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21. 发明授权

US06322790B1 Compositions and methods for eliciting an immune response using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy 失效
标题翻译：使用热休克/应激蛋白 - 肽复合物结合过继免疫治疗引发免疫应答的组合物和方法
公开(公告)号：US06322790B1
公开(公告)日：2001-11-27
申请号：US09135712
申请日：1998-08-18
申请人： Pramod K. Srivastava
发明人： Pramod K. Srivastava
IPC分类号： A01N6300
CPC分类号： A61K39/0011 , A61K2039/5154 , A61K2039/5158 , A61K2039/6043 , A61K2039/622 , Y02A50/466 , Y10S530/806 , Y10S530/807 , A61K2300/00
摘要： The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic noeplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule in combination with administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. “Antigenic molecule” as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex when administered intradermally are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96. In another embodiment, the effective amounts of the complex when administered subcutaneously are in the range of 10 to 600 micrograms for complexes comprising hsp70, 50 to 5000 micrograms for hsp90, and 10 to 600 micrograms for gp96.
摘要翻译：本发明涉及引发免疫应答的方法和组合物以及预防和治疗原发性和转移性中隔性疾病和感染性疾病。本发明的方法包括施用包含有效量的复合物的组合物，其中复合物基本上由非共价结合于抗原性分子的热休克蛋白（hsp）组合施用，与施用非共价hsps复合物致敏的抗原呈递细胞组合与抗原分子结合。本文所用的“抗原分子”是指hsps与体内内源性相关的肽以及外源性抗原/免疫原（即hsps在体内不复合）或其抗原/免疫原性片段及其衍生物。在优选的实施方案中，复合物是个体自体的。在一个具体实施方案中，当皮内给药时复合物的有效量对于包含hsp70,5-49微克对于hsp90的复合物和对于gp96为0.1至9.0微克的复合物为0.1至9.0微克。在另一个实施方案中，当皮下投与时，复合物的有效量对于包含hsp70,50-6000微克对于hsp90的复合物和对于gp96为10至600微克的复合物为10至600微克。

22. 发明授权

US6156302A Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes 失效
标题翻译：使用用热休克蛋白 - 表位复合物敏化的巨噬细胞的采用免疫治疗
公开(公告)号：US6156302A
公开(公告)日：2000-12-05
申请号：US107696
申请日：1998-06-30
申请人： Pramod K. Srivastava
发明人： Pramod K. Srivastava
IPC分类号： A61K38/00 , A61K31/00 , A61K35/12 , A61K38/19 , A61K39/00 , A61P31/00 , A61P35/00 , A61P35/02 , A01N63/00 , A61K39/385 , A61K45/05 , C07K14/435
CPC分类号： A61K39/0011 , A61K38/191 , A61K38/20 , A61K38/21 , A61K2039/5154 , A61K2039/6043 , A61K2039/622
摘要： The present invention relates to methods and compositions for enhancing immunological responses and for the prevention and treatment of infectious diseases or primary and metastatic neoplastic diseases based on the administration of macrophages and/or other antigen presenting cells (APC) sensitized with heat shock proteins non-covalently bound to peptide complexes and/or antigenic components. APC are incubated in the presence of hsp-peptide complexes and/or antigenic components in vitro. The sensitized cells are reinfused into the patient with or without treatment with cytokines including but not limited to interferon-.alpha., interferon-.alpha., interleukin-2, interleukin-4, interleukin-6 and tumor neurosis factor.
摘要翻译：本发明涉及用于增强免疫应答和用于预防和治疗感染性疾病或原发性和转移性肿瘤性疾病的方法和组合物，其基于施用热休克蛋白非特异性的巨噬细胞和/或其他抗原呈递细胞（APC）共价结合肽复合物和/或抗原成分。 APC在体外在hsp-肽复合物和/或抗原成分存在下孵育。致敏细胞用或不用细胞因子包括但不限于干扰素-α，干扰素-α，白细胞介素-2，白细胞介素-4，白细胞介素-6和肿瘤神经元因子治疗而被再灌注入患者。

