公开(公告)号：US5554148A

公开(公告)日：1996-09-10

申请号：US453571

申请日：1995-05-26

Applicant: Patrick Aebischer ,  Paul C. DiCesare ,  Moses Goddard ,  Paul J. Mulhauser

Inventor： Patrick Aebischer ,  Paul C. DiCesare ,  Moses Goddard ,  Paul J. Mulhauser

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: Refillable immunoisolatory neurological therapy devices for local and controlled delivery of a biologically active factor to the brain of a patient. The devices include a cell chamber adapted for infusion with nsecretory cells and having at least one semipermeable or permselective surface across which biologically active factors secreted by the cells can be delivered to the brain. The devices also include means for introducing secretory cells into the cell chamber, and means for renewing the cells or cell medium.

Abstract translation: 用于局部和控制地将生物活性因子递送到患者脑部的可补充的免疫隔离神经治疗装置。 所述装置包括适于与分泌细胞一起输注并具有至少一个半透性或选择性选择性表面的细胞室，细胞分泌的生物活性因子可以被输送到脑。 所述装置还包括用于将分泌细胞引入细胞室的装置和用于更新细胞或细胞培养基的装置。

公开(公告)号：US5389535A

公开(公告)日：1995-02-14

申请号：US169169

申请日：1993-12-17

Applicant: Patrick Aebischer ,  Lars Wahlberg

Inventor： Patrick Aebischer ,  Lars Wahlberg

IPC: A61F2/02 ,  A61K9/00 ,  A61K9/48 ,  A61K35/12 ,  A61M31/00 ,  B01J13/02 ,  B01J13/04 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04 ,  C12N11/08 ,  C12M1/40

CPC classification number: A61K9/0092 ,  A61F2/022 ,  A61K35/12 ,  A61K9/0024 ,  A61K9/0085 ,  A61K9/4816 ,  A61K9/4833 ,  A61M31/002 ,  B01J13/02 ,  B01J13/04 ,  C12N11/04 ,  C12N11/08 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  A61K2035/126 ,  A61K2035/128 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Methods and systems are disclosed for encapsulating viable cells which produce biologically-active factors. The cells are encapsulated within a semipermeable, polymeric membrane by co-extruding an aqueous cell suspension and a polymeric solution through a common port to form a tubular extrudate having a polymeric outer coating which encapsulates the cell suspension. For example, the cell suspension and the polymeric solution can be extruded through a common extrusion port having at least two concentric bores, such that the cell suspension is extruded through the inner bore and the polymeric solution is extruded through the outer bore. The polymeric solution coagulates to form an outer coating. As the outer coating is formed, the ends of the tubular extrudate can be sealed to form a cell capsule. In one embodiment, the tubular extrudate is sealed at intervals to define separate cell compartments connected by polymeric links.

Abstract translation: 公开了用于包封产生生物活性因子的活细胞的方法和系统。 通过将水性细胞悬浮液和聚合物溶液共挤出通过共同的口以形成具有封装细胞悬浮液的聚合物外涂层的管状挤出物，将细胞包封在半透膜聚合物膜内。 例如，细胞悬浮液和聚合物溶液可以通过具有至少两个同心孔的共同挤出口挤出，使得细胞悬浮液通过内孔挤出并且聚合物溶液通过外孔挤出。 聚合物溶液凝结形成外涂层。 当形成外涂层时，管状挤出物的端部可被密封以形成电池盒。 在一个实施方案中，管状挤出物间隔密封以限定通过聚合物连接物连接的分离的细胞室。

公开(公告)号：US5158881A

公开(公告)日：1992-10-27

申请号：US461999

申请日：1990-01-08

Applicant: Patrick Aebischer ,  Lars Wahlberg

Inventor： Patrick Aebischer ,  Lars Wahlberg

IPC: A61J3/07 ,  A61F2/02 ,  A61K9/00 ,  A61K9/48 ,  A61K9/50 ,  A61K35/12 ,  A61K35/13 ,  A61M31/00 ,  B01J13/02 ,  B01J13/04 ,  C12N5/00 ,  C12N5/071 ,  C12N5/0793 ,  C12N11/04 ,  C12N11/08

CPC classification number: A61K9/0024 ,  A61F2/022 ,  A61K35/13 ,  A61K9/0085 ,  A61K9/0092 ,  A61K9/4816 ,  A61K9/4833 ,  A61M31/002 ,  B01J13/02 ,  B01J13/04 ,  C12N11/04 ,  C12N11/08 ,  C12N5/0012 ,  C12N5/0614 ,  C12N5/0619 ,  A61M2210/0687 ,  A61M2210/0693 ,  C12N2533/30

