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1. 发明申请

WO2010129537A1 PHOSPHOPEPTIDES AS MELANOMA VACCINES 审中-公开
标题翻译：磷酸盐作为微生物疫苗
公开(公告)号：WO2010129537A1
公开(公告)日：2010-11-11
申请号：PCT/US2010/033530
申请日：2010-05-04
申请人： THE JOHNS HOPKINS UNIVERSITY , UNIVERSITY OF VIRGINIA PATENT FOUNDATION , TOPALIAN, Suzanne L. , DEPONTIEU, Florence A. , HUNT, Donald F. , SHABANOWITZ, Jeffrey , QIAN, Jie , ENGELHARD, Victor H. , ZARLING, Angela Lee
发明人： TOPALIAN, Suzanne L. , DEPONTIEU, Florence A. , HUNT, Donald F. , SHABANOWITZ, Jeffrey , QIAN, Jie , ENGELHARD, Victor H. , ZARLING, Angela Lee
IPC分类号： C07K2/00 , A61K39/385 , A61K39/00
CPC分类号： C07K14/4748 , A61K39/0011 , A61K39/39 , A61K2039/5154 , A61K2039/5158 , G01N33/5743
摘要： We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome "fingerprints". We generated HLA-DRβ1*0101-restricted CD4 + T cells specific for a phospho-MART-1 peptide identified in two melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen presenting cells as well as for intact melanoma cells. MHC II-restricted phosphopeptides recognizable by human CD4 + T cells are potential targets for cancer immunotherapy.
摘要翻译：我们使用顺序亲和分离，生物化学富集，质谱测序和比较分析鉴定了总共175个HLA-DR相关磷酸肽。许多来源于可能在癌症发展，生长和转移中起作用的源蛋白质。大多数仅由黑素瘤或转化的B细胞表达，表明可能定义细胞类型特异性磷酸酯“指纹”。我们产生HLA-DRß1* 0101限制性CD4 + T细胞，特异于两种黑素瘤细胞系中鉴定的磷酸化MART-1肽。这些T细胞对磷酸肽脉冲的抗原呈递细胞以及完整的黑素瘤细胞显示出特异性。人CD4 + T细胞可识别的MHC II限制性磷酸肽是癌症免疫治疗的潜在靶标。

2. 发明申请

WO2011149909A2 CLASS I MHC PHOSPHOPEPTIDES FOR CANCER IMMUNOTHERAPY AND DIAGNOSIS 审中-公开
标题翻译：第一类MHC磷酸化酶对于癌症的免疫和诊断
公开(公告)号：WO2011149909A2
公开(公告)日：2011-12-01
申请号：PCT/US2011/037699
申请日：2011-05-24
申请人： HUNT, Donald F. , SHABANOWITZ, Jeffrey , COTTINE, Jennifer , ENGLISH, Ann M. , NORRIS, Andrew , ENGELHARD, Victor H. , COBBOLD, Mark , CUMMINGS, Kara L. , ZARLING, Angela , OBENG, Rebecca C.
发明人： HUNT, Donald F. , SHABANOWITZ, Jeffrey , COTTINE, Jennifer , ENGLISH, Ann M. , NORRIS, Andrew , ENGELHARD, Victor H. , COBBOLD, Mark , CUMMINGS, Kara L. , ZARLING, Angela , OBENG, Rebecca C.
IPC分类号： C07K14/74 , C07K7/00 , C07K16/20 , A61K38/17 , A61K39/395 , G01N33/68 , A61P35/00
CPC分类号： C07K7/06 , A61K38/00 , A61K39/0011 , C07K7/08 , C07K14/70539 , C07K16/18 , G01N33/5743 , G01N33/57492 , G01N33/6893 , G01N2333/70539 , G01N2440/14
摘要： A set of phosphorylated peptides are presented by HLA A*0101, A*0201, A*0301, B*4402, B*2705, B*1402, and B*0702 on the surface of melanoma cells. They have the potential to (a) stimulate an immune response to the cancer, (b) to function as immunotherapeutics in adoptive T-cell therapy or as a vaccine, (c) to facilitate antibody recognition of the tumor boundaries in surgical pathology samples, and (d) act as biomarkers for early detection of the disease. Phosphorylated peptides are also presented for other cancers.
摘要翻译：一组磷酸化肽由黑素瘤细胞表面上的HLA A * 0101，A * 0201，A * 0301，B * 4402，B * 2705，B * 1402和B * 0702呈现。它们具有（a）刺激对癌症的免疫应答的潜力，（b）在过继性T细胞治疗或疫苗中用作免疫治疗剂，（c）促进手术病理样品中肿瘤边界的抗体识别，和（d）作为早期检测疾病的生物标志物。磷酸化肽也可用于其他癌症。

