JP6302847B2 - 頻度が一致したサブユニットからの、対をなす免疫受容体鎖の決定 - Google Patents
頻度が一致したサブユニットからの、対をなす免疫受容体鎖の決定 Download PDFInfo
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Description
多くの重要な免疫機能はT細胞受容体 (TCR) によって媒介され、TCRは、抗原ペプチドと主要組織適合遺伝子複合体 (MHC) 分子とからなる複合体に共に結合するαサブユニットおよびβサブユニットを含む。いくつかの重要な疾患は異常なT細胞機能によって生じると考えられている:例えば、癌は、免疫監視、すなわち形質転換細胞のクローンをそれらが腫瘍に成長する前に検出し破壊するT細胞機能、の不全によって生じると考えられており;自己免疫疾患は、自己抗原に対するT細胞の過活動性のまたは異常な応答によって生じると考えられている;Abbas et al, Cellular and Molecular Immunology, Fourth Edition (W.B. Saunders Company, 2000)(非特許文献1)。したがって、癌および自己免疫疾患の両方を治療するためのいくつかの治療アプローチでは、T細胞機能を利用することに関心が寄せられている;例えば、Molloy et al, Current Opinion in Pharmacology, 5: 438-443 (2005)(非特許文献2);Morgan et al, Science, 314: 126-129 (2006)(非特許文献3);Turcotte and Rosenberg, Adv. Surg., 45: 341-360 (2011)(非特許文献4)。このようなアプローチにおける共通の課題は、関心対象の標的へと特異的に結合できる受容体全体を形成するように相伴うTCRαサブユニットおよびTCRβサブユニットを同定し単離することである。典型的には、関心対象のT細胞を同定し、各サブユニットをコードする核酸を単離し解析できるようにクローン的に増殖させる。しかしながら、TCRが、メラノーマにおけるMART-1などの共通の疾患抗原に特異的でない限り、単一細胞解析、クローニング、および受容体単離の過程を、それぞれの患者について繰り返さなくてはならない。
本発明の実施は、特記されない限り、当技術分野の技術の範囲内にある、分子生物学(組換え技法を含む)、バイオインフォマティクス、細胞生物学、および生化学の従来の技法および説明を使用することができる。このような従来の技法には、血液細胞のサンプリングおよび解析、核酸の配列決定および解析などが含まれるが、これらに限定されない。適切な技法の具体的な例は、本明細書における以下の実施例を参照することによって知ることができる。しかしながら、その他の同等な従来の手順もまた、当然ながら用いることができる。このような従来の技法および説明は、Genome Analysis: A Laboratory Manual Series (Vols. I-IV);PCR Primer: A Laboratory Manual;およびMolecular Cloning: A Laboratory Manual(いずれもCold Spring Harbor Laboratory Pressによる)などの標準的な実験室マニュアルにおいて見出すことができる。
上記の通り、特定の頻度におけるサブセットすべてを解析する必要はない。例えばf = 0.001といった選択された頻度であるかまたはそれに近い頻度を有するリンパ球が多数存在する場合には、サブセットの50パーセントにおいてそろって現れるすべての対が、同じ頻度の他のどの対とも識別され得るまで、サブセットの総数に占めるより大きな部分を用いることによって、それらすべてを分離することができる。これは、50パーセントの全く同じサブセット中に2つの異なるリンパ球が出現する確率は、サブセットの一部分が増加するにつれて無限小となるためである。
再構成されたT細胞受容体には、個々におよび一群として種々の用途があり、これには、免疫療法のための結合化合物として、養子免疫療法のためのトランスフェクトT細胞の成分として、ワクチン中の抗原供給源として、および免疫状態の指標としての用途が含まれるが、これらに限定されない。可溶型の合致したTCR鎖は、例えば、Jakobsen et al、米国特許第7,329,731号および第7,666,604号によって教示されるような、特有の抗癌療法のためのT細胞捕捉剤に連結される高親和性結合成分として使用することができる;上記特許は参照により本明細書に組み入れられる。合致したTCR鎖を用いてベクターを構築することができ、次いでこれを、患者の養子免疫療法のための自己T細胞へのトランスフェクションに用いることができる。この適用の1つの態様では、患者を癌抗原で免疫する前および免疫した後に、TCRを解析する試料を取得すことができ、その結果、増大した抗癌TCR鎖を容易に合致させ、これを選択する。このような適用を開示している参考文献には、Turcotte et al, Adv. Surg., 45: 341-360 (2011);Morgan et al, Science, 314: 126-129 (2006);Walchli et al, PlosOne, 6: e27930 (2011);Robbins et al、米国特許出願公開第2010/0034834号などが含まれる。
クロノタイププロファイルは、免疫細胞の試料から得られ得る。例えば、免疫細胞には、T細胞および/またはB細胞が含まれ得る。T細胞(Tリンパ球)には、例えばT細胞受容体を発現する細胞が含まれる。T細胞には、ヘルパーT細胞(エフェクターT細胞またはTh細胞)、細胞傷害性T細胞 (CTL)、記憶T細胞、および調節性T細胞が含まれる。1つの局面において、T細胞の試料は少なくとも1,000個のT細胞を含む;しかしより典型的には、試料は少なくとも10,000個のT細胞を含み、およびより典型的には少なくとも100,000個のT細胞を含む。別の局面において、試料は、細胞1000〜1,000,000個の範囲の数のT細胞を含む。免疫細胞の試料はまたB細胞を含み得る。B細胞には、例えば、形質B細胞、記憶B細胞、B1細胞、B2細胞、辺縁帯B細胞、および濾胞性B細胞が含まれる。B細胞は免疫グロブリン(抗体、B細胞受容体)を発現し得る。上記のように、1つの局面において、B細胞の試料は少なくとも1,000個のB細胞を含む;しかしより典型的には、試料は少なくとも10,000個のB細胞を含み、およびより典型的には少なくとも100,000個のB細胞を含む。別の局面において、試料は、B細胞1000〜1,000,000個の範囲の数のB細胞を含む。
標的核酸集団のアンプリコンは、様々な増幅技法により生成され得る。本発明の1つの局面においては、マルチプレックスPCRが、核酸の混合物、特に組換え免疫分子、例えばT細胞受容体またはそれらの一部分を含む混合物のメンバーを増幅するのに使用される。そのような免疫分子のマルチプレックスPCRを実施するための手引きは、参照により組み入れられる以下の参考文献において見出される:Morley、米国特許第5,296,351号;Gorski、米国特許第5,837,447号;Dau、米国特許第6,087,096号;Von Dongen et al、米国特許出願公開第2006/0234234号;欧州特許公報EP 1544308B1等。
本発明の方法では、任意のハイスループット核酸配列決定技法を使用することができる。好ましくは、このような技法は、そこから少なくとも1000種のクロノタイプが決定され得る、および好ましくはそこから少なくとも10,000〜1,000,000種のクロノタイプが決定され得る大量の配列データを、費用に対して効果の高い方法で生成する能力を有する。DNA配列決定技法は、標識されたターミネーターまたはプライマーおよびスラブまたはキャピラリー中でのゲル分離を用いるジデオキシ配列決定反応(サンガー法)、可逆的に停止される標識ヌクレオチドを用いる合成による配列決定、パイロシークエンシング、454配列決定、標識オリゴヌクレオチドプローブのライブラリーに対するアレル特異的ハイブリダイゼーション、標識クローンのライブラリーに対するアレル特異的ハイブリダイゼーションおよびその後のライゲーションを用いる合成による配列決定、重合工程中における標識ヌクレオチドの組み込みのリアルタイムモニタリング、ポロニーシークエンシング、ならびにSOLiD配列決定を含む。分離された分子の配列決定は、最近になって、ポリメラーゼまたはリガーゼを用いる連続的または単回の伸長反応によって、およびプローブのライブラリーを用いる単回または連続的なディファレンシャルハイブリダイゼーションによって実証されている。これらの反応は、多くのクローン配列に対して並列で実施され、現在の商業利用においては1億超の配列の並列化が実現している。したがってこれらの配列決定アプローチは、T細胞受容体(TCR)および/またはB細胞受容体(BCR)のレパートリーの研究に使用することができる。本発明の1つの局面においては、個々の分子を固相表面上で空間的に単離し、その表面上で配列決定を並列で行う工程を含むハイスループットの配列決定法が使用される。そのような固相表面は、非多孔性表面(例えば、Solexa配列決定におけるようなもの、例えばBentley et al, Nature,456: 53-59 (2008)、またはComplete Genomics配列決定、例えばDrmanac et al, Science, 327: 78-81 (2010))、ビーズまたは粒子に結合された鋳型を含み得るウェルのアレイ(例えば、454と共に用いるもの、例えばMargulies et al, Nature, 437: 376-380 (2005)、またはIon Torrent配列決定、米国特許出願公開第2010/0137143号もしくは第2010/0304982号)、微細加工膜(例えば、SMRT配列決定と共に用いるもの、例えばEid et al, Science, 323: 133-138 (2009))、またはビーズアレイ(SOLiD配列決定またはポロニーシークエンシングと共に用いるもの、例えばKim et al, Science, 316: 1481-1414 (2007))を含み得る。別の局面において、そのような方法は、単離された分子を、それらを固相表面上で空間的に単離する前または後のいずれかにおいて増幅する工程を含む。先行増幅は、エマルジョンベースの増幅、例えばエマルジョンPCR、またはローリングサークル増幅を含み得る。特に関心対象となるものは、参照により組み入れられる、Bentley et al(上記で引用)および製造元の説明書(例えば、TruSeq(商標)Sample Preparation Kit and Data Sheet, Illumina, Inc., San Diego, CA, 2010);さらに以下の参考文献、米国特許第6,090,592号;同第6,300,070号;同第7,115,400号;およびEP0972081B1に記載されるような、個々の鋳型分子を固相表面上で空間的に単離し、その後にそれらをブリッジPCRにより並列で増幅して個別のクローン集団またはクラスターを形成し、次いで配列決定する、Solexaベースの配列決定である。1つの態様において、固相表面上に配置され増幅される個々の分子は、1 cm2あたり少なくとも105クラスターの密度;または1 cm2あたり少なくとも5×105の密度;または1 cm2あたり少なくとも106クラスターの密度のクラスターを形成する。1つの態様においては、比較的高いエラー率を有する配列決定化学が使用される。そのような態様において、そのような化学によりもたらされる平均品質スコアは、配列リード長の単調に下降する関数である。1つの態様において、そのような下降は、配列リードの0.5パーセントが1〜75位に少なくとも1つのエラーを有する;配列リードの1パーセントが76〜100位に少なくとも1つのエラーを有する;および配列リードの2パーセントが101〜125位に少なくとも1つのエラーを有することに相当する。
配列リードデータからのクロノタイプの構築は、一部、そのようなデータを生成するのに使用された配列決定法に依存しており、これは、方法が異なると、予想リード長およびデータ品質が異なるためである。1つのアプローチにおいて、解析用の配列リードデータの生成にSolexaシーケンサーが使用される。1つの態様において、少なくとも100万の鋳型分子をもたらすための少なくとも0.5〜1.0×106個のリンパ球を提供する試料が得られ、鋳型分子は、任意の増幅後に、対応する100万またはそれ以上の鋳型分子クローン集団(またはクラスター)をもたらし得る。Solexaアプローチを含む最もハイスループットな配列決定アプローチについては、配列決定の精度を増大させるべく高い冗長度で各鋳型配列が決定されるように、そのようなクラスターレベルでの過剰サンプリングが望ましい。Solexaベースでの実施について、好ましくは、各々独立した鋳型の配列は10回またはそれ以上決定される。予想リード長およびデータ品質が異なる他の配列決定アプローチについては、同等の配列決定精度のために異なる冗長度レベルが使用され得る。当業者は、上記のパラメータ、例えば試料サイズ、冗長度等が、特定の用途に関連する設計上の選択事項であることを認識している。
1つの態様において、体細胞超変異を起こしたIgHベースのクロノタイプは、以下のようにして決定される。体細胞変異は、(関連セグメントの、通常はV、JまたはCの)対応する参照配列の塩基と異なり、かつ統計的に有意な数のリードに存在する、配列決定された塩基と定義される。1つの態様においては、Cリードが、マッピングされたJセグメントに関する体細胞変異を発見するのに使用され得、同様に、Vセグメントに関してはVリードが使用され得る。JまたはVセグメントに直接マッピングされるかまたはNDN境界までのクロノタイプ伸長物の内側であるかのいずれかのCおよびVリードのみが使用される。このようにして、NDN領域は回避され、以前にクロノタイプの決定に使用された同じ「配列情報」が、変異の発見に使用されることはない(実際は異なる組換えNDN領域であるにすぎないのに誤って変異ヌクレオチドとして分類されるのを回避するため)。セグメントタイプごとに、マッピングされたセグメント(優性のアレル)がスキャホールドとして使用され、リードのマッピング段階でこのアレルにマッピングされたすべてのリードが考慮される。少なくとも1つのリードがマッピングされている参照配列の各位置が、体細胞変異について解析される。1つの態様において、非参照塩基を有効な変異として受諾する基準は、以下のものを含む:1)所定の変異塩基を有する少なくともN個のリード、2)少なくとも所定の分数N/Mのリード(Mはこの塩基位置にマッピングされたリードの総数である);および3)2項分布、変異塩基におけるN個のリードの平均Qスコアおよび非変異塩基を有するリードの数(M-N)に基づく統計的な切り捨て。好ましくは、上記のパラメータは、クロノタイプ単位での変異の誤発見率が1000中1未満、より好ましくは10000中1未満となるように選択される。
この実施例では、TCRβ鎖を解析する。解析は、TCRβ配列の増幅、配列決定、および解析を含む。1つのプライマーは、Cβ1およびCβ2の共通配列に相補的であり、全48種のVセグメントを増幅することができる34種のVプライマーが存在する。Cβ1またはCβ2は、J/C結合部から10位および14位の位置で互いに異なっている。Cβ1またはCβ2のプライマーは16bpの位置で終了し、Cβ1またはCβ2に対する優先性はない。34種のVプライマーを、Van Dongen等の米国特許出願公開第2006/0234234号(参照により本明細書に組み入れられる)に開示の元のプライマーセットから改変する。改変されたプライマーは、参照により本明細書に組み入れられるFahamらの米国特許出願公開第2010/0151471号に開示されている。
本明細書において他に具体的に規定されない限り、本明細書で用いられる核酸化学、生化学、遺伝学、および分子生物学の用語および記号は、当分野における標準的な論文および教科書、例えば、Kornberg and Baker, DNA Replication, Second Edition (W.H. Freeman, New York, 1992);Lehninger, Biochemistry, Second Edition (Worth Publishers, New York, 1975);Strachan and Read, Human Molecular Genetics, Second Edition (Wiley-Liss, New York, 1999);Abbas et al, Cellular and Molecular Immunology, 6th edition (Saunders, 2007)の用語および記号に従っている。
Claims (7)
- 以下の工程を含む、試料中の対をなす免疫受容体鎖を決定する方法:
