公开(公告)号：US07915396B2

公开(公告)日：2011-03-29

申请号：US12544978

申请日：2009-08-20

申请人： Syed V. S. Kashmiri ,  Jeffrey Schlom ,  Eduardo A. Padlan

发明人： Syed V. S. Kashmiri ,  Jeffrey Schlom ,  Eduardo A. Padlan

IPC分类号： C07H21/04 ,  C12P21/04 ,  C12N7/00 ,  C12N15/00 ,  A61K39/395 ,  C07K16/00 ,  C12P21/08

CPC分类号： C07K16/465 ,  C07K16/30 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/92

摘要： Humanized anti-TAG-72 CC49 monoclonal antibodies are disclosed herein. The antibodies include a light chain Complementarity Determining Region (L-CDR)1, a L-CDR2, and a L-CDR3; and a heavy chain Complementarity Determining Region (H-CDR)1, a H-CDR2, and a H-CDR3 from humanized antibody HuCC49V10. The L-CDR1, L-CDR2, L-CDR3 are within a HuCC49V10 light chain framework region that includes the corresponding amino acid from LEN at position 5, 19, 21, and 106 in the light chain. The H-CDR1, H-CDR2, and H-CDR3 are within a heavy chain HuCC49V10 framework comprising a human 21/28′ CL residue at positions 20, 38, 48, 66, 67, 69, and 80 in the heavy chain. These humanized CC49 antibodies retain binding affinity for TAG-72 and have reduced immunogenicity, as compared to a parental HuCC49V10 antibody. Methods are disclosed herein for using these antibodies in the treatment or diagnosis of a tumor, such as a carcinoma, expressing TAG-72.

摘要翻译： 本文公开了人源化抗TAG-72 CC49单克隆抗体。 抗体包括轻链互补决定区（L-CDR）1，L-CDR2和L-CDR3; 和来自人源化抗体HuCC49V10的重链互补决定区（H-CDR）1，H-CDR2和H-CDR3。 L-CDR1，L-CDR2，L-CDR3位于HuCC49V10轻链框架区内，其包含轻链中位置5,19,21和106处的LEN的相应氨基酸。 H-CDR1，H-CDR2和H-CDR3在重链HuCC49V10框架内，包含重链中20,38,48,66,67,69和80位的人21 / 28'CL残基。 与亲本的HuCC49V10抗体相比，这些人源化CC49抗体对TAG-72保留结合亲和力并具有降低的免疫原性。 本文公开了使用这些抗体来治疗或诊断表达TAG-72的肿瘤例如癌症的方法。

公开(公告)号：US20100055121A1

公开(公告)日：2010-03-04

申请号：US12528796

申请日：2008-02-27

申请人： Jeffrey Schlom ,  Claudia N. Palena ,  Andrei P. Kozlov

发明人： Jeffrey Schlom ,  Claudia N. Palena ,  Andrei P. Kozlov

IPC分类号： A61K39/12 ,  C07K7/06 ,  C07H21/04 ,  C12N15/63 ,  C12N1/19 ,  C12N7/01 ,  A61K35/76 ,  C12N5/02 ,  A61K35/12 ,  G01N33/53

CPC分类号： C12N15/113 ,  A61K39/00 ,  A61K2039/53 ,  C07K14/4702 ,  C07K14/82 ,  G01N33/56972 ,  G01N33/574 ,  G01N2333/70517 ,  Y02A50/466

摘要： It is disclosed herein that Brachyury is expressed in human tumors, specifically in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testes, as well as in lung, colon and prostate carcinomas. Immunogenic Brachyury polypeptides are disclosed herein. These polypeptides can be used in diagnostic assays for Brachyury expression, as well as for inducing an immune response to Brachyury. Polynucleotides encoding the immunogenic Brachyury polypeptides, vectors including these polypeptides, host cells transformed with these vectors, and methods of using these polypeptides, polynucleotides, vectors, and host cells are provided. Methods of diagnosing a Brachyury-expressing cancer are also provided. Exemplary cancers include lung, colon, small intestine, stomach, kidney, bladder, uterus, ovary, and testes and prostate cancers. Methods of treating cancer are also disclosed.

