公开(公告)号：US06331525B1

公开(公告)日：2001-12-18

申请号：US09379434

申请日：1999-08-23

申请人： Henry C. Chiou ,  Dennis J. Carlo

发明人： Henry C. Chiou ,  Dennis J. Carlo

IPC分类号： A61K4800

CPC分类号： C12N15/87 ,  A61K38/212 ,  A61K47/645 ,  A61K48/00 ,  A61K48/0058 ,  A61K48/0066

摘要： A molecular complex comprising a gene encoding interferon releasably linked to a conjugate of a nucleic acid binding agent and a ligand which binds to a component on the surface of a cell. In a preferred embodiment, the gene encodes human IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The complex can be used to obtain targeted expression of interferon in selected cells either in vivo or in vitro.

摘要翻译： 一种分子复合物，其包含编码干扰素的基因，其可释放地连接到核酸结合剂和与细胞表面上的组分结合的配体。 在优选的实施方案中，该基因编码人IFN-α，IFN-β或IFN-γ。 该复合物可用于在体内或体外获得选定细胞中干扰素的靶向表达。

公开(公告)号：US06221352B1

公开(公告)日：2001-04-24

申请号：US08471209

申请日：1995-06-06

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39395

CPC分类号： G01N33/56972 ,  A61K39/00 ,  A61K39/0008 ,  A61K48/00 ,  A61K2039/53 ,  C07K14/7051 ,  C07K16/2809 ,  C07K16/4258 ,  G01N2800/285

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific &bgr;-chain variable regions of T cell receptors, designated V&bgr;3, V&bgr;4, V&bgr;12, V&bgr;14 and V&bgr;17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供疫苗和疫苗接种脊椎动物的方法，以便预防或控制特定的T细胞介导的病症，包括自身免疫疾病和T细胞的不受调节的复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 这样的肽可以结合到MHC抗原呈递细胞或超级抗原完成的常规抗原。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于脊椎动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供与自身免疫性疾病如类风湿性关节炎（RA）和多发性硬化（MS）的发病机制相关的T细胞受体的特定β链可变区，称为Vbeta3，Vbeta4，Vbeta12，Vbeta14和Vbeta17。 还提供了检测，预防和治疗RA和MS的手段。 还提供了将编码可用作本发明的疫苗的多肽的DNA或RNA给予个体的组织细胞的方法。

公开(公告)号：US06207645B1

公开(公告)日：2001-03-27

申请号：US08276776

申请日：1994-07-18

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K4800

CPC分类号： C07K16/2809 ,  A61K39/00 ,  A61K39/0008 ,  A61K48/00 ,  A61K2039/53 ,  C07K14/7051 ,  C07K16/4258 ,  G01N33/56972 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens complexed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific &bgr;-chain variable regions of T cell receptors, designated V&bgr;3, V&bgr;4, V&bgr;12, V&bgr;14 and V&bgr;17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供疫苗和疫苗接种脊椎动物的方法，以便预防或控制特定的T细胞介导的病症，包括自身免疫疾病和T细胞的不受调节的复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 这样的肽可以结合与MHC抗原呈递细胞或超级抗原复合的常规抗原。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于脊椎动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供与自身免疫性疾病如类风湿性关节炎（RA）和多发性硬化（MS）的发病机制相关的T细胞受体的特定β链可变区，称为Vbeta3，Vbeta4，Vbeta12，Vbeta14和Vbeta17。 还提供了检测，预防和治疗RA和MS的手段。 还提供了将编码可用作本发明的疫苗的多肽的DNA或RNA给予个体的组织细胞的方法。

公开(公告)号：US6159470A

公开(公告)日：2000-12-12

申请号：US464506

申请日：1995-06-05

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  C07K14/725 ,  G01N33/564 ,  G01N33/569 ,  A61K39/395

CPC分类号： C07K14/7051 ,  G01N33/564 ,  G01N33/56972 ,  A61K2039/53 ,  A61K39/00 ,  G01N2800/102 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the mammal in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides a specific .beta.-chain variable region of the T cell receptor, designated V.beta.17, which is central to the pathogenesis of rheumatoid arthritis (RA). Also provided are means to detect, prevent and treat RA.

摘要翻译： 本发明提供疫苗和疫苗接种哺乳动物的手段，以便预防或控制特定的T细胞介导的病理学或治疗T细胞的未调节复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于哺乳动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供了称为Vβ17的T细胞受体的特异性β链可变区，其为类风湿性关节炎（RA）的发病机制的核心。 还提供了检测，预防和治疗RA的手段。

公开(公告)号：US5928930A

公开(公告)日：1999-07-27

申请号：US464137

申请日：1995-06-05

申请人： Jonas Salk ,  Dennis J. Carlo

发明人： Jonas Salk ,  Dennis J. Carlo

IPC分类号： A61M1/36 ,  A61P31/18 ,  C07K14/16 ,  C12N7/04

CPC分类号： C07K14/005 ,  A61M1/3687 ,  C12N2740/16122 ,  Y10S530/826

摘要： The present invention provides a non-infectious immunotherapeutic containing retroviral particles devoid of outer envelope proteins or containing selected antigens isolated from a retrovirus. There is also provided a vaccine effective against HIV. In one aspect, the immunogen is useful for immunizing an individual previously infected by a retrovirus including HIV, so as to induce immunoprotective factors protective against progression of the infection. In another aspect, the vaccine is useful for vaccinating an individual not previously infected with HIV in order to prevent subsequently acquired infection. In another aspect, there is provided a method of rendering a viral immunogen non-infectious. The immunogen may also be used to produce antibodies for passive immunotherapy, alone or in conjunction with active immunotherapy, in individuals infected with a retrovirus, including HIV, preferably those individuals exhibiting low levels of antibodies to retroviral gene products other than the outer envelope.