3. 发明申请

WO9522561A3 PEPTIDES RECOGNIZED BY MELANOMA-SPECIFIC CYTOTOXIC LYMPHOCYTES, AND USES THEREFOR 审中-公开
标题翻译：由特异性细胞因子淋巴细胞识别的肽及其用途
公开(公告)号：WO9522561A3
公开(公告)日：1996-03-07
申请号：PCT/US9501991
申请日：1995-02-16
申请人： UNIV VIRGINIA , SLINGLUFF CRAIG L , ENGELHARD VICTOR H , HUNT DONALD F , SHABANOWITZ JEFFREY , COX ANDREA L
发明人： SLINGLUFF CRAIG L , ENGELHARD VICTOR H , HUNT DONALD F , SHABANOWITZ JEFFREY , COX ANDREA L
IPC分类号： A61K39/00 , C07K14/47 , C12N9/02 , C07K14/705
CPC分类号： C12Y110/03001 , A61K39/00 , C07K14/4748 , C12N9/0059
摘要： Melanoma-specific CTL epitopes have been identified through improvements in the art of identification of epitope-reconstituting peptides dissociated from MHC Class I molecules on the surface of the tumor cells. Peptides homologous with a segment of the melanoma/melanocyte antigen pMel-17 have proven to be highly potent stimulators of HLA-A2+CTL in several CTL cell lines. These and kindred peptides may be used to stimulate CTLs for use in adoptive immunotherapy, or incorporated into immunogenic conjugates for use as vaccines.

4. 发明申请

WO2011149909A3 CLASS I MHC PHOSPHOPEPTIDES FOR CANCER IMMUNOTHERAPY AND DIAGNOSIS 审中-公开
标题翻译： I类MHC磷酸化酶用于癌症免疫和诊断
公开(公告)号：WO2011149909A3
公开(公告)日：2012-04-26
申请号：PCT/US2011037699
申请日：2011-05-24
申请人： HUNT DONALD F , SHABANOWITZ JEFFREY , COTTINE JENNIFER , ENGLISH ANN M , NORRIS ANDREW , ENGELHARD VICTOR H , COBBOLD MARK , CUMMINGS KARA L , ZARLING ANGELA , OBENG REBECCA C
发明人： HUNT DONALD F , SHABANOWITZ JEFFREY , COTTINE JENNIFER , ENGLISH ANN M , NORRIS ANDREW , ENGELHARD VICTOR H , COBBOLD MARK , CUMMINGS KARA L , ZARLING ANGELA , OBENG REBECCA C
IPC分类号： C07K14/74 , A61K38/17 , A61K39/395 , A61P35/00 , C07K7/00 , C07K16/20 , G01N33/68
CPC分类号： C07K7/06 , A61K38/00 , A61K39/0011 , C07K7/08 , C07K14/70539 , C07K16/18 , G01N33/5743 , G01N33/57492 , G01N33/6893 , G01N2333/70539 , G01N2440/14
摘要： A set of phosphorylated peptides are presented by HLA A*0101, A*0201, A*0301, B*4402, B*2705, B*1402, and B*0702 on the surface of melanoma cells. They have the potential to (a) stimulate an immune response to the cancer, (b) to function as immunotherapeutics in adoptive T-cell therapy or as a vaccine, (c) to facilitate antibody recognition of the tumor boundaries in surgical pathology samples, and (d) act as biomarkers for early detection of the disease. Phosphorylated peptides are also presented for other cancers.
摘要翻译：一组磷酸化肽由黑素瘤细胞表面上的HLA A * 0101，A * 0201，A * 0301，B * 4402，B * 2705，B * 1402和B * 0702呈现。它们有可能（a）刺激对癌症的免疫应答，（b）在过继T细胞治疗或疫苗中起到免疫治疗的作用，（c）促进手术病理样本中肿瘤边界的抗体识别，和（d）作为早期发现疾病的生物标志物。磷酸化肽也用于其他癌症。