23. 发明授权

US6136315A Compositions and methods using complexes of heat shock protein 70 and antigenic molecules for the treatment and prevention of neoplastic diseases 有权
标题翻译：使用热休克蛋白70和抗原分子复合物的组合物和方法用于治疗和预防肿瘤疾病
公开(公告)号：US6136315A
公开(公告)日：2000-10-24
申请号：US150204
申请日：1998-09-09
申请人： Pramod K. Srivastava
发明人： Pramod K. Srivastava
IPC分类号： A61K38/00 , A61K31/00 , A61K38/21 , A61K38/22 , A61K39/00 , A61K39/295 , A61P31/00 , A61P35/00 , A61P35/02 , C07K14/47 , G01N33/569 , G01N33/574 , A61K39/002 , A61K39/38 , A61K39/385
CPC分类号： A61K39/0011 , G01N33/56977 , G01N33/574 , A61K2039/5152 , A61K2039/52 , A61K2039/525 , A61K2039/6043 , A61K2039/622 , Y10S435/81
摘要： The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96. The invention also provides a method for measuring tumor rejection in vivo in an individual, preferably a human, comprising measuring the generation by the individual of MHC Class I-restricted CD8+ cytotoxic T lymphocytes specific to the tumor. Methods of purifying hsp70-peptide complexes are also provided.
摘要翻译：本发明涉及引发免疫应答和预防和治疗原发性和转移性肿瘤性疾病和传染病的方法和组合物。本发明的方法包括施用包含有效量的复合物的组合物，其中复合物基本上由非共价结合于抗原分子的热休克蛋白（hsp）组成。本文所用的“抗原分子”是指hsps与体内内源性相关的肽以及外源性抗原/免疫原（即hsps在体内不复合）或其抗原/免疫原性片段及其衍生物。在优选的实施方案中，复合物是个体自体的。复合物的有效量对于包含hsp70，hsp90为50-1000微克，gp96为10-600微克的复合物为10-600微克。本发明还提供了一种在个体，优选人体内测量体内肿瘤排斥的方法，包括测量个体对肿瘤特异性的MHC I类限制性CD8 +细胞毒性T淋巴细胞的产生。还提供了纯化hsp70-肽复合物的方法。

24. 发明授权

US5997873A Method of preparation of heat shock protein 70-peptide complexes 失效
标题翻译：热休克蛋白70肽复合物的制备方法
公开(公告)号：US5997873A
公开(公告)日：1999-12-07
申请号：US180685
申请日：1994-01-13
申请人： Pramod K. Srivastava
发明人： Pramod K. Srivastava
IPC分类号： A61K38/00 , A61K39/00 , A61P37/04 , C07K14/47 , A61K39/385 , A61K38/02 , A01N37/18 , A23J1/00
CPC分类号： A61K39/0005 , A61K39/0011 , C07K14/4702 , A61K38/00 , Y10S436/823 , Y10S530/806 , Y10S530/828
摘要： The present invention relates to methods of preparing a purified non-covalent heat shock protein 70-peptide complex capable of eliciting an immune response in a mammal comprising purifying heat shock protein 70-peptide complexes from mammalian tumor cells or mammalian cells infected with a virus, bacteria, or other infectious agent in the absence of ATP.
摘要翻译：本发明涉及制备能够在哺乳动物中引发免疫应答的纯化非共价热休克蛋白70-肽复合物的方法，包括从哺乳动物肿瘤细胞或感染病毒的哺乳动物细胞中纯化热休克蛋白70-肽复合物，细菌或其他感染因子。