公开(公告)号：US5916806A

公开(公告)日：1999-06-29

申请号：US464139

申请日：1995-06-05

申请人： Jonas Salk ,  Dennis J. Carlo

发明人： Jonas Salk ,  Dennis J. Carlo

IPC分类号： A61M1/36 ,  A61P31/18 ,  C07K14/16 ,  C07K16/00

CPC分类号： C07K14/005 ,  A61M1/3687 ,  C12N2740/16122 ,  Y10S530/826

摘要： The present invention provides a non-infectious immunotherapeutic containing retroviral particles devoid of outer envelope proteins or containing selected antigens isolated from a retrovirus. There is also provided a vaccine effective against HIV. In one aspect, the immunogen is useful for immunizing an individual previously infected by a retrovirus including HIV, so as to induce immunoprotective factors protective against progression of the infection. In another aspect, the vaccine is useful for vaccinating an individual not previously infected with HIV in order to prevent subsequently acquired infection. In another aspect, there is provided a method of rendering a viral immunogen non-infectious. The immunogen may also be used to produce antibodies for passive immunotherapy, alone or in conjunction with active immunotherapy, in individuals infected with a retrovirus, including HIV, preferably those individuals exhibiting low levels of antibodies to retroviral gene products other than the outer envelope.

公开(公告)号：US5861164A

公开(公告)日：1999-01-19

申请号：US146454

申请日：1993-11-01

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  C07K14/725 ,  A61K38/00

CPC分类号： C07K14/7051 ,  A61K2039/53 ,  A61K39/00

摘要： The present invention provides vaccines and a means vaccinating a host so as to prevent or control specific T cell medicated proliferative diseases. The vaccine is composed of a pharmaceutically acceptable medium and a segment of the T cell receptor (TCR) present on the surface of the T cells mediating the disease. The vaccine is administered to the host in a manner that induces an immune response directed against the TCR of a pathologic T cell. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. Means of determining an appropriate amino acid sequence for such a vaccine are also provided.

摘要翻译： 本发明提供疫苗和接种宿主的方法，以便预防或控制特异性T细胞药物增殖性疾病。 疫苗由存在于介导该疾病的T细胞表面上的T细胞受体（TCR）的药学上可接受的介质和​​片段组成。 以诱导针对病理T细胞的TCR的免疫应答的方式将疫苗施用于宿主。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 还提供了确定这种疫苗的适当氨基酸序列的方法。

公开(公告)号：US5612035A

公开(公告)日：1997-03-18

申请号：US103418

申请日：1993-08-06

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  C07K14/725 ,  A61K38/00

CPC分类号： C07K14/7051 ,  A61K2039/53 ,  A61K39/00 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a host so as to prevent or control specific T cell mediated pathologies. The vaccine is composed of a polypeptide whose amino acid sequence corresponds to a segment of the T cell receptor (TCR) present on the surface of the pathogenic T cells. The vaccine is administered to the host in a manner that induces an immune response directed against the TCR of pathologic T cells. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. Means of determining an appropriate amino acid sequence for such a vaccine are also provided.

摘要翻译： 本发明提供疫苗和疫苗接种宿主的方法，以便预防或控制特定的T细胞介导的病理学。 疫苗由多肽组成，其氨基酸序列对应于存在于病原性T细胞表面上的T细胞受体（TCR）的区段。 将疫苗以诱导针对病理T细胞的TCR的免疫应答的方式施用于宿主。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 还提供了确定这种疫苗的适当氨基酸序列的方法。

公开(公告)号：US4250265A

公开(公告)日：1981-02-10

申请号：US84973

申请日：1979-10-15

申请人： Dennis J. Carlo ,  Arpi Hagopian ,  Peter J. Kniskern

发明人： Dennis J. Carlo ,  Arpi Hagopian ,  Peter J. Kniskern

IPC分类号： A61K39/10 ,  C07G7/00

CPC分类号： A61K39/099 ,  A61K2039/552 ,  Y10S424/825

摘要： A sub-cellular antigenic fraction of Bordetella bronchiseptica protects against the incidence and severity of swine atropic rhinitis.

摘要翻译： 支气管炎博德特氏菌的亚细胞抗原级分可以防止猪嗜性性鼻炎的发生率和严重程度。

公开(公告)号：US6090387A

公开(公告)日：2000-07-18

申请号：US472040

申请日：1995-06-06

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  A61K48/00 ,  C07K14/725 ,  C07K16/28 ,  C07K16/42 ,  C12N15/12 ,  G01N33/569 ,  C07K7/06 ,  C07K14/44

CPC分类号： C07K16/2809 ,  A61K39/0008 ,  C07K14/7051 ,  C07K16/4258 ,  G01N33/56972 ,  A61K2039/53 ,  A61K39/00 ,  A61K48/00 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific .beta.-chain variable regions of T cell receptors, designated V.beta.3, V.beta.4, V.beta.12, V.beta.14 and V.beta.17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供疫苗和疫苗接种脊椎动物的方法，以便预防或控制特定的T细胞介导的病症，包括自身免疫疾病和T细胞的不受调节的复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 这样的肽可以结合到MHC抗原呈递细胞或超级抗原完成的常规抗原。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于脊椎动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供特定的β链可变区T细胞受体，称为Vβ3，Vβ4，Vβ12，Vβ14和Vβ17，其与自身免疫疾病的发病机制相关，例如类风湿性关节炎 （RA）和多发性硬化（MS）。 还提供了检测，预防和治疗RA和MS的手段。 还提供了将编码可用作本发明的疫苗的多肽的DNA或RNA给予个体的组织细胞的方法。