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1. 发明授权

EP3262196B1 METHOD FOR DETERMINING HLA STATUS USING IMMUNE REPERTOIRE SEQUENCING 有权转让
公开(公告)号：EP3262196B1
公开(公告)日：2020-12-09
申请号：EP16756268.5
申请日：2016-02-24
申请人： Adaptive Biotechnologies Corp. , Fred Hutchinson Cancer Research Center
发明人： EMERSON, Ryan O. , RIEDER, Mark , ROBINS, Harlan S. , DEWITT III, William , CARLSON, Christopher
IPC分类号： C12Q1/6881 , C12Q1/6883 , C12P19/34 , G01N33/50 , C12Q1/68 , C12Q1/6869 , C12Q1/70

2. 发明公开

EP3212790A1 HIGHLY-MULTIPLEXED SIMULTANEOUS DETECTION OF NUCLEIC ACIDS ENCODING PAIRED ADAPTIVE IMMUNE RECEPTOR HETERODIMERS FROM MANY SAMPLES 有权转让
标题翻译：从多个样品高度多元化地同时检测编码配对免疫受体异构体的核酸
公开(公告)号：EP3212790A1
公开(公告)日：2017-09-06
申请号：EP15854358.7
申请日：2015-10-29
申请人： Adaptive Biotechnologies Corp. , Fred Hutchinson Cancer Research Center
发明人： EMERSON, Ryan, O. , SHERWOOD, Anna, M. , ROBINS, Harlan, S.
IPC分类号： C12N15/10 , C12Q1/68
摘要： The invention is directed to methods for highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune heterodimers from a large number of biological samples containing lymphocytes of interest. Methods of the invention comprise performing a single pairing assay on a pool of source samples to determine nucleic acids encoding paired cognate receptor heterodimer chains in the combined pool. Separately, single-locus, high-throughput sequencing is performed on each individual sample to determine the plurality of sequences encoding one of the two receptor polypeptide chains. Pairs of cognate sequences determined in the pooled sample may then be mapped back to a single source sample by comparing the expression patterns of the single-locus sequences.
摘要翻译：本发明涉及用于高度多路复用同时检测来自大量含感兴趣淋巴细胞的生物样品的编码配对的适应性免疫异二聚体的核酸的方法。本发明的方法包括对源样品池执行单配对测定以确定组合池中编码配对同源受体异源二聚体链的核酸。单独地，对每个单独的样品进行单基因座，高通量测序以确定编码两种受体多肽链中的一种的多个序列。然后通过比较单个基因座序列的表达模式，可以将合并样品中确定的一对同源序列映射回单一来源样品。

3. 发明公开

EP3092318A4 METHODS FOR DEFINING AND PREDICTING IMMUNE RESPONSE TO ALLOGRAFT 审中-公开
标题翻译： VERFAHREN ZUR定义UND VORHERSAGE DER免费AUF ALLOTRANSPLANTATE
公开(公告)号：EP3092318A4
公开(公告)日：2017-08-16
申请号：EP15735285
申请日：2015-01-09
申请人： ADAPTIVE BIOTECHNOLOGIES CORP , UNIV NORTHWESTERN
发明人： EMERSON RYAN O , KIRSCH ILAN , MATHEW JAMES , LEVENTHAL JOSEPH
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C12Q2600/118 , C12Q2600/156
摘要： Methods are provided for predicting and determining a subject's immune response to allograft. Methods include assessing immune response to an allograft by characterizing the diversity and distribution of clones of the adaptive immune repertoire. Methods are also provided for characterizing the adaptive immune response of a subject to an allograft using a mixed lymphocyte reaction culture.
摘要翻译：提供了用于预测和确定受试者对同种异体移植物的免疫应答的方法。方法包括通过表征适应性免疫库的克隆的多样性和分布来评估对同种异体移植物的免疫应答。还提供了使用混合淋巴细胞反应培养物表征受试者对同种异体移植物的适应性免疫应答的方法。