5. 发明申请

WO2009155007A1 METHOD AND APPARATUS FOR GENERATION OF REAGENT IONS IN A MASS SPECTROMETER 审中-公开
标题翻译：用于在大量光谱仪中产生试剂离子的方法和装置
公开(公告)号：WO2009155007A1
公开(公告)日：2009-12-23
申请号：PCT/US2009/045350
申请日：2009-05-27
申请人： THERMO FINNIGAN LLC , UNIVERSITY OF VIRGINIA PATENT FOUNDATION , SHABANOWITZ, Jeffrey , COMPTON, Philip, D. , EARLEY, Lee , STAFFORD, George, C. , HUNT, Donald, F. , MULLEN, Christopher
发明人： SHABANOWITZ, Jeffrey , COMPTON, Philip, D. , EARLEY, Lee , STAFFORD, George, C. , HUNT, Donald, F. , MULLEN, Christopher
IPC分类号： H01J49/00 , H01J49/10
CPC分类号： H01J49/12 , H01J49/0072
摘要： A front-end reagent ion source for a mass spectrometer is disclosed. Reagent vapor is supplied to a reagent ionization volume located within a chamber of the mass spectrometer and maintained at a low vacuum pressure. Reagent ions are formed by interaction of the reagent vapor molecules with an electrical discharge (e.g., a glow discharge) within the ionization volume, and pass into the chamber of the mass spectrometer. At least one ion optical element located along the analyte ion path transports the reagent ions to successive chambers of the mass spectrometer. The reagent ions may be combined with the analyte ions to perform ion-ion studies such as electron transfer dissociation (ETD).
摘要翻译：公开了用于质谱仪的前端试剂离子源。将试剂蒸气供给到位于质谱仪室内的试剂电离体并保持在低真空压力下。试剂离子通过试剂蒸气分子与离子化体积内的放电（例如，辉光放电）的相互作用而形成，并进入质谱仪的室。沿着分析物离子路径定位的至少一个离子光学元件将试剂离子输送到质谱仪的连续室。试剂离子可与分析物离子组合以进行离子离子研究，例如电子转移离解（ETD）。

6. 发明申请

WO2017214037A1 RAPID IDENTIFICATION AND SEQUENCE ANALYSIS OF INTACT PROTEINS IN COMPLEX MIXTURES 审中-公开
标题翻译：复杂混合物中纯蛋白的快速鉴定和序列分析
公开(公告)号：WO2017214037A1
公开(公告)日：2017-12-14
申请号：PCT/US2017/035953
申请日：2017-06-05
申请人： HUNT, Donald F. , ENGLISH, Ann M. , URGIN, Scott A. , BAI, Dina L. , SHABANOWITZ, Jeffrey , SYKA, John Edward Philip
发明人： HUNT, Donald F. , ENGLISH, Ann M. , URGIN, Scott A. , BAI, Dina L. , SHABANOWITZ, Jeffrey , SYKA, John Edward Philip
IPC分类号： H01J49/42 , H01J49/00 , H01J49/04 , H01J49/26
摘要： The present disclosure relates to novel and improved methods of analyzing proteins, peptides and polypeptides by mass spectrometry using ion-ion reactions. More specifically the disclosure relates to improved methods for implementing the m/z selective arresting of ion-ion reactions within the ion-ion reaction cell of a mass spectrometer system during a period where ion-ion reactions are performed.
摘要翻译：本公开涉及使用离子 - 离子反应通过质谱法分析蛋白质，肽和多肽的新颖和改进的方法。更具体地，本公开涉及用于在执行离子 - 离子反应的时间段期间在质谱仪系统的离子 - 离子反应池内实施离子 - 离子反应的m / z选择性捕获的改进方法。

