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1. 发明授权

US07226595B2 Modified Chimeric superantigens and their use 有权
标题翻译：改性嵌合超级抗原及其用途
公开(公告)号：US07226595B2
公开(公告)日：2007-06-05
申请号：US10283838
申请日：2002-10-30
申请人： Per Antonsson , Per Bjork , Mikael Dohlsten , Terje Kalland , Lars Abrahmsen , Johan Hansson , Göran Forsberg
发明人： Per Antonsson , Per Bjork , Mikael Dohlsten , Terje Kalland , Lars Abrahmsen , Johan Hansson , Göran Forsberg
IPC分类号： A61K39/00
CPC分类号： C07K16/3023 , A61K38/00 , A61K47/68 , C07K14/31 , C07K16/3046 , C07K19/00 , C07K2317/732 , C07K2319/00
摘要： A conjugate between a target-seeking moiety and a modified superantigen, characterized in that the superantigen is a wild-type superantigen (SA I) in which an amino acid residue in a superantigen region (region I) determining binding to TCR, preferably TCRVβ, and T cell activation have been replaced by another amino acid residue while retaining the ability to activate a subset of T cells.In preferred embodiment the modified superantigen is a chimer between at least two wild-type superantigens (SA I, SA II etc) characterized in that one or more amino acid residues in a region determining binding to TCR and T cell activation have been interchanged between various wild-type superantigens.A therapeutic method making use of modified/chimeric superantigens as defined in the preceding paragraphs.An antibody preparation in which the cysteine residues that provide for interchain disulfide bonds have been mutated so as to forbid interchain disulfide bridges, preferably to serine residues, for use as pharmaceutical.
摘要翻译：目标寻找部分和修饰的超抗原之间的缀合物，其特征在于超抗原是野生型超抗原（SAI），其中超抗原区（区域I）中的氨基酸残基确定结合TCR，优选TCRVβ，并且T细胞激活已被另一个氨基酸残基替代，同时保留激活T细胞亚群的能力。在优选实施方案中，修饰的超抗原是至少两种野生型超级抗原（SA I，SA II等）之间的嵌合体，其特征在于确定结合TCR和T细胞活化的区域中的一个或多个氨基酸残基已经在各种野生型超抗原。使用前面段落中定义的修饰/嵌合超级抗原的治疗方法。其中提供链间二硫键的半胱氨酸残基已被突变以防止链间二硫键，优选丝氨酸残基用作药物的抗体制剂。

2. 发明授权

US06514498B1 Modified/chimeric superantigens and their use 失效
标题翻译：改良/嵌合型超抗原及其用途
公开(公告)号：US06514498B1
公开(公告)日：2003-02-04
申请号：US08695692
申请日：1996-08-12
申请人： Per Antonsson , Per Björk , Mikael Dohlsten , Johan Hansson , Göran Forsberg , Lars Abrahmsén , Terje Kalland
发明人： Per Antonsson , Per Björk , Mikael Dohlsten , Johan Hansson , Göran Forsberg , Lars Abrahmsén , Terje Kalland
IPC分类号： A61K3944
CPC分类号： C07K14/31 , A61K38/00 , A61K47/6817 , A61K47/6851 , A61K2039/505 , C07K16/3023 , C07K16/3046 , C07K19/00 , C07K2317/55 , C07K2317/73 , C07K2317/732 , C07K2319/00
摘要： A conjugate between a target-seeking moiety and a modified superantigen, characterized in that the superantigen is a wild-type superantigen (SA I) in which an amino acid residue in a superantigen region (region I) determining binding to TCR, referably TCRV&bgr;, and T cell activation has been replaced by another amino acid residue while retaining the ability to activate a subset of T cells. In a preferred embodiment the modified superantigen is a chimer between at least two wild-type superantigens (SA I, SA II etc) characterized in that one or more amino acid residues in a region determining binding to TCR and T cell activation have been interchanged between various wild-type superantigens. A therapeutic method making use of modified/chimeric superantigens as defined in the preceding paragraphs. An antibody preparation in which the cysteine residues that provide for interchain disulfide bonds have been mutated so as to forbid interchain disulfide bridges, preferably to serine residues, for use as a pharmaceutical.
摘要翻译：靶寻求部分和修饰的超抗原之间的缀合物，其特征在于超抗原是野生型超抗原（SAI），其中确定结合TCR的超抗原区（区域I）中的氨基酸残基，可以指TCRVβ，并且T细胞激活已被另一个氨基酸残基取代，同时保留激活T细胞亚群的能力。在优选实施方案中，修饰的超抗原是至少两种野生型超级抗原（SAI，SA II等）之间的嵌合体，其特征在于确定结合TCR和T细胞活化的区域中的一个或多个氨基酸残基已经在各种野生型超级抗原之间互换.1。一种使用前述段落中定义的修饰/嵌合超级抗原的治疗方法。抗体制备其中提供链间二硫键的半胱氨酸残基已被突变，以便禁止链间二硫键，优选为丝氨酸残基，用于用作药物。

