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1. 发明申请

US20050043512A1 Human glioma antigen originating in testis 审中-公开
标题翻译：源自睾丸的人神经胶质瘤抗原
公开(公告)号：US20050043512A1
公开(公告)日：2005-02-24
申请号：US10496860
申请日：2002-11-29
申请人： Masahiro Toda , Yutaka Kawakami , Ryo Ueda
发明人： Masahiro Toda , Yutaka Kawakami , Ryo Ueda
IPC分类号： A61P35/00 , C07K14/47 , C07K16/30 , C12N1/21 , C12N15/12 , G01N33/574 , C12Q1/68 , A61K39/00 , C07H21/04
CPC分类号： C07K14/47 , A61K2121/00 , C07K14/4748 , C07K16/3053 , G01N33/57488
摘要： The present invention provides a testis-derived antigenic protein having an immunity induction activity comparable to a glioma antigenic protein and a gene encoding the same, etc., which can be applied to diagnosis and treatment of glioma. A testis-derived antigenic protein having an immunity induction activity comparable to a glioma antigenic protein and a gene encoding the same which can be applied to diagnosis and treatment of glioma are prepared by the steps of: extracting total RNA from testis, synthesizing cDNA, and constructing a λ phage cDNA library by introducing the cDNA into a λ phage vector and infecting Escherichia coli with the vector; reacting thus constructed λ phage cDNA library with the serum of a glioma patient, and using a labeled anti-IgG antibody to detect positive clones that react with the antibody in the serum; repeating the screening process several times on the detected positive clones to confirm the antibody reactivity; and isolating an antigen from the confirmed positive clones and performing serum screening using the isolated antigen and a glioma patient serum and a serum of a healthy individual, etc.
摘要翻译：本发明提供具有与神经胶质瘤抗原蛋白质相当的免疫诱导活性的睾丸衍生抗原蛋白及其编码基因的基因等，可用于诊断和治疗神经胶质瘤。通过以下步骤制备具有与神经胶质瘤抗原蛋白质相当的免疫诱导活性的睾丸衍生抗原蛋白和可用于诊断和治疗神经胶质瘤的基因，其可以从睾丸提取总RNA，合成cDNA和通过将cDNA引入λ噬菌体载体并用载体感染大肠杆菌构建λ噬菌体cDNA文库; 将如此构建的λ噬菌体cDNA文库与胶质瘤患者的血清反应，并使用标记的抗-IgG抗体检测与血清中的抗体反应的阳性克隆; 在检测到的阳性克隆上重复筛选过程数次，以确认抗体反应性; 并从确认的阳性克隆中分离抗原，并使用分离的抗原和神经胶质瘤患者血清和健康个体的血清等进行血清筛选。

2. 发明申请

US20060105330A1 Diagnostics and remedies for malignant brain tumor 审中-公开
标题翻译：恶性脑肿瘤的诊断和治疗
公开(公告)号：US20060105330A1
公开(公告)日：2006-05-18
申请号：US10506382
申请日：2003-03-04
申请人： Masahiro Toda , Yutaka Kawakami , Masakazu Ueda , Yohei Ohashi
发明人： Masahiro Toda , Yutaka Kawakami , Masakazu Ueda , Yohei Ohashi
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： A61K31/7088 , A61K38/00 , A61K48/00 , C07K14/82 , C12Q1/683 , C12Q1/686 , C12Q1/6886 , C12Q2600/154 , G01N33/57407 , C12Q2521/331 , C12Q2523/125
摘要： It is intended to provide a diagnosis method and diagnostics for cancers such as human glioma and a therapeutic method and remedies for cancers such as human glioma by identifying tumor suppressive genes or cancer genes useful in diagnosing or treating cancers such as human glioma. Tumor suppressive genes such as RFX1 gene and BGT-1 gene and cancer genes such as HOXD9 gene are screened by comparing a human glioma- or human glioma cell line-origin genomic DNA with a normal tissue-origin genomic DNA in the degree of methylation in CpG island cytosine residues. By targeting these tumor suppressive genes or cancers genes, cancers such as human glioma are diagnosed or treated
摘要翻译：本发明旨在通过鉴定可用于诊断或治疗诸如人神经胶质瘤的癌症的肿瘤抑制基因或癌基因来提供诸如人神经胶质瘤的癌症的诊断方法和诊断方法以及用于诸如人神经胶质瘤的癌症的治疗方法。通过将人神经胶质瘤或人神经胶质瘤细胞系来源的基因组DNA与正常组织来源的基因组DNA在甲基化程度中进行比较来筛选肿瘤抑制基因如RFX1基因和BGT-1基因和癌基因如HOXD9基因 G岛胞嘧啶残基。通过靶向这些肿瘤抑制基因或癌基因，诊断或治疗诸如人胶质瘤的癌症