(a) 試料を複数のサブセットに分割する工程であって、該試料が、免疫受容体鎖の対を発現するリンパ球を含む、工程;
(b) 各サブセットに存在するヌクレオチド配列のリストを、サブセットごとに決定する工程であって、各サブセットの前記リストに免疫受容体の第1鎖をコードする第1ヌクレオチド配列が出現するかまたは出現せず、各サブセットの前記リストに免疫受容体の第2鎖をコードする第2ヌクレオチド配列が出現するかまたは出現しない、工程;
(c) (i) 各サブセットにおいてそろって出現するかまたは出現しないかのいずれかである、前記第1鎖と前記第2鎖をコードする前記第1ヌクレオチド配列と前記第2ヌクレオチド配列、および (ii) 少なくとも1つのサブセットにおいてそろって出現しかつ少なくとも1つのサブセットにおいて出現しない前記第1鎖と前記第2鎖をコードする前記第1ヌクレオチド配列と前記第2ヌクレオチド配列を、対をなす免疫受容体鎖として同定する工程。 - 望ましい数の対をなす免疫受容体が得られるまで、前回の複数のどのサブセットとも異なる別の複数のサブセットに対して工程(a)〜(c)を繰り返す工程をさらに含む、請求項1に記載の方法。
- 免疫受容体鎖がT細胞受容体α鎖およびT細胞受容体β鎖である、請求項1に記載の方法。
- 免疫受容体鎖がB細胞受容体重鎖可変領域およびB細胞受容体軽鎖可変領域である、請求項1に記載の方法。
- 試料が、免疫受容体鎖の対を発現するリンパ球の集団を含み、かつ該集団がサイズを有し、かつ該集団の異なるリンパ球が各々、該集団内での頻度を有する、請求項1に記載の方法。
- 複数のサブセットの数が、集団のサイズ、および対をなす免疫受容体鎖が決定されるリンパ球の頻度に依存する、請求項5に記載の方法。
- 試料のサイズおよび複数のサブセットの数が、該試料のリンパ球が2項モデルに従って該サブセットに分配されるように選択される、請求項1に記載の方法。
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Publication number | Priority date | Publication date | Assignee | Title |
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US9365901B2 (en) | 2008-11-07 | 2016-06-14 | Adaptive Biotechnologies Corp. | Monitoring immunoglobulin heavy chain evolution in B-cell acute lymphoblastic leukemia |
CN102272327B (zh) | 2008-11-07 | 2015-11-25 | 赛昆塔公司 | 通过序列分析监测状况的方法 |
US9506119B2 (en) | 2008-11-07 | 2016-11-29 | Adaptive Biotechnologies Corp. | Method of sequence determination using sequence tags |
US8628927B2 (en) | 2008-11-07 | 2014-01-14 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
US8748103B2 (en) | 2008-11-07 | 2014-06-10 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
US9528160B2 (en) | 2008-11-07 | 2016-12-27 | Adaptive Biotechnolgies Corp. | Rare clonotypes and uses thereof |
US9394567B2 (en) | 2008-11-07 | 2016-07-19 | Adaptive Biotechnologies Corporation | Detection and quantification of sample contamination in immune repertoire analysis |
PT2387627E (pt) | 2009-01-15 | 2016-06-03 | Adaptive Biotechnologies Corp | Determinação do perfil de imunidade adaptativa e métodos de geração de anticorpos monoclonais |
SG176691A1 (en) | 2009-06-25 | 2012-01-30 | Hutchinson Fred Cancer Res | Method of measuring adaptive immunity |
US9043160B1 (en) | 2009-11-09 | 2015-05-26 | Sequenta, Inc. | Method of determining clonotypes and clonotype profiles |
US10385475B2 (en) | 2011-09-12 | 2019-08-20 | Adaptive Biotechnologies Corp. | Random array sequencing of low-complexity libraries |
US9279159B2 (en) | 2011-10-21 | 2016-03-08 | Adaptive Biotechnologies Corporation | Quantification of adaptive immune cell genomes in a complex mixture of cells |
ES2683037T3 (es) | 2011-12-09 | 2018-09-24 | Adaptive Biotechnologies Corporation | Diagnóstico de tumores malignos linfoides y detección de enfermedad residual mínima |
US9499865B2 (en) | 2011-12-13 | 2016-11-22 | Adaptive Biotechnologies Corp. | Detection and measurement of tissue-infiltrating lymphocytes |
ES2662128T3 (es) | 2012-03-05 | 2018-04-05 | Adaptive Biotechnologies Corporation | Determinación de cadenas de receptor inmunitario emparejadas a partir de la frecuencia de subunidades coincidentes |
JP5756247B1 (ja) | 2012-05-08 | 2015-07-29 | アダプティブ バイオテクノロジーズ コーポレイション | マルチプレックスpcr反応における増幅バイアスを測定し校正する組成物及び方法 |
EP2904111B1 (en) | 2012-10-01 | 2017-12-06 | Adaptive Biotechnologies Corporation | Immunocompetence assessment by adaptive immune receptor diversity and clonality characterization |
US10150996B2 (en) | 2012-10-19 | 2018-12-11 | Adaptive Biotechnologies Corp. | Quantification of adaptive immune cell genomes in a complex mixture of cells |
SG11201506991VA (en) * | 2013-03-15 | 2015-10-29 | Adaptive Biotechnologies Corp | Uniquely tagged rearranged adaptive immune receptor genes in a complex gene set |
US9708657B2 (en) | 2013-07-01 | 2017-07-18 | Adaptive Biotechnologies Corp. | Method for generating clonotype profiles using sequence tags |
EP3091074B1 (en) | 2013-11-21 | 2019-08-07 | Repertoire Genesis Incorporation | T cell receptor and b cell receptor repertoire analysis system, and use of same in treatment and diagnosis |
ES2741740T3 (es) | 2014-03-05 | 2020-02-12 | Adaptive Biotechnologies Corp | Métodos que usan moléculas sintéticas que contienen segmentos de nucleótidos aleatorios |
US10066265B2 (en) | 2014-04-01 | 2018-09-04 | Adaptive Biotechnologies Corp. | Determining antigen-specific t-cells |
US11390921B2 (en) | 2014-04-01 | 2022-07-19 | Adaptive Biotechnologies Corporation | Determining WT-1 specific T cells and WT-1 specific T cell receptors (TCRs) |
EP3517625B1 (en) * | 2014-05-22 | 2021-01-20 | The University of British Columbia | Methods for determining lymphocyte receptor chain pairs |
EP3715455A1 (en) * | 2014-10-29 | 2020-09-30 | Adaptive Biotechnologies Corp. | Highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune receptor heterodimers from many samples |
US10246701B2 (en) | 2014-11-14 | 2019-04-02 | Adaptive Biotechnologies Corp. | Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture |
WO2016086029A1 (en) | 2014-11-25 | 2016-06-02 | Adaptive Biotechnologies Corporation | Characterization of adaptive immune response to vaccination or infection using immune repertoire sequencing |
ES2858306T3 (es) | 2015-02-24 | 2021-09-30 | Adaptive Biotechnologies Corp | Método para determinar el estado de HLA mediante secuenciación del repertorio inmunitario |
CA2979726A1 (en) | 2015-04-01 | 2016-10-06 | Adaptive Biotechnologies Corp. | Method of identifying human compatible t cell receptors specific for an antigenic target |
US10539564B2 (en) | 2015-07-22 | 2020-01-21 | Roche Sequencing Solutions, Inc. | Identification of antigen epitopes and immune sequences recognizing the antigens |
WO2017013170A1 (en) | 2015-07-22 | 2017-01-26 | F. Hoffmann-La Roche Ag | Identification of antigen epitopes and immune sequences recognizing the antigens |
WO2017048614A1 (en) * | 2015-09-15 | 2017-03-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of isolating tumor-reactive t cell receptors from tumor or peripheral blood |
US10428325B1 (en) | 2016-09-21 | 2019-10-01 | Adaptive Biotechnologies Corporation | Identification of antigen-specific B cell receptors |
US10550429B2 (en) | 2016-12-22 | 2020-02-04 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11254980B1 (en) | 2017-11-29 | 2022-02-22 | Adaptive Biotechnologies Corporation | Methods of profiling targeted polynucleotides while mitigating sequencing depth requirements |
WO2019157529A1 (en) | 2018-02-12 | 2019-08-15 | 10X Genomics, Inc. | Methods characterizing multiple analytes from individual cells or cell populations |
WO2019217758A1 (en) | 2018-05-10 | 2019-11-14 | 10X Genomics, Inc. | Methods and systems for molecular library generation |
EP3670667A1 (en) * | 2018-12-19 | 2020-06-24 | Paris Sciences et Lettres - Quartier Latin | Identification of cognate pairs of ligands and receptors |
WO2020146740A1 (en) | 2019-01-10 | 2020-07-16 | Iovance Biotherapeutics, Inc. | System and methods for monitoring adoptive cell therapy clonality and persistence |
US11111489B1 (en) | 2021-01-06 | 2021-09-07 | Think Therapeutics, Inc. | Multiplexed testing of lymphocytes for antigen specificity |
AU2022245323A1 (en) | 2021-03-24 | 2023-09-28 | Genentech, Inc. | Efficient tcr gene editing in t lymphocytes |
GB202104943D0 (en) * | 2021-04-07 | 2021-05-19 | Petmedix Ltd | A method for identifying lead sequences |
Family Cites Families (365)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3270960A (en) | 1964-09-11 | 1966-09-06 | Sperry Rand Corp | Fluid sensor |
