公开(公告)号：US5935795A

公开(公告)日：1999-08-10

申请号：US452242

申请日：1995-05-26

申请人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

发明人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

IPC分类号： A61K38/00 ,  A61K9/00 ,  A61K9/22 ,  A61K31/00 ,  A61K39/395 ,  A61M37/00 ,  A61P25/00 ,  A61P25/16 ,  A61P25/26 ,  A61P25/28 ,  C07H15/12 ,  C07K20060101 ,  C07K1/20 ,  C07K1/22 ,  C07K14/47 ,  C07K14/475 ,  C07K14/52 ,  C07K16/00 ,  C07K16/24 ,  C12N20060101 ,  C12N1/21 ,  C12N1/22 ,  C12N5/02 ,  C12N5/06 ,  C12N5/08 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12P21/06 ,  C12P21/08 ,  C12R1/19 ,  C12R1/91 ,  C07K16/22 ,  C12N5/12 ,  G01N33/53

CPC分类号： A61K9/0085 ,  C07K14/475 ,  A61K38/00 ,  Y10S530/809 ,  Y10S530/839

摘要： A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process. Antibodies to GDNF are disclosed, as well as methods for identifying members of the GDNF family of neurotrophic factors.

摘要翻译： 已经鉴定了一种称为神经胶质细胞系衍生的神经营养因子（GDNF）的新型神经营养因子，并从B49胶质母细胞瘤细胞的无血清生长条件培养基中分离。 编码GDNF的大鼠和人类基因已被克隆并测序。 已经将编码GDNF的基因亚克隆到载体中，并且该载体已经用于转化宿主细胞，以便在重组DNA过程中产生生物活性的GDNF。 公开了GDNF的抗体，以及用于鉴定GDNF家族神经营养因子成员的方法。

公开(公告)号：US06362319B1

公开(公告)日：2002-03-26

申请号：US08452229

申请日：1995-05-26

申请人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

发明人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

IPC分类号： C07K14475

CPC分类号： A61K9/0085 ,  A61K38/00 ,  C07K14/475 ,  Y10S530/809 ,  Y10S530/839

摘要： A novel neurotrophic factor referred to as glial derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

摘要翻译： 已经鉴定并分离了一种称为神经胶质神经营养因子（GDNF）的新型神经营养因子，其从B49胶质母细胞瘤细胞的无血清生长条件培养基中分离。 编码GDNF的大鼠和人类基因已被克隆并测序。 编码GDNF的基因已经被亚克隆到载体中，并且该载体已被用于转化宿主细胞，以便在重组DNA过程中产生生物活性的GDNF。

公开(公告)号：US6093802A

公开(公告)日：2000-07-25

申请号：US451374

申请日：1995-05-26

申请人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

发明人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

IPC分类号： A61K38/00 ,  A61K9/00 ,  A61K9/22 ,  A61K31/00 ,  A61K39/395 ,  A61M37/00 ,  A61P25/00 ,  A61P25/16 ,  A61P25/26 ,  A61P25/28 ,  C07H15/12 ,  C07K20060101 ,  C07K1/20 ,  C07K1/22 ,  C07K14/47 ,  C07K14/475 ,  C07K14/52 ,  C07K16/00 ,  C07K16/24 ,  C12N20060101 ,  C12N1/21 ,  C12N1/22 ,  C12N5/02 ,  C12N5/06 ,  C12N5/08 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12P21/06 ,  C12P21/08 ,  C12R1/19 ,  C12R1/91 ,  C07K14/48

CPC分类号： A61K9/0085 ,  C07K14/475 ,  A61K38/00 ,  Y10S530/809 ,  Y10S530/839

摘要： A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

摘要翻译： 已经鉴定了一种称为神经胶质细胞系衍生的神经营养因子（GDNF）的新型神经营养因子，并从B49胶质母细胞瘤细胞的无血清生长条件培养基中分离。 编码GDNF的大鼠和人类基因已被克隆并测序。 编码GDNF的基因已经被亚克隆到载体中，并且该载体已被用于转化宿主细胞，以便在重组DNA过程中产生生物活性的GDNF。