3. 发明申请

US20050249705A1 Antitumor agents with the use of hsv 失效
标题翻译：使用hsv的抗肿瘤剂
公开(公告)号：US20050249705A1
公开(公告)日：2005-11-10
申请号：US10513193
申请日：2003-05-02
申请人： Masahiro Toda , Yutaka Kawakami , Yukihiko Iizuka , Yoko Ueda , Yoshihiro Iwahori
发明人： Masahiro Toda , Yutaka Kawakami , Yukihiko Iizuka , Yoko Ueda , Yoshihiro Iwahori
IPC分类号： C12N5/06 , A61K35/76 , A61K38/00 , A61K38/16 , A61K39/245 , A61P35/00 , A61P35/04 , A61P37/02 , A61P43/00 , C07K14/035 , C12N7/04 , A61K48/00
CPC分类号： C07K14/005 , A61K35/763 , A61K38/00 , A61K39/12 , A61K39/245 , A61K41/0019 , A61K2039/5156 , A61K2039/5252 , A61K2039/57 , A61K2039/585 , C12N7/00 , C12N2710/16622 , C12N2710/16632 , C12N2710/16634 , C12N2710/16661
摘要： It is intended to provide highly safe antitumor agents which exhibit an antitumor effect on human remote tumors such as metastatic tumors too and by which an antitumor immune reaction enabling an immune therapy for cancer can be induced, tumor immunity inducers, T cell activators, dendritic cell activators, a method of treating cancer using the same, etc. Inactivated herpes simplex virus (inactivated HSV), herpes simplex virus glycoprotein D (HSVgD), etc. are employed as the active ingredients of antitumor agents, tumor immunity inducers, T cell activators or dendritic cell activators. As a specific example of the treatment for the above-described inactivation, citation may be made of a combination of UV-irradiation using ultraviolet light at 254 nm at 4 J/m2 for 30 minutes with heating at 56° C. for 30 minutes.
摘要翻译：旨在提供高度安全的抗肿瘤剂，其对人类远端肿瘤如转移瘤也具有抗肿瘤作用，通过该抗肿瘤作用可以诱导能够诱导癌症免疫治疗的抗肿瘤免疫反应，肿瘤免疫诱导剂，T细胞激活剂，树突细胞活化剂，使用其治疗癌症的方法等。使用灭活的单纯疱疹病毒（失活的HSV），单纯疱疹病毒糖蛋白D（HSVgD）等作为抗肿瘤剂，肿瘤免疫诱导剂，T细胞激活剂的活性成分或树突状细胞激活剂。作为上述失活的处理的具体例，可以列举使用紫外线照射的组合，使用254nm的紫外线，4J / m 2，30分钟，加热 56℃30分钟。

