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1. 发明申请

WO2012054825A1 ANTI-MAGE-A3 T CELL RECEPTORS AND RELATED MATERIALS AND METHODS OF USE 审中-公开
标题翻译：抗-MAGE-A3细胞受体及相关材料及其使用方法
公开(公告)号：WO2012054825A1
公开(公告)日：2012-04-26
申请号：PCT/US2011/057272
申请日：2011-10-21
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , MORGAN, Richard A. , CHINNASAMY, Nachimuthu , ROSENBERG, Steven A. , WARGO, Jennifer A.
发明人： MORGAN, Richard A. , CHINNASAMY, Nachimuthu , ROSENBERG, Steven A. , WARGO, Jennifer A.
IPC分类号： C07K14/705
CPC分类号： C07K14/7051 , A61K2039/5156
摘要： The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for melanoma antigen family A (MAGE A)-3. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention.
摘要翻译：本发明提供了对黑素瘤抗原家族A（MAGE A）-3具有抗原特异性的分离或纯化的T细胞受体（TCR）。本发明还提供了相关的多肽和蛋白质，以及相关的核酸，重组表达载体，宿主细胞和细胞群。本发明进一步提供的是抗体或其抗原结合部分，以及与本发明的TCR有关的药物组合物。通过本发明进一步提供了检测宿主中癌症存在的方法以及在宿主中治疗或预防癌症的方法。

2. 发明申请

WO2012024203A1 METHODS OF IDENTIFYING CENTRAL MEMORY T CELLS AND OBTAINING ANTIGEN-SPECIFIC T CELL POPULATIONS 审中-公开
标题翻译：鉴定中央记忆T细胞和获得抗原特异性T细胞群体的方法
公开(公告)号：WO2012024203A1
公开(公告)日：2012-02-23
申请号：PCT/US2011/047719
申请日：2011-08-15
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , KAMMULA, Udai S.
发明人： KAMMULA, Udai S.
IPC分类号： C12N5/0783
CPC分类号： C12N5/0636 , A61K39/0011 , A61K2039/5158 , C12N2501/2302
摘要： The invention provides a method of obtaining a population of antigen-specific T cells comprising: (i) dividing PBMCs from peripheral blood of a host into more than one sub-population; (ii) contacting the PBMCs of each sub-population with an antigen; (iii) obtaining a sample of the contacted PBMCs from each sub-population; (iv) measuring the quantity of 1) IL-2 mRNA and 2) IFN- γ mRNA expressed by the PBMCs of each sample; (v) determining the IL-2 index of each sample; (vi) identifying one or more samples with an IL-2 index determined in (v) of greater than or equal to about 10 to identify one or more antigen-reactive, central memory T cell sub-populations; (vii) dividing the antigen-reactive, central memory T cell sub-population(s) identified in (vi) into microcultures; (viii) identifying one or more antigen-reactive microcultures; and (ix) expanding the microculture(s).
摘要翻译：本发明提供了一种获得抗原特异性T细胞群的方法，包括：（i）将来自宿主的外周血的PBMC分成多于一个亚群; （ii）使每个子群体的PBMC与抗原接触; （iii）从每个子群体获得接触的PBMC的样品; （iv）测量1）IL-2 mRNA的量和2）IFN- 由每个样品的PBMC表达的mRNA; （v）确定每个样品的IL-2指数; （vi）用（v）中确定的IL-2指数（大于或等于约10）鉴定一个或多个样品以鉴定一个或多个抗原反应性中枢记忆T细胞亚群; （vii）将（vi）中鉴定的抗原反应性中心记忆T细胞亚群分为微量培养物; （viii）鉴定一个或多个抗原反应性微量培养物; 和（ix）扩大微型文化。

