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    METHODS AND COMPOSITIONS FOR MODULATING RESPONSIVENESS TO CORTICOSTEROIDS
    1.
    发明申请
    METHODS AND COMPOSITIONS FOR MODULATING RESPONSIVENESS TO CORTICOSTEROIDS 审中-公开
    调节对角质疏螺旋体的响应的方法和组合物

    公开(公告)号：WO0119373A3

    公开(公告)日：2001-10-04

    申请号：PCT/US0024725

    申请日：2000-09-08

    Applicant: BASF AG ,  SEKUT LES ,  CARTER ADAM ,  GHAYUR TARIQ ,  BANERJEE SUBHASHIS ,  TRACEY DANIEL E

    Inventor： SEKUT LES ,  CARTER ADAM ,  GHAYUR TARIQ ,  BANERJEE SUBHASHIS ,  TRACEY DANIEL E

    IPC: A61K31/57 ,  A61K39/395 ,  A61K45/06 ,  C07K16/28

    CPC classification number: C07K16/28 ,  A61K31/57 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  A61K2300/00

    Abstract: Method for modulating responsiveness to corticosteroids in a subject are provided. In the method of the invention, an agent which antagonizes a target that regulates production of IFN- gamma in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an IL-18 antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In yet another embodiment, the agent is an NK cell antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. In yet another preferred embodiment, the agent is an anti-asialo-GM1 antibody or an NK1.1 antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders. Pharmaceutical compositions comprising an agent which antagonizes a target that regulates production of IFN- gamma in a subject, a corticosteroid and a pharmaceutically acceptable carrier are also provided. A preferred composition comprises an ICE inhibitor, a corticosteroid and a pharmaceuticaly acceptable carrier.

    Abstract translation: 提供了调节受试者对皮质类固醇的反应性的方法。 在本发明的方法中，将拮抗受试者中IFN-γ产生的靶标拮抗剂的试剂与皮质类固醇组合给予受试者，使得受试者对皮质类固醇的反应性与皮质类固醇相比被调节 单独对受试者施用。 在一个实施方案中，该药剂是IL-18拮抗剂。 在另一个实施方案中，该药剂是白细胞介素-12（IL-12）拮抗剂。 在另一个实施方案中，该药剂是NK细胞拮抗剂。 在优选的实施方案中，所述试剂是半胱天冬酶家族蛋白酶，优选ICE抑制剂的抑制剂。 在另一个优选的实施方案中，所述试剂是抗IL-12单克隆抗体。 在另一个优选的实施方案中，该试剂是抗脱唾液酸-GM1抗体或NK1.1抗体。 其它优选的试剂包括磷酸二酯酶IV抑制剂和β-2激动剂。 本发明的方法可用于治疗各种炎症和免疫疾病和病症。 还提供了包含拮抗受试者中的IFN-γ生成的靶的药剂，皮质类固醇和药学上可接受的载体的药物组合物。 优选的组合物包含ICE抑制剂，皮质类固醇和药物可接受的载体。

    COMPOSITIONS FOR MODULATING RESPONSIVENESS TO CORTICOSTEROIDS
    2.
    发明申请
    COMPOSITIONS FOR MODULATING RESPONSIVENESS TO CORTICOSTEROIDS 审中-公开
    用于调节对角质素的响应的组合物

    公开(公告)号：WO9841232A3

    公开(公告)日：2000-10-05

    申请号：PCT/US9804916

    申请日：1998-03-12

    Applicant: BASF AG ,  SEKUT LES ,  CARTER ADAM ,  GHAYUR TARIQ ,  BANERJEE SUBHASHIS ,  TRACEY DANIEL E

    Inventor： SEKUT LES ,  CARTER ADAM ,  GHAYUR TARIQ ,  BANERJEE SUBHASHIS ,  TRACEY DANIEL E

    IPC: A61K45/06 ,  A61K31/40 ,  A61K31/505 ,  A61K38/20 ,  A61K38/46 ,  A61K39/395 ,  A61P3/10 ,  A61P9/02 ,  A61P11/06 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07K16/24 ,  A61K31/57

    CPC classification number: C07K16/244 ,  A61K31/56 ,  A61K38/1793 ,  A61K45/06 ,  A61K2300/00

    Abstract: Method for modulating responsiveness to corticosteroids in a subjet are provided. In the method of the invention, an agent which antagonizes a target that regulates production of IFN- gamma in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an IL-18 antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In yet another embodiment, the agent is an NK cell antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. In yet another preferred embodiment, the agent is an anti-asialo-GM1 antibody or an NK1.1 antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders. Pharmaceutical compositions comprising an agent which antagonizes a target that regulates production of IFN- gamma in a subject, a corticosteroid and a pharmaceutically acceptable carrier are also provided. A preferred composition comprises an ICE inhibitor, a corticosteroid and a pharmaceutically acceptable carrier.