4. 发明公开

EP2788509A4 DIAGNOSIS OF LYMPHOID MALIGNANCIES AND MINIMAL RESIDUAL DISEASE DETECTION 有权转让
标题翻译： DIAGNOSE VON LYMPHOID-MALIGNITÄTUND NACHWEIS MINIMALER RESTERKRANKUNGEN
公开(公告)号：EP2788509A4
公开(公告)日：2015-10-28
申请号：EP12856015
申请日：2012-12-07
申请人： ADAPTIVE BIOTECHNOLOGIES CORP
发明人： SHERWOOD ANNA M , ROBINS HARLAN S
IPC分类号： C12Q1/68
CPC分类号： G06F19/22 , C12Q1/6886 , C12Q2600/112 , C12Q2600/158
摘要： Methods are described for diagnosis of a lymphoid hematological malignancy in a subject prior to treatment, and for detecting minimal residual disease (MRD) in the subject after treatment for the malignancy, by high throughput quantitative sequencing (HTS) of multiple unique adaptive immune receptor (TCR or Ig) encoding DNA molecules that have been amplified from DNA isolated from blood samples or other lymphoid cell-containing samples. Amplification employs oligonucleotide primer sets designed to amplify CDR3-encoding sequences within substantially all possible human VDJ or VJ combinations. Disease-characteristic adaptive immune receptor clonotypes occur, prior to treatment, at a relative frequency of at least 15-30% of rearranged receptor CDR3-encoding gene regions. Following treatment, persistence of at least one such clonotype at a detectable frequency of at least 10−6 or at least 10−5 receptor CDR3-encoding regions indicates MRD. Improved quantitative embodiments are provided by inclusion of a template composition for amplification factor determination and related methods.
摘要翻译：描述了用于在治疗前对受试者的淋巴血液恶性肿瘤进行诊断的方法，以及通过多种独特的适应性免疫受体的高通量定量测序（HTS）检测治疗恶性肿瘤后受试者中的最小残留病变（MRD） TCR或Ig）编码从分离自血液样本或其他含淋巴细胞样品的DNA扩增的DNA分子。扩增使用设计用于在基本上所有可能的人类VDJ或VJ组合中扩增CDR3编码序列的寡核苷酸引物组。疾病特征适应性免疫受体克隆型在治疗前以相对频率发生在重排的受体CDR3编码基因区域的至少15-30％。在治疗后，以至少10-6或至少10-5个受体CDR3编码区的可检测频率持续存在至少一种此类克隆型，表示MRD。通过包括用于扩增因子测定的模板组合物和相关方法来提供改进的定量实施方案。

6. 发明公开

EP3715455A1 HIGHLY-MULTIPLEXED SIMULTANEOUS DETECTION OF NUCLEIC ACIDS ENCODING PAIRED ADAPTIVE IMMUNE RECEPTOR HETERODIMERS FROM MANY SAMPLES 审中-公开
公开(公告)号：EP3715455A1
公开(公告)日：2020-09-30
申请号：EP20159836.4
申请日：2015-10-29
申请人： Adaptive Biotechnologies Corp. , Fred Hutchinson Cancer Research Center
发明人： EMERSON, Ryan, O. , SHERWOOD, Anna M. , ROBINS, Harlan S.
IPC分类号： C12N15/10 , C12Q1/68
摘要： The invention is directed to methods for highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune heterodimers from a large number of biological samples containing lymphocytes of interest. Methods of the invention comprise performing a single pairing assay on a pool of source samples to determine nucleic acids encoding paired cognate receptor heterodimer chains in the combined pool. Separately, single-locus, high-throughput sequencing is performed on each individual sample to determine the plurality of sequences encoding one of the two receptor polypeptide chains. Pairs of cognate sequences determined in the pooled sample may then be mapped back to a single source sample by comparing the expression patterns of the single-locus sequences.

7. 发明公开

EP3114240A4 METHODS USING RANDOMER-CONTAINING SYNTHETIC MOLECULES 有权
公开(公告)号：EP3114240A4
公开(公告)日：2017-10-25
申请号：EP15758762
申请日：2015-03-05
申请人： ADAPTIVE BIOTECHNOLOGIES CORP
发明人： SHERWOOD ANNA M , EMERSON RYAN O , ROBINS HARLAN S , RIEDER MARK J , PARSONS JOE
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6811 , C07H21/00 , C12N15/00 , C12Q1/68 , C12Q1/6827 , C12Q1/6846 , C12Q1/686 , C12Q1/6869 , C12Q2537/143 , G01N33/53 , G01N33/566 , G06F19/18 , C12Q2545/101
摘要： Methods are provided for correction of amplification bias and quantitation of adaptive immune cells in a sample using synthetic templates that include random oligonucleotide sequences.

8. 发明公开

EP3224384A1 CHARACTERIZATION OF ADAPTIVE IMMUNE RESPONSE TO VACCINATION OR INFECTION USING IMMUNE REPERTOIRE SEQUENCING 审中-公开
标题翻译：使用免疫重复序列分析对接种或感染进行自适应免疫反应的特征
公开(公告)号：EP3224384A1
公开(公告)日：2017-10-04
申请号：EP15864123.3
申请日：2015-11-24
申请人： Adaptive Biotechnologies Corp. , Fred Hutchinson Cancer Research Center
发明人： ROBINS, Harlan S. , EMERSON, Ryan O. , DEWITT, William Sumner, III
IPC分类号： C12Q1/68 , G01N33/53 , G06F19/22
CPC分类号： C12Q1/6881 , C12Q1/6883 , C12Q1/6886 , C12Q2600/156
摘要： Methods of monitoring and measuring dynamic adaptive immune cell responses are provided. High-throughput sequencing of T cell receptor and immunoglobulin loci is used to characterize the breadth of an effector cell response to a stimulus, such as a vaccine or infection. Unique responding effector cell clones and abundance thereof can be determined. Additionally, methods for determining the contribution of responding effector cells to the immunological memory compartment are provided.
摘要翻译：提供了监测和测量动态适应性免疫细胞应答的方法。 T细胞受体和免疫球蛋白基因座的高通量测序用于表征效应细胞对刺激物（例如疫苗或感染）的应答的广度。可以确定独特的应答效应细胞克隆及其丰度。另外，提供了确定响应效应细胞对免疫记忆隔室的贡献的方法。

