公开(公告)号：US20050196400A1

公开(公告)日：2005-09-08

申请号：US10263182

申请日：2002-10-03

申请人： Marc Better ,  Arnold Horwitz ,  Randy Robinson ,  Shau-Ping Lei ,  Changtung Chang

发明人： Marc Better ,  Arnold Horwitz ,  Randy Robinson ,  Shau-Ping Lei ,  Changtung Chang

IPC分类号： A61K39/395 ,  C07K16/30 ,  C12N15/86 ,  G01N33/574

CPC分类号： C12N15/85 ,  C07K16/30 ,  C07K2317/14 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76

摘要： Gene expression elements and their use in production of chimeric antibodies with human constant regions and murine variable regions, and mouse human chimeric antibodies having specificity to human tumor cells, methods of their production, and their use.

摘要翻译： 基因表达元件及其在产生具有人恒定区和鼠可变区的嵌合抗体中的用途以及对人肿瘤细胞具有特异性的小鼠人嵌合抗体，其生产方法及其用途。

公开(公告)号：US20050009097A1

公开(公告)日：2005-01-13

申请号：US10816276

申请日：2004-03-31

申请人： Marc Better ,  Arnold Horwitz

发明人： Marc Better ,  Arnold Horwitz

IPC分类号： C07K16/30 ,  G01N33/574 ,  G01N33/53 ,  C07K16/40 ,  C12P21/04

CPC分类号： C07K16/30 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/73 ,  G01N33/57492

摘要： Human engineered anti-Ep-CAM antibodies and various uses therefore are disclosed. These human engineered anti-Ep-CAM antibodies have high affinity binding to Ep-CAM with low immunogenicity.

摘要翻译： 因此公开了人工抗Ep-CAM抗体和各种用途。 这些人工构建的抗Ep-CAM抗体与Ep-CAM具有高亲和力结合，免疫原性低。

公开(公告)号：US20150344844A1

公开(公告)日：2015-12-03

申请号：US14614400

申请日：2015-02-04

申请人： Marc Better ,  Steven A. Feldman ,  Steven A. Rosenberg

发明人： Marc Better ,  Steven A. Feldman ,  Steven A. Rosenberg

IPC分类号： C12N5/0783 ,  C07K16/28 ,  A61K39/395 ,  C07K14/725 ,  A61K35/17 ,  A61K38/17

CPC分类号： C12N5/0636 ,  A61K35/17 ,  A61K38/1774 ,  A61K39/0011 ,  A61K39/39558 ,  A61K2039/5156 ,  A61K2039/5158 ,  C07K14/7051 ,  C07K16/2896 ,  C07K2319/74 ,  C12N2500/90 ,  C12N2501/2302 ,  C12N2501/515 ,  C12N2510/00

摘要： Provided herein are methods for manufacturing T cells. In certain embodiments, methods for manufacturing T cells which express a cell surface receptor that recognizes a specific antigenic moiety on the surface of a target cell are provided. Such methods may include, but are not limited to, steps of (1) enriching a population of lymphocytes obtained from a donor subject; (2) stimulating the population of lymphocytes with one or more T-cell stimulating agents to produce a population of activated T cells, wherein the stimulation is performed in a closed system using serum-free culture medium; (3) transducing the population of activated T cells with a viral vector comprising a nucleic acid molecule which encodes the cell surface receptor, using a single cycle transduction to produce a population of transduced T cells, wherein the transduction is performed in a closed system using serum-free culture medium; and (4) expanding the population of transduced T cells for a predetermined time to produce a population of engineered T cells, wherein the expansion is performed in a closed system using serum-free culture medium. Also provided herein are populations of engineered T cells produced by the methods described herein and pharmaceutical compositions thereof.

摘要翻译： 本文提供了制造T细胞的方法。 在某些实施方案中，提供了用于制造表达识别靶细胞表面上的特定抗原部分的细胞表面受体的T细胞的方法。 这样的方法可以包括但不限于以下步骤：（1）富集从供体受试者获得的淋巴细胞群; （2）用一种或多种T细胞刺激剂刺激淋巴细胞群以产生一群活化的T细胞，其中所述刺激在使用无血清培养基的封闭系统中进行; （3）使用包含编码细胞表面受体的核酸分子的病毒载体转导活化的T细胞群，使用单循环转导产生转导的T细胞群，其中转导在封闭系统中进行，使用 无血清培养基; 和（4）扩增转导的T细胞群体预定的时间以产生一组工程化T细胞，其中使用无血清培养基在封闭系统中进行扩增。 本文还提供了通过本文所述的方法产生的工程化T细胞群及其药物组合物。