3. 发明申请

US20050260215A1 Conjugate between a modified superantigen and a target-seeking compound and the use of the conjugate 审中-公开
标题翻译：修饰的超抗原和寻靶化合物之间的缀合以及缀合物的使用
公开(公告)号：US20050260215A1
公开(公告)日：2005-11-24
申请号：US11193748
申请日：2005-07-29
申请人： Lars Abrahmsen , Per Bjork , Mikael Dohlsten , Terje Kalland
发明人： Lars Abrahmsen , Per Bjork , Mikael Dohlsten , Terje Kalland
IPC分类号： C12N15/09 , A61K38/00 , A61K39/00 , A61K39/395 , A61K47/48 , C07K14/31 , C07K16/30 , C07K16/32 , C07K16/46 , C07K19/00 , C12N15/00 , C12N15/01 , C12P21/02 , C12R1/44
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6863 , A61K2039/505 , C07K14/31 , C07K16/3046 , C07K19/00 , C07K2317/55 , C07K2319/00 , C07K2319/30 , Y10S514/885
摘要： Methods of lysing cells associated with a disease condition, and method of treating a disease condition by lysing cells associated with the condition, by administering to a mammal a therapeutically effective amount of a conjugate comprising a biospecific affinity counterpart and a peptide that is derived from Staphylococcal enterotoxin A, that has the ability to bind to a Vβ of a T cell receptor and has been modified at amino acid position 47, 128, 187, 225 or 227, in order to have reduced ability to bind to MHC class II antigens.
摘要翻译：通过向哺乳动物施用治疗有效量的包含生物特异性亲和对应物和衍生自葡萄球菌的肽的缀合物来治疗与疾病状况相关的细胞的裂解方法和通过裂解与病症相关的细胞来治疗疾病状况的方法肠毒素A，其具有结合T细胞受体的Vbeta的能力，并且已经在氨基酸位置47,128,187,225或227处被修饰，以便具有降低与MHC II类抗原结合的能力。

4. 发明授权

US07226601B1 Conjugate between a modified superantigen and a target-seeking compound and the use of the conjugate 失效
标题翻译：修饰的超抗原和寻靶化合物之间的缀合以及缀合物的使用
公开(公告)号：US07226601B1
公开(公告)日：2007-06-05
申请号：US08765695
申请日：1995-06-07
申请人： Lars Abrahmsen , Per Bjork , Mikael Dohlsten , Terje Kalland
发明人： Lars Abrahmsen , Per Bjork , Mikael Dohlsten , Terje Kalland
IPC分类号： C07K16/46 , C07K19/00 , A61K39/395
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6863 , A61K2039/505 , C07K14/31 , C07K16/3046 , C07K19/00 , C07K2317/55 , C07K2319/00 , C07K2319/30 , Y10S514/885
摘要： A method for the treatment of a disease in a mammal by administering a therapeutically effective amount of a conjugate comprising a biospecific affinity counterpart and a peptide, wherein the peptide contains an amino acid sequence that is derived from staphylococcal enterotoxin A, binds to a Vβ of a T cell receptor, and has a D227A mutation so that the peptide has a modified ability to bind to MHC class II antigens.
摘要翻译：一种通过施用治疗有效量的包含生物特异性亲和对应物和肽的缀合物来治疗哺乳动物疾病的方法，其中所述肽含有衍生自葡萄球菌肠毒素A的氨基酸序列，其结合到 T细胞受体，并且具有D227A突变，使得肽具有与MHC II类抗原结合的修饰能力。