7. 发明申请

WO2005033267A3 ANTIGENS TARGETED BY PREVALENT PATHOGENIC T CELLS IN TYPE 1 DIABETES AND USES THEREOF 审中-公开
标题翻译： 1型糖尿病中预防性致病性T细胞靶向的抗原及其用途
公开(公告)号：WO2005033267A3
公开(公告)日：2005-12-15
申请号：PCT/US2004015752
申请日：2004-05-20
申请人： EINSTEIN COLL MED , DILORENZO TERESA P , EVANS ANNE M , HUNT DONALD F , LIEBERMAN SCOTT M , NATHENSON STANLEY G , SANTAMARIA PERE , SHABANOWITZ JEFFREY
发明人： DILORENZO TERESA P , EVANS ANNE M , HUNT DONALD F , LIEBERMAN SCOTT M , NATHENSON STANLEY G , SANTAMARIA PERE , SHABANOWITZ JEFFREY
IPC分类号： A61K38/04 , A61K39/00 , A61K39/38 , C07K5/00 , C07K14/47 , C07K16/00 , C07K17/00 , C12N20060101 , G01N33/53
CPC分类号： C07K14/4711
摘要： The present invention is based on the identification of a predominant ligand of CD8 T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8 T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8 T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN/A/I/L/V)FL, FLWSVFWLI, (T/A)YY/G/T)FLNFM, LR(L/V)(F/L)(G/N)IDLL, KWCANPDWI, and SFCKSASIP. Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8 T cell that is cytotoxic to pancreatic islet beta-cells from destroying a mammalian beta-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.
摘要翻译：本发明基于鉴定负责1型糖尿病的CD8 + T细胞的主要配体。该配体是胰岛特异性葡萄糖-6-磷酸酶催化亚单位相关蛋白（IGRP）。鉴定了来自IGRP的几种CD8 + T细胞结合肽，包括含有IGRP序列的氨基酸206-214的肽，其与自身免疫中病原性CD8 + T细胞最流行的T细胞受体具有高亲合力糖尿病。因此，本发明提供包含YLKTN / A / I / L / V）FL，FLWSVFWLI，（T / A）YY / G / T）FLNFM，LR（L / V）（F / L）（G / N）IDLL，KWCANPDWI和SFCKSASIP。还提供了长度为8-10个氨基酸且与哺乳动物IGRP完全同源的寡肽组合物，其中寡肽能够结合人MHC I类分子。此外，提供使用上述组合物治疗哺乳动物的各种方法，其中哺乳动物处于或具有1型糖尿病的风险。还提供了防止对胰岛β细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物β细胞的方法，其中该方法也使用上述组合物。还提供了用于确定哺乳动物是否处于或患有1型糖尿病的风险的方法，其中所述方法使用上述组合物。