公开(公告)号：US5693493A

公开(公告)日：1997-12-02

申请号：US450731

申请日：1995-05-25

申请人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horwitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

发明人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horwitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

IPC分类号： A61K38/00 ,  C07K14/43 ,  C07K16/30 ,  C07K16/46 ,  C12N9/88 ,  C12N15/70 ,  C12N15/81 ,  C12N15/00 ,  C12P21/04 ,  C12P21/06

CPC分类号： C12N15/70 ,  C07K14/43 ,  C07K16/3046 ,  C07K16/462 ,  C12N15/81 ,  C12N9/88 ,  A61K38/00 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/034 ,  C07K2319/036 ,  C07K2319/30

摘要： The invention relates to cDNA genetic sequences, vehicles containing same as well as hosts transformed therewith, for the production of chimeric immunoglobulin molecules, functional fragments thereof and immunoglobulin derivatives exhibiting novel functional properties comprising human constant region modules and non-human variable region modules, or for class switching antibody molecules and/or chains. The invention also relates to DNA coding for pectate lyase signal peptide has been cloned on a plasmid to create a secretion vector which is capable of producing a chosen protein which is transported across the bacterial membrane. The secretion vector has been used to secrete extracellular thaumatin and extracellular chimeric antibody fragments. The proteins produced by this vector have biological activity. The thaumatin is properly folded and the antibody fragments are capable of binding antigens on target cancer cells. The invention also relates to the secretion of chimeric antibodies and fragments thereof from yeast in functional form.

公开(公告)号：US06204023B1

公开(公告)日：2001-03-20

申请号：US08472691

申请日：1995-06-06

申请人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horwitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

发明人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horwitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

IPC分类号： A61K39395

CPC分类号： C12N15/70 ,  A61K38/00 ,  C07K14/43 ,  C07K16/3046 ,  C07K16/462 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/034 ,  C07K2319/036 ,  C07K2319/30 ,  C12N9/88 ,  C12N15/81

摘要： The invention relates to cDNA genetic sequences, vehicles containing same as well as hosts tansformed therewith, for the production of chimeric immunoglobulin molecules, functional fragments thereof and immunoglobulin derivatives exhibiting novel functional properties comprising human constant region modules and non-human variable region modules, or for class switching antibody molecules and/or chains. The invention also relates to DNA coding for pectate lyase signal peptide has been cloned on a plasmid to create a secretion vector which is capable of producing a chosen protein which is transported across the bacterial membrane. The secretion vector has been used to secrete extracellular thaumatin and extracellular chimeric antibody fragments. The proteins produced by this vector have biological activity. The thaumatin is properly folded and the antibody fragments are capable of binding antigens on target cancer cells. The invention also relates to the secretion of chimeric antibodies and fragments thereof from yeast in functional form.

摘要翻译： 本发明涉及cDNA遗传序列，含有其的载体以及与其一起改造的宿主，用于产生嵌合免疫球蛋白分子，其功能片段和表现出包括人恒定区模块和非人可变区模块的新功能特性的免疫球蛋白衍生物，或 用于类交换抗体分子和/或链。本发明还涉及将编码果胶酶裂解酶信号肽的DNA克隆在质粒上以产生能够产生选择的蛋白质的分泌载体，所述蛋白质通过细菌膜传输。 已经使用分泌载体来分泌细胞外的奇异果甜蛋白和细胞外嵌合抗体片段。 由该载体产生的蛋白质具有生物活性。 正确地折叠奇异果甜蛋白，抗体片段能够结合靶癌细胞上的抗原。 本发明还涉及从功能形式的酵母中分泌嵌合抗体及其片段。

公开(公告)号：US5576195A

公开(公告)日：1996-11-19

申请号：US357234

申请日：1994-12-09

申请人： Randy R. Robinson ,  Marc Better ,  Shau-Ping Lei ,  Gary L. Wilcox

发明人： Randy R. Robinson ,  Marc Better ,  Shau-Ping Lei ,  Gary L. Wilcox

IPC分类号： A61K38/00 ,  C07K14/43 ,  C07K16/30 ,  C07K16/46 ,  C12N9/88 ,  C12N15/70 ,  C12N15/81 ,  C12P21/00 ,  C12N1/21 ,  C12N15/31 ,  C12N15/62