9. 发明公开

EP3132059A4 QUANTIFICATION OF ADAPTIVE IMMUNE CELL GENOMES IN A COMPLEX MIXTURE OF CELLS 有权转让
标题翻译：量子化学VON ADAPTIVEN IMMUNZELLGENOMEN在EINER KOMPLEXEN MISCHUNG VON ZELLEN
公开(公告)号：EP3132059A4
公开(公告)日：2017-09-06
申请号：EP15779750
申请日：2015-03-05
申请人： ADAPTIVE BIOTECHNOLOGIES CORP , HUTCHINSON FRED CANCER RES
发明人： ROBINS HARLAN SAUL , CARLSON CHRISTOPHER SCOTT , RIEDER MARK J , SHERWOOD ANNA M , EMERSON RYAN O
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C12Q2600/156 , C12Q2600/16
摘要： A relative representation of adaptive immune cells in a biological sample is quantified using multiplex PCR and sequencing of adaptive immune cells, control genes, and synthetic template molecules. Disclosed herein are methods for quantifying a number of adaptive immune cells in a biological sample, and methods for quantifying a relative representation of adaptive immune cells in a biological sample that comprises a mixture of cells comprising adaptive immune cells and cells that are not adaptive immune cells. Methods are provided for amplifying by multiplex PCR and sequencing a first set of synthetic templates each comprising one TCR or IgV segment and one TCR of Ig J or C segment and a unique bar code.
摘要翻译：使用多重PCR和适应性免疫细胞，对照基因和合成模板分子的测序对生物样品中适应性免疫细胞的相对表示进行定量。本文公开了用于量化生物样品中的适应性免疫细胞的数量的方法，以及用于量化生物样品中适应性免疫细胞的相对表示的方法，所述生物样品包含含有适应性免疫细胞和非适应性免疫细胞的细胞的混合物。提供了通过多重PCR扩增和测序第一组合成模板的方法，每个合成模板包含一个TCR或IgV片段和一个Ig J或C片段的TCR以及独特的条形码。

10. 发明公开

EP3126522A4 DETERMINING ANTIGEN-SPECIFIC T-CELLS AND B-CELLS 无效
标题翻译： BESTIMMUNG VON ANTIGENSPEZIFISCHEN T-ZELLEN UND B-ZELLEN
公开(公告)号：EP3126522A4
公开(公告)日：2017-08-16
申请号：EP15772627
申请日：2015-04-01
申请人： ADAPTIVE BIOTECHNOLOGIES CORP
发明人： KLINGER MARK , FAHAM MALEK
IPC分类号： C12Q1/68 , A61K39/395 , C12N5/07 , C12N5/16 , G01N33/00
CPC分类号： C12Q1/6881 , C12Q2600/106 , C12Q2600/158 , C12Q2600/16
摘要： The invention is directed to methods for determining antigen-specific T cells. In some embodiments, methods of the invention may be implemented by the steps of reacting under interaction conditions one or more antigens with T cells in a plurality of subsets of a tissue sample, such as peripheral blood; sorting antigen-interacting T cells from other T cells; separately sequencing for each subset recombined nucleic acid encoding a segment of a TCR chain from a sample of T cells prior to exposure to antigen and from a sample of T cells isolated based on their interaction with antigen, thereby forming a clonotype profile for the former sample and the latter sample for each subset; and identifying as antigen-specific T cells those T cells associated with a clonotype whose frequency increases in the latter sample relative to its frequency in the former sample.
摘要翻译：本发明涉及确定抗原特异性T细胞的方法。在一些实施方案中，本发明的方法可以通过以下步骤实施：在相互作用条件下使一种或多种抗原与组织样品的多个子集中的T细胞例如外周血反应; 分选来自其他T细胞的抗原相互作用T细胞; 在暴露于抗原之前和从基于它们与抗原的相互作用分离的T细胞样品中分别对来自T细胞样品的编码TCR链区段的每个亚组重组核酸进行测序，由此形成前样品的克隆型谱以及每个子集的后一个样本; 并鉴定与抗原特异性T细胞相关的与克隆型相关的T细胞，其频率在后者样品中相对于其在前样品中的频率增加。

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