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1. 发明授权

US08211422B2 Chimeric receptor genes and cells transformed therewith 失效
标题翻译：嵌合受体基因和转化的细胞
公开(公告)号：US08211422B2
公开(公告)日：2012-07-03
申请号：US08547263
申请日：1995-10-24
申请人： Zelig Eshhar , Daniel Schindler , Tova Waks , Gideon Gross , Steven A. Rosenberg , Patrick Hwu
发明人： Zelig Eshhar , Daniel Schindler , Tova Waks , Gideon Gross , Steven A. Rosenberg , Patrick Hwu
IPC分类号： A61K48/00
CPC分类号： C07K14/7155 , A61K35/17 , A61K38/00 , C07K14/7051 , C07K14/70535 , C07K16/1045 , C07K16/3046 , C07K16/32 , C07K16/4291 , C07K16/44 , C07K2319/00 , C12N2799/027
摘要： Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.
摘要翻译：适于赋予具有抗体型特异性的淋巴细胞的嵌合受体基因包括编码特异性抗体的单链Fv结构域的第一基因片段和编码全部或部分跨膜和细胞质结构域的第二基因片段，以及任选的细胞外结构域，的免疫细胞触发分子。嵌合受体基因当转染到免疫细胞时，将抗体识别位点和免疫细胞触发部分表达到一个连续的链中。转化的淋巴细胞可用于治疗方法。

2. 发明授权

US07741465B1 Chimeric receptor genes and cells transformed therewith 失效
标题翻译：嵌合受体基因和转化的细胞
公开(公告)号：US07741465B1
公开(公告)日：2010-06-22
申请号：US08084994
申请日：1993-07-02
申请人： Zelig Eshhar , Daniel Schindler , Tova Waks , Gideon Gross
发明人： Zelig Eshhar , Daniel Schindler , Tova Waks , Gideon Gross
IPC分类号： C07H21/04 , C12N15/74 , C12N5/00
CPC分类号： C07K16/32 , C07K16/4291 , C07K16/44 , C07K2317/52 , C07K2317/622
摘要： Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.
摘要翻译：适于赋予具有抗体型特异性的淋巴细胞的嵌合受体基因包括编码特异性抗体的单链Fv结构域的第一基因片段和编码全部或部分跨膜和细胞质结构域的第二基因片段，以及任选的细胞外结构域，的免疫细胞触发分子。嵌合受体基因当转染到免疫细胞时，将抗体识别位点和免疫细胞触发部分表达到一个连续的链中。转化的淋巴细胞可用于治疗方法。

3. 发明申请

US20120093842A1 CHIMERIC RECEPTOR GENES AND CELLS TRANSFORMED THEREWITH 审中-公开
标题翻译： CHIMERIC受体基因和细胞转化
公开(公告)号：US20120093842A1
公开(公告)日：2012-04-19
申请号：US13281560
申请日：2011-10-26
申请人： Zelig Eshhar , Daniel Schindler , Tova Waks , Gideon Gross , Steven A. Rosenberg , Patrick Hwu
发明人： Zelig Eshhar , Daniel Schindler , Tova Waks , Gideon Gross , Steven A. Rosenberg , Patrick Hwu
IPC分类号： A61K35/00 , A61P35/00
CPC分类号： C07K14/7155 , A61K35/17 , A61K38/00 , C07K14/7051 , C07K14/70535 , C07K16/1045 , C07K16/3046 , C07K16/32 , C07K16/4291 , C07K16/44 , C07K2319/00 , C12N2799/027
摘要： Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.
摘要翻译：适于赋予具有抗体型特异性的淋巴细胞的嵌合受体基因包括编码特异性抗体的单链Fv结构域的第一基因片段和编码全部或部分跨膜和细胞质结构域的第二基因片段，以及任选的细胞外结构域，的免疫细胞触发分子。嵌合受体基因当转染到免疫细胞时，将抗体识别位点和免疫细胞触发部分表达到一个连续的链中。转化的淋巴细胞可用于治疗方法。