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
DE3211263A1 (de) | 1981-03-31 | 1983-01-27 | Otsuka Pharmaceutical Co. Ltd., Tokyo | Human-interferon verwandte peptide, antigene und antikoerper, sowie verfahren zu deren herstellung |
DE3238353A1 (de) | 1982-10-15 | 1984-04-19 | Max Planck Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | Verfahren zur simultanen quantitativen bestimmung der blutzellen und reagenz hierfuer |
US5189147A (en) | 1984-06-13 | 1993-02-23 | Massachusetts Institute Of Technology | Meterodimeric T lymphocyte receptor antibody |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
DE3541033A1 (de) | 1985-11-19 | 1987-05-21 | Boehringer Mannheim Gmbh | Verfahren zur quantifizierung von zellpopulationen bzw. subpopulationen sowie hierfuer geeignetes reagenz |
US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
US4942124A (en) | 1987-08-11 | 1990-07-17 | President And Fellows Of Harvard College | Multiplex sequencing |
US5149625A (en) | 1987-08-11 | 1992-09-22 | President And Fellows Of Harvard College | Multiplex analysis of DNA |
US5667967A (en) | 1990-05-01 | 1997-09-16 | The Board Of Trustees Of The Leland Stanford Junior University | T-cell receptor varible transcripts as disease related markers |
US5506126A (en) | 1988-02-25 | 1996-04-09 | The General Hospital Corporation | Rapid immunoselection cloning method |
US5168038A (en) | 1988-06-17 | 1992-12-01 | The Board Of Trustees Of The Leland Stanford Junior University | In situ transcription in cells and tissues |
US5296351A (en) | 1988-10-20 | 1994-03-22 | Alexander A. Morley | Method for diagnosis of monoclonality in leukaemia and lymphoma |
US5075217A (en) | 1989-04-21 | 1991-12-24 | Marshfield Clinic | Length polymorphisms in (dC-dA)n ·(dG-dT)n sequences |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US5231012A (en) | 1989-06-28 | 1993-07-27 | Schering Corporation | Nucleic acids encoding cytokine synthesis inhibitory factor (interleukin-10) |
CA2020958C (en) | 1989-07-11 | 2005-01-11 | Daniel L. Kacian | Nucleic acid sequence amplification methods |
US5298396A (en) | 1989-11-15 | 1994-03-29 | National Jewish Center For Immunology And Respiratory Medicine | Method for identifying T cells disease involved in autoimmune disease |
US5336598A (en) | 1989-11-15 | 1994-08-09 | National Jewish Center For Immunology And Respiratory Medicine | Method for diagnosing a superantigen caused pathologial condition via assay of T-cells |
US5126022A (en) | 1990-02-28 | 1992-06-30 | Soane Tecnologies, Inc. | Method and device for moving molecules by the application of a plurality of electrical fields |
US6054034A (en) | 1990-02-28 | 2000-04-25 | Aclara Biosciences, Inc. | Acrylic microchannels and their use in electrophoretic applications |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US6916605B1 (en) | 1990-07-10 | 2005-07-12 | Medical Research Council | Methods for producing members of specific binding pairs |
EP0542810A1 (en) | 1990-08-02 | 1993-05-26 | B.R. Centre Limited | Methods for the production of proteins with a desired function |
US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
IE76732B1 (en) | 1990-08-07 | 1997-11-05 | Becton Dickinson Co | One step test for absolute counts |
US5699798A (en) | 1990-08-10 | 1997-12-23 | University Of Washington | Method for optically imaging solid tumor tissue |
US5635354A (en) | 1991-01-09 | 1997-06-03 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method for describing the repertoires of antibodies (Ab) and of T-cell receptors (TcR) of an individual's immune system |
US5364759B2 (en) | 1991-01-31 | 1999-07-20 | Baylor College Medicine | Dna typing with short tandem repeat polymorphisms and identification of polymorphic short tandem repeats |
IE920447A1 (en) | 1991-02-12 | 1992-08-12 | Roussel Uclaf | NUCLEOTIDE SEQUENCES CODING FOR ß-CHAIN VARIABLE REGIONS OF¹HUMAN T-LYMPHOCYTE RECEPTORS, CORRESPONDING PEPTIDE SEGMENTS¹AND DIAGNOSTIC AND THERAPEUTIC APPLICATIONS |
JP3080178B2 (ja) | 1991-02-18 | 2000-08-21 | 東洋紡績株式会社 | 核酸配列の増幅方法およびそのための試薬キット |
US6091000A (en) | 1991-03-15 | 2000-07-18 | Duke University | SCID mouse engrafted with human synovium tissue |
JP3266311B2 (ja) | 1991-05-02 | 2002-03-18 | 生化学工業株式会社 | 新規ポリペプチドおよびこれを用いる抗hiv剤 |
US20040018489A1 (en) | 1991-09-09 | 2004-01-29 | Ma Wupo | Detection of RNA |
US5674679A (en) | 1991-09-27 | 1997-10-07 | Amersham Life Science, Inc. | DNA cycle sequencing |
US5981179A (en) | 1991-11-14 | 1999-11-09 | Digene Diagnostics, Inc. | Continuous amplification reaction |
US5256542A (en) | 1992-03-09 | 1993-10-26 | Tanox Biosystems, Inc. | Selecting low frequency antigen-specific single B lymphocytes with correction for background noise |
US5213960A (en) | 1992-03-09 | 1993-05-25 | Tanox Biosystems, Inc. | Methods for selecting low frequency antigen-specific single B lymphocytes |
US5837447A (en) | 1992-04-15 | 1998-11-17 | Blood Center Research Foundation, Inc., The | Monitoring an immune response by analysis of amplified immunoglobulin or T-cell-receptor nucleic acid |
US5587128A (en) | 1992-05-01 | 1996-12-24 | The Trustees Of The University Of Pennsylvania | Mesoscale polynucleotide amplification devices |
US5498392A (en) | 1992-05-01 | 1996-03-12 | Trustees Of The University Of Pennsylvania | Mesoscale polynucleotide amplification device and method |
US5981176A (en) | 1992-06-17 | 1999-11-09 | City Of Hope | Method of detecting and discriminating between nucleic acid sequences |
US5925517A (en) | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
WO1995028481A1 (en) | 1994-04-18 | 1995-10-26 | New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery | Conserved t-cell receptor sequences |
US6001229A (en) | 1994-08-01 | 1999-12-14 | Lockheed Martin Energy Systems, Inc. | Apparatus and method for performing microfluidic manipulations for chemical analysis |
US6090592A (en) | 1994-08-03 | 2000-07-18 | Mosaic Technologies, Inc. | Method for performing amplification of nucleic acid on supports |
FR2724182B1 (fr) | 1994-09-02 | 1996-12-13 | Pasteur Institut | Obtention d'un anticorps monoclonal recombinant a partir d'un anticorps monoclonal humain anti-rhesus d, sa production en cellules d'insecte, et ses utilisations |
US5604097A (en) | 1994-10-13 | 1997-02-18 | Spectragen, Inc. | Methods for sorting polynucleotides using oligonucleotide tags |
US5846719A (en) | 1994-10-13 | 1998-12-08 | Lynx Therapeutics, Inc. | Oligonucleotide tags for sorting and identification |
US5776737A (en) | 1994-12-22 | 1998-07-07 | Visible Genetics Inc. | Method and composition for internal identification of samples |
US6919434B1 (en) | 1995-02-20 | 2005-07-19 | Sankyo Co., Ltd. | Monoclonal antibodies that bind OCIF |
US5698396A (en) | 1995-06-07 | 1997-12-16 | Ludwig Institute For Cancer Research | Method for identifying auto-immunoreactive substances from a subject |
AU7437996A (en) | 1995-10-11 | 1997-04-30 | Leonard Adleman | Large scale dna sequencing by position sensitive hybridization |
WO1997013877A1 (en) | 1995-10-12 | 1997-04-17 | Lynx Therapeutics, Inc. | Measurement of gene expression profiles in toxicity determination |
US6087096A (en) | 1995-11-13 | 2000-07-11 | Dau; Peter C. | Method of intrafamily fragment analysis of the T cell receptor α and β chain CDR3 regions |
US5854033A (en) | 1995-11-21 | 1998-12-29 | Yale University | Rolling circle replication reporter systems |
KR19990087749A (ko) | 1996-03-13 | 1999-12-27 | 시오노 요시히코 | 류마티스성 관절염에 특이적인 인간 티 세포 클론 |
