公开(公告)号：EP0792369B1

公开(公告)日：2000-04-05

申请号：EP95940324.7

申请日：1995-11-16

申请人： CAYLA

发明人： TIRABY, Gérard ,  REYNES, Jean-Paul ,  TIRABY, Michèle ,  CAZAUX, Christophe ,  DROCOURT, Daniel

IPC分类号： C12N15/85 ,  C12N15/54 ,  C12N15/55 ,  A61K48/00 ,  A61K38/43

CPC分类号： C12N9/1211 ,  A61K38/00 ,  A61K48/00 ,  C12N9/1077 ,  C12N9/78 ,  C12Y204/02009 ,  C12Y207/01021 ,  C12Y207/04009 ,  Y02A50/473

摘要： Two groups of hybrid suicide genes are disclosed, where the genes of one group specifically activate 5-fluorocytosine, a pyrimidine nucleobase analogue, while the genes of the other group activate azidothymidine, a pyrimidine nucleobase analogue, into derivatives toxic for mammalian cells. A variety of methods are also disclosed for selectively killing transfected tumour cells or immune cells using a single hybrid suicide gene or a combination of two hybrid suicide genes selected for the complementarity of their antimetabolic activities. Furthermore, eukaryotic vectors including two suicide gene expression units, i.e. a first unit sensitising the tumour cells to 5-fluorocytosine or 5-fluorouracil, and a second making HIV-infected cells synergistically resistant to azidothymidine.

公开(公告)号：EP0910406A1

公开(公告)日：1999-04-28

申请号：EP97915994.0

申请日：1997-02-14

申请人： Heska Corporation

发明人： HAANES, Elizabeth, J. ,  FRANK, Rexann, A.

IPC分类号： C12N15 ,  A61K31 ,  A61K39 ,  A61P31 ,  A61P33 ,  A61P37 ,  C07K14 ,  C12N5 ,  C12N7

CPC分类号： C12N15/86 ,  C07K14/005 ,  C12N7/00 ,  C12N9/1211 ,  C12N2710/16721 ,  C12N2710/16722 ,  C12N2710/16743

摘要： The present invention includes novel recombinant canine herpesvirus (CHV) and novel recombinant CHV genomes, and particularly to those CHV and CHV genomes that contain heterologous nucleic acid molecules. The present invention also relates to the use of such genomes and viruses in a variety of applications, including therapeutic compositions to protect animals from disease. The present invention also relates to novel isolated CHV nucleic acid molecules, to CHV proteins encoded by such nucleic acid molecules, and to antibodies raised against such CHV proteins as well as to the use of such CHV nucleic acid molecules, proteins and antibodies as therapeutic compositions to protect an animal from CHV. The present invention also includes constructs comprising CHV nucleic acid molecules that include heterologous nucleic acid molecules, to recombinant vectors including such constructs, and to the use of such constructs and vectors in the production of recombinant CHV and recombinant CHV genomes.

公开(公告)号：EP0674716B1

公开(公告)日：1998-09-02

申请号：EP94902825.2

申请日：1993-12-16

申请人： UNIVERSITE PIERRE ET MARIE CURIE PARIS VI

发明人： KLATZMANN, David ,  CARUSO, Manuel

IPC分类号： C12N15/86 ,  C12N9/12 ,  A61K48/00 ,  C12N5/10

CPC分类号： C12N9/1211 ,  A61K38/00 ,  A61K48/00 ,  C12N15/86 ,  C12N2740/13043

摘要： The invention relates to recombinant retroviral vectors, derived from Moloney MuLV, carrying a suicide gene susceptible of transforming an inactive substance into a toxic substance for cells going through a division process, said vectors being characterized by the presence in their structure of LTR sequences from variants of MuLV, and having the properties: (a) of not being inactivated during passage through the carcino-embryonic or line germinal cells of mice; (b) the expression of the suicide gene kills only the cells in the course of division.

公开(公告)号：EP0845537A1

公开(公告)日：1998-06-03

申请号：EP97121051.3

申请日：1990-08-17

申请人： CHIRON CORPORATION

发明人： Gruber, Harry E. ,  Jolly, Douglas J. ,  Respess, James G. ,  Laikind, Paul K. ,  Chang, Stephen M. ,  Chada, Sunil D. ,  Warner, John ,  Barber, Jack R. ,  St. Louis, Daniel C.

IPC分类号： C12N15/86 ,  A61K48/00

CPC分类号： C12N15/86 ,  A01K2217/05 ,  A01K2267/03 ,  A61K35/13 ,  A61K39/0011 ,  A61K48/00 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/57 ,  C12N9/1211 ,  C12N2740/13022 ,  C12N2740/13023 ,  C12N2740/13043 ,  C12N2740/16023 ,  C12N2740/16122 ,  C12N2740/16222 ,  C12N2740/16322

摘要： The present invention relates to replication-defective recombinant retroviruses for therapeutic use. In particular, it relates to use of replication-defective recombinant retroviruses carrying a vector construct capable of expressing in human cells an enzyme which converts an agent with little or no cytotoxicity into a cytotoxic agent in the treatment of graft vs host disease.