3. 发明申请

WO2011081904A1 DELIVERY OF TRANSTHYRETIN ACROSS THE BLOOD-BRAIN BARRIER AS A TREATMENT FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译：作为治疗阿尔茨海默病的血脑屏障的血液透析递送
公开(公告)号：WO2011081904A1
公开(公告)日：2011-07-07
申请号：PCT/US2010/060205
申请日：2010-12-14
申请人： THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , UNIVERSITY OF MARYLAND, COLLEGE PARK , MARUGAN, Juan Jose , ZHENG, Wei , MURO-GALINDO, Silvia
发明人： MARUGAN, Juan Jose , ZHENG, Wei , MURO-GALINDO, Silvia
IPC分类号： C07K14/47 , C07K14/705 , C07K19/00 , A61K38/17 , A61K39/44 , C12N1/16 , C12N1/21 , C12N5/10
CPC分类号： C07K14/70525 , A61K38/00 , A61K47/6811 , A61K47/6849 , C07K14/4717 , C07K2319/33
摘要： The invention provides a composition comprising transthyretin and an ICAM-1 targeting agent, wherein the transthyretin and ICAM-1 targeting agent are coupled together, as well as methods of preparing such compositions. The invention further provides a diabody capable of binding specifically to ICAM-1 and transthyretin. The invention also provides a method of use of such composition in the manufacture of a medicament for treating an amyloid-β related neurodegenerative disease, comprising administering to a subject a composition comprising transthyretin coupled to an ICAM-1 targeting agent in an amount effective to treat the neurodegenerative disease, wherein the composition is administered to the subject outside of the blood-brain barrier.
摘要翻译：本发明提供了包含转甲状腺素蛋白和ICAM-1靶向剂的组合物，其中转甲状腺素蛋白和ICAM-1靶向剂偶联在一起，以及制备这种组合物的方法。本发明还提供能够特异性结合ICAM-1和转甲状腺素蛋白的双抗体。本发明还提供了这种组合物在制备用于治疗淀粉样蛋白ß相关神经变性疾病的药物中的应用的方法，包括向受试者施用包含与有效治疗的量的ICAM-1靶向剂偶联的转甲状腺素蛋白的组合物所述神经变性疾病，其中所述组合物在所述血脑屏障外给予受试者。

4. 发明申请

WO2010126766A1 INDUCIBLE INTERLEUKIN-12 审中-公开
标题翻译：可诱导的白细胞介素12
公开(公告)号：WO2010126766A1
公开(公告)日：2010-11-04
申请号：PCT/US2010/031988
申请日：2010-04-22
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , MORGAN, Richard, A. , ROSENBERG, Steven, A. , ZHANG, Ling , RESTIFO, Nicholas, P.
发明人： MORGAN, Richard, A. , ROSENBERG, Steven, A. , ZHANG, Ling , RESTIFO, Nicholas, P.
IPC分类号： C07K14/54 , C07K14/705
CPC分类号： C07K14/5434 , A61K38/00 , C07K14/4702 , Y02A50/411
摘要： The invention provides an isolated or purified nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12. The invention also provides a nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12, wherein the NFAT promoter is located 3' of the nucleotide sequence encoding IL-12. Also provided are related recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. The invention further provides the use of the inventive nucleic acids or related materials in the treatment or prevention of cancer or an infectious disease in a mammal and in the induction of IL-12 expression in a mammal.
摘要翻译：本发明提供了分离或纯化的核酸，其包含编码与编码IL-12的核苷酸序列可操作地相关的活化T细胞（NFAT）启动子核因子的核苷酸序列。本发明还提供了一种核酸，其包含编码与编码IL-12的核苷酸序列可操作地相关的活化的T细胞（NFAT）启动子的核因子的核苷酸序列，其中所述NFAT启动子位于编码IL-12的核苷酸序列的3' 12。还提供了相关的重组表达载体，宿主细胞，细胞群和药物组合物。本发明进一步提供了本发明的核酸或相关材料在哺乳动物中治疗或预防癌症或感染性疾病以及在哺乳动物中诱导IL-12表达的用途。