8. 发明申请

WO2005033267A2 ANTIGENS TARGETED BY PREVALENT PATHOGENIC T CELLS IN TYPE 1 DIABETES AND USES THEREOF 审中-公开
标题翻译：预防性1型糖尿病致病T细胞靶向抗原及其应用
公开(公告)号：WO2005033267A2
公开(公告)日：2005-04-14
申请号：PCT/US2004/015752
申请日：2004-05-20
申请人： ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY , DILORENZO, Teresa, P. , EVANS, Anne, M. , HUNT, Donald, F. , LIEBERMAN, Scott, M. , NATHENSON, Stanley, G. , SANTAMARIA, Pere , SHABANOWITZ, Jeffrey
发明人： DILORENZO, Teresa, P. , EVANS, Anne, M. , HUNT, Donald, F. , LIEBERMAN, Scott, M. , NATHENSON, Stanley, G. , SANTAMARIA, Pere , SHABANOWITZ, Jeffrey
IPC分类号： C12N
CPC分类号： C07K14/4711
摘要： The present invention is based on the identification of a predominant ligand of CD8 + T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8 + T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8 + T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN/A/I/L/V)FL, FLWSVFWLI, (T/A)YY/G/T)FLNFM, LR(L/V)(F/L)(G/N)IDLL, KWCANPDWI, and SFCKSASIP. Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8 + T cell that is cytotoxic to pancreatic islet β-cells from destroying a mammalian β-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.
摘要翻译：本发明基于鉴定负责1型糖尿病的CD8 + T细胞的主要配体。该配体是胰岛特异性葡萄糖-6-磷酸酶催化亚基相关蛋白（IGRP）。鉴定了来自IGRP的几种CD8 + T细胞结合肽，包括含有IGRP序列的氨基酸206-214的肽，其对致病性CD8 ^{的最普遍的T细胞受体具有高亲和力 > + T细胞在自身免疫性糖尿病中的作用。本发明因此提供了包含YLKTN / A / I / L / V）FL，FLWSVFWLI，（T / A）YY / G / T）FLNFM，LR（L / V）（F / L） N）IDLL，KWCANPDWI和SFCKSASIP。还提供长度为8-10个氨基酸并与哺乳动物IGRP完全同源的寡肽组合物，其中寡肽能够结合人类MHC I类分子。另外，提供了使用上述组合物治疗哺乳动物的各种方法，其中哺乳动物有患1型糖尿病的风险或具有1型糖尿病。还提供了防止对胰岛β-细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物β-细胞的方法，其中所述方法也使用上述组合物。还提供了用于确定哺乳动物是否有患1型糖尿病或患有1型糖尿病的方法，其中所述方法使用上述组合物。}

9. 发明申请

WO1995022561A2 PEPTIDES RECOGNIZED BY MELANOMA-SPECIFIC CYTOTOXIC LYMPHOCYTES, AND USES THEREFOR 审中-公开
标题翻译：由特异性细胞因子淋巴细胞识别的肽及其用途
公开(公告)号：WO1995022561A2
公开(公告)日：1995-08-24
申请号：PCT/US1995001991
申请日：1995-02-16
申请人： UNIVERSITY OF VIRGINIA PATENT FOUNDATION , SLINGLUFF, Craig, L. , ENGELHARD, Victor, H. , HUNT, Donald, F. , SHABANOWITZ, Jeffrey , COX, Andrea, L.
发明人： UNIVERSITY OF VIRGINIA PATENT FOUNDATION
IPC分类号： C07K14/705
CPC分类号： C12Y110/03001 , A61K39/00 , C07K14/4748 , C12N9/0059
摘要： Melanoma-specific CTL epitopes have been identified through improvements in the art of identification of epitope-reconstituting peptides dissociated from MHC Class I molecules on the surface of the tumor cells. Peptides homologous with a segment of the melanoma/melanocyte antigen pMel-17 have proven to be highly potent stimulators of HLA-A2 CTL in several CTL cell lines. These and kindred peptides may be used to stimulate CTLs for use in adoptive immunotherapy, or incorporated into immunogenic conjugates for use as vaccines.
摘要翻译：已经通过在肿瘤细胞表面上从MHC I类分子解离的表位重组肽鉴定技术的改进技术来鉴定黑素瘤特异性CTL表位。与黑素瘤/黑素细胞抗原pMel-17的片段同源的肽已被证明是几种CTL细胞系中HLA-A2 + CTL的高效刺激剂。这些和亲和的肽可以用于刺激用于过继性免疫治疗的CTL，或掺入用作疫苗的免疫原性缀合物中。

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