US6458530B1 (en) | 1996-04-04 | 2002-10-01 | Affymetrix Inc. | Selecting tag nucleic acids |
US6416948B1 (en) | 1996-06-03 | 2002-07-09 | The Governors Of The University Of Alberta | Methods for detection of rearranged DNA |
CA2658290C (en) | 1996-06-04 | 2012-04-10 | University Of Utah Research Foundation | Monitoring hybridization during pcr using fluorescent dye specific to double-stranded dna |
WO1998001738A2 (en) | 1996-06-20 | 1998-01-15 | Cornell Research Foundation, Inc. | Identification of abnormalities in the expression of t and b cell antigen receptors as disease indicators |
US6074827A (en) | 1996-07-30 | 2000-06-13 | Aclara Biosciences, Inc. | Microfluidic method for nucleic acid purification and processing |
ATE347103T1 (de) | 1996-09-06 | 2006-12-15 | Ortho Mcneil Pharm Inc | Reinigung von antigenspezifischen t-zellen |
US5935793A (en) | 1996-09-27 | 1999-08-10 | The Chinese University Of Hong Kong | Parallel polynucleotide sequencing method using tagged primers |
US6228589B1 (en) | 1996-10-11 | 2001-05-08 | Lynx Therapeutics, Inc. | Measurement of gene expression profiles in toxicity determination |
GB9626815D0 (en) | 1996-12-23 | 1997-02-12 | Cemu Bioteknik Ab | Method of sequencing DNA |
GB9704444D0 (en) | 1997-03-04 | 1997-04-23 | Isis Innovation | Non-invasive prenatal diagnosis |
DE69837913T2 (de) | 1997-04-01 | 2008-02-07 | Solexa Ltd., Saffron Walden | Verfahren zur vervielfältigung von nukleinsäure |
US6143496A (en) | 1997-04-17 | 2000-11-07 | Cytonix Corporation | Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly |
DK1019496T3 (da) | 1997-07-07 | 2005-01-10 | Medical Res Council | In vitro-sorteringsmetode |
US7572582B2 (en) | 1997-09-12 | 2009-08-11 | Exiqon A/S | Oligonucleotide analogues |
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
US6803019B1 (en) | 1997-10-15 | 2004-10-12 | Aclara Biosciences, Inc. | Laminate microstructure device and method for making same |
EP1025265A1 (en) | 1997-10-23 | 2000-08-09 | Exact Laboratories, Inc. | Methods for detecting contamination in molecular diagnostics using pcr |
US7351578B2 (en) | 1999-12-10 | 2008-04-01 | Invitrogen Corp. | Use of multiple recombination sites with unique specificity in recombinational cloning |
US6210910B1 (en) | 1998-03-02 | 2001-04-03 | Trustees Of Tufts College | Optical fiber biosensor array comprising cell populations confined to microcavities |
JP4262799B2 (ja) | 1998-04-16 | 2009-05-13 | 平田機工株式会社 | 生タイヤ供給方法 |
DE19833738A1 (de) | 1998-07-27 | 2000-02-03 | Michael Giesing | Verfahren zur Isolierung von Krebszellen aus zellhaltigen Körperflüssigkeiten sowie Sets zur Durchführung dieses Verfahrens |
US6787308B2 (en) | 1998-07-30 | 2004-09-07 | Solexa Ltd. | Arrayed biomolecules and their use in sequencing |
DE19844931C1 (de) | 1998-09-30 | 2000-06-15 | Stefan Seeger | Verfahren zur DNS- oder RNS-Sequenzierung |
AR021833A1 (es) | 1998-09-30 | 2002-08-07 | Applied Research Systems | Metodos de amplificacion y secuenciacion de acido nucleico |
US6541608B1 (en) | 1999-02-23 | 2003-04-01 | Baylor College Of Medicine | T cell receptor Vβ-Dβ-Jβ sequence and methods for its detection |
US6307024B1 (en) | 1999-03-09 | 2001-10-23 | Zymogenetics, Inc. | Cytokine zalpha11 Ligand |
US6300070B1 (en) | 1999-06-04 | 2001-10-09 | Mosaic Technologies, Inc. | Solid phase methods for amplifying multiple nucleic acids |
US6440706B1 (en) | 1999-08-02 | 2002-08-27 | Johns Hopkins University | Digital amplification |
NZ517202A (en) | 1999-08-24 | 2004-05-28 | Medarex Inc | Human CTLA-4 antibodies and their uses |
US20040209314A1 (en) | 1999-09-06 | 2004-10-21 | Institut National De La Sante Et De La Recherche Medicale France | Means for detection and purification of CD8+ T lymphocyte populations specific to peptides presented in the context of HLA |
US6235483B1 (en) | 2000-01-31 | 2001-05-22 | Agilent Technologies, Inc. | Methods and kits for indirect labeling of nucleic acids |
US20040121364A1 (en) | 2000-02-07 | 2004-06-24 | Mark Chee | Multiplex nucleic acid reactions |
US7955794B2 (en) | 2000-09-21 | 2011-06-07 | Illumina, Inc. | Multiplex nucleic acid reactions |
WO2001075172A1 (en) | 2000-03-31 | 2001-10-11 | University Of Southern California | Epigenetic sequences for esophageal adenocarcinoma |
AUPQ687600A0 (en) | 2000-04-13 | 2000-05-11 | Flinders Technologies Pty Ltd | A method of detection |
US20030207300A1 (en) | 2000-04-28 | 2003-11-06 | Matray Tracy J. | Multiplex analytical platform using molecular tags |
US6596492B2 (en) | 2000-07-11 | 2003-07-22 | Colorado State University Research Foundation | PCR materials and methods useful to detect canine and feline lymphoid malignancies |
US7567870B1 (en) | 2000-07-31 | 2009-07-28 | Institute For Systems Biology | Multiparameter analysis for predictive medicine |
WO2002012437A2 (en) | 2000-08-03 | 2002-02-14 | Schooten Wim Van | Production of humanized antibodies in transgenic animals |
US6939451B2 (en) | 2000-09-19 | 2005-09-06 | Aclara Biosciences, Inc. | Microfluidic chip having integrated electrodes |
DE60131903T2 (de) | 2000-10-24 | 2008-11-27 | The Board of Trustees of the Leland S. Stanford Junior University, Palo Alto | Direkte multiplex charakterisierung von genomischer dna |
US6778724B2 (en) | 2000-11-28 | 2004-08-17 | The Regents Of The University Of California | Optical switching and sorting of biological samples and microparticles transported in a micro-fluidic device, including integrated bio-chip devices |
US6947748B2 (en) | 2000-12-15 | 2005-09-20 | Adaptix, Inc. | OFDMA with adaptive subcarrier-cluster configuration and selective loading |
AU2002253981B2 (en) | 2001-02-20 | 2008-02-21 | Abeome Corporation | Rapid production of monoclonal antibodies |
US7265208B2 (en) | 2001-05-01 | 2007-09-04 | The Regents Of The University Of California | Fusion molecules and treatment of IgE-mediated allergic diseases |
WO2002094009A2 (en) | 2001-05-24 | 2002-11-28 | Guard Inc. | Methods for selecting and producing animals having a predicted level of immune response |
US20050260570A1 (en) | 2001-05-29 | 2005-11-24 | Mao Jen-I | Sequencing by proxy |
US7026121B1 (en) | 2001-06-08 | 2006-04-11 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
US6720144B1 (en) | 2001-06-21 | 2004-04-13 | Quest Diagnostics | Detection of clonal T-cell receptor-γ gene rearrangement by PCR/temporal temperature gradient gel electrophoresis (TTGE) |
CA2492220C (en) | 2001-07-15 | 2014-03-18 | Keck Graduate Institute | Nucleic acid amplification using nicking agents |
US20030096277A1 (en) | 2001-08-30 | 2003-05-22 | Xiangning Chen | Allele specific PCR for genotyping |
AU2002322518A1 (en) | 2001-08-31 | 2003-03-18 | Rosetta Inpharmactis Llc | Methods for preparing nucleic acid samples |
EP1421115B1 (en) | 2001-08-31 | 2005-03-02 | Avidex Limited | Soluble t cell receptor |
WO2003025202A2 (en) | 2001-09-19 | 2003-03-27 | Alexion Pharmaceuticals, Inc. | Engineered templates and their use in single primer amplification |
CA2466502A1 (en) | 2001-11-09 | 2003-05-15 | Source Precision Medicine, Inc. | Identification, monitoring and treatment of disease and characterization of biological condition using gene expression profiles |
GB2382137A (en) | 2001-11-20 | 2003-05-21 | Mats Gullberg | Nucleic acid enrichment |
GB0128153D0 (en) | 2001-11-23 | 2002-01-16 | Bayer Ag | Profiling of the immune gene repertoire |
WO2003052101A1 (en) | 2001-12-14 | 2003-06-26 | Rosetta Inpharmatics, Inc. | Sample tracking using molecular barcodes |
GB0130267D0 (en) | 2001-12-19 | 2002-02-06 | Neutec Pharma Plc | Focussed antibody technology |