4. 发明授权

US07384627B2 Antitumor agents with the use of HSV 失效
标题翻译：使用HSV的抗肿瘤剂
公开(公告)号：US07384627B2
公开(公告)日：2008-06-10
申请号：US10513193
申请日：2003-05-02
申请人： Masahiro Toda , Yutaka Kawakami , Yukihiko Iizuka , Yoko Ueda , Yoshihiro Iwahori
发明人： Masahiro Toda , Yutaka Kawakami , Yukihiko Iizuka , Yoko Ueda , Yoshihiro Iwahori
IPC分类号： A61K49/00 , A61K39/245
CPC分类号： C07K14/005 , A61K35/763 , A61K38/00 , A61K39/12 , A61K39/245 , A61K41/0019 , A61K2039/5156 , A61K2039/5252 , A61K2039/57 , A61K2039/585 , C12N7/00 , C12N2710/16622 , C12N2710/16632 , C12N2710/16634 , C12N2710/16661
摘要： It is intended to provide highly safe antitumor agents which exhibit an antitumor effect on human remote tumors such as metastatic tumors too and by which an antitumor immune reaction enabling an immune therapy for cancer can be induced, tumor immunity inducers, T cell activators, dendritic cell activators, a method of treating cancer using the same, etc. Inactivated herpes simplex virus (inactivated HSV), herpes simplex virus glycoprotein D (HSVgD), etc. are employed as the active ingredients of antitumor agents, tumor immunity inducers, T cell activators or dendritic cell activators. As a specific example of the treatment for the above-described inactivation, citation may be made of a combination of UV-irradiation using ultraviolet light at 254 nm at 4 J/m2 for 30 minutes with heating at 56° C. for 30 minutes.
摘要翻译：旨在提供高度安全的抗肿瘤剂，其对人类远端肿瘤如转移瘤也具有抗肿瘤作用，通过该抗肿瘤作用可以诱导能够诱导癌症免疫治疗的抗肿瘤免疫反应，肿瘤免疫诱导剂，T细胞激活剂，树突状细胞活化剂，使用其治疗癌症的方法等。使用灭活的单纯疱疹病毒（失活的HSV），单纯疱疹病毒糖蛋白D（HSVgD）等作为抗肿瘤剂，肿瘤免疫诱导剂，T细胞激活剂的活性成分或树突状细胞激活剂。作为上述失活的处理的具体例，可以列举使用紫外线照射的组合，使用254nm的紫外线，4J / m 2，30分钟，加热 56℃30分钟。

5. 发明申请

US20070243160A1 REMEDIES FOR NERVE DAMAGES 审中-公开
标题翻译：对神经损害的补救措施
公开(公告)号：US20070243160A1
公开(公告)日：2007-10-18
申请号：US11539476
申请日：2006-10-06
申请人： Masahiro Toda , Yutaka Kawakami , Yoshiaki Toyama , Yuji Mikami
发明人： Masahiro Toda , Yutaka Kawakami , Yoshiaki Toyama , Yuji Mikami
IPC分类号： A61K45/00 , A61P25/00
CPC分类号： A61K38/193 , A61K35/16 , A61K38/1808 , A61K38/1841 , A61K38/185 , A61K38/204 , A61K38/208
摘要： The present invention provides a remedy for a nerve dysfunctional disorder such as a central nervous system damage including a spinal cord injury and a cerebral infarction and the like having an excellent nerve regeneration promoting action which can be administered not only by injecting into a injured site but also by various administration methods including intravenous administration, which can be easily handled and stored over a long time, and can be prepared in a large amount at any time. Said remedy for a nerve dysfunctional disorder such as a central nervous system damage including a spinal cord injury and a cerebral infarction and the like are prepared by using the following as active ingredients: one or more substances selected from a substance secreted from dendritic cells such as IL-12, GM-CSF and the like, a substance inducing and proliferating dendritic cells, a substance activating dendritic cells; a substance inducing the expression of a neurotrophic factor in nerve tissues, a substance inducing and proliferating microglias and macrophages in nerve tissues; and a vector which can expresses the aforementioned substances; or dendritic cell subsets secreting a neurotrophic factor such as NT-3, CNTF, TGF-β1, IL-6, and EGF.
摘要翻译：本发明提供了神经功能障碍性疾病的补救措施，例如包括脊髓损伤和脑梗死等的中枢神经系统损伤，其具有优异的神经再生促进作用，其不仅可以通过注射到受伤部位而被施用，也可以通过静脉内给药等各种施用方法，能够容易地长时间处理和储存，并且可以在任何时间大量制备。通过使用以下作为活性成分，可以制备神经功能障碍障碍如中枢神经系统损伤（包括脊髓损伤和脑梗塞等）的一种或多种物质：选自树突状细胞分泌的物质，例如 IL-12，GM-CSF等，诱导和增殖树突状细胞的物质，激活树突状细胞的物质; 诱导神经组织中神经营养因子表达的物质，在神经组织中诱导和增殖微小神经细胞和巨噬细胞的物质; 和可以表达上述物质的载体; 或分泌神经营养因子如NT-3，CNTF，TGF-β1，IL-6和EGF的树突状细胞亚群。