摘要翻译： 本文公开了Brachyury在人肿瘤中，特别是在小肠，胃，肾，膀胱，子宫，卵巢和睾丸以及肺，结肠和前列腺癌的肿瘤中表达。 免疫原性Brachyury多肽在本文中公开。 这些多肽可用于Brachyury表达的诊断测定，以及用于诱导Brachyury的免疫应答。 提供了编码免疫原性Brachyury多肽的多核苷酸，包括这些多肽的载体，用这些载体转化的宿主细胞，以及使用这些多肽，多核苷酸，载体和宿主细胞的方法。 还提供了诊断Brachyury表达癌症的方法。 示例性的癌症包括肺，结肠，小肠，胃，肾，膀胱，子宫，卵巢，睾丸和前列腺癌。 还公开了治疗癌症的方法。

公开(公告)号：US20090311780A1

公开(公告)日：2009-12-17

申请号：US12544978

申请日：2009-08-20

申请人： Syed V.S. Kashmiri ,  Jeffrey Schlom ,  Eduardo A. Padlan

发明人： Syed V.S. Kashmiri ,  Jeffrey Schlom ,  Eduardo A. Padlan

IPC分类号： C07H21/04 ,  C12N15/63 ,  C12N1/21 ,  C12N5/10

CPC分类号： C07K16/465 ,  C07K16/30 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/92

摘要： Humanized anti-TAG-72 CC49 monoclonal antibodies are disclosed herein. The antibodies include a light chain Complementarity Determining Region (L-CDR)1, a L-CDR2, and a L-CDR3; and a heavy chain Complementarity Determining Region (H-CDR)1, a H-CDR2, and a H-CDR3 from humanized antibody HuCC49V10. The L-CDR1, L-CDR2, L-CDR3 are within a HuCC49V10 light chain framework region that includes the corresponding amino acid from LEN at position 5, 19, 21, and 106 in the light chain. The H-CDR1, H-CDR2, and H-CDR3 are within a heavy chain HuCC49V10 framework comprising a human 21/28′ CL residue at positions 20, 38, 48, 66, 67, 69, and 80 in the heavy chain. These humanized CC49 antibodies retain binding affinity for TAG-72 and have reduced immunogenicity, as compared to a parental HuCC49V10 antibody. Methods are disclosed herein for using these antibodies in the treatment or diagnosis of a tumor, such as a carcinoma, expressing TAG-72.

摘要翻译： 本文公开了人源化抗TAG-72 CC49单克隆抗体。 抗体包括轻链互补决定区（L-CDR）1，L-CDR2和L-CDR3; 和来自人源化抗体HuCC49V10的重链互补决定区（H-CDR）1，H-CDR2和H-CDR3。 L-CDR1，L-CDR2，L-CDR3位于HuCC49V10轻链框架区内，其包含轻链中位置5,19,21和106处的LEN的相应氨基酸。 H-CDR1，H-CDR2和H-CDR3在重链HuCC49V10框架内，包含重链中20,38,48,66,67,69和80位的人21 / 28'CL残基。 与亲本的HuCC49V10抗体相比，这些人源化CC49抗体对TAG-72保留结合亲和力并具有降低的免疫原性。 本文公开了使用这些抗体来治疗或诊断表达TAG-72的肿瘤例如癌症的方法。

公开(公告)号：US20080279887A1

公开(公告)日：2008-11-13

申请号：US12112819

申请日：2008-04-30

申请人： Jeffrey Schlom ,  Judith Kantor ,  James W. Hodge

发明人： Jeffrey Schlom ,  Judith Kantor ,  James W. Hodge

IPC分类号： A61K39/00

CPC分类号： C07K14/70532 ,  A61K39/00 ,  A61K48/00 ,  C07K14/705 ,  C07K14/70503 ,  C12N2799/021 ,  C12N2799/023 ,  Y02A50/466

摘要： The present invention is a composition of recombinant virus which has incorporated into its genome or portion thereof a gene encoding an antigen to a disease causing agent and a recombinant virus which has incorporated into its genome or portion thereof a gene encoding an immunostimulatory molecule(s) for the purpose of stimulating an immune response against the disease causing agent. Methods of treatment of diseases such as cancer and diseases caused by pathogenic microorganisms is provide using the composition.

摘要翻译： 本发明是一种重组病毒的组合物，其在其基因组或其部分中掺入编码抗原的疾病引起剂和重组病毒，所述重组病毒在其基因组或其部分掺入了编码免疫刺激分子的基因， 目的是刺激针对疾病引发剂的免疫应答。 使用该组合物提供治疗由病原微生物引起的癌症和疾病等疾病的方法。

公开(公告)号：US20080274055A1

公开(公告)日：2008-11-06

申请号：US11813092

申请日：2005-12-30

申请人： Syed Kashmiri ,  Rafia Mehdi Kashmiri ,  Jeffrey Schlom ,  Eduardo A. Padlan