Abstract: Methods and systems are disclosed for encapsulating viable cells which produce biologically-active factors. The cells are encapsulated within a semipermeable, polymeric membrane by co-extruding an aqueous cell suspension and a polymeric solution through a common port to form a tubular extrudate having a polymeric outer coating which encapsulates the cell suspension. For example, the cell suspension and the polymeric solution can be extruded through a common extrusion port having at least two concentric bores, such that the cell suspension is extruded through the inner bore and the polymeric solution is extruded through the outer bore. The polymeric solution coagulates to form an outer coating. As the outer coating is formed, the ends of the tubular extrudate can be sealed to form a cell capsule. In one embodiment, the tubular extrudate is sealed at intervals to define separate cell compartments connected by polymeric links.

Abstract translation: 公开了用于包封产生生物活性因子的活细胞的方法和系统。 通过将水性细胞悬浮液和聚合物溶液共挤出通过共同的口以形成具有封装细胞悬浮液的聚合物外涂层的管状挤出物，将细胞包封在半透膜聚合物膜内。 例如，细胞悬浮液和聚合物溶液可以通过具有至少两个同心孔的共同挤出口挤出，使得细胞悬浮液通过内孔挤出并且聚合物溶液通过外孔挤出。 聚合物溶液凝结形成外涂层。 当形成外涂层时，管状挤出物的端部可被密封以形成电池盒。 在一个实施方案中，管状挤出物间隔密封以限定通过聚合物连接物连接的分离的细胞室。

公开(公告)号：US4878913A

公开(公告)日：1989-11-07

申请号：US93371

申请日：1987-09-04

Applicant: Patrick Aebischer ,  Robert F. Valentini ,  Pierre M. Galletti

Inventor： Patrick Aebischer ,  Robert F. Valentini ,  Pierre M. Galletti

IPC: A61F2/72

CPC classification number: A61F2/72

Abstract: Devices and methods for transmitting neural signals from a proximal stump of a transected nerve to a prosthetic apparatus are disclosed employing microelectrodes, preferably conductive fiber networks, capable of sensing electrical signals from a nerve and transmitting such signals to a prosthetic apparatus; and a semipermeable guidance channel disposed about the microelectrodes. The channels include an opening adapted to receive the proximal stump of a transected nerve, such that the channel promotes the growth of the stump and the formation of an electrical connection between the transected nerve and the microelectrode.

公开(公告)号：US20110106062A1

公开(公告)日：2011-05-05

申请号：US12940090

申请日：2010-11-05

Applicant: Osiris Marroquin ,  Patrick Aebischer ,  Maurizio Molinari ,  Nicolas Bouche

Inventor： Osiris Marroquin ,  Patrick Aebischer ,  Maurizio Molinari ,  Nicolas Bouche

IPC: A61M37/00

CPC classification number: A61M5/14276 ,  A61K9/0024 ,  A61K9/0085 ,  A61K9/0092

Abstract: The present invention is directed to devices and methods for in situ delivering an antibody or a fragment thereof to a host. In particular, the invention relates to devices and methods for in situ delivering an antibody or a fragment thereof to patient suffering for a neurodegenerative disorder or other diseases treated by antibody administration.

Abstract translation: 本发明涉及将抗体或其片段原位递送至宿主的装置和方法。 特别地，本发明涉及将抗体或其片段原位递送给患有神经退行性疾病或通过抗体给药治疗的其它疾病的患者的装置和方法。

公开(公告)号：US6027721A

公开(公告)日：2000-02-22

申请号：US650726

申请日：1996-05-20

Applicant: Joseph P. Hammang ,  Patrick Aebischer

Inventor： Joseph P. Hammang ,  Patrick Aebischer

IPC: A61K9/48 ,  A61K48/00 ,  C12N15/85 ,  C12N15/00

CPC classification number: A61K48/00

Abstract: Methods and devices are provided for gene therapy using encapsulated packaging cell lines to deliver viral particles carrying at least one heterologous gene encoding at least one biologically active molecule.

Abstract translation: 提供了使用包封的包装细胞系进行基因治疗的方法和装置，以递送携带至少一种编码至少一种生物活性分子的异源基因的病毒颗粒。

公开(公告)号：US5935849A

公开(公告)日：1999-08-10

申请号：US279773

申请日：1994-07-20

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

CPC classification number: A61L27/3839 ,  A61L27/18 ,  A61L27/227 ,  C07K14/82 ,  C12N5/0012 ,  C12N5/0068 ,  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.