25. 发明授权

US5985270A Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes 失效
公开(公告)号：US5985270A
公开(公告)日：1999-11-16
申请号：US527546
申请日：1995-09-13
申请人： Pramod K. Srivastava
发明人： Pramod K. Srivastava
IPC分类号： A61K38/00 , A61K31/00 , A61K35/12 , A61K38/19 , A61K39/00 , A61P31/00 , A61P35/00 , A61P35/02 , A01N63/00 , A61K39/385 , A61K45/05 , C07K14/435
CPC分类号： A61K39/0011 , A61K38/191 , A61K38/20 , A61K38/21 , A61K2039/5154 , A61K2039/6043 , A61K2039/622
摘要： The present invention relates to methods and compositions for enhancing immunological responses and for the prevention and treatment of infectious diseases or primary and metastatic neoplastic diseases based on the administration of macrophages and/or other antigen presenting cells (APC) sensitized with heat shock proteins non-covalently bound to peptide complexes and/or antigenic components. APC are incubated in the presence of hsp-peptide complexes and/or antigenic components in vitro. The sensitized cells are reinfused into the patient with or without treatment with cytokines including but not limited to interferon-.alpha., interferon-.alpha., interleukin-2, interleukin-4, interleukin-6 and tumor neurosis factor.

26. 发明授权

US08877204B2 Methods and compositions for the treatment of cancer and infectious disease using alpha (2) macroglobulin-antigenic molecule complexes 有权
标题翻译：使用α（2）巨球蛋白 - 抗原分子复合物治疗癌症和传染病的方法和组合物
公开(公告)号：US08877204B2
公开(公告)日：2014-11-04
申请号：US10546106
申请日：2004-02-20
申请人： Pramod K. Srivastava , Robert J. Binder
发明人： Pramod K. Srivastava , Robert J. Binder
IPC分类号： A61K38/00 , A61K39/00 , A61K38/57 , A61K38/17
CPC分类号： A61K47/4833 , A61K38/1709 , A61K38/57 , A61K39/0011 , A61K39/385 , A61K39/39533 , A61K45/06 , A61K47/646 , A61K2039/6031 , A61K2039/605 , A61K2300/00
摘要： The present invention relates to the use of alpha (2) macroglobulin complexes isolated from the serum of a mammal. The invention also relates to methods for making such complexes and compositions comprising alpha (2) macroglobulin complexes, isolated from the serum of a mammal, wherein such compositions are used in methods for the treatment and prevention of cancer and infectious disease. The invention also relates to methods for treating and preventing cancer and infectious disease using such complexes comprising, isolated from the serum of a mammal. The invention also encompasses methods for production of alpha (2) macroglobulin complexes.
摘要翻译：本发明涉及从哺乳动物血清分离的α（2）巨球蛋白复合物的用途。本发明还涉及制备这样的复合物和组合物的方法，所述组合物和组合物包含从哺乳动物血清分离的α（2）巨球蛋白复合物，其中所述组合物用于治疗和预防癌症和感染性疾病的方法中。本发明还涉及使用这样的复合物治疗和预防癌症和感染性疾病的方法，所述复合物包含从哺乳动物血清中分离的方法。本发明还包括生产α（2）巨球蛋白复合物的方法。

27. 发明授权

US06455503B1 Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens 失效
标题翻译：应激蛋白 - 肽复合物作为针对细胞内病原体的预防和治疗性疫苗
公开(公告)号：US06455503B1
公开(公告)日：2002-09-24
申请号：US09412420
申请日：1999-10-05
申请人： Pramod K. Srivastava
发明人： Pramod K. Srivastava
IPC分类号： A61K3800
CPC分类号： A61K39/39 , A61K39/12 , A61K39/385 , A61K47/646 , A61K2039/55522 , A61K2039/57 , A61K2039/6043 , A61K2039/622 , C07K14/47 , C07K17/02 , C12N2760/16122 , C12N2760/16134 , Y02A50/403 , Y02A50/41 , Y02A50/466 , Y02A50/478 , Y10S436/823 , Y10S530/806
摘要： Disclosed is a family of vaccines that contain stress protein-peptide complexes which when administered to a mammal are operative to initiate in the mammal a cytotoxic T cell response against cells infected with a preselected intracellular pathogen. Also disclosed are methodologies for preparing and administering vaccines containing such stress protein-peptide complexes.
摘要翻译：公开了一种含有应激蛋白 - 肽复合物的疫苗，其在施用于哺乳动物时可操作以在哺乳动物中引发针对感染了预选的细胞内病原体的细胞的细胞毒性T细胞应答。还公开了制备和施用含有这种应激蛋白 - 肽复合物的疫苗的方法。