公开(公告)号：US07226758B1

公开(公告)日：2007-06-05

申请号：US08182183

申请日：1992-09-17

申请人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

发明人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

IPC分类号： C12N15/18 ,  C12N15/85 ,  C12N15/63 ,  C12N15/70

CPC分类号： A61K9/0085 ,  A61K38/00 ,  C07K14/475 ,  Y10S530/809 ,  Y10S530/839

摘要： A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

摘要翻译： 已经鉴定了一种称为神经胶质细胞系衍生的神经营养因子（GDNF）的新型神经营养因子，并从B49胶质母细胞瘤细胞的无血清生长条件培养基中分离。 编码GDNF的大鼠和人类基因已被克隆并测序。 编码GDNF的基因已经被亚克隆到载体中，并且该载体已被用于转化宿主细胞，以便在重组DNA过程中产生生物活性的GDNF。

公开(公告)号：US06221376B1

公开(公告)日：2001-04-24

申请号：US08935268

申请日：1997-09-22

申请人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

发明人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

IPC分类号： A61F200

CPC分类号： A61K9/0085 ,  A61K38/00 ,  C07K14/475 ,  Y10S530/809 ,  Y10S530/839

摘要： A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified. Genes encoding GDNF have been cloned and sequenced. Methods and devices are disclosed for the delivery of GDNF using either an implantable cell which expresses human GDNF or a biocompatible semipermeable membrane containing genetically engineered cells which express and secrete the neurotrophic factor.

摘要翻译： 已经鉴定了称为神经胶质细胞系衍生的神经营养因子（GDNF）的新型神经营养因子。 编码GDNF的基因已被克隆并测序。 公开了使用表达人GDNF的可植入细胞或含有表达和分泌神经营养因子的基因工程细胞的生物相容性半透膜的GDNF递送方法和装置。

公开(公告)号：US6015572A

公开(公告)日：2000-01-18

申请号：US453176

申请日：1995-05-30

申请人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

发明人： Leu-Fen H. Lin ,  Franklin D. Collins ,  Daniel H. Doherty ,  Jack Lile ,  Susan Bektesh

IPC分类号： A61K38/00 ,  A61K9/00 ,  A61K9/22 ,  A61K31/00 ,  A61K39/395 ,  A61M37/00 ,  A61P25/00 ,  A61P25/16 ,  A61P25/26 ,  A61P25/28 ,  C07H15/12 ,  C07K20060101 ,  C07K1/20 ,  C07K1/22 ,  C07K14/47 ,  C07K14/475 ,  C07K14/52 ,  C07K16/00 ,  C07K16/24 ,  C12N20060101 ,  C12N1/21 ,  C12N1/22 ,  C12N5/02 ,  C12N5/06 ,  C12N5/08 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12P21/06 ,  C12P21/08 ,  C12R1/19 ,  C12R1/91 ,  A61F2/00 ,  C12N11/04

CPC分类号： A61K9/0085 ,  C07K14/475 ,  A61K38/00 ,  Y10S530/809 ,  Y10S530/839

摘要： A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process. An implantable device containing recombinant GDNF secreting cells encapsulated in a semipermeable membrane may be used to treat nerve damage in patients suffering from disorders such as Parkinson's disease.

摘要翻译： 从B49胶质母细胞瘤细胞的无血清生长培养基中鉴定并分离出称为神经胶质细胞系衍生的神经营养因子（GDNF）的新型神经营养因子。 编码GDNF的大鼠和人类基因已被克隆并测序。 编码GDNF的基因已经被亚克隆到载体中，并且该载体已被用于转化宿主细胞，以便在重组DNA过程中产生生物活性的GDNF。 可以使用含有包封在半透膜中的重组GDNF分泌细胞的可植入装置来治疗患有帕金森病等病症的患者的神经损伤。

公开(公告)号：US5235043A

公开(公告)日：1993-08-10

申请号：US594126

申请日：1990-10-09

申请人： Frank Collins ,  Susan Bektesh ,  Tadahiko Kohno ,  Jack Lile

发明人： Frank Collins ,  Susan Bektesh ,  Tadahiko Kohno ,  Jack Lile

IPC分类号： A61K38/00 ,  A61P25/28 ,  C07K14/475 ,  C07K14/48 ,  C07K14/50 ,  C12N15/09 ,  C12N15/12 ,  C12N15/70 ,  C12Q1/68 ,  C12R1/32

CPC分类号： C07K14/475 ,  C07K14/48 ,  C07K14/503 ,  C12N15/70 ,  A61K38/00 ,  Y10S435/849

摘要： This invention describes processes for producing mature human members of the NGF/BDNF family of neurotrophic proteins that are fully biologically active. In addition, the gene encoding human BDNF and processes for obtaining the same are disclosed.A previously-unreported member of the NGF/BDNF family of neurotrophic proteins, NGF-3, has been identified and a portion of the gene encoding for the NGF-3 has been described. Processes for identifying additional previously unreported members of the NGF/BDNF family are also described.