CN1688708A (zh) | 2002-01-09 | 2005-10-26 | 曼盛基因技术有限公司 | 检测t细胞增殖的基因序列方法 |
AUPS028002A0 (en) | 2002-02-01 | 2002-02-28 | Ausman Engineering And Associates Pty Ltd | A bearing assembly |
US7323306B2 (en) | 2002-04-01 | 2008-01-29 | Brookhaven Science Associates, Llc | Genome signature tags |
US7157274B2 (en) | 2002-06-24 | 2007-01-02 | Cytonome, Inc. | Method and apparatus for sorting particles |
AU2003299503A1 (en) | 2002-05-16 | 2004-06-15 | Vanderbilt University | Method for predicting autoimmune diseases |
AU2003247129A1 (en) | 2002-07-01 | 2004-01-19 | Centre National De La Recherche Scientifique (Cnrs) | System, method, device, and computer program product for extraction, gathering, manipulation, and analysis of peak data from an automated sequencer |
US7691994B2 (en) | 2002-07-03 | 2010-04-06 | Brewer Jamie L | Compositions and methods for the detection of human T cell receptor variable family gene expression |
CA2800113C (en) | 2002-07-12 | 2015-02-03 | The Johns Hopkins University | Reagents and methods for engaging unique clonotypic lymphocyte receptors |
ATE470722T1 (de) | 2002-07-19 | 2010-06-15 | Althea Technologies Inc | Strategien zur genexpressionsanalyse |
US7157228B2 (en) | 2002-09-09 | 2007-01-02 | Bioarray Solutions Ltd. | Genetic analysis and authentication |
US7459273B2 (en) | 2002-10-04 | 2008-12-02 | Affymetrix, Inc. | Methods for genotyping selected polymorphism |
DK2418287T3 (da) | 2002-10-11 | 2013-12-16 | Univ Erasmus | Nucleinsyre-amplifikationsprimere til PCR-baseret klonalitetsundersøgelser af TCR-betagenet |
US20050009096A1 (en) | 2002-10-11 | 2005-01-13 | The Regents Of The University Of California | Method for diagnosis and prognosis of multiple sclerosis |
WO2004044209A1 (en) | 2002-11-13 | 2004-05-27 | Monoquant Pty Ltd | A method of detection |
EP2365331B1 (en) | 2002-11-14 | 2015-11-04 | Valneva | Method to clone a single antigen-specfic lymphocyte. |
EP1578954A4 (en) | 2002-12-11 | 2010-08-11 | Coley Pharm Group Inc | 5'-CPG NUCLEIC ACIDS AND USE METHOD |
WO2004063706A2 (en) | 2003-01-08 | 2004-07-29 | Maxx Genetech Co., Ltd. | Method of detecting over-expression of t-cell receptor genes by real-time pcr |
AU2004254552B2 (en) | 2003-01-29 | 2008-04-24 | 454 Life Sciences Corporation | Methods of amplifying and sequencing nucleic acids |
GB0304068D0 (en) | 2003-02-22 | 2003-03-26 | Avidex Ltd | Substances |
US20070042349A1 (en) | 2003-04-24 | 2007-02-22 | Ogle Brenda M | Methods for assessing biologic diversity |
AU2003902299A0 (en) | 2003-05-13 | 2003-05-29 | Flinders Medical Centre | A method of analysing a marker nucleic acid molecule |
WO2005020784A2 (en) | 2003-05-23 | 2005-03-10 | Mount Sinai School Of Medicine Of New York University | Surrogate cell gene expression signatures for evaluating the physical state of a subject |
US20050010030A1 (en) | 2003-07-02 | 2005-01-13 | Zang Jingwu Z. | T cell receptor CDR3 sequence and methods for detecting and treating rheumatoid arthritis |
WO2005010145A2 (en) | 2003-07-05 | 2005-02-03 | The Johns Hopkins University | Method and compositions for detection and enumeration of genetic variations |
TW200510723A (en) | 2003-07-15 | 2005-03-16 | Bioarray Solutions Ltd | Concurrent optimization in selection of primer and capture probe sets for nucleic acid analysis |
US20060228350A1 (en) | 2003-08-18 | 2006-10-12 | Medimmune, Inc. | Framework-shuffling of antibodies |
US20050048498A1 (en) | 2003-08-29 | 2005-03-03 | Applera Corporation | Compositions, methods, and kits for assembling probes |
US7365179B2 (en) | 2003-09-09 | 2008-04-29 | Compass Genetics, Llc | Multiplexed analytical platform |
TWI333977B (en) | 2003-09-18 | 2010-12-01 | Symphogen As | Method for linking sequences of interest |
US7057907B2 (en) | 2003-11-21 | 2006-06-06 | Fairchild Semiconductor Corporation | Power converter having improved control |
FR2863274B1 (fr) | 2003-12-05 | 2012-11-16 | Commissariat Energie Atomique | Procede d'evaluation quantitative d'un rearrangement ou d'une recombinaison genetique ciblee d'un individu et ses applications. |
WO2005053603A2 (en) | 2003-12-08 | 2005-06-16 | Yeda Research And Development Co. Ltd. | Antigen receptor variable region typing |
WO2005059176A1 (en) | 2003-12-15 | 2005-06-30 | Institut Pasteur | Repertoire determination of a lymphocyte b population |
US20080166718A1 (en) | 2003-12-15 | 2008-07-10 | Institut Pasteur | Repertoire determination of a lymphocyte B population |
ATE421998T1 (de) | 2003-12-15 | 2009-02-15 | Pasteur Institut | Ermittlung des repertoires von b-lymphozyten populationen |
WO2006019407A2 (en) | 2004-02-18 | 2006-02-23 | The Trustees Of Boston University | Method for detecting and quantifying rare mutations/polymorphisms |
US20060046258A1 (en) | 2004-02-27 | 2006-03-02 | Lapidus Stanley N | Applications of single molecule sequencing |
US20070161001A1 (en) | 2004-03-04 | 2007-07-12 | Dena Leshkowitz | Quantifying and profiling antibody and t cell receptor gene expression |
JP4480423B2 (ja) | 2004-03-08 | 2010-06-16 | 独立行政法人科学技術振興機構 | 免疫細胞クローンの拡大の有無の判定方法 |
DE102004016437A1 (de) | 2004-04-04 | 2005-10-20 | Oligene Gmbh | Verfahren zur Erkennung von Signaturen in komplexen Genexpressionsprofilen |
WO2005111242A2 (en) | 2004-05-10 | 2005-11-24 | Parallele Bioscience, Inc. | Digital profiling of polynucleotide populations |
JP2007536939A (ja) | 2004-05-14 | 2007-12-20 | アモークス インコーポレーティッド | 免疫細胞バイオセンサーおよびその使用方法 |
EP1598429A1 (en) | 2004-05-19 | 2005-11-23 | Amplion Ltd. | Detection of amplicon contamination during PCR exhibiting two different annealing temperatures |
GB0412973D0 (en) | 2004-06-10 | 2004-07-14 | Celltech R&D Ltd | Identification of antibody producing cells |
US20060020397A1 (en) | 2004-07-21 | 2006-01-26 | Kermani Bahram G | Methods for nucleic acid and polypeptide similarity search employing content addressable memories |
CN101087890A (zh) | 2004-07-26 | 2007-12-12 | 帕拉列勒生物科学公司 | 多个基因组的同时分析 |
US20060094018A1 (en) | 2004-08-03 | 2006-05-04 | Bauer A R Jr | Discovery and a method for the early detection of pancreatic cancer and other disease conditions |
US7820382B2 (en) | 2004-08-03 | 2010-10-26 | Bauer A Robert | Method for the early detection of breast cancer, lung cancer, pancreatic cancer and colon polyps, growths and cancers as well as other gastrointestinal disease conditions and the preoperative and postoperative monitoring of transplanted organs from the donor and in the recipient and their associated conditions related and unrelated to the organ transplantation |
SI1773885T1 (sl) | 2004-08-05 | 2010-08-31 | Genentech Inc | Humanizirani anti-CMET antagonisti |
CA2580412A1 (en) | 2004-09-13 | 2006-03-23 | Government Of The United States Of America, Represented By The Secretary , Department Of Health And Human Services | Compositions comprising t cell receptors and methods of use thereof |
US7170050B2 (en) | 2004-09-17 | 2007-01-30 | Pacific Biosciences Of California, Inc. | Apparatus and methods for optical analysis of molecules |
CA2585462A1 (en) | 2004-10-29 | 2006-05-11 | Benaroya Research Institute At Virginia Mason | Methods of generating antigen-specific cd4+cd25+ regulatory t cells, compositions and methods of use |
US7966988B2 (en) | 2005-01-11 | 2011-06-28 | Exxonmobil Research And Engineering Company | Method for controlling soot induced lubricant viscosity increase |
US8029783B2 (en) | 2005-02-02 | 2011-10-04 | Genentech, Inc. | DR5 antibodies and articles of manufacture containing same |