摘要翻译： 本发明涉及用于治疗用途的复制缺陷型重组逆转录病毒。 特别地，本发明涉及携带能够在人类细胞中表达转化具有很少或没有细胞毒性的药剂转化为细胞毒性剂的药物的载体构建体的复制缺陷型重组逆转录病毒在治疗移植物抗宿主病方面的用途。

公开(公告)号：EP0557459B1

公开(公告)日：1997-10-22

申请号：EP92902004.8

申请日：1991-11-12

申请人： IMMUNEX CORPORATION

发明人： LUPTON, Stephen, D.

IPC分类号： C12N15/65 ,  C12N15/62 ,  C12N5/10

CPC分类号： C12N9/1211 ,  A61K48/00 ,  C12N15/62 ,  C12N15/65

摘要： The invention provides selectable fusion genes comprising a dominant positive selectable gene fused to and in reading frame with a negative selectable gene. The selectable fusion gene encodes a single bifunctional fusion protein which is capable of conferring a dominant positive selectable phenotype and a negative selectable phenotype on a cellular host. A dominant positive selectable phenotype is conferred, for example, by the hph gene for hygromycin B resistance (Hmr). A dominant negative selectable phenotype is conferred, for example, by the HSV-I TK gene for gansiclovir sensitivity (GCVs). The present invention also provides recombinant expression vectors, for example, retroviral vectors, which include selectable fusion genes, and cells transduced with the recombinant expression vectors. The bifunctional selectable fusion genes are expressed and regulated as a single genetic entity, permitting co-regulation and co-expression with a high degree of efficiency.

公开(公告)号：EP0792369A1

公开(公告)日：1997-09-03

申请号：EP95940324.0

申请日：1995-11-16

申请人： CAYLA

发明人： TIRABY, Gérard ,  REYNES, Jean-Paul ,  TIRABY, Michèle ,  CAZAUX, Christophe ,  DROCOURT, Daniel

IPC分类号： A61K38 ,  C12N9 ,  C12N15 ,  A61K48

CPC分类号： C12N9/1211 ,  A61K38/00 ,  A61K48/00 ,  C12N9/1077 ,  C12N9/78 ,  C12Y204/02009 ,  C12Y207/01021 ,  C12Y207/04009 ,  Y02A50/473

摘要： Two groups of hybrid suicide genes are disclosed, where the genes of one group specifically activate 5-fluorocytosine, a pyrimidine nucleobase analogue, while the genes of the other group activate azidothymidine, a pyrimidine nucleobase analogue, into derivatives toxic for mammalian cells. A variety of methods are also disclosed for selectively killing transfected tumour cells or immune cells using a single hybrid suicide gene or a combination of two hybrid suicide genes selected for the complementarity of their antimetabolic activities. Furthermore, eukaryotic vectors including two suicide gene expression units, i.e. a first unit sensitising the tumour cells to 5-fluorocytosine or 5-fluorouracil, and a second making HIV-infected cells synergistically resistant to azidothymidine.

公开(公告)号：EP0653943A4

公开(公告)日：1996-10-02

申请号：EP93917068

申请日：1993-07-09

申请人： BAYLOR COLLEGE MEDICINE

发明人： LEDLEY FRED D

IPC分类号： C12N15/09 ,  A61K31/70 ,  A61K38/00 ,  A61K47/48 ,  A61K48/00 ,  A61P29/00 ,  A61P43/00 ,  C07H21/04 ,  C07K14/705 ,  C07K14/715 ,  C12N5/10 ,  C12N9/06 ,  C12N9/12 ,  C12N9/14 ,  C12N15/113 ,  C12N15/85 ,  C12N15/87 ,  C12N15/88 ,  A61K39/395 ,  C12N15/90

CPC分类号： C12N15/1137 ,  A01K2217/05 ,  A01K2217/30 ,  A01K2227/107 ,  A01K2267/0306 ,  A01K2267/0325 ,  A01K2267/0368 ,  A61K38/00 ,  A61K47/645 ,  A61K48/00 ,  C07K14/705 ,  C07K14/715 ,  C12N9/0046 ,  C12N9/1211 ,  C12N9/14 ,  C12N15/8509 ,  C12N15/87 ,  C12N15/88 ,  C12Y114/99001

摘要： A method of transfecting a cell in a structure of a joint is disclosed, wherein a DNA vector containing a nucleic acid cassette encoding, for example, a cell ablation agent or a therapeutic agent, is directly injected into the joint. The invention also includes a transfected synovial cell.

