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1. 发明授权

US09279011B2 Phosphopeptides as melanoma vaccines 有权
标题翻译：磷酸肽作为黑素瘤疫苗
公开(公告)号：US09279011B2
公开(公告)日：2016-03-08
申请号：US13318821
申请日：2010-05-04
申请人： Suzanne L. Topalian , Florence A Depontieu , Donald F. Hunt , Jeffrey Shabanowitz , Jie Qian , Victor H. Engelhard , Angela Lee Zarling
发明人： Suzanne L. Topalian , Florence A Depontieu , Donald F. Hunt , Jeffrey Shabanowitz , Jie Qian , Victor H. Engelhard , Angela Lee Zarling
IPC分类号： A61K39/00 , A61K47/00 , C07K14/47 , G01N33/574 , C12Q1/68 , A61K39/39
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，表明定义细胞类型特异性磷酸酯“指纹”的潜力。我们产生HLA-DR和bgr。1 * 0101限制性CD4 + T细胞，特异于在两个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

US20130259883A1 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：US20130259883A1
公开(公告)日：2013-10-03
申请号：US13699563
申请日：2011-05-24
申请人： Donald F. Hunt , Jeffrey Shabanowitz , Jennifer Cottine , Ann M. English , Andrew Norris , Victor H. Engelhard , Mark Cobbold , Kara L. Cummings , Angela Zarling , Rebecca C. Obeng , Jie Qian
发明人： Donald F. Hunt , Jeffrey Shabanowitz , Jennifer Cottine , Ann M. English , Andrew Norris , Victor H. Engelhard , Mark Cobbold , Kara L. Cummings , Angela Zarling , Rebecca C. Obeng , Jie Qian
IPC分类号： C07K7/06 , C07K16/18 , G01N33/68 , C07K7/08 , A61K39/00
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。它们有可能（a）刺激对癌症的免疫应答，（b）在过继性T细胞治疗或疫苗中起到免疫治疗的作用，（c）促进外科病理样本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

US20120177669A1 PHOSPHOPEPTIDES AS MELANOMA VACCINES 有权
标题翻译：磷酸盐作为微生物疫苗
公开(公告)号：US20120177669A1
公开(公告)日：2012-07-12
申请号：US13318821
申请日：2010-05-04
申请人： Suzanne L. Topalian , Florence Depontieu , Donald Hunt , Jeffrey Shabanowitz , Jie Qian , Victor Engelhard , Angela Zaring
发明人： Suzanne L. Topalian , Florence Depontieu , Donald Hunt , Jeffrey Shabanowitz , Jie Qian , Victor Engelhard , Angela Zaring
IPC分类号： A61K39/00 , A61K35/12 , C07K16/30 , A61P35/00 , A61P35/04 , A61P37/04 , C12N5/0784 , C07K7/08 , C07K14/74 , C07K14/47 , G01N33/566 , C07K7/06 , C12N5/0783
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，表明定义细胞类型特异性磷酸酯“指纹”的潜力。我们产生HLA-DR和bgr。1 * 0101限制性CD4 + T细胞，特异于在两个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。

4. 发明授权

US07019112B1 Peptides recognized by melanoma-specific A1-, A2- and A3-restricted cytoxic lymphocytes, and uses therefor 失效
标题翻译：由黑素瘤特异性A1-，A2-和A3-限制性细胞毒性淋巴细胞识别的肽及其用途
公开(公告)号：US07019112B1
公开(公告)日：2006-03-28
申请号：US08816454
申请日：1997-03-12
申请人： Craig L. Slingluff , Donald F. Hunt , Jeffrey Shabanowitz , Andrea L. Cox , Victor H. Engelhard , David Kittlesen , Jonathan Skipper , Ronald C. Hendrikson
发明人： Craig L. Slingluff , Donald F. Hunt , Jeffrey Shabanowitz , Andrea L. Cox , Victor H. Engelhard , David Kittlesen , Jonathan Skipper , Ronald C. Hendrikson
IPC分类号： C07K7/06
CPC分类号： C07K7/06 , C07K7/08
摘要： Melanoma-specific, A1- and A3-restricted CTL epitopes have been identified in tyrosinase and pMel-17, respectively, and may be used in the design of vaccines.
摘要翻译：已经在酪氨酸酶和pMel-17中鉴定了黑素瘤特异性，A1-和A3限制性CTL表位，并且可以用于疫苗的设计。

