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1. 发明公开

EP0323865A1 Novel immunosuppressant agent 失效
标题翻译：免疫抑制剂Mittel。
公开(公告)号：EP0323865A1
公开(公告)日：1989-07-12
申请号：EP89200003.5
申请日：1989-01-02
申请人： Merck & Co., Inc.
发明人： Monaghan, Richard L. , Sigal, Nolan H. , Kaplan, Louis , Byrne, Keven M. , Borris, Robert P. , Dumont, Francis J. , Garrity, George M. , Zink, Deborah L.
IPC分类号： C12P1/06 , A61K35/66 , A61K39/00
CPC分类号： C12P17/188
摘要： Described is a process for producing a new immunosuppressant, "immunomycin", by novel fermentation conditions of Streptomyces hygroscopicus var. ascomyceticus . The immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants. Also described is a new method of use utilizing known "ascomycin" as an immunosuppressant.
摘要翻译：描述了通过吸水链霉菌变种的新型发酵条件生产新的免疫抑制剂“免疫霉素”的方法。子囊。免疫抑制剂可用于预防异种器官移植的人宿主排斥反应。骨髓和心脏移植。还描述了利用已知的“子囊霉素”作为免疫抑制剂的新方法。

2. 发明公开

EP0379342A2 New FK-506 cytosolic binding protein 失效转让
标题翻译：蛋白质蛋白酶Cytosol，das FK-506 binden kann。
公开(公告)号：EP0379342A2
公开(公告)日：1990-07-25
申请号：EP90300459.6
申请日：1990-01-17
申请人： Merck & Co., Inc.
发明人： Siekierka, John J. , Staruch, Marie J. , Sigal, Nolan H. , Mumford, Richard A. , Hung, Hsueh-Yun
IPC分类号： C07K15/12 , G01N33/68
CPC分类号： C12N9/90 , C12N15/90
摘要： A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 µg FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H₂N-Gly-Val-Gln-Val-Glu-Thr-Ile-Ser-Pro-Gly-Asp-Gly-Arg-Thr-Phe-Pro-Lys-Arg-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Gly-Lys-Lys-Phe-Asp (wherein X is undefined). The HCB protein is isolated from the cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g. Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyses the cis-trans isomerization of proline-containing peptide bonds.
摘要翻译：具有约26μgFK-506 / mg蛋白质和约10-12千道尔顿分子量的特异性结合活性的新的均匀胞质结合（HCB）蛋白可逆地结合免疫抑制剂FK-506而不是环孢霉素A（CSA ）。蛋白质在56℃下加热稳定30分钟，保持其FK-506结合亲和力，并具有（部分）氨基末端氨基酸序列：H2N-Gly-Val-Gln-Val-Glu-Thr-Ile- Ser-Pro-Gly-Asp-Gly-Arg-Thr-Phe-Pro-Ly-Arg-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp -Gly-Lys-Lys-Phe-Asp（其中X未定义）。 HCB蛋白从哺乳动物组织的细胞溶质中分离，优选人肿瘤T细胞系，例如， Jurkat，可用于涉及FK-506大环内酯型免疫抑制剂的诊断和纯化程序。 HCB蛋白还催化含脯氨酸肽键的顺式 - 反式异构化。

3. 发明公开

EP0256713A3 Therapeutic human antipseudomonas aeruginosa antibodies 失效
标题翻译：治疗人类抗精神病药物AERUGINOSA抗体
公开(公告)号：EP0256713A3
公开(公告)日：1989-02-15
申请号：EP87306750.8
申请日：1987-07-30
申请人： Merck & Co., Inc.
发明人： Gammon, Maureen , Sigal, Nolan H. , Zweerink, Hans J. , Miner, Karen M.
IPC分类号： C12P21/00 , C07K15/00 , C12N5/00 , C12N15/00 , A61K39/40 , G01N33/569 , G01N33/577
CPC分类号： C07K16/1214 , A61K38/00
摘要： Human lymphoblastoid cell lines and hybridomas are developed which secrete antibodies specifically reactive with lipopolysaccharide that is present on the surface of Pseudomonas aeruginosa . The individual monoclonal antibodies are immunospecific for one or more of the Fisher immunotypes of P. aeruginosa . The anti-Pseudomonas monoclonal antibodies are used individually or in combination to therapeutically or prophylactically treat P. aeruginosa infections. One or more of the monoclonal antibodies are co-administered with one or more antibiotics to therapeutically or prophylactically treat immunocompromised and immunosuppressed individuals.