5. 发明申请

US20060062795A1 Conjugate between a modified superantigen and a target-seeking compound and the use of the conjugate 审中-公开
标题翻译：修饰的超抗原和寻靶化合物之间的缀合以及缀合物的使用
公开(公告)号：US20060062795A1
公开(公告)日：2006-03-23
申请号：US11193869
申请日：2005-07-29
申请人： Lars Abrahmsen , Per Bjork , Mikael Dohlsten , Terje Kalland
发明人： Lars Abrahmsen , Per Bjork , Mikael Dohlsten , Terje Kalland
IPC分类号： A61K39/395 , C07K16/46
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6863 , A61K2039/505 , C07K14/31 , C07K16/3046 , C07K19/00 , C07K2317/55 , C07K2319/00 , C07K2319/30 , Y10S514/885
摘要： Conjugates comprising a biospecific affinity counterpart and a peptide that is derived from Staphylococcal enterotoxin A, that has the ability to bind to a Vβ of a T cell receptor and has been modified at amino acid position 47, 128, 187, 225 or 227, in order to have reduced ability to bind to MHC class II antigens. Such conjugates are useful, for example, as therapeutic agents, for example, as anti-cancer agents.
摘要翻译：包含生物特异性亲和对应物和衍生自葡萄球菌肠毒素A的肽的缀合物，其具有结合T细胞受体的Vbeta并在氨基酸位置47,128,187,225或227处被修饰的能力，以降低与MHC II类抗原结合的能力。这样的缀合物可用作例如治疗剂，例如作为抗癌剂。

6. 发明授权

US06962694B1 Cytolysis of target cells by superantigen conjugates inducing T-cell activation 失效
标题翻译：通过诱导T细胞活化的超抗原共轭物对靶细胞进行细胞溶解
公开(公告)号：US06962694B1
公开(公告)日：2005-11-08
申请号：US09463470
申请日：1998-07-21
申请人： Morten Soegaard , Lars Abrahmsen , Peter Lando , Goran Forsberg , Terje Kalland , Mikael Dohlsten
发明人： Morten Soegaard , Lars Abrahmsen , Peter Lando , Goran Forsberg , Terje Kalland , Mikael Dohlsten
IPC分类号： C12N15/09 , A61K38/00 , A61K39/00 , A61K39/085 , A61K39/385 , A61K39/395 , A61K45/00 , A61K47/48 , A61P35/00 , A61P37/00 , C07K14/31 , C07K14/47 , C07K14/715 , C07K16/00 , C07K19/00 , C12N5/10
CPC分类号： C07K14/47 , A61K47/642 , A61K47/6801 , A61K47/6813 , A61K47/6829 , A61K47/6863 , C07K2319/035
摘要： A method for inactivating target cells in the presence of T cells by bringing the two types of cells in contact with a superantigen (SAG) in the presence of an immune modulator, characterized in that at least one of the superantigen and the immune modulator is in the form of a conjugate between a “free” superantigen (Sag) and a moiety targeting the conjugate to the target cells. A superantigen conjugate complying with the formula (1) (T)x(Sag)y(IM)z; a) T is a targeting moiety, Sag corresponds to a free superantigen, IM is an immune modulator that is not a superantigen and T, Sag and IM are linked together via organic linkers B; b) x, y and z are integers that typically are selected among 0-10 and represent the number of moieties T, Sag and IM, respectively, in a given conjugate molecule, with the provision that y>0 and also one or both of x and z>0. The superantigen conjugate is preferably a triple fusion protein. A targeted immune modulator, characterized in that it is a conjugate between a targeting moiety (T″′) and a modified immune modulator (IM″′). The conjugate complies with a formula analogous to formula (1) except for the imperative presence of the modified immune modulator. A superantigen moiety may be present. A DNA molecule encoding a superantigen and an immune modulator.
摘要翻译：一种通过在免疫调节剂存在下使两种类型的细胞与超抗原（SAG）接触而在T细胞存在下灭活靶细胞的方法，其特征在于，超抗原和免疫调节剂中的至少一种在 “自由”超抗原（Sag）与靶向靶细胞靶向缀合物的部分之间的缀合物的形式。符合公式（1）（T）的超抗原缀合物（S）（S））（IM）z a）T是靶向部分，Sag对应于游离超抗原，IM是不是超抗原的免疫调节剂，T，Sag和IM通过有机接头B连接在一起; b）x，y和z是通常在0-10中选择并且分别代表给定共轭分子中部分T，Sag和IM的数目的整数，其规定y> 0，并且还包括一个或两个 x和z> 0。超抗原缀合物优选为三重融合蛋白。靶向免疫调节剂，其特征在于它是靶向部分（T“'”和修饰的免疫调节剂（IM“）之间的缀合物。该缀合物符合类似于式（1）的式，除了修饰的免疫调节剂的命令性存在。可能存在超抗原部分。编码超抗原和免疫调节剂的DNA分子。