FR2881436B1 (fr) | 2005-02-03 | 2007-04-27 | Commissariat Energie Atomique | Procede de determination de la diversite des lymphocytes t dans un echantillon biologique |
US7393665B2 (en) | 2005-02-10 | 2008-07-01 | Population Genetics Technologies Ltd | Methods and compositions for tagging and identifying polynucleotides |
CA2598025A1 (en) | 2005-02-16 | 2006-08-24 | Wyeth | Methods and systems for diagnosis, prognosis and selection of treatment of leukemia |
US7537894B2 (en) | 2005-03-02 | 2009-05-26 | The University Of Chicago | Methods and kits for monitoring Barrett's metaplasia |
WO2006099164A2 (en) | 2005-03-10 | 2006-09-21 | Applera Corporation | Methods for multiplex amplification |
EP1856293A2 (en) | 2005-03-16 | 2007-11-21 | Compass Genetics, Llc | Methods and compositions for assay readouts on multiple analytical platforms |
JP2008538496A (ja) | 2005-04-12 | 2008-10-30 | 454 ライフ サイエンシーズ コーポレイション | ウルトラディープ配列決定を用いて配列変異体を決定するための方法 |
WO2006116155A2 (en) | 2005-04-21 | 2006-11-02 | The Regents Of The University Of California | A method for diagnosis and prognosis of multiple sclerosis subtypes |
US20060263789A1 (en) | 2005-05-19 | 2006-11-23 | Robert Kincaid | Unique identifiers for indicating properties associated with entities to which they are attached, and methods for using |
US7208795B2 (en) | 2005-05-24 | 2007-04-24 | Atmel Corporation | Low-cost, low-voltage single-layer polycrystalline EEPROM memory cell integration into BiCMOS technology |
SG162795A1 (en) | 2005-06-15 | 2010-07-29 | Callida Genomics Inc | Single molecule arrays for genetic and chemical analysis |
US20070020670A1 (en) | 2005-07-07 | 2007-01-25 | Hematologics, Inc. | Methods for detecting and confirming minimal disease |
US20070020640A1 (en) | 2005-07-21 | 2007-01-25 | Mccloskey Megan L | Molecular encoding of nucleic acid templates for PCR and other forms of sequence analysis |
GB0521521D0 (en) | 2005-10-21 | 2005-11-30 | Medical Res Council | Diagnostic methods and kits |
GB0522310D0 (en) | 2005-11-01 | 2005-12-07 | Solexa Ltd | Methods of preparing libraries of template polynucleotides |
US20070105165A1 (en) | 2005-11-04 | 2007-05-10 | Charles Goolsby | Composite profiles of cell antigens and target signal transduction proteins for analysis and clinical management of hematologic cancers |
US7375211B2 (en) | 2005-11-18 | 2008-05-20 | Kou Zhong C | Method for detection and quantification of T-cell receptor Vβ repertoire |
US8137936B2 (en) | 2005-11-29 | 2012-03-20 | Macevicz Stephen C | Selected amplification of polynucleotides |
US7544473B2 (en) | 2006-01-23 | 2009-06-09 | Population Genetics Technologies Ltd. | Nucleic acid analysis using sequence tokens |
WO2007087312A2 (en) | 2006-01-23 | 2007-08-02 | Population Genetics Technologies Ltd. | Molecular counting |
SG170028A1 (en) | 2006-02-24 | 2011-04-29 | Callida Genomics Inc | High throughput genome sequencing on dna arrays |
WO2007101441A1 (en) | 2006-03-06 | 2007-09-13 | Symphogen A/S | Recombinant polyclonal antibody for treatment of respiratory syncytial virus infections |
ES2546848T3 (es) | 2006-03-10 | 2015-09-29 | Epigenomics Ag | Un método para identificar una muestra biológica para el análisis de la metilación |
ES2545264T3 (es) | 2006-04-04 | 2015-09-09 | Keygene N.V. | Detección de alto rendimiento de marcadores moleculares basada en fragmentos de restricción |
EP2021460A4 (en) | 2006-05-11 | 2010-11-17 | Univ Maryland Biotech Inst | GENERAL PROCEDURE FOR GENERATING HUMAN ANTIBODY REACTIONS IN VITRO |
WO2007136518A2 (en) | 2006-05-17 | 2007-11-29 | Torrey Pines Institute For Molecular Studies | Treatment of autoimmune disorders |
AU2006345511B2 (en) | 2006-05-25 | 2013-03-21 | Institute For Advanced Study | Methods for identifying sequence motifs, and applications thereof |
US7833716B2 (en) | 2006-06-06 | 2010-11-16 | Gen-Probe Incorporated | Tagged oligonucleotides and their use in nucleic acid amplification methods |
EP2027253A4 (en) | 2006-06-12 | 2014-04-30 | Pacific Biosciences California | SUBSTATES FOR EFFECTING ANALYSIS REACTIONS |
US8372584B2 (en) | 2006-06-14 | 2013-02-12 | The General Hospital Corporation | Rare cell analysis using sample splitting and DNA tags |
US20100027896A1 (en) | 2006-06-28 | 2010-02-04 | Amir Geva | Automated application interaction using a virtual operator |
US7553949B2 (en) | 2006-06-30 | 2009-06-30 | Applied Biosystems, Llc | Reversible terminator nucleotides and methods of use |
WO2008108803A2 (en) | 2006-07-13 | 2008-09-12 | Amaox, Ltd. | Immune cell biosensors and methods of using same |
US8394590B2 (en) | 2006-08-02 | 2013-03-12 | California Institute Of Technology | Capture agents and related methods and systems for detecting and/or sorting targets |
US20080274904A1 (en) | 2006-08-10 | 2008-11-06 | Niall Anthony Gormley | Method of target enrichment |
WO2008026927A2 (en) | 2006-08-30 | 2008-03-06 | Academisch Medisch Centrum | Process for displaying t- and b-cell receptor repertoires |
WO2008039694A2 (en) | 2006-09-26 | 2008-04-03 | St. Jude Children's Research Hospital | Methods and compositions for monitoring t cell receptor diversity |
US8088379B2 (en) | 2006-09-26 | 2012-01-03 | The United States Of America As Represented By The Department Of Health And Human Services | Modified T cell receptors and related materials and methods |
JP5026047B2 (ja) | 2006-10-18 | 2012-09-12 | 株式会社膠原病研究所 | 自己免疫疾患の発症に関わる自己応答性t細胞またはt細胞受容体の同定方法、およびその利用 |
WO2008140484A2 (en) | 2006-11-09 | 2008-11-20 | Xdx, Inc. | Methods for diagnosing and monitoring the status of systemic lupus erythematosus |
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US7862999B2 (en) | 2007-01-17 | 2011-01-04 | Affymetrix, Inc. | Multiplex targeted amplification using flap nuclease |
EP2121983A2 (en) | 2007-02-02 | 2009-11-25 | Illumina Cambridge Limited | Methods for indexing samples and sequencing multiple nucleotide templates |
WO2008104184A2 (en) | 2007-03-01 | 2008-09-04 | Symphogen A/S | Method for cloning cognate antibodies |
WO2008147879A1 (en) | 2007-05-22 | 2008-12-04 | Ryan Golhar | Automated method and device for dna isolation, sequence determination, and identification |
JP2010528608A (ja) | 2007-06-01 | 2010-08-26 | 454 ライフ サイエンシーズ コーポレイション | 複合的な混合物から個々の試料を特定するためのシステムおよび方法 |
US8454906B2 (en) | 2007-07-24 | 2013-06-04 | The Regents Of The University Of California | Microfabricated droplet generator for single molecule/cell genetic analysis in engineered monodispersed emulsions |
CA2693979A1 (en) | 2007-07-26 | 2009-02-05 | Pacific Biosciences Of California, Inc. | Molecular redundant sequencing |
ITRM20070429A1 (it) | 2007-08-06 | 2009-02-07 | Uni Cattolica Del Sacro Cuor E | Mezzi per la diagnosi la prevenzione e la cura dell'artrite reumatoide. |
CN101842159B (zh) | 2007-08-09 | 2014-09-24 | 赛路拉公司 | 关联的多参数单细胞测定及残余生物材料回收的方法和装置 |
US8268564B2 (en) | 2007-09-26 | 2012-09-18 | President And Fellows Of Harvard College | Methods and applications for stitched DNA barcodes |
US20100285984A1 (en) | 2007-09-28 | 2010-11-11 | Wettstein Peter J | Assessing t cell repertoires |
US7960116B2 (en) | 2007-09-28 | 2011-06-14 | Pacific Biosciences Of California, Inc. | Nucleic acid sequencing methods and systems |
WO2009062125A1 (en) | 2007-11-07 | 2009-05-14 | Genentech, Inc. | Methods and compositions for assessing responsiveness of b-cell lymphoma to treatment with anti-cd40 antibodies |
EP2060637A1 (en) | 2007-11-14 | 2009-05-20 | Koninklijke Philips Electronics N.V. | Means and methods for detection of nucleic acids |
