公开(公告)号：US09804163B2

公开(公告)日：2017-10-31

申请号：US13814337

申请日：2011-08-05

申请人： Jeffrey Gildersleeve ,  Christopher Campbell ,  Oyindasola Oyelaran ,  James Gulley ,  Jeffrey Schlom

发明人： Jeffrey Gildersleeve ,  Christopher Campbell ,  Oyindasola Oyelaran ,  James Gulley ,  Jeffrey Schlom

IPC分类号： A61K39/00 ,  C07K14/705 ,  C07K16/00 ,  C07K16/30 ,  G01N33/574

CPC分类号： G01N33/57434 ,  A61K39/0011 ,  A61K2039/5252 ,  A61K2039/5256 ,  A61K2039/545 ,  A61K2039/55583 ,  A61K2039/575 ,  A61K2039/585 ,  C12N2710/24043 ,  C12N2710/24143 ,  G01N33/57469 ,  G01N2400/02 ,  G01N2800/52

摘要： The invention provides a method for predicting the clinical response to a cancer vaccine in a patient having cancer, a method for determining the immune response to a cancer vaccine in a patient having cancer who has been administered a cancer vaccine, a method for determining the long-term survival in a patient having cancer, corresponding kits therefor, as well as methods of for improving the efficacy of a virus-based vaccine.

公开(公告)号：US08883448B2

公开(公告)日：2014-11-11

申请号：US12623062

申请日：2009-11-20

申请人： Jeffrey Schlom ,  Scott Abrams

发明人： Jeffrey Schlom ,  Scott Abrams

IPC分类号： C12N15/11 ,  C07H21/04 ,  C07K14/82 ,  A61K39/00

CPC分类号： C07K14/82 ,  A61K39/00

摘要： Mutant ras oncogene peptides may induce specific anti-ras cellular immune responses in vaccinated patients. Moreover, a human CD8+ CTL epitope(s) reflecting a specific point mutation in the K-ras oncogene at codon 12 was identified. The mutant ras peptide has implications for both active and passive immunotherapies in selected carcinoma patients. A nested 10-mer peptide was identified [i.e., ras5-14(Asp12)], which was shown to bind to HLA-A2 and display specific functional capacity for expansion of the in vivo-primed CD8+ CTL precursors.

摘要翻译： 突变ras致癌基因肽可能在接种疫苗的患者中诱导特异性抗ras细胞免疫应答。 此外，鉴定了在密码子12反映K-ras致癌基因中的特异性点突变的人CD8 + CTL表位。 突变型ras肽对所选癌症患者的主动和被动免疫疗法都有影响。 鉴定了嵌合的10聚体肽[即ras5-14（Asp12）]，其显示与HLA-A2结合并显示用于体内引发的CD8 + CTL前体扩增的特异功能能力。

公开(公告)号：US20130156813A1

公开(公告)日：2013-06-20

申请号：US13814337

申请日：2011-08-05

申请人： Jeffrey Gildersleeve ,  Christopher Campbell ,  Oyindasola Oyelaran ,  James Gulley ,  Jeffrey Schlom

发明人： Jeffrey Gildersleeve ,  Christopher Campbell ,  Oyindasola Oyelaran ,  James Gulley ,  Jeffrey Schlom

IPC分类号： A61K39/00

CPC分类号： G01N33/57434 ,  A61K39/0011 ,  A61K2039/5252 ,  A61K2039/5256 ,  A61K2039/545 ,  A61K2039/55583 ,  A61K2039/575 ,  A61K2039/585 ,  C12N2710/24043 ,  C12N2710/24143 ,  G01N33/57469 ,  G01N2400/02 ,  G01N2800/52

摘要： The invention provides a method for predicting the clinical response to a cancer vaccine in a patient having cancer, a method for determining the immune response to a cancer vaccine in a patient having cancer who has been administered a cancer vaccine, a method for determining the long-term survival in a patient having cancer, corresponding kits therefor, as well as methods of for improving the efficacy of a virus-based vaccine.

摘要翻译： 本发明提供了一种用于预测患有癌症的患者中的癌症疫苗的临床应答的方法，用于确定患有癌症疫苗的癌症患者中的癌症疫苗的免疫应答的方法，用于确定该癌症疫苗的方法 在患有癌症的患者中的生存期，以及相应的试剂盒，以及用于改善基于病毒的疫苗的功效的方法。

公开(公告)号：US20120149102A1

公开(公告)日：2012-06-14

申请号：US13399471

申请日：2012-02-17

申请人： Jeffrey Schlom ,  Elene Barzaga ,  Sam Zaremba

发明人： Jeffrey Schlom ,  Elene Barzaga ,  Sam Zaremba

IPC分类号： C12N5/10 ,  C12N15/63 ,  C12N1/21 ,  C12N15/12

CPC分类号： C07K14/70503 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00 ,  Y10S435/81

摘要： The invention provides a polypeptide comprising an agonist of a MHC Class I binding native sequence having amino acid substitution(s) and enhanced immunogenicity compared to the native sequence. The invention provides DNA encoding the polypeptide, as well as vectors and cells comprising the DNA and methods comprising the administration of the polypeptide.

摘要翻译： 本发明提供了包含与天然序列相比具有氨基酸取代和增强的免疫原性的MHC I类结合天然序列激动剂的多肽。 本发明提供了编码多肽的DNA，以及包含DNA的载体和细胞以及包含多肽施用的方法。

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。