包括向个体植入包含产生产物或提供代谢功能的分离细胞的免疫隔离载体。