发明人： Syed Kashmiri ,  Rafia Mehdi Kashmiri ,  Jeffrey Schlom ,  Eduardo A. Padlan

IPC分类号： A61K39/395 ,  C07K16/30 ,  G01N33/574 ,  A61K49/00 ,  C12N15/13 ,  C12N15/79 ,  C12N5/10 ,  A61P35/00

CPC分类号： C07K16/3007 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

摘要： The present disclosure provides humanized COL-1 monoclonal antibodies that retain CEA binding affinity, compared to a parent antibody. Also disclosed herein are humanized COL-1 monoclonal antibodies that have reduced immunogenicity, compared to a parent antibody. The disclosed humanized COL-1 antibodies include substitution of framework residues with residues from the corresponding positions of a homologous human sequence. In several embodiments, methods are disclosed for the use of a humanized COL-1 antibody in the detection or treatment of a CEA-expressing tumor or cell in a subject. Also disclosed is a kit including the humanized COL-1 antibodies described herein.

摘要翻译： 本公开提供与亲本抗体相比保留CEA结合亲和力的人源化COL-1单克隆抗体。 本文还公开了与亲本抗体相比具有降低的免疫原性的人源化COL-1单克隆抗体。 公开的人源化COL-1抗体包括用来自同源人序列的相应位置的残基取代框架残基。 在几个实施方案中，公开了在检测或治疗受试者中表达CEA的肿瘤或细胞的情况下使用人源化COL-1抗体的方法。 还公开了包含本文所述的人源化COL-1抗体的试剂盒。

公开(公告)号：US20080050810A1

公开(公告)日：2008-02-28

申请号：US11776437

申请日：2007-07-11

申请人： Syed Kashmiri ,  Eduardo Padlan ,  Jeffrey Schlom

发明人： Syed Kashmiri ,  Eduardo Padlan ,  Jeffrey Schlom

IPC分类号： C12N15/85 ,  C07H21/02 ,  C07H21/04 ,  C12N5/10 ,  C12N15/64

CPC分类号： A61K49/0002 ,  A61K38/00 ,  A61K51/1045 ,  A61K2039/505 ,  C07K16/30 ,  C07K16/3046 ,  C07K16/4208 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2799/026 ,  G01N33/5743

摘要： The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Determining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.

摘要翻译： 本发明针对具有最小鼠含量的CC49单克隆抗体的小鼠 - 人嵌合变体。 本发明的第一方面提供了存在CC49的全部六（三个重链和三个轻链）互补决定区（CDR）的人源化单克隆抗体（HuCC49）的CDR变体。 本发明的第二方面提供了仅存在来自CC49的至少一个CDR的特异性确定区（SDR）的人源化单克隆抗体（HuCC49）的SDR变体。 本发明还涉及制备使用变体的变体和治疗方法的生物技术方法。

公开(公告)号：US20070098691A1

公开(公告)日：2007-05-03

申请号：US11606929

申请日：2006-12-01

申请人： Jeffrey Schlom ,  Kwong-yok Tsang ,  Sam Zaremba

发明人： Jeffrey Schlom ,  Kwong-yok Tsang ,  Sam Zaremba

IPC分类号： A61K48/00 ,  C07K14/82 ,  C12N15/86 ,  C12N7/00 ,  C12N5/06

CPC分类号： A61K39/0011 ,  A61K38/00 ,  A61K39/00 ,  A61K2035/124 ,  A61K2039/5154 ,  A61K2039/5156 ,  A61K2039/5158 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55527 ,  C12N5/0636 ,  C12N9/6445 ,  C12N2710/24143 ,  Y10S435/975

摘要： The invention is a prostate specific antigen oligo-epitope peptide which comprises more than one PSA epitope peptide, which conforms to one or more human HLA class I motifs. The prostate specific antigen oligo-epitope peptide in combination with various HLA-class I molecules or interactions with various T-cell receptors elicits PSA specific cellular immune responses. The prostate specific antigen oligo-epitope peptide is useful as an immunogen in the prevention or treatment of prostatic cancer, in the inhibition of prostatic cancer cells and in the establishment and characterization of PSA-specific cytotoxic T-cell lines.