5. 发明授权

US4156814A Apparatus for producing ions of thermally labile or nonvolatile solids 失效
公开(公告)号：US4156814A
公开(公告)日：1979-05-29
申请号：US822216
申请日：1977-08-05
申请人： Donald F. Hunt , Jeffrey Shabanowitz
发明人： Donald F. Hunt , Jeffrey Shabanowitz
IPC分类号： H01J49/04 , H01J49/14
CPC分类号： H01J49/0409 , H01J49/142
摘要： An apparatus for ionizing and vaporizing non-volatile or thermally labile molecules of a sample for introduction into a mass spectrometer analyzer which comprises a housing containing an ionization chamber; an ion exit port for the introduction of gaseous ions from said ionization chamber into a mass spectrometer analyzer on the portion of the housing attached to said mass spectrometer analyzer; inlet means for introducing a gaseous reactant into said ionization chamber within said housing; inlet means for admitting high energy radiation into said ionization chamber within said housing to at least partially ionize the molecules of said gaseous reactant; aperture means open into said ionization chamber of said housing for admitting a conductive emitter characterized by having a conductive element of a highly irregular surface upon which is deposited said sample for analysis into said mass spectrometer analyzer; and a vacuum exit aperture in said housing by which the pressure within said ionization chamber can be reduced.

6. 发明授权

US4175234A Apparatus for producing ions of thermally labile or nonvolatile solids 失效
标题翻译：用于产生热不稳定或非挥发性固体的离子的装置
公开(公告)号：US4175234A
公开(公告)日：1979-11-20
申请号：US916151
申请日：1978-06-16
申请人： Donald F. Hunt , Jeffrey Shabanowitz
发明人： Donald F. Hunt , Jeffrey Shabanowitz
IPC分类号： H01J49/14 , H01J49/16 , H01J27/00
CPC分类号： H01J49/145 , H01J49/16
摘要： An apparatus for ionizing and vaporizing non-volatile or thermally labile molecules of a sample for introduction into a mass spectrometer analyzer which comprises a housing containing an ionization chamber; an ion exit port for the introduction of gaseous ions from said ionization chamber into a mass spectrometer analyzer on the portion of the housing attached to said mass spectrometer analyzer; inlet means for introducing a gaseous reactant into said ionization chamber within said housing; inlet means for admitting high energy radiation into said ionization chamber within said housing to at least partially ionize the molecules of said gaseous reactant; aperture means open into said ionization chamber of said housing for admitting a conductive emitter characterized by having a conductive element of a highly irregular surface upon which is deposited said sample for analysis into said mass spectrometer analyzer; and a vacuum exit aperture in said housing by which the pressure within said ionization chamber can be reduced.
摘要翻译：一种用于离子化和蒸发样品的非挥发性或热不稳定分子的装置，用于引入质谱仪分析仪，其包括含有电离室的壳体; 离子出口，用于将气态离子从所述电离室引入质谱仪分析仪，所述质谱仪分析仪附着在所述质谱仪分析仪上; 用于将气体反应物引入所述壳体内的所述电离室的入口装置; 入口装置，用于将高能量辐射进入所述壳体内的所述电离室，以使所述气态反应物的分子至少部分电离; 开口意味着通向所述壳体的所述电离室，用于允许导电发射器，其特征在于具有高度不规则表面的导电元件，在其上沉积所述样品用于分析所述质谱仪分析仪; 以及所述壳体中的真空出口孔，通过该真空出口孔可以减小所述电离室内的压力。