4. 发明授权

US5912172A Endowing lymphocytes with antibody specificity 失效
公开(公告)号：US5912172A
公开(公告)日：1999-06-15
申请号：US474819
申请日：1995-06-07
申请人： Zelig Eshhar , Gideon Gross , Tova Waks
发明人： Zelig Eshhar , Gideon Gross , Tova Waks
IPC分类号： C07K14/725 , C07K16/44 , C12N15/13 , C07H21/04 , C07K16/46
CPC分类号： C07K14/7051 , C07K16/44 , C07K2317/56 , C07K2319/00 , C07K2319/02
摘要： There are produced recombinant gene pairs which endow mononuclear cells, mainly various lymphocyte type cells, with antibody-type specificity. In specific gene pairs the rearranged gene pairs code for a binding site of an antibody molecule from the same species, of the T-cell receptor gene, or another species. Gene pairs of the invention code, for example, for antibodies specific towards tumor-specific antigens, viral antigens, modified self antigens, bacterial or fungal antigens, autoimmune type disease antigens and the like. The invention further relates to expression vectors for the effective transfection of such cell types comprising such a recombinant gene pair, to methods for producing same and to pharmaceutical compositions comprising as active ingredient an effective quantity of lymphocytes transfected with such gene pairs.

5. 发明授权

US5906936A Endowing lymphocytes with antibody specificity 失效
标题翻译：赋予淋巴细胞抗体特异性
公开(公告)号：US5906936A
公开(公告)日：1999-05-25
申请号：US55396
申请日：1993-05-04
申请人： Zelig Eshhar , Gideon Gross , Tova Waks
发明人： Zelig Eshhar , Gideon Gross , Tova Waks
IPC分类号： C07K14/725 , C07K16/44 , C12N15/13 , C07H21/04 , C07K16/46
CPC分类号： C07K14/7051 , C07K16/44 , C07K2317/56 , C07K2319/00 , C07K2319/02
摘要： There are produced recombinant gene pairs which endow mononuclear cells, mainly various lymphocyte type cells, with antibody-type specificity. In specific gene pairs the rearranged gene pairs code for a binding site of an antibody molecule from the same species, of the T-cell receptor gene, or another species. Gene pairs of the invention code, for example, for antibodies specific towards tumor-specific antigens, viral antigens, modified self antigens, bacterial or fungal antigens, autoimmune type disease antigens and the like. The invention further relates to expression vectors for the effective transfection of such cell types comprising such a recombinant gene pair, to methods for producing same and to pharmaceutical compositions comprising as active ingredient an effective quantity of lymphocytes transfected with such gene pairs.
摘要翻译：产生了具有抗体型特异性的单核细胞，主要是各种淋巴细胞型细胞的重组基因对。在特定基因对中，重排的基因对编码来自相同物种，T细胞受体基因或其他物种的抗体分子的结合位点。本发明的基因对编码例如针对肿瘤特异性抗原特异性抗体，病毒抗原，修饰的自身抗原，细菌或真菌抗原，自身免疫型疾病抗原等。本发明进一步涉及用于有效转染包含这种重组基因对的这种细胞类型的表达载体，其生产方法和包含作为活性成分的有效量的用这种基因对转染的淋巴细胞的药物组合物。

6. 发明申请

US20080286312A1 Membrane-anchored beta2 microglobulincovalently linked to MHC class I peptide epitopes 审中-公开
标题翻译：膜锚定的β2微球蛋白与MHC I类肽表位共价连接
公开(公告)号：US20080286312A1
公开(公告)日：2008-11-20
申请号：US11541566
申请日：2006-10-03
申请人： Gideon Gross , Alon Margalit
发明人： Gideon Gross , Alon Margalit
IPC分类号： A61K39/00 , C07H21/00 , C12N15/63 , A61P37/02 , C12N5/00
CPC分类号： C07K14/70539 , A61K39/00 , A61K2039/5154 , A61K2039/53 , C07K14/005 , C07K14/705 , C07K14/70578 , C07K2319/00 , C07K2319/03 , C12N2740/16222
摘要： The invention provides a polynucleotide comprising a sequence encoding a polypeptide that is capable of high level presentation of antigenic peptides on antigen-presenting cells, wherein the polypeptide comprises a β2-microglobulin molecule that is linked through its carboxyl terminal to a bridge peptide which spans the whole distance to the cell membrane, said bridge peptide being linked to a polypeptide stretch consisting of the full or partial transmembrane and/or cytoplasmic domains selected from the group consisting of a toll-like receptor (TLR) polypeptide, a CD40 polypeptide, and TLR and CD40 polypeptides fused in tandem, that allows the anchorage of the β2-microglobulin molecule to the cell membrane, and through its amino terminal to at least one antigenic peptide comprising an MHC class I epitope, wherein said antigenic peptide is preferably derived from a tumor-associated antigen or from a pathogenic antigen. Antigen presenting cells and DNA and cellular vaccines for treatment of cancer and infectious diseases, are also provided.
摘要翻译：本发明提供了一种多核苷酸，其包含编码能够在抗原呈递细胞上高水平呈递抗原肽的多肽的序列，其中所述多肽包含通过其羧基末端连接到桥接肽的β2-微球蛋白分子，所述桥肽跨越所述桥肽与由全部或部分跨膜和/或细胞质结构域组成的多肽延伸连接，所述全部或部分跨膜和/或细胞质结构域选自一种toll样受体（TLR）多肽，CD40多肽和TLR 和CD40多肽共同融合，其允许β2-微球蛋白分子锚定于细胞膜，并通过其氨基末端至少包含MHC I类表位的抗原肽，其中所述抗原肽优选衍生自肿瘤相关抗原或来自致病性抗原。还提供抗原呈递细胞和用于治疗癌症和感染性疾病的DNA和细胞疫苗。