摘要翻译： 本发明是前列腺特异性抗原寡表位肽，其包含多于一种PSA表位肽，其与一个或多个人HLA I类基序一致。 前列腺特异性抗原寡表位肽与各种HLA-I类分子的组合或与各种T细胞受体的相互作用引起PSA特异性细胞免疫应答。 前列腺特异性抗原寡表位肽可用作预防或治疗前列腺癌，抑制前列腺癌细胞以及PSA特异性细胞毒性T细胞系的建立和表征中的免疫原。

公开(公告)号：US20070048860A1

公开(公告)日：2007-03-01

申请号：US11321868

申请日：2005-12-30

申请人： Jeffrey Schlom ,  James Hodge ,  Sam Zaremba ,  Maria Salazar

发明人： Jeffrey Schlom ,  James Hodge ,  Sam Zaremba ,  Maria Salazar

IPC分类号： A61K39/12 ,  C12N15/00

CPC分类号： A61K39/0011 ,  A61K2039/53 ,  A61K2039/57 ,  C07K14/70503 ,  C12N2700/00 ,  C12N2710/10343 ,  C12N2710/24043 ,  C12N2710/24143

摘要： The present invention relates to novel modified CEA agonist (or antagonist) peptides, polypeptides and proteins containing a modified epitope therein, nucleic acids coding therefor, vectors comprising said nucleic acids, mixtures and compositions of the aforementioned agents, and their advantageous use in generating CEA-specific immune responses and/or in the treatment of cancers and the present invention further relates to the foregoing combined with one or more costimulatory molecules.

摘要翻译： 本发明涉及新型修饰的CEA激动剂（或拮抗剂）肽，其中含有修饰的表位的多肽和蛋白质，其编码的核酸，包含所述核酸的载体，前述试剂的混合物和组合物及其在产生CEA中的有利用途 特异性免疫应答和/或治疗癌症，并且本发明进一步涉及与一种或多种共刺激分子组合的前述物质。

公开(公告)号：US06969609B1

公开(公告)日：2005-11-29

申请号：US09856988

申请日：1999-11-12

申请人： Jeffrey Schlom ,  James Hodge ,  Dennis Panicali

发明人： Jeffrey Schlom ,  James Hodge ,  Dennis Panicali

IPC分类号： A61K35/12 ,  A61K39/00 ,  A61K48/00 ,  C07K14/705 ,  C12N15/863 ,  C12N5/10 ,  C12N5/16 ,  C12N5/22 ,  C12N15/85 ,  A16K48/00

CPC分类号： C12N15/86 ,  A61K35/12 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/57 ,  C07K14/70503 ,  C07K14/70525 ,  C07K14/70528 ,  C07K14/70532 ,  C12N2710/24043 ,  C12N2710/24143 ,  Y02A50/41 ,  Y02A50/412 ,  Y02A50/464 ,  Y02A50/478

摘要： The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of them costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater that the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+and CD8+T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced and antigen-presenting functions.

摘要翻译： 本发明是编码并表达至少三种或更多共刺激分子的重组载体。 重组载体可另外含有编码一种或多种靶抗原或其免疫表位的基因。 证明了它们共刺激分子对增强的T细胞活化的协同作用。 使用含有编码三个共刺激分子的基因的重组载体的T细胞活化程度远远大于含有一个共刺激分子的重组载体构建物的总和，并且使用两个共刺激分子更大。 使用三重共刺激载体的结果在低水平的第一信号或低刺激剂与T细胞比率的条件下最显着。 在分离的CD4 +和/或CD8 + T细胞中都观察到这种现象。 本发明的重组载体可用作抗癌和致病微生物的免疫原和疫苗，并且提供宿主细胞，包括具有增强和抗原呈递功能的树突状细胞和脾细胞。

公开(公告)号：US20050186202A1

公开(公告)日：2005-08-25

申请号：US10927433

申请日：2004-08-25

申请人： Syed Kashmiri ,  Eduardo Padlan ,  Jeffrey Schlom

发明人： Syed Kashmiri ,  Eduardo Padlan ,  Jeffrey Schlom

IPC分类号： A61K38/00 ,  A61K51/10 ,  C07K16/30 ,  A61K39/395 ,  C07K16/44

CPC分类号： A61K49/0002 ,  A61K38/00 ,  A61K51/1045 ,  A61K2039/505 ,  C07K16/30 ,  C07K16/3046 ,  C07K16/4208 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2799/026 ,  G01N33/5743

摘要： The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Deter/mining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.

摘要翻译： 本发明针对具有最小鼠含量的CC49单克隆抗体的小鼠 - 人嵌合变体。 本发明的第一方面提供了存在CC49的全部六（三个重链和三个轻链）互补决定区（CDR）的人源化单克隆抗体（HuCC49）的CDR变体。 本发明的第二方面提供了仅存在来自CC49的至少一个CDR的特异性检测/开采区域（SDR）的人源化单克隆抗体（HuCC49）的SDR变体。 本发明还涉及制备使用变体的变体和治疗方法的生物技术方法。