5. 发明申请

WO2009102697A2 METHODS OF OBTAINING ANTIGEN-SPECIFIC T CELL POPULATIONS 审中-公开
标题翻译：获得抗原特异性细胞群体的方法
公开(公告)号：WO2009102697A2
公开(公告)日：2009-08-20
申请号：PCT/US2009/033649
申请日：2009-02-10
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , KAMMULA, Udai S.
发明人： KAMMULA, Udai S.
IPC分类号： C12N5/08 , A61K35/12
CPC分类号： A61K39/0011 , A61K2035/124 , C12N5/0636 , C12N5/0638 , C12Q1/6881 , G01N33/56972
摘要： The invention provides a method of obtaining a population of antigen-specific T cells from peripheral blood of a host. An embodiment of the method of the invention comprises (i) dividing PBMCs from peripheral blood of a host into more than one sub-population; (ii) contacting the PBMCs with an antigen and IL-2; (iii) obtaining a sample of PBMCs from each sub-population; (iv) identifying an antigen-reactive sub-population by determining by high throughput quantitative PCR the expression of a factor produced by the PBMCs of each sample; (v) dividing the antigen-reactive sub-population into microcultures; (vi) identifying the antigen-reactive microculture; and (vii) expanding the microculture, thereby obtaining a population of T cells specific for the antigen. The invention also provides a population of T cells obtained by the inventive method, a pharmaceutical composition comprising the same, and a method of treating a disease in a host using the pharmaceutical composition. Related isolating and screening methods are further provided.
摘要翻译：本发明提供从宿主的外周血获得抗原特异性T细胞群体的方法。本发明方法的一个实施方案包括：（i）将来自宿主的外周血的PBMC分成多于一个亚群; （ii）使PBMC与抗原和IL-2接触; （iii）从每个子群体获得PBMC的样品; （iv）通过高通量定量PCR确定由每个样品的PBMC产生的因子的表达来鉴定抗原反应性亚群体; （v）将抗原反应性亚群分为微量培养物; （vi）鉴定抗原反应性微量培养物; 和（vii）扩大微量培养物，从而获得对抗原特异性的T细胞群体。本发明还提供了通过本发明方法获得的一组T细胞，包含其的药物组合物和使用该药物组合物治疗宿主中的疾病的方法。进一步提供相关的分离和筛选方法。

6. 发明申请

WO2009042570A2 MODIFIED T CELL RECEPTORS AND RELATED MATERIALS AND METHODS 审中-公开
标题翻译：修饰的T细胞受体及相关材料和方法
公开(公告)号：WO2009042570A2
公开(公告)日：2009-04-02
申请号：PCT/US2008/077333
申请日：2008-09-23
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , ROBBINS, Paul F. , ROSENBERG, Steven A. , MORGAN, Richard A.
发明人： ROBBINS, Paul F. , ROSENBERG, Steven A. , MORGAN, Richard A.
IPC分类号： C07K14/735
CPC分类号： C07K14/705
摘要： The invention is directed to a modified T cell receptor (TCR) comprising an amino acid sequence of a wild-type (WT) TCR with one or more amino acid substitutions in the CDR2 and/or CDR3 regions of the alpha and/or beta chains of the TCR, wherein the modified TCR, as compared to the WT TCR, (i) has an enhanced ability to recognize target cells when expressed by CD4 + T cells and/or CD8 + T cells and (ii) does not exhibit a decrease in antigen specificity when expressed by the CD4 + T cells and/or CD8 + T cells. Polypeptides, proteins, nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, and pharmaceutical compositions related to the modified TCR also are part of the invention. Further, the invention is directed to methods of treating or preventing a disease in a host and methods of detecting a diseased cell in a host.
摘要翻译：本发明涉及包含野生型（WT）TCR的氨基酸序列的修饰的T细胞受体（TCR），其在CDR2和/或CDR3区中具有一个或多个氨基酸取代的TCR的α和/或β链，其中与WT TCR相比，修饰的TCR（i）具有增强的当由CD4 + T细胞表达时识别靶细胞的能力和 /或CD8 + T细胞和（ii）当由CD4 + T细胞和/或CD8 + T细胞表达时不表现出抗原特异性的降低 T细胞。与修饰的TCR相关的多肽，蛋白质，核酸，重组表达载体，宿主细胞，细胞群，抗体和药物组合物也是本发明的一部分。此外，本发明涉及治疗或预防宿主中疾病的方法和检测宿主中患病细胞的方法。