公开(公告)号：EP0729515A1

公开(公告)日：1996-09-04

申请号：EP95901512.0

申请日：1994-11-18

申请人： THE WELLCOME FOUNDATION LIMITED

发明人： RICHARDS, Cynthia, Ann ,  HUBER, Brian

IPC分类号： C12N15 ,  A61K31 ,  A61K35 ,  A61K38 ,  A61K48 ,  A61P35 ,  C07H19 ,  C07H21 ,  C07K14 ,  C12N5 ,  C12N7 ,  C12N9 ,  C12R1

CPC分类号： C12N15/86 ,  A61K31/70 ,  A61K31/711 ,  A61K35/768 ,  A61K38/50 ,  A61K48/00 ,  C07H19/06 ,  C07H19/16 ,  C07H21/00 ,  C07K14/765 ,  C12N7/00 ,  C12N9/12 ,  C12N9/1211 ,  C12N15/85 ,  C12N2740/13043 ,  C12N2740/13045 ,  C12N2740/13051 ,  C12N2740/13062 ,  C12N2810/60 ,  C12N2830/008 ,  C12N2830/85 ,  C12N2840/20 ,  C12Y305/04001 ,  A61K2300/00

摘要： The invention relates to the transcriptional regulatory sequence (TRS) of carcinoembryonic antigen (CEA) and molecular chimaera comprising the CEA TRS and DNA encoding a heterologous enzyme. CEA TRS is capable of targeting expression of the heterologous enzyme to CEA+ cells and the heterologous enzyme is preferably an enzyme capable of catalysing the production of an agent cytotoxic or cytostatic to CEA+ cells. For example the enzyme may be cytosine deaminase which is capable of catalysing formation of the cytotoxic compound 5-fluorouracil from the non toxic compound 5-fluorocytosine.

公开(公告)号：EP0674716A1

公开(公告)日：1995-10-04

申请号：EP94902825.0

申请日：1993-12-16

申请人： UNIVERSITE PIERRE ET MARIE CURIE PARIS VI

发明人： KLATZMANN, David ,  CARUSO, Manuel

IPC分类号： C12N15 ,  A61K31 ,  A61K38 ,  A61K48 ,  A61P35 ,  C12N5 ,  C12N9

CPC分类号： C12N9/1211 ,  A61K38/00 ,  A61K48/00 ,  C12N15/86 ,  C12N2740/13043

摘要： The invention relates to recombinant retroviral vectors, derived from Moloney MuLV, carrying a suicide gene susceptible of transforming an inactive substance into a toxic substance for cells going through a division process, said vectors being characterized by the presence in their structure of LTR sequences from variants of MuLV, and having the properties: (a) of not being inactivated during passage through the carcino-embryonic or line germinal cells of mice; (b) the expression of the suicide gene kills only the cells in the course of division.

公开(公告)号：EP0657541A1

公开(公告)日：1995-06-14

申请号：EP95100250.0

申请日：1990-08-29

申请人： THE WELLCOME FOUNDATION LIMITED

发明人： Huber, Brian ,  Richards, Cynthia Ann ,  Krenitsky, Thomas Anthony

IPC分类号： C12N15/85 ,  C12N15/52 ,  C12N15/86 ,  C12N7/01 ,  A61K48/00 ,  A61K31/70

CPC分类号： C07H19/06 ,  A61K31/70 ,  A61K31/711 ,  A61K38/00 ,  A61K48/00 ,  C07H19/16 ,  C07H21/00 ,  C07K14/765 ,  C12N7/00 ,  C12N9/1211 ,  C12N15/85 ,  C12N15/86 ,  C12N2740/13023 ,  C12N2740/13043 ,  C12N2740/13045 ,  C12N2810/60 ,  C12N2830/008 ,  C12N2830/85 ,  C12Y207/01021 ,  A61K2300/00

摘要： Novel molecular chimaeras produced by recombinant DNA techniques are described. They comprise a target tissue specific transcriptional regulatory sequence (TRS) linked and controlling the expression of a heterologous enzyme for example Varicella Zoster Virus Thymidine Kinase (VZV TK) gene. A molecular chimaera is packaged into a synthetic retroviral particle which is capable of infecting mammalian tissue. This in turn may be administered to a patient, and the TRS will be selectively transcriptionally activated in the target tissue (for example cancerous tissue). Administration of compounds which are selectively metabolised by the enzyme produce cytotoxic or cytostatic metabolites in situ thereby selectively killing or arresting the growth of the target cell.

摘要翻译： 描述了通过重组DNA技术产生的新分子嵌合体。 它们包含连接并控制异源酶例如水痘带状疱疹病毒胸苷激酶（VZV TK）基因表达的靶组织特异性转录调节序列（TRS）。 分子嵌合体被包装成能够感染哺乳动物组织的合成逆转录病毒颗粒。 这又可以被施用于患者，并且TRS将在目标组织（例如癌性组织）中被选择性地转录激活。 施用由酶选择性代谢的化合物原位产生细胞毒性或细胞抑制性代谢物，从而选择性杀死或阻止靶细胞的生长。