28. 发明授权

US06410028B1 Therapeutic and prophylactic methods using heat shock proteins 有权
公开(公告)号：US06410028B1
公开(公告)日：2002-06-25
申请号：US09372022
申请日：1999-08-09
申请人： Pramod K. Srivastava
发明人： Pramod K. Srivastava
IPC分类号： A61K39385
CPC分类号： C07K14/47 , A61K38/00 , A61K39/0011 , A61K2039/6043 , A61K2039/622 , Y02A50/403 , Y02A50/41 , Y02A50/466 , Y02A50/478 , Y10S530/82 , Y10S530/822 , Y10S530/823 , Y10S530/824 , Y10S530/825 , Y10S530/826 , Y10S530/827 , Y10S530/828
摘要： The present invention relates to immunogenic complexes of heat shock proteins (hsp) noncovalently bound to exogenous antigenic molecules which when administered to an individual elicit specific immunological responses in the host. Methods of prevention and treatment of cancer and infectious disease are provided.

29. 发明授权

US06399070B1 Methods and compositions for eliciting an immune response with hsp90-peptide complexes 失效
标题翻译：用hsp90-肽复合物引发免疫应答的方法和组合物
公开(公告)号：US06399070B1
公开(公告)日：2002-06-04
申请号：US09440177
申请日：1999-11-15
申请人： Pramod K. Srivastava , Rajiv Y. Chandawarkar
发明人： Pramod K. Srivastava , Rajiv Y. Chandawarkar
IPC分类号： A61K39385
CPC分类号： A61K39/0011 , A61K2039/6043 , A61K2039/622 , Y02A50/466
摘要： The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. Optionally, the methods further comprise administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. “Antigenic molecule” as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96.
摘要翻译：本发明涉及引发免疫应答和预防和治疗原发性和转移性肿瘤性疾病和传染病的方法和组合物。本发明的方法包括施用包含有效量的复合物的组合物，其中复合物基本上由非共价结合于抗原分子的热休克蛋白（hsp）组成。任选地，所述方法还包括施用用非共价结合于抗原分子的hsps复合物致敏的抗原呈递细胞。本文所用的“抗原分子”是指hsps与体内内源性相关的肽以及外源性抗原/免疫原（即hsps在体内不复合）或其抗原/免疫原性片段及其衍生物。在优选的实施方案中，复合物是个体自体的。在一个具体实施方案中，对于包含hsp70,5-449微克对于hsp90和对于gp96为0.1至9.0微克的复合物，复合物的有效量在0.1至9.0微克范围内。

30. 发明授权

US06383491B1 Prevention of infectious diseases with hsp90-peptide complexes 失效
标题翻译：用hsp90肽复合物预防传染病
公开(公告)号：US06383491B1
公开(公告)日：2002-05-07
申请号：US09439682
申请日：1999-11-15
申请人： Pramod K. Srivastava , Rajiv Y. Chandawarkar
发明人： Pramod K. Srivastava , Rajiv Y. Chandawarkar
IPC分类号： A61K39385
CPC分类号： A61K39/0011 , A61K2039/6043 , A61K2039/622 , Y02A50/466
摘要： The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. Optionally, the methods further comprise administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. “Antigenic molecule” as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment; the effective amounts of the complex are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96.
摘要翻译：本发明涉及引发免疫应答和预防和治疗原发性和转移性肿瘤性疾病和传染病的方法和组合物。本发明的方法包括施用包含有效量的复合物的组合物，其中复合物基本上由非共价结合于抗原分子的热休克蛋白（hsp）组成。任选地，所述方法还包括施用用非共价结合于抗原分子的hsps复合物致敏的抗原呈递细胞。本文所用的“抗原分子”是指hsps与体内内源性相关的肽以及外源性抗原/免疫原（即hsps在体内不复合）或其抗原/免疫原性片段及其衍生物。在优选的实施方案中，复合物是个体自体的。在具体实施例中; 复合物的有效量在0.1至9.0微克范围内，对于包含hsp70,5-49微克对于hsp90和对于gp96为0.1至9.0微克的复合物。

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