4. 发明公开

EP0256713A2 Therapeutic human antipseudomonas aeruginosa antibodies 失效
标题翻译： Therapeutische，menschliche Antipseudomonas-Aeruginosa-Antikörper。
公开(公告)号：EP0256713A2
公开(公告)日：1988-02-24
申请号：EP87306750.8
申请日：1987-07-30
申请人： Merck & Co., Inc.
发明人： Gammon, Maureen , Sigal, Nolan H. , Zweerink, Hans J. , Miner, Karen M.
IPC分类号： C12P21/00 , C07K15/00 , C12N5/00 , C12N15/00 , A61K39/40 , G01N33/569 , G01N33/577
CPC分类号： C07K16/1214 , A61K38/00
摘要： Human lymphoblastoid cell lines and hybridomas are developed which secrete antibodies specifically reactive with lipopolysaccharide that is present on the surface of Pseudomonas aeruginosa . The individual monoclonal antibodies are immunospecific for one or more of the Fisher immunotypes of P. aeruginosa . The anti-Pseudomonas monoclonal antibodies are used individually or in combination to therapeutically or prophylactically treat P. aeruginosa infections. One or more of the monoclonal antibodies are co-administered with one or more antibiotics to therapeutically or prophylactically treat immunocompromised and immunosuppressed individuals.
摘要翻译：开发人淋巴母细胞样细胞系和杂交瘤，其分泌与存在于铜绿假单胞菌表面的脂多糖特异性反应的抗体。单个单克隆抗体对于铜绿假单胞菌的一种或多种Fisher免疫型是免疫特异性的。抗假单胞菌单克隆抗体单独或组合用于治疗或预防性治疗铜绿假单胞菌感染。一种或多种单克隆抗体与一种或多种抗生素共同施用以治疗或预防性地治疗免疫受损和免疫抑制的个体。

5. 发明授权

EP0379342B1 New FK-506 cytosolic binding protein 失效转让
标题翻译：从胞质溶胶蛋白时，FK-506可结合。
公开(公告)号：EP0379342B1
公开(公告)日：1994-10-05
申请号：EP90300459.6
申请日：1990-01-17
申请人： Merck & Co., Inc.
发明人： Siekierka, John J. , Staruch, Marie J. , Sigal, Nolan H. , Mumford, Richard A. , Hung, Hsueh-Yun
IPC分类号： C07K15/12 , G01N33/68
CPC分类号： C12N9/90 , C12N15/90

6. 发明公开

EP0379342A3 New FK-506 cytosolic binding protein 失效转让
标题翻译：新FK-506 CYTOSOLIC结合蛋白
公开(公告)号：EP0379342A3
公开(公告)日：1990-11-28
申请号：EP90300459.6
申请日：1990-01-17
申请人： Merck & Co., Inc.
发明人： Siekierka, John J. , Staruch, Marie J. , Sigal, Nolan H. , Mumford, Richard A. , Hung, Hsueh-Yun
IPC分类号： C07K15/12 , G01N33/68
CPC分类号： C12N9/90 , C12N15/90
摘要： A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 µg FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H₂N-Gly-Val-Gln-Val-Glu-Thr-Ile-Ser-Pro-Gly-Asp-Gly-Arg-Thr-Phe-Pro-Lys-Arg-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Gly-Lys-Lys-Phe-Asp (wherein X is undefined). The HCB protein is isolated from the cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g. Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyses the cis-trans isomerization of proline-containing peptide bonds.

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