6. 发明申请

US20050226852A1 Method of inducing growth of nerve stem cells 审中-公开
标题翻译：诱导神经干细胞生长的方法
公开(公告)号：US20050226852A1
公开(公告)日：2005-10-13
申请号：US10509529
申请日：2003-03-27
申请人： Masahiro Toda , Hideyuki Okano , Yutaka Kawakami , Yoshiaki Toyama , Yuji Mikami , Masanori Sakaguchi
发明人： Masahiro Toda , Hideyuki Okano , Yutaka Kawakami , Yoshiaki Toyama , Yuji Mikami , Masanori Sakaguchi
IPC分类号： A61P25/00 , C12N5/02 , C12N5/0797 , A61K45/00 , C12N5/08
CPC分类号： C12N5/0623 , C12N2501/11 , C12N2501/115 , C12N2501/22 , C12N2506/11
摘要： It is intended to provide a method of efficiently inducing the growth of nerve stem cells, which are most important in transplantation therapy for nerve damage and neurological dysfunction, either in vitro or in vivo, a method of using the nerve stem cells obtained by the above growth induction method, etc. A mammalian nerve tissue containing nerve stem cells is separated and the nerve stem cells are selectively cultured in a medium containing growth factors such as EGF and FGF. Next, the nerve stem cells are co-cultured with dendritic cell such as an immature dendritic cell subset having a CD11c surface marker on the cell surface, spleen cells or blood cell-type cells such as CD8-positive T cells. Alternatively, the nerve stem cells after the culture are further cultured in the presence of GM-CSF or the nerve stem cells after the culture are further cultured in a culture supernatant of dendritic cells or a culture supernatant of blood cell-type cells.
摘要翻译：旨在提供一种有效诱导神经干细胞生长的方法，其在体外或体内用于神经损伤和神经功能障碍的移植治疗中是最重要的，使用由上述获得的神经干细胞的方法生长诱导方法等。分离含有神经干细胞的哺乳动物神经组织，并在含有生长因子如EGF和FGF的培养基中选择性培养神经干细胞。接下来，将神经干细胞与树突状细胞共同培养，例如在细胞表面上具有CD11c表面标志物的未成熟树突状细胞亚群，脾细胞或血液细胞型细胞如CD8阳性T细胞。或者，培养后的神经干细胞在GM-CSF存在下进一步培养，或者培养后的神经干细胞进一步在树突状细胞的培养上清液或血细胞型细胞的培养上清液中培养。

7. 发明授权

US07763586B2 Melanoma antigens and their use in diagnostic and therapeutic methods 有权
公开(公告)号：US07763586B2
公开(公告)日：2010-07-27
申请号：US11932826
申请日：2007-10-31
申请人： Yutaka Kawakami , Steven A. Rosenberg
发明人： Yutaka Kawakami , Steven A. Rosenberg
IPC分类号： A61K38/00 , C07K5/00
CPC分类号： C07K14/47 , A61K38/00 , A61K39/00 , A61K39/0011 , A61K2039/5256 , A61K2039/53 , C07K14/4748 , G01N33/5743
摘要： The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.