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。

公开(公告)号：US5869077A

公开(公告)日：1999-02-09

申请号：US449562

申请日：1995-05-24

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

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

Abstract: A method for treating diabetes in a patient comprising subcutaneously implanting in the patient at least one immunoisolatory vehicle comprising a core comprising a volume of at least 1 .mu.l and at least about 10.sup.4 living cells which secrete insulin, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and a surrounding external jacket of a biocompatible thermoplastic or hydrogel free of said cells projecting externally thereof, said jacket being permselective and immunoisolatory, said jacket having a molecular weight cutoff permitting passage of molecules between the patient and core through said jacket wherein the insulin is released from the immunoisolatory vehicle into the patient's body to treat diabetes.

Abstract translation: 一种用于治疗患者的糖尿病的方法，包括在患者体内皮下植入至少一种免疫隔离性载体，所述至少一种免疫隔离载体包含至少含有至少1μl的体积和分泌胰岛素的至少约104个活细胞的核，所述细胞分散在生物相容性基质 包括水凝胶或细胞外基质组分，以及不含所述细胞从外部突出的生物相容性热塑性或水凝胶的外围护套，所述护套是选择性选择性的和免疫型的，所述护套具有分子量截留允许分子在患者和核心之间通过 通过所述护套，其中将胰岛素从免疫免疫介质释放到患者体内以治疗糖尿病。

公开(公告)号：US5858747A

公开(公告)日：1999-01-12

申请号：US447810

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 ,  C12N11/04 ,  C12N5/06 ,  C12N5/08 ,  C12N11/02

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: Methods and compositions are provided for controlling cell distribution within an implantable 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 bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. The bioartificial organ typically has a semipermeable membrane encapsulating a cell-containing core, and is preferably immunoisolatory. Cells can be grown on microcarriers and then loaded into the bioartificial organ. The microcarriers may be coated with an extracellular matrix component such as collagen to cause decreased cell proliferation or increased cell differentiation. Microcarriers containing cells can be suspended in a proliferation inhibiting hydrogel matrix prior to encapsulation.

Abstract translation: 提供了用于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可植入的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; 将细胞暴露于照射下，和（3）用细胞外基质分子，影响细胞增殖或粘附的分子，或惰性支架或其组合修饰生物人造器官的生长表面。 这些处理可以组合使用。 生物人造器官通常具有包封含细胞核的半透膜，并且优选地是免疫隔离的。 细胞可以在微载体上生长，然后装入生物人造器官。 微载体可以用细胞外基质组分如胶原包被，以引起细胞增殖减少或细胞分化增加。 含有细胞的微载体可以在包封之前悬浮于增殖抑制水凝胶基质中。

公开(公告)号：US5800829A

公开(公告)日：1998-09-01

申请号：US449274

申请日：1995-05-24

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: A61K9/00 ,  A61K35/12 ,  A61K9/50 ,  A61K9/14

CPC classification number: A61K9/0092 ,  A61K9/0024 ,  A61K2035/126 ,  A61K2035/128 ,  C12N2510/00

Abstract: A method of making an immunoisolatory vehicle comprised of a core comprising living cells dispersed in a biocompatible matrix is disclosed, the cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to an individual, and an external jacket surrounding said core which is a biocompatible, permselective thermoplastic or hydrogel, said jacket being free of said cells, comprising coextruding a suspension comprising said cells dispersed in a precursor matrix material comprising extracellular matrix components or a biocompatible hydrogel precursor, and a solution of a biocompatible jacket precursor from a nested dual-bore extrusion nozzle, wherein the suspension of (a) is coextruded from the inner bore and the solution of (b) is coextruded from the outer bore of the nozzle, to form said jacket as the solution of (b) and the suspension of (a) arc coextruded; and exposing the vehicle to a treatment that forms a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells and comprising a biocompatible matrix from the precursor matrix of solution (a).

Abstract translation: 公开了一种制备由包含分散在生物相容性基质中的活细胞的核心组成的免疫隔离性载体的方法，所述细胞能够分泌生物活性产物或向个体提供代谢或免疫功能，以及围绕所述 核心，其是生物相容的选择性热塑性或水凝胶，所述护套不含所述细胞，包括共挤出包含分散在包含细胞外基质组分或生物相容性水凝胶前体的前体基质材料中的所述细胞的悬浮液，以及生物相容性护套前体 从嵌套的双孔挤出喷嘴中，其中（a）的悬浮液从内孔共挤出并且（b）的溶液从喷嘴的外孔共挤出，形成作为（b）的溶液的所述夹套， 和（a）电弧共挤出的悬浮液; 并将载体暴露于形成包含体积至少为1μl和至少104个细胞并且包含来自溶液（a）的前体基质的生物相容性基质的核心的处理。