WO2009070767A2 (en) | 2007-11-28 | 2009-06-04 | Whitehead Institute For Biomedical Research | Systemic instigation systems to study tumor growth or metastasis |
EP2062982A1 (fr) | 2007-11-26 | 2009-05-27 | ImmunID | Procédé d'étude de la diversité combinatoire V(D)J |
CN101225441B (zh) | 2007-12-05 | 2010-12-01 | 浙江大学 | 一种检测克隆特异性t淋巴细胞tcr bv cdr3基因组成的方法 |
US20100021894A1 (en) | 2007-12-20 | 2010-01-28 | Northwestern University | Nanoparticle-Based Colorimetric Detection Of Cysteine |
US8621502B2 (en) | 2007-12-21 | 2013-12-31 | Microsoft Corporation | Obtaining user reactions to video |
US7767400B2 (en) | 2008-02-03 | 2010-08-03 | Helicos Biosciences Corporation | Paired-end reads in sequencing by synthesis |
EP2088432A1 (en) | 2008-02-11 | 2009-08-12 | MorphoSys AG | Methods for identification of an antibody or a target |
US20110054009A1 (en) | 2008-02-28 | 2011-03-03 | The Ohio State University Research Foundation | MicroRNA-Based Methods and Compositions for the Diagnosis, Prognosis and Treatment of Prostate Related Disorders |
EP2250496A4 (en) | 2008-02-28 | 2011-08-31 | Univ Ohio State Res Found | MICRO-RNA SIGNATURES ASSOCIATED WITH CYTOGENETICS AND PROGNOSIS IN ACUTE MYELOID LEUKEMIA (AML) AND USES THEREOF |
US20090226975A1 (en) | 2008-03-10 | 2009-09-10 | Illumina, Inc. | Constant cluster seeding |
TW200938840A (en) | 2008-03-12 | 2009-09-16 | Emo Biomedicine Corp | A method for in vitro study of immune modulation using pig blood cell |
EP2100970B1 (en) | 2008-03-13 | 2017-05-10 | National Institute of Immunology | Ig genes specific oligonucleotides and uses thereof |
BRPI0909212A2 (pt) | 2008-03-28 | 2015-08-18 | Pacific Biosciences California | Composições e método para sequeciamento de ácido nucléico |
ATE530497T1 (de) | 2008-03-31 | 2011-11-15 | Sony Deutschland Gmbh | Verfahren zur herstellung einer membran mit konischer pore |
US9012148B2 (en) | 2008-04-16 | 2015-04-21 | Jian Han | Method for evaluating and comparing immunorepertoires |
US8911948B2 (en) | 2008-04-30 | 2014-12-16 | Integrated Dna Technologies, Inc. | RNase H-based assays utilizing modified RNA monomers |
EP2277049A4 (en) | 2008-05-09 | 2012-05-30 | Univ Duke | AUTOANTIBODIES IN THE DETECTION AND TREATMENT OF CANCER |
US9068181B2 (en) | 2008-05-23 | 2015-06-30 | The General Hospital Corporation | Microfluidic droplet encapsulation |
DE102008025656B4 (de) | 2008-05-28 | 2016-07-28 | Genxpro Gmbh | Verfahren zur quantitativen Analyse von Nukleinsäuren, Marker dafür und deren Verwendung |
WO2009145925A1 (en) | 2008-05-30 | 2009-12-03 | Massachusetts Institute Of Technology | Compositions and methods for spatial separation and screening of cells |
WO2009151628A2 (en) | 2008-06-12 | 2009-12-17 | Gov't Of The Usa, As Represented By The Secretary, Department Of Health Human Services | Monitoring tcr-b to determine hiv therapy and disease progression |
TW201022492A (en) | 2008-06-25 | 2010-06-16 | Baylor Res Inst | Blood transcriptional signature of mycobacterium tuberculosis infection |
US8394583B2 (en) | 2008-07-24 | 2013-03-12 | The Board Of Regents Of The University Of Texas System | VH4 codon signature for multiple sclerosis |
EP3629022A1 (en) | 2008-07-25 | 2020-04-01 | Richard W. Wagner | Protein screening methods |
US8586310B2 (en) | 2008-09-05 | 2013-11-19 | Washington University | Method for multiplexed nucleic acid patch polymerase chain reaction |
JP2012503773A (ja) | 2008-09-23 | 2012-02-09 | クァンタライフ・インコーポレーテッド | 液滴ベースの分析システム |
US9156010B2 (en) | 2008-09-23 | 2015-10-13 | Bio-Rad Laboratories, Inc. | Droplet-based assay system |
US8699361B2 (en) | 2008-09-30 | 2014-04-15 | Qualcomm Incorporated | Out-of-synchronization handling method and apparatus |
US20100137143A1 (en) | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US8546128B2 (en) | 2008-10-22 | 2013-10-01 | Life Technologies Corporation | Fluidics system for sequential delivery of reagents |
US8628927B2 (en) | 2008-11-07 | 2014-01-14 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
US9506119B2 (en) | 2008-11-07 | 2016-11-29 | Adaptive Biotechnologies Corp. | Method of sequence determination using sequence tags |
US8748103B2 (en) | 2008-11-07 | 2014-06-10 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
US20140234835A1 (en) | 2008-11-07 | 2014-08-21 | Sequenta, Inc. | Rare clonotypes and uses thereof |
US9394567B2 (en) | 2008-11-07 | 2016-07-19 | Adaptive Biotechnologies Corporation | Detection and quantification of sample contamination in immune repertoire analysis |
US8691510B2 (en) * | 2008-11-07 | 2014-04-08 | Sequenta, Inc. | Sequence analysis of complex amplicons |
CN102272327B (zh) | 2008-11-07 | 2015-11-25 | 赛昆塔公司 | 通过序列分析监测状况的方法 |
US9365901B2 (en) | 2008-11-07 | 2016-06-14 | Adaptive Biotechnologies Corp. | Monitoring immunoglobulin heavy chain evolution in B-cell acute lymphoblastic leukemia |
US9528160B2 (en) | 2008-11-07 | 2016-12-27 | Adaptive Biotechnolgies Corp. | Rare clonotypes and uses thereof |
WO2010060051A2 (en) | 2008-11-21 | 2010-05-27 | Emory University | Systems biology approach predicts the immunogenicity of vaccines |
US8367330B2 (en) | 2008-12-22 | 2013-02-05 | Quest Diagnostics Investments Incorporated | Methods for detecting TCR-gamma gene rearrangement |
CN102272326B (zh) | 2008-12-30 | 2014-11-12 | 森托科尔奥索生物科技公司 | 预测强直性脊柱炎患者对于抗TNFα抗体的临床反应的血清标记物 |
PT2387627E (pt) | 2009-01-15 | 2016-06-03 | Adaptive Biotechnologies Corp | Determinação do perfil de imunidade adaptativa e métodos de geração de anticorpos monoclonais |
US9329170B2 (en) | 2009-01-20 | 2016-05-03 | The Board Of Trustees Of The Leland Stanford Junior University | Single cell gene expression for diagnosis, prognosis and identification of drug targets |
US20100323348A1 (en) | 2009-01-31 | 2010-12-23 | The Regents Of The University Of Colorado, A Body Corporate | Methods and Compositions for Using Error-Detecting and/or Error-Correcting Barcodes in Nucleic Acid Amplification Process |
US8574835B2 (en) | 2009-05-29 | 2013-11-05 | Life Technologies Corporation | Scaffolded nucleic acid polymer particles and methods of making and using |
US8673627B2 (en) | 2009-05-29 | 2014-03-18 | Life Technologies Corporation | Apparatus and methods for performing electrochemical reactions |
SG176691A1 (en) | 2009-06-25 | 2012-01-30 | Hutchinson Fred Cancer Res | Method of measuring adaptive immunity |
US8497071B2 (en) | 2009-06-29 | 2013-07-30 | California Institute Of Technology | Isolation of unknown rearranged T-cell receptors from single cells |
AU2010273941A1 (en) | 2009-07-17 | 2012-02-09 | Brown University | Detection of short RNA sequences |
WO2011035870A1 (en) | 2009-09-22 | 2011-03-31 | Roche Diagnostics Gmbh | Determination of kir haplotypes associated with disease |
GB0917094D0 (en) | 2009-09-29 | 2009-11-11 | Ucl Biomedica Plc | T-cell receptor |
US9043160B1 (en) | 2009-11-09 | 2015-05-26 | Sequenta, Inc. | Method of determining clonotypes and clonotype profiles |
US9315857B2 (en) | 2009-12-15 | 2016-04-19 | Cellular Research, Inc. | Digital counting of individual molecules by stochastic attachment of diverse label-tags |
US8835358B2 (en) | 2009-12-15 | 2014-09-16 | Cellular Research, Inc. | Digital counting of individual molecules by stochastic attachment of diverse labels |
US8545248B2 (en) | 2010-01-07 | 2013-10-01 | Life Technologies Corporation | System to control fluid flow based on a leak detected by a sensor |
KR101323827B1 (ko) | 2010-01-08 | 2013-10-31 | 키스트 유럽 에프게엠베하 | 강직성척추염 진단용 프라이머 및 이를 이용한 강직성 척추염 진단 방법 |