    Abstract translation: 提供了一种用于调节子流体中对皮质类固醇的反应性的方法。 在本发明的方法中，将拮抗受试者中IFN-γ产生的靶标拮抗剂的试剂与皮质类固醇组合给予受试者，使得受试者对皮质类固醇的反应性与皮质类固醇相比被调节 单独对受试者施用。 在一个实施方案中，该药剂是IL-18拮抗剂。 在另一个实施方案中，该药剂是白细胞介素-12（IL-12）拮抗剂。 在另一个实施方案中，该药剂是NK细胞拮抗剂。 在优选的实施方案中，所述试剂是半胱天冬酶家族蛋白酶，优选ICE抑制剂的抑制剂。 在另一个优选的实施方案中，所述试剂是抗IL-12单克隆抗体。 在另一个优选的实施方案中，该试剂是抗脱唾液酸-GM1抗体或NK1.1抗体。 其它优选的试剂包括磷酸二酯酶IV抑制剂和β-2激动剂。 本发明的方法可用于治疗各种炎症和免疫疾病和病症。 还提供了包含拮抗受试者中的IFN-γ生成的靶的药剂，皮质类固醇和药学上可接受的载体的药物组合物。 优选的组合物包含ICE抑制剂，皮质类固醇和药学上可接受的载体。

    METHODS AND COMPOSITIONS FOR MODULATING RESPONSIVENESS TO CORTICOSTEROIDS
    6.
    发明专利
    METHODS AND COMPOSITIONS FOR MODULATING RESPONSIVENESS TO CORTICOSTEROIDS 未知

    公开(公告)号：SK122199A3

    公开(公告)日：2000-12-11

    申请号：SK122199

    申请日：1998-03-12

    Applicant: BASF AG

    Inventor： SEKUT LES ,  CARTER ADAM ,  GHAYUR TARIQ ,  BANERJEE SUBHASHIS ,  TRACEY DANIEL E

    IPC: A61K31/40 ,  A61K45/06 ,  A61K31/505 ,  A61K38/20 ,  A61K38/46 ,  A61K39/395 ,  A61P3/10 ,  A61P9/02 ,  A61P11/06 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07K16/24 ,  A61K39/00

    Abstract: Method for modulating responsiveness to corticosteroids in a subjet are provided. In the method of the invention, an agent which antagonizes a target that regulates production of IFN- gamma in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an IL-18 antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In yet another embodiment, the agent is an NK cell antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. In yet another preferred embodiment, the agent is an anti-asialo-GM1 antibody or an NK1.1 antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders. Pharmaceutical compositions comprising an agent which antagonizes a target that regulates production of IFN- gamma in a subject, a corticosteroid and a pharmaceutically acceptable carrier are also provided. A preferred composition comprises an ICE inhibitor, a corticosteroid and a pharmaceutically acceptable carrier.

    8.
    发明专利
    未知

    公开(公告)号：ES2146192T1

    公开(公告)日：2000-08-01

    申请号：ES98912929

    申请日：1998-03-12

    Applicant: BASF AG

    Inventor： SEKUT LES ,  CARTER ADAM ,  GHAYUR TARIQ ,  BANERJEE SUBHASHIS ,  TRACEY DANIEL E

    IPC: A61K31/40 ,  A61K45/06 ,  A61K31/505 ,  A61K38/20 ,  A61K38/46 ,  A61K39/395 ,  A61P3/10 ,  A61P9/02 ,  A61P11/06 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07K16/24 ,  A61K39/00

    Abstract: Method for modulating responsiveness to corticosteroids in a subjet are provided. In the method of the invention, an agent which antagonizes a target that regulates production of IFN- gamma in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an IL-18 antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In yet another embodiment, the agent is an NK cell antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. In yet another preferred embodiment, the agent is an anti-asialo-GM1 antibody or an NK1.1 antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders. Pharmaceutical compositions comprising an agent which antagonizes a target that regulates production of IFN- gamma in a subject, a corticosteroid and a pharmaceutically acceptable carrier are also provided. A preferred composition comprises an ICE inhibitor, a corticosteroid and a pharmaceutically acceptable carrier.

    TRANSGENIC NONHUMAN ANIMAL HAVING FUNCTIONALLY DISRUPTED INTERLEUKIN-1.BETA. CONVERTING ENZYME GENE
    10.
    发明专利
    TRANSGENIC NONHUMAN ANIMAL HAVING FUNCTIONALLY DISRUPTED INTERLEUKIN-1.BETA. CONVERTING ENZYME GENE 未知

    公开(公告)号：CA2202549A1

    公开(公告)日：1996-04-25

    申请号：CA2202549

    申请日：1995-10-13

    Applicant: BASF AG

    Inventor： SESHADRI TARA ,  PASKIND MICHAEL ,  ALLEN HAMISH ,  BANERJEE SUBHASHIS ,  LI PING

    IPC: A01K67/027 ,  C12N5/10 ,  C12N9/64 ,  C12N15/09 ,  C12N15/57 ,  C12N15/85 ,  C12P21/00 ,  C12Q1/37 ,  G01N33/15 ,  C12N15/90 ,  C12Q1/00 ,  G01N33/53

    Abstract: A transgenic nonhuman animal having somatic and germ cells in which at least one allele of an endogenous interleukin-1.beta. converting enzyme (ICE) gene is functionally disrupted is provided. The animal may be heterozygous or, mo re preferably, homozygous for the ICE gene disruption and is preferably a mouse . In homozygous animals, secretion of mature interleukin-1.beta. and interleuk in- 1.alpha. is substantially reduced relative to non-mutant animals. The animal s of the invention can be used as positive controls to evaluate the efficacy o f ICE inhibitors and to identify disease conditions that can be treated with I CE inhibitors. A transgenic nonhuman animal having functionally disrupted endogenous ICE genes but which has been reconstituted with a human ICE gene is also provided. This animal can be used to identify agents that inhibit human ICE in vivo. Nucleic acid constructs for functionally disrupting an endogeno us ICE gene in a host cell, recombinant vectors including the nucleic acid construct, and host cells into which the nucleic acid construct has been introduced are also encompassed by the invention.

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