7. 发明申请

WO2008039818A2 MODIFIED T CELL RECEPTORS AND RELATED MATERIALS AND METHODS 审中-公开
标题翻译：改良的T细胞受体及相关材料与方法
公开(公告)号：WO2008039818A2
公开(公告)日：2008-04-03
申请号：PCT/US2007/079487
申请日：2007-09-26
申请人： GOVERNMENT OF THE UNITED STATES OF AMERICA, REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , MEDIGENE LIMITED , ROBBINS, Paul F. , MORGAN, Richard A. , ROSENBERG, Steven A. , BENNETT, Alan David
发明人： ROBBINS, Paul F. , MORGAN, Richard A. , ROSENBERG, Steven A. , BENNETT, Alan David
IPC分类号： C07K14/725 , C12Q1/02 , C07K16/28 , A61K38/17
CPC分类号： G01N33/505 , A61K38/00 , C07K14/7051 , G01N33/5091
摘要： The invention is directed to a modified T cell receptor (TCR) comprising an amino acid sequence of a wild-type (WT) TCR with no more than three amino acid substitutions, wherein the modified TCR, as compared to the WT TCR, (i) has an enhanced ability to recognize target cells when expressed by CD4 + T cells and (ii) does not exhibit a decrease in antigen specificity when expressed by CD8 + T cells. Polypeptides, proteins, nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, and pharmaceutical compositions related to the modified TCR also are part of the invention. Further, the invention is directed to methods of detecting a diseased cell in a host, methods of treating or preventing a disease in a host, and methods of identifying a candidate adoptive immunotherapy TCR.
摘要翻译：本发明涉及包含不超过三个氨基酸取代的野生型（WT）TCR的氨基酸序列的修饰的T细胞受体（TCR），其中与WT TCR相比，修饰的TCR（i ）当由CD4 + T细胞表达时具有增强的识别靶细胞的能力，和（ii）当由CD8 + T细胞表达时，其抗原特异性没有降低。多肽，蛋白质，核酸，重组表达载体，宿主细胞，细胞群，抗体和与修饰的TCR相关的药物组合物也是本发明的一部分。此外，本发明涉及检测宿主中的病变细胞的方法，治疗或预防宿主疾病的方法，以及鉴定候选的过继性免疫治疗TCR的方法。

8. 发明申请

WO2007130785A2 MATERIALS AND METHODS FOR TREATING PNEUMOCYSTIS PNEUMONIA 审中-公开
标题翻译：用于治疗肺炎肺炎的材料和方法
公开(公告)号：WO2007130785A2
公开(公告)日：2007-11-15
申请号：PCT/US2007/066925
申请日：2007-04-19
申请人： GOVERNMENT OF THE UNITED STATES OF AMERICA, REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , KEANE-MYERS, Andrea , SPOLSKI, Rosanne , LEONARD, Warren J.
发明人： KEANE-MYERS, Andrea , SPOLSKI, Rosanne , LEONARD, Warren J.
CPC分类号： A61K38/20 , A61K45/06 , G01N2333/375 , G01N2333/715 , G01N2500/00 , G01N2800/12 , A61K2300/00
摘要： The invention provides a method of identifying or characterizing an agent that modulates Pneumocystis pneumonia. The method comprises (a) administering the agent to an interleukin 21 receptor (IL-21R) -/- knockout non-human mammalian model, and (b) determining the effect of the agent on Pneumocystis pneumonia in the IL-21R -/- knockout non-human mammalian model. The invention further provides a method for the prophylaxis or treatment of Pneumocystis pneumonia in a mammal. The method comprises administering to the mammal a therapeutically effective amount of an IL-21 polypeptide, an IL-21 polypeptide variant, a biologically-active fragment of either of the foregoing, or a nucleic acid encoding any of the foregoing.
摘要翻译：本发明提供了鉴定或表征调节肺孢子虫肺炎的药剂的方法。该方法包括（a）向白细胞介素21受体（IL-21R）敲除非人哺乳动物模型施用该试剂，和（b）测定该药物对肺孢子虫肺炎的作用 IL-21R - / - / - 敲除非人哺乳动物模型。本发明还提供了一种预防或治疗哺乳动物肺孢子虫肺炎的方法。该方法包括向哺乳动物施用治疗有效量的IL-21多肽，IL-21多肽变体，前述任一项的生物活性片段或编码前述任何一种的核酸。