7. 发明申请

US20050226885A1 Cytolysis of target cells by superantigen conjugates inducing T-cell activation 审中-公开
标题翻译：通过诱导T细胞活化的超抗原共轭物对靶细胞进行细胞溶解
公开(公告)号：US20050226885A1
公开(公告)日：2005-10-13
申请号：US11023086
申请日：2004-12-27
申请人： Morten Soegaard , Lars Abrahmsen , Peter Lando , Goran Forsberg , Terje Kalland , Mikael Dohlsten
发明人： Morten Soegaard , Lars Abrahmsen , Peter Lando , Goran Forsberg , Terje Kalland , Mikael Dohlsten
IPC分类号： C12N15/09 , A61K38/00 , A61K39/00 , A61K39/085 , A61K39/385 , A61K39/395 , A61K45/00 , A61K47/48 , A61P35/00 , A61P37/00 , C07K14/31 , C07K14/47 , C07K14/715 , C07K16/00 , C07K19/00 , C12N5/10
CPC分类号： C07K14/47 , A61K47/642 , A61K47/6801 , A61K47/6813 , A61K47/6829 , A61K47/6863 , C07K2319/035
摘要： A method for inactivating target cells in the presence of T cells by bringing the two types of cells in contact with a superantigen (SAG) in the presence of an immune modulator, characterized in that at least one of the superantigen and the immune modulator is in the form of a conjugate between a “free” superantigen (Sag) and a moiety targeting the conjugate to the target cells. A superantigen conjugate complying with the formula (1): (T)x(Sag)y(IM)z; a) T is a targeting moiety, Sag corresponds to a free superantigen, IM is an immune modulator that is not a superantigen and T, Sag and IM are linked together via organic linkers B; b) x, y and z are integers that typically are selected among 0-10 and represent the number of moieties T, Sag and IM, respetively, in a given conjugate molecule, with the provision that y>0 and also one or both of x and z>0. The superantigen conjugate is preferably a triple fusion protein. A targeted immune modulator, characterized in that it is a conjugate between a targeting moiety (T′″) and a modified immune modulator (IM′″). The conjugate complies with a formula analogous to formula (I) except for the imperative presence of the modified immune modulator. A superantigen moiety may be present. A DNA molecule encoding a superantigen and an immune modulator.
摘要翻译：一种通过在免疫调节剂存在下使两种类型的细胞与超抗原（SAG）接触而在T细胞存在下灭活靶细胞的方法，其特征在于，超抗原和免疫调节剂中的至少一种在 “自由”超抗原（Sag）与靶向靶细胞靶向缀合物的部分之间的缀合物的形式。符合式（1）的超抗原共轭：（T）X（Sag）Y（IM）z a）T是靶向部分，Sag对应于游离超抗原，IM是不是超抗原的免疫调节剂，T，Sag和IM通过有机接头B连接在一起; b）x，y和z是通常在0-10中选择的整数，并且在给定的共轭分子中分别表示部分T，Sag和IM的数目，其规定y> 0，并且还包括一个或两个 x和z> 0。超抗原缀合物优选为三重融合蛋白。靶向免疫调节剂，其特征在于它是靶向部分（T“'”和修饰的免疫调节剂（IM“）之间的缀合物。除了修饰的免疫调节剂的命令存在之外，缀合物符合类似于式（I）的式。可能存在超抗原部分。编码超抗原和免疫调节剂的DNA分子。