7. 发明申请

US20060003315A1 Membrane-anchored beta2 microglobulin covalently linked to mhc class 1 peptide epitopes 审中-公开
标题翻译：膜锚定的β2微球蛋白与mhc 1类肽表位共价连接
公开(公告)号：US20060003315A1
公开(公告)日：2006-01-05
申请号：US10517784
申请日：2003-06-12
申请人： Gideon Gross , Alon Margalit
发明人： Gideon Gross , Alon Margalit
IPC分类号： C12Q1/70 , C12Q1/68 , C07H21/04 , C07K14/16
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/5154 , A61K2039/53 , C07K14/70539 , C07K2319/00 , C07K2319/02 , C07K2319/03 , C07K2319/035 , C07K2319/04 , C07K2319/40 , C12N15/625 , C12N2740/16322
摘要： The invention provides a polynucleotide comprising a sequence encoding a polypeptide comprising a beta2-microglobulin molecule linked through its carboxyl terminal to a polypeptide stretch that allows the anchorage of the beta2-microglobulin molecule to the cell membrane, and through its amino terminal to at least one antigenic peptide comprising a MHC class I epitope, wherein said antigenic peptide is not related to an autoimmune disease and is preferably derived from a tumor-associated antigen or from a pathogenic antigen. Antigen presenting cells, and DNA and cellular vaccines for treatment of cancer and infectious diseases, are also provided.
摘要翻译：本发明提供了一种多核苷酸，其包含编码多肽的序列，所述多肽包含通过其羧基末端连接的多肽片段的β2-微球蛋白分子，其允许β2-微球蛋白分子锚定于细胞膜，并通过其氨基末端至少一个包含MHC I类表位的抗原肽，其中所述抗原肽与自身免疫疾病无关，并且优选衍生自肿瘤相关抗原或来自致病性抗原。还提供了抗原呈递细胞，以及用于治疗癌症和感染性疾病的DNA和细胞疫苗。

8. 发明授权

US07319143B2 Genetically-engineered MHC molecules 失效
标题翻译：基因工程MHC分子
公开(公告)号：US07319143B2
公开(公告)日：2008-01-15
申请号：US10297060
申请日：2001-05-31
申请人： Gideon Gross , Alon Margalit
发明人： Gideon Gross , Alon Margalit
IPC分类号： C12N5/00 , C07H21/04 , C07K1/00
CPC分类号： C07K14/7051 , A61K38/00 , C07K14/70539
摘要： The invention provides DNA molecules encoding a chimeric polypeptide comprising (a) a component of a MHC molecule capable of association on a cell surface with an endogenous MHC molecule component of the same class, and (b) an intracellular region of a signal transduction element capable of activating T cells. Component (a) may be a monomorphic component and is preferably beta 2-microglobulin, or a polymorphic class I or class II component. The signal transduction element (b) capable of activating T cells may be a component of T-cell receptor CD3, preferably the CD3 zeta (zeta) polypeptide, a B cell receptor polypeptide or an Fc receptor polypeptide. Immune cells such as a CTLs expressing said chimeric MHC molecules specifically eliminate or inactivate harmful T cells and are useful for treating graft rejection and autoimmune diseases.
摘要翻译：本发明提供了编码嵌合多肽的DNA分子，其包含（a）能够在细胞表面上与相同类别的内源性MHC分子组分结合的MHC分子的成分，和（b）能够产生信号转导元件的细胞内区域的活化T细胞。组分（a）可以是单形成分，优选β2-微球蛋白，或多态性I类或II类成分。能够活化T细胞的信号转导元件（b）可以是T细胞受体CD3，优选CD3ζ（ζ）多肽，B细胞受体多肽或Fc受体多肽的组分。免疫细胞如表达所述嵌合MHC分子的CTL特异性地消除或失活有害的T细胞，并且可用于治疗移植物排斥反应和自身免疫性疾病。

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