CPC分类号： C07K14/43 ,  C07K16/3046 ,  C07K16/462 ,  C12N15/70 ,  C12N15/81 ,  C12N9/88 ,  A61K38/00 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/034 ,  C07K2319/036 ,  C07K2319/30

摘要： The invention relates to DNA coding for a pectate lyase signal peptide which has been inserted into plasmids to create secretion vectors which are capable of producing a chosen protein by directing transport across the bacterial membrane. The secretion vectors have been used to secrete extracellular thaumatin and extracellular antibody fragments. The proteins produced by these vectors have biological activity. The thaumatin is properly folded and the antibody fragments are capable of binding antigens on target cancer cells.

摘要翻译： 本发明涉及编码果胶裂解酶信号肽的DNA，其已经插入到质粒中以产生分泌载体，其能够通过引导跨细菌膜的转运来产生选择的蛋白质。 已经使用分泌载体来分泌细胞外丘脑蛋白和细胞外抗体片段。 由这些载体产生的蛋白质具有生物活性。 正确地折叠奇异果甜蛋白，抗体片段能够结合靶癌细胞上的抗原。

公开(公告)号：US20050260705A1

公开(公告)日：2005-11-24

申请号：US10963414

申请日：2004-10-12

申请人： Marc Better

发明人： Marc Better

IPC分类号： C12N15/09 ,  C12N1/21 ,  C12N15/63 ,  C12N15/70 ,  C12P21/02 ,  C12P21/06 ,  C07H21/04 ,  C07K14/705

CPC分类号： C12P21/02 ,  C12N15/635 ,  C12N15/70

摘要： The present invention relates generally to improved methods for the expression of recombinant protein products under the transcriptional control of an inducible promoter, such as an araB promoter, in bacterial host cells that are deficient in one or more of the active transport systems for the inducer of the inducible promoter. The present invention also relates to improved bacterial host cells that are deficient in one or more of the active transport systems for an inducer of an inducible promoter, such as arabinose for an araB promoter, and contain an expression vector encoding a recombinant polypeptide under the transcriptional control of the inducible promoter, such as an araB promoter.

摘要翻译： 本发明一般涉及用于在细菌宿主细胞中的诱导型启动子如araB启动子的转录控制下表达重组蛋白产物的改进方法，所述细菌宿主细胞缺乏一种或多种用于诱导剂的诱导剂的活性转运体系 诱导型启动子。 本发明还涉及改进的细菌宿主细胞，其缺乏一种或多种用于诱导型启动子的诱导物的活性转运系统，例如araB启动子的阿拉伯糖，并且在转录下含有编码重组多肽的表达载体 诱导型启动子的控制，如araB启动子。

公开(公告)号：US20050054835A1

公开(公告)日：2005-03-10

申请号：US10717243

申请日：2003-11-18

申请人： Marc Better ,  Stephen Carroll ,  Gary Studnicka

发明人： Marc Better ,  Stephen Carroll ,  Gary Studnicka

IPC分类号： A61K38/00 ,  A61K47/48 ,  A61P35/00 ,  A61P37/06 ,  C07K14/415 ,  C07K16/00 ,  C07K16/16 ,  C07K16/28 ,  C12N1/21 ,  C12N15/29 ,  C07H21/04 ,  C07K16/46 ,  C12N5/06 ,  C12N15/74 ,  C12P21/04

CPC分类号： C07K14/415 ,  A61K38/00 ,  A61K47/6825 ,  A61K47/6849 ,  A61K2121/00 ,  C07K16/00 ,  C07K16/16 ,  C07K16/28 ,  C07K16/2896 ,  C07K2317/24 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2319/00 ,  Y10S530/866

摘要： The present invention provides purified and isolated polynucleotides encoding Type I ribosome-inactivating proteins (RIPs) and analogs of the RIPs having a cysteine available for disulfide bonding to targeting molecules. Vectors comprising the polynucleotides and host cells transformed with the vectors are also provided. The RIPs and RIP analogs are particularly suited for use as components of cytotoxic therapeutic agents of the invention which include gene fusion products and immunoconjugates. Cytotoxic therapeutic agents or immunotoxins according to the present invention may be used to selectively eliminate any cell type to which the RIP component is targeted by the specific binding capacity of the second component of the agent, and are suited for treatment of diseases where the elimination of a particular cell type is a goal, such as autoimmune disease, cancer and graft-versus-host disease.