公开(公告)号：US5606031A

公开(公告)日：1997-02-25

申请号：US266080

申请日：1994-06-27

申请人： Jack Lile ,  Tadahiko Kohno ,  Duane Bonam ,  Mary S. Rosendahl

发明人： Jack Lile ,  Tadahiko Kohno ,  Duane Bonam ,  Mary S. Rosendahl

IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K1/113 ,  C07K1/14 ,  C07K14/475 ,  C07K14/48 ,  C07K14/50 ,  C07K14/52 ,  C12N1/20 ,  C12N1/21 ,  C12N15/00 ,  C12N15/18 ,  C12N15/70 ,  C12P21/02 ,  C07K1/18 ,  C07K1/36 ,  C12N15/12

CPC分类号： C07K14/503 ,  C07K1/1133 ,  C07K14/475 ,  C07K14/48 ,  C12N15/70 ,  A61K38/00

摘要： A process for the production of biologically active recombinant neurotrophic factor from the NGF/BDNF family is described. The process is comprised of a) constructing a synthetic neurotrophic factor gene suitable for expression in a bacterial expression system; b) the synthetic neurotrophic factor gene is expressed in a bacterial expression system; c) the neurotrophic factor is solubilized and sulfonylated; d) sulfonylated neurotrophic factor is allowed to refold in the presence of polyethylene glycol and urea; and e) biologically active neurotrophic factor is isolated and purified.

摘要翻译： 描述了从NGF / BDNF家族生产生物活性重组神经营养因子的方法。 该方法包括：a）构建适合在细菌表达系统中表达的合成神经营养因子; b）合成的神经营养因子基因在细菌表达系统中表达; c）神经营养因子被溶解并磺酰化; d）使磺酰化神经营养因子在聚乙二醇和尿素存在下重折叠; 和e）分离和纯化生物活性的神经营养因子。

公开(公告)号：US20170335308A1

公开(公告)日：2017-11-23

申请号：US15526772

申请日：2015-11-13

申请人： Mark C. SLEEVI ,  Jack LILE ,  Merck Sharp & Dohme Corp.

发明人： Mark C. Sleevi ,  Jack Lile

IPC分类号： C12N9/76

CPC分类号： C12N9/6427 ,  C12Y304/21004 ,  G06F17/2715 ,  G06F17/274 ,  G06F17/2775 ,  G06N3/0454 ,  G06N3/088

摘要： A process for producing recombinant trypsin from prokaryote host cells in high yield and high specific activity is described. In particular, a process for producing recombinant trypsin from E. coli is described.

公开(公告)号：US5986070A

公开(公告)日：1999-11-16

申请号：US918101

申请日：1997-08-27

申请人： Frank D. Collins ,  Jack Lile ,  Susan Becktesh ,  Tadahiko Kohno ,  Drizislav Mismer, deceased

发明人： Frank D. Collins ,  Jack Lile ,  Susan Becktesh ,  Tadahiko Kohno ,  Drizislav Mismer, deceased

IPC分类号： A61K38/00 ,  C07K14/475 ,  C07K14/48 ,  C07K14/50 ,  C12N15/70 ,  C07K1/14

CPC分类号： C12N15/70 ,  C07K14/475 ,  C07K14/48 ,  C07K14/503 ,  A61K38/00

摘要： This invention describes processes for producing mature human members of the NGF/BDNF family of neurotrophic proteins that are fully biologically active. In addition, the gene encoding human BDNF and human BDNF are disclosed. A previously-unreported member of the NGF/BDNF family of neurotrophic proteins, NGF-3, has been identified and a portion of the gene encoding for the NGF-3 has been described.

摘要翻译： 本发明描述了用于产生完全生物活性的神经营养蛋白NGF / BDNF家族的成熟人成员的方法。 此外，公开了编码人BDNF和人BDNF的基因。 已经鉴定了NGF / BDNF神经营养蛋白家族NGF-3之前未报道的成员，并且已经描述了编码NGF-3的一部分基因。