9. 发明申请

WO2012129201A1 METHODS OF GROWING TUMOR INFILTRATING LYMPHOCYTES IN GAS-PERMEABLE CONTAINERS 审中-公开
标题翻译：在气体渗透性容器中增加肿瘤浸润淋巴细胞的方法
公开(公告)号：WO2012129201A1
公开(公告)日：2012-09-27
申请号：PCT/US2012/029744
申请日：2012-03-20
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , WILSON WOLF MANUFACTURING CORPORATION , ROSENBERG, Steven A. , DUDLEY, Mark E. , STRONCEK, David , SABATINO, Marianna , JIN, Jianjian , SOMERVILLE, Robert , WILSON, John R.
发明人： ROSENBERG, Steven A. , DUDLEY, Mark E. , STRONCEK, David , SABATINO, Marianna , JIN, Jianjian , SOMERVILLE, Robert , WILSON, John R.
IPC分类号： C12N5/0783 , A61K35/12
CPC分类号： C12N5/0634 , A61K39/0011 , A61K2035/124 , A61K2039/5158 , C12N5/0638 , C12N2501/2302 , C12N2501/2315 , C12N2501/515 , C12N2502/11
摘要： An embodiment of the invention provides TIL prepared by obtaining a tumor tissue sample obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample and expanding the number of TIL in a gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; for use in promoting the regression of cancer in a mammal. Methods of preparing an expanded number of TIL are also provided.
摘要翻译：本发明的一个实施方案提供了通过获得从肿瘤组织样品获得肿瘤浸润淋巴细胞（TIL）的肿瘤组织样品获得的TIL，并且使用照射的同种异体饲养细胞和/或照射扩大含有细胞培养基的透气容器中的TIL数自体饲养细胞; 用于促进哺乳动物癌症的消退。还提供了制备扩展数量的TIL的方法。

10. 发明申请

WO2012061283A1 RAPID MOLECULAR ASSAYS FOR SPECIFIC DETECTION AND QUANTITATION OF LOA LOA MICROFILAREMIA 审中-公开
标题翻译：用于特异性检测和定量LOA微波辐射的快速分析测定
公开(公告)号：WO2012061283A1
公开(公告)日：2012-05-10
申请号：PCT/US2011/058565
申请日：2011-10-31
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , NUTMAN, Thomas B. , FINK, Doran
发明人： NUTMAN, Thomas B. , FINK, Doran
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6888 , C12Q2600/16
摘要： A series of quantitative assays capable of quantifying Loa loa microfilaria burden from small-volume blood samples is provided. The present invention also provides methods of use of the quantitative assays to identify individuals at risk for encephalopathy due to antifilarial treatment, and also provides oligonucleotide primers used in the assay methods.
摘要翻译：提供了一系列能够从小体积血液样本中定量分析罗氏微丝ia病负荷的定量分析。本发明还提供了使用定量测定来鉴定由于抗亲和处理引起的脑病风险的个体的方法，并且还提供了用于测定方法的寡核苷酸引物。

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