摘要翻译： 本发明提供了编码I型核糖体失活蛋白（RIP）的纯化和分离的多核苷酸以及具有可用于二硫键与靶向分子的半胱氨酸的RIP的类似物。 还提供了包含用载体转化的多核苷酸和宿主细胞的载体。 RIP和RIP类似物特别适合用作本发明的细胞毒性治疗剂的组分，其包括基因融合产物和免疫缀合物。 根据本发明的细胞毒性治疗剂或免疫毒素可以用于选择性地消除RIP组分靶向的任何细胞类型，其中药剂的第二组分的特异性结合能力，并且适用于治疗消除 特定的细胞类型是目标，例如自身免疫疾病，癌症和移植物抗宿主病。

公开(公告)号：US5846818A

公开(公告)日：1998-12-08

申请号：US472696

申请日：1995-06-06

申请人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horowitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

发明人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horowitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

IPC分类号： A61K38/00 ,  C07K14/43 ,  C07K16/30 ,  C07K16/46 ,  C12N9/88 ,  C12N15/70 ,  C12N15/81 ,  C12N15/00 ,  C12N15/31 ,  C12N15/62 ,  C12P21/00

CPC分类号： C07K14/43 ,  C07K16/3046 ,  C07K16/462 ,  C12N15/70 ,  C12N15/81 ,  C12N9/88 ,  A61K38/00 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/034 ,  C07K2319/036 ,  C07K2319/30

摘要： The invention is directed to the pectate lyase B secretion signal and its use to express operably linked sequences in bacterial hosts.

摘要翻译： 本发明涉及果胶裂解酶B分泌信号及其在细菌宿主中表达可操作连接序列的用途。

公开(公告)号：US5698435A

公开(公告)日：1997-12-16

申请号：US467140

申请日：1995-06-06

申请人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horwitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

发明人： Randy R. Robinson ,  Alvin Y. Liu ,  Arnold H. Horwitz ,  Marc Better ,  Randolph Wall ,  Shau-Ping Lei ,  Gary L. Wilcox

IPC分类号： A61K38/00 ,  C07K14/43 ,  C07K16/30 ,  C07K16/46 ,  C12N9/88 ,  C12N15/70 ,  C12N15/81 ,  C12N15/00 ,  C12N5/00 ,  C12P21/04 ,  C12P21/06

CPC分类号： C12N15/70 ,  C07K14/43 ,  C07K16/3046 ,  C07K16/462 ,  C12N15/81 ,  C12N9/88 ,  A61K38/00 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/034 ,  C07K2319/036 ,  C07K2319/30

摘要： The invention relates to cDNA genetic sequences, vehicles containing same as well as hosts transformed therewith, for the production of chimeric immunoglobulin molecules, functional fragments thereof and immunoglobulin derivatives exhibiting novel functional properties comprising human constant region modules and non-human variable region modules, or for class switching antibody molecules and/or chains. The invention also relates to DNA coding for pectate lyase signal peptide has been cloned on a plasmid to create a secretion vector which is capable of producing a chosen protein which is transported across the bacterial membrane. The secretion vector has been used to secrete extracellular thaumatin and extracellular chimeric antibody fragments. The proteins produced by this vector have biological activity. The thaumatin is properly folded and the antibody fragments are capable of binding antigens on target cancer cells. The invention also relates to the secretion of chimeric antibodies and fragments thereof from yeast in functional form.

摘要翻译： 本发明涉及cDNA遗传序列，含有相同载体的载体以及用其转化的宿主，用于产生嵌合免疫球蛋白分子，其功能片段和表现出包括人恒定区模块和非人可变区模块的新功能特性的免疫球蛋白衍生物，或 用于类交换抗体分子和/或链。 本发明还涉及编码果胶裂解酶信号肽的DNA已经克隆在质粒上以产生能够产生选择的蛋白质的分泌载体，所述蛋白质通过细菌膜转运。 已经使用分泌载体来分泌细胞外的奇异果甜蛋白和细胞外嵌合抗体片段。 由该载体产生的蛋白质具有生物活性。 正确地折叠奇异果甜蛋白，抗体片段能够结合靶癌细胞上的抗原。 本发明还涉及从功能形式的酵母中分泌嵌合抗体及其片段。