8. 发明授权

US06197299B1 Antibody conjugates 失效
标题翻译：抗体缀合物
公开(公告)号：US06197299B1
公开(公告)日：2001-03-06
申请号：US09154310
申请日：1998-09-16
申请人： Mikael Dohlsten , Eva Åkerblom , Peter A. Lando , Terje Kalland , Gunnar Hedlund
发明人： Mikael Dohlsten , Eva Åkerblom , Peter A. Lando , Terje Kalland , Gunnar Hedlund
IPC分类号： A61K39395
CPC分类号： A61K39/385 , A61K2039/505 , A61K2039/6037 , A61K2039/6068 , A61K2039/627 , C07K16/28
摘要： A soluble antibody conjugate comprising an antibody linked to a structure which is recognized by T-cells and has the ability to direct T-cells to lyse the target cell, which is recognized by the antibody. The conjugate is characterized by the structure being a superantigen. One important mode is a method for the lysis of target cells, wherein the target cells are contacted with a target cell lysis effective amount of the conjugate. The method of lysis is part of a potent treatment regime for cancer, autoimmunity, parasitic infestations and fungal, viral and bacterial infections. The specification also describes modes such as the synthesis of the conjugate and pharmaceutical compositions and their manufacture.
摘要翻译：一种可溶性抗体缀合物，其包含与由T细胞识别并具有引导T细胞裂解靶细胞的能力的抗体连接的抗体，其被抗体识别。缀合物的特征在于结构是超抗原。一种重要的模式是用于裂解靶细胞的方法，其中靶细胞与靶细胞裂解有效量的缀合物接触。溶解的方法是癌症，自身免疫，寄生虫感染和真菌，病毒和细菌感染的有效治疗方案的一部分。说明书还描述了诸如缀合物的合成和药物组合物及其制造的模式。

9. 发明授权

US6042837A Methods of staphylococcal enterotoxin directed cell-mediated cytotoxicity (SDCC) 失效
标题翻译：葡萄球菌肠毒素定向细胞介导的细胞毒性（SDCC）
公开(公告)号：US6042837A
公开(公告)日：2000-03-28
申请号：US596555
申请日：1996-02-05
申请人： Terje Kalland , Gunnar Hedlund , Mikael Dohlsten , Peter Lando
发明人： Terje Kalland , Gunnar Hedlund , Mikael Dohlsten , Peter Lando
IPC分类号： A61K38/16 , A61P31/04 , A61K39/085
CPC分类号： A61K38/164
摘要： Methods of staphylococcal enterotoxin directed cell-mediated cytotoxicity (SDCC), including methods of lysing malignant cells expressing MHC Class II antigens using SDCC, by the administration of staphylococcal enterotoxin to a living body.
摘要翻译：葡萄球菌肠毒素定向细胞介导的细胞毒性（SDCC）的方法，包括通过将葡萄球菌肠毒素施用于活体来裂解使用SDCC表达MHC II类抗原的恶性细胞的方法。

10. 发明授权

US5691350A Use of linomide for treatment of retrovirus infections specifically HIV infections 失效
标题翻译：使用线粒体治疗逆转录病毒感染，特别是艾滋病毒感染
公开(公告)号：US5691350A
公开(公告)日：1997-11-25
申请号：US462050
申请日：1995-06-05
申请人： Bo Nilsson , Terje Kalland
发明人： Bo Nilsson , Terje Kalland
IPC分类号： A61K31/4704 , A61K31/47
CPC分类号： A61K31/4704
摘要： The present invention concerns the use of Linomide.RTM. or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of retrovirus infections. Specifically the invention concerns the treatment of HIV infections.
摘要翻译：本发明涉及Linomide TM或其药学上可接受的盐在制备用于治疗逆转录病毒感染的药物中的用途。具体地，本发明涉及HIV感染的治疗。

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