8. 发明授权

US07745212B2 Melanoma antigens and their use in diagnostic and therapeutic methods 有权
标题翻译：黑素瘤抗原及其在诊断和治疗方法中的应用
公开(公告)号：US07745212B2
公开(公告)日：2010-06-29
申请号：US11932338
申请日：2007-10-31
申请人： Yutaka Kawakami , Steven A. Rosenberg
发明人： Yutaka Kawakami , Steven A. Rosenberg
IPC分类号： C12N15/00
CPC分类号： C07K14/47 , A61K38/00 , A61K39/00 , A61K39/0011 , A61K2039/5256 , A61K2039/53 , C07K14/4748 , G01N33/5743
摘要： The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.
摘要翻译：本发明提供编码被称为MART-1的T淋巴细胞识别的黑素瘤抗原的核酸序列。本发明还涉及使用本发明的核酸序列，蛋白质或抗体诊断，评估或预测患有黑素瘤或转移性黑素瘤的哺乳动物的生物测定。本发明还提供衍生自MART-1黑素瘤抗原的免疫原性肽和称为gp100的第二黑素瘤抗原。本发明还提供衍生自MART-1黑素瘤抗原或gp100抗原的免疫原性肽，其已被修饰以增强其免疫原性。所提供的蛋白质和肽可以作为预防或治疗黑素瘤的免疫原或疫苗。

9. 发明申请

US20080233637A1 MELANOMA ANTIGENS AND THEIR USE IN DIAGNOSTIC AND THERAPEUTIC METHODS 有权
标题翻译： MELANOMA抗原及其在诊断和治疗方法中的应用
公开(公告)号：US20080233637A1
公开(公告)日：2008-09-25
申请号：US11932255
申请日：2007-10-31
申请人： Yutaka Kawakami , Steven A. Rosenberg
发明人： Yutaka Kawakami , Steven A. Rosenberg
IPC分类号： C12N15/00 , C12N5/00
CPC分类号： C07K14/47 , A61K38/00 , A61K39/00
摘要： The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MRT-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.
摘要翻译：本发明提供编码被称为MART-1的T淋巴细胞识别的黑素瘤抗原的核酸序列。本发明还涉及使用本发明的核酸序列，蛋白质或抗体诊断，评估或预测患有黑素瘤或转移性黑素瘤的哺乳动物的生物测定。本发明还提供衍生自MRT-1黑素瘤抗原的免疫原性肽和称为gp100的第二黑素瘤抗原。本发明还提供衍生自MART-1黑素瘤抗原或gp100抗原的免疫原性肽，其已被修饰以增强其免疫原性。所提供的蛋白质和肽可以作为预防或治疗黑素瘤的免疫原或疫苗。

10. 发明授权

US07232887B2 Melanoma antigens and their use in diagnostic and therapeutic methods 有权
标题翻译：黑素瘤抗原及其在诊断和治疗方法中的应用
公开(公告)号：US07232887B2
公开(公告)日：2007-06-19
申请号：US10685977
申请日：2003-10-15
申请人： Yutaka Kawakami , Steven A. Rosenberg
发明人： Yutaka Kawakami , Steven A. Rosenberg
IPC分类号： C07K16/00
CPC分类号： C07K14/47 , A61K38/00 , A61K39/00 , A61K39/0011 , A61K2039/5256 , A61K2039/53 , C07K14/4748 , G01N33/5743
摘要： The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.
摘要翻译：本发明提供编码被称为MART-1的T淋巴细胞识别的黑素瘤抗原的核酸序列。本发明还涉及使用本发明的核酸序列，蛋白质或抗体诊断，评估或预测患有黑素瘤或转移性黑素瘤的哺乳动物的生物测定。本发明还提供衍生自MART-1黑素瘤抗原的免疫原性肽和称为gp100的第二黑素瘤抗原。本发明还提供衍生自MART-1黑素瘤抗原或gp100抗原的免疫原性肽，其已被修饰以增强其免疫原性。所提供的蛋白质和肽可以作为预防或治疗黑素瘤的免疫原或疫苗。

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