7. 发明授权

US11538675B2 Rapid identification and sequence analysis of intact proteins in complex mixtures 有权
公开(公告)号：US11538675B2
公开(公告)日：2022-12-27
申请号：US16307615
申请日：2017-06-05
申请人： Donald F. Hunt , Ann M. English , Scott A. Ugrin , Dina L. Bai , Jeffrey Shabanowitz , John Edward Philip Syka
发明人： Donald F. Hunt , Ann M. English , Scott A. Ugrin , Dina L. Bai , Jeffrey Shabanowitz , John Edward Philip Syka
IPC分类号： H01J49/00 , G01N33/68 , H01J49/04 , H01J49/42
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.

8. 发明授权

US08119984B2 Method and apparatus for generation of reagent ions in a mass spectrometer 有权
标题翻译：用于在质谱仪中产生试剂离子的方法和装置
公开(公告)号：US08119984B2
公开(公告)日：2012-02-21
申请号：US12473570
申请日：2009-05-28
申请人： Jeffrey Shabanowitz , Philip D. Compton , Lee Earley , George C. Stafford, Jr. , Donald F. Hunt , Christopher Mullen
发明人： Jeffrey Shabanowitz , Philip D. Compton , Lee Earley , George C. Stafford, Jr. , Donald F. Hunt , Christopher Mullen
IPC分类号： 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）。

9. 发明申请

US20090294649A1 Method and Apparatus for Generation of Reagent Ions in a Mass Spectrometer 有权
标题翻译：用于在质谱仪中产生试剂离子的方法和装置
公开(公告)号：US20090294649A1
公开(公告)日：2009-12-03
申请号：US12473570
申请日：2009-05-28
申请人： Jeffrey Shabanowitz , Philip D. Compton , Lee Earley , George C. Stafford, JR. , Donald F. Hunt , Christopher Mullen
发明人： Jeffrey Shabanowitz , Philip D. Compton , Lee Earley , George C. Stafford, JR. , Donald F. Hunt , Christopher Mullen
IPC分类号： B01D59/44 , H01J49/00 , H01J27/00
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）。

10. 发明授权

US08758767B2 Antigens targeted by prevalent pathogennic T cells in type 1 diabetes and uses thereof 有权
标题翻译： 1型糖尿病中流行的病原性T细胞靶向的抗原及其用途
公开(公告)号：US08758767B2
公开(公告)日：2014-06-24
申请号：US10557273
申请日：2004-05-20
申请人： Teresa P. DiLorenzo , Anne M. Evans , Donald F. Hunt , Scott M. Lieberman , Stanley G. Nathenson , Pere Santamaria , Jeffrey Shabanowitz
发明人： Teresa P. DiLorenzo , Anne M. Evans , Donald F. Hunt , Scott M. Lieberman , Stanley G. Nathenson , Pere Santamaria , Jeffrey Shabanowitz
IPC分类号： A61K39/00 , A61K39/385
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 (SEQ ID NO:3), FLWSVFWLI (SEQ ID NO:4), (T/A)YY(G/T)FLNFM (SEQ ID NO:5), LR(L/V)(F/L)(G/N)IDLL (SEQ ID NO:6), KWCANPDWI (SEQ ID NO:7), and SFCKSASIP (SEQ ID NO:8). 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：本发明基于负责1型糖尿病的CD8 + T细胞的主要配体的鉴定。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，其对自身免疫性糖尿病中病原性CD8 + T细胞最流行的T细胞受体具有高亲合力。因此，本发明提供包含YLKTN（A / I / L / V）FL（SEQ ID NO：3），FLWSVFWLI（SEQ ID NO：4），（T / A）YY（G / T）FLNFM SEQ ID NO：5），LR（L / V）（F / L）（G / N）IDLL（SEQ ID NO：6），KWCANPDWI（SEQ ID NO：7）和SFCKSASIP（SEQ ID NO：8）。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细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物和细胞的方法，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。

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