GB201000375D0 (en) | 2010-01-09 | 2010-02-24 | Univ Cardiff | T Cell clonotypes |
WO2011106738A2 (en) | 2010-02-25 | 2011-09-01 | Fred Hutchinson Cancer Research Center | Use of tcr clonotypes as biomarkers for disease |
EP2367000A1 (en) * | 2010-03-04 | 2011-09-21 | Charité Universitätsmedizin Berlin | High throughput analysis of T-cell receptor repertoires |
DK3144673T3 (da) | 2010-05-06 | 2019-09-09 | Adaptive Biotechnologies Corp | Overvågning af en lymfoid neoplasma anvendende klontypeprofiler |
CA2796822C (en) | 2010-05-07 | 2021-10-05 | The Board Of Trustees Of The Leland Standford Junior University | Measurement and comparison of immune diversity by high-throughput sequencing |
US20130123120A1 (en) | 2010-05-18 | 2013-05-16 | Natera, Inc. | Highly Multiplex PCR Methods and Compositions |
AU2011226792A1 (en) | 2010-06-11 | 2012-01-12 | Life Technologies Corporation | Alternative nucleotide flows in sequencing-by-synthesis methods |
CN103069006A (zh) | 2010-07-23 | 2013-04-24 | 艾索特里克斯遗传实验室有限责任公司 | 区别表达的胚胎或母源基因组区的鉴定及其用途 |
WO2012017081A1 (en) * | 2010-08-06 | 2012-02-09 | Ludwig-Maximilians-Universität München | Identification of t cell target antigens |
WO2012027503A2 (en) | 2010-08-24 | 2012-03-01 | Fred Hutchinson Cancer Research Center | Method of measuring adaptive immunity |
BR122020026648B1 (pt) | 2010-09-20 | 2021-12-07 | Biontech Cell & Gene Therapies Gmbh | Receptor de células t com especificidade para ny-eso-1, composição farmacêutica compreendendo o mesmo e uso do mesmo |
CA2811185C (en) | 2010-09-21 | 2020-09-22 | Population Genetics Technologies Ltd. | Increasing confidence of allele calls with molecular counting |
WO2012045012A2 (en) | 2010-09-30 | 2012-04-05 | Raindance Technologies, Inc. | Sandwich assays in droplets |
CA2814047C (en) | 2010-10-08 | 2017-11-14 | President And Fellows Of Harvard College | High-throughput immune sequencing |
CA2814049C (en) | 2010-10-08 | 2021-07-13 | President And Fellows Of Harvard College | High-throughput single cell barcoding |
WO2012055929A1 (en) | 2010-10-26 | 2012-05-03 | Illumina, Inc. | Sequencing methods |
AU2011323107B2 (en) | 2010-11-05 | 2015-09-10 | Illumina, Inc. | Linking sequence reads using paired code tags |
WO2012083069A2 (en) | 2010-12-15 | 2012-06-21 | The Board Of Trustees Of The Leland Stanford Junior University | Measurement and monitoring of cell clonality |
EP2652155B1 (en) | 2010-12-16 | 2016-11-16 | Gigagen, Inc. | Methods for massively parallel analysis of nucleic acids in single cells |
EP2659408B1 (en) | 2010-12-29 | 2019-03-27 | Life Technologies Corporation | Time-warped background signal for sequencing-by-synthesis operations |
WO2012092455A2 (en) | 2010-12-30 | 2012-07-05 | Life Technologies Corporation | Models for analyzing data from sequencing-by-synthesis operations |
US9920110B2 (en) | 2011-03-09 | 2018-03-20 | Cell Signaling Technology, Inc. | Methods and reagents for creating monoclonal antibodies |
US8759036B2 (en) | 2011-03-21 | 2014-06-24 | Affymetrix, Inc. | Methods for synthesizing pools of probes |
EP3907297A1 (en) | 2011-04-15 | 2021-11-10 | The Johns Hopkins University | Safe sequencing system |
SG194233A1 (en) | 2011-04-28 | 2013-12-30 | Univ Leland Stanford Junior | Identification of polynucleotides associated with a sample |
CA2836494C (en) | 2011-05-24 | 2023-01-03 | Biontech Ag | Individualized vaccines for cancer |
WO2013033721A1 (en) | 2011-09-02 | 2013-03-07 | Atreca, Inc. | Dna barcodes for multiplexed sequencing |
US20140356339A1 (en) | 2011-09-09 | 2014-12-04 | Sequenta Inc. | Sequence-based measures of immune response |
US10385475B2 (en) | 2011-09-12 | 2019-08-20 | Adaptive Biotechnologies Corp. | Random array sequencing of low-complexity libraries |
US20140256592A1 (en) | 2011-10-11 | 2014-09-11 | Sequenta, Inc. | Determining responsiveness of autoimmune patients to dmard treatment |
US9279159B2 (en) | 2011-10-21 | 2016-03-08 | Adaptive Biotechnologies Corporation | Quantification of adaptive immune cell genomes in a complex mixture of cells |
US20130137108A1 (en) | 2011-10-25 | 2013-05-30 | Anubhav Tripathi | Magnetic bead separation apparatus and method |
ES2619713T3 (es) | 2011-11-04 | 2017-06-26 | Adaptive Biotechnologies Corporation | Clonotipos de receptores de células T compartidos entre pacientes con espondilitis anquilosante |
WO2013085855A1 (en) | 2011-12-05 | 2013-06-13 | Sequenta, Inc. | Clonotypes as biometric specimen tags |
ES2683037T3 (es) | 2011-12-09 | 2018-09-24 | Adaptive Biotechnologies Corporation | Diagnóstico de tumores malignos linfoides y detección de enfermedad residual mínima |
WO2013086462A1 (en) | 2011-12-09 | 2013-06-13 | Sequenta, Inc. | Method of measuring immune activation |
US9499865B2 (en) | 2011-12-13 | 2016-11-22 | Adaptive Biotechnologies Corp. | Detection and measurement of tissue-infiltrating lymphocytes |
US20150031553A1 (en) | 2011-12-13 | 2015-01-29 | Sequenta, Inc. | Method of measuring immune activation |
JP2015504661A (ja) | 2011-12-20 | 2015-02-16 | シーケンタ インコーポレイテッド | 免疫レパートリー解析による、濾胞性リンパ腫からびまん性大細胞型b細胞リンパ腫への形質転換のモニタリング |
US20150031555A1 (en) | 2012-01-24 | 2015-01-29 | Gigagen, Inc. | Method for correction of bias in multiplexed amplification |
WO2013117746A1 (en) | 2012-02-09 | 2013-08-15 | Memed Diagnostics Ltd. | Signatures and determinants for diagnosing infections and methods of use thereof |
PL3363901T3 (pl) | 2012-02-17 | 2021-07-05 | Fred Hutchinson Cancer Research Center | Kompozycje i sposoby dokładnej identyfikacji mutacji |
ES2776673T3 (es) | 2012-02-27 | 2020-07-31 | Univ North Carolina Chapel Hill | Métodos y usos para etiquetas moleculares |
WO2013131074A1 (en) | 2012-03-02 | 2013-09-06 | Diogenix, Inc. | Methods and reagents for evaluating autoimmune disease and determining antibody repertoire |
ES2662128T3 (es) | 2012-03-05 | 2018-04-05 | Adaptive Biotechnologies Corporation | Determinación de cadenas de receptor inmunitario emparejadas a partir de la frecuencia de subunidades coincidentes |
US20150038346A1 (en) | 2012-03-05 | 2015-02-05 | Sequenta, Inc. | Monitoring immune responsiveness to cancer vaccination |
WO2013134302A1 (en) | 2012-03-05 | 2013-09-12 | Sequenta, Inc. | Monitoring immune responsiveness to cancer vaccination |
WO2013138510A1 (en) | 2012-03-13 | 2013-09-19 | Patel Abhijit Ajit | Measurement of nucleic acid variants using highly-multiplexed error-suppressed deep sequencing |
SG11201406538VA (en) | 2012-04-13 | 2014-11-27 | Sequenta Inc | Detection and quantitation of sample contamination in immune repertoire analysis |
WO2013158936A1 (en) | 2012-04-20 | 2013-10-24 | Sequenta, Inc | Monitoring immunoglobulin heavy chain evolution in b-cell acute lymphoblastic leukemia |
WO2013163263A2 (en) | 2012-04-24 | 2013-10-31 | Gen9, Inc. | Methods for sorting nucleic acids and multiplexed preparative in vitro cloning |
JP5756247B1 (ja) | 2012-05-08 | 2015-07-29 | アダプティブ バイオテクノロジーズ コーポレイション | マルチプレックスpcr反応における増幅バイアスを測定し校正する組成物及び方法 |
WO2013181428A2 (en) | 2012-05-31 | 2013-12-05 | Sequenta, Inc. | Predicting relapse of chronic lymphocytic leukemia patients treated by allogeneic stem cell transplantation |
US20130324422A1 (en) | 2012-06-04 | 2013-12-05 | Sequenta, Inc. | Detecting disease-correlated clonotypes from fixed samples |
CN104520443A (zh) | 2012-06-11 | 2015-04-15 | 赛昆塔公司 | 使用序列标签的序列确定方法 |
EP2861761A1 (en) | 2012-06-15 | 2015-04-22 | Adaptive Biotechnologies Corporation | Uniquely tagged rearranged adaptive immune receptor genes in a complex gene set |
US20150154352A1 (en) | 2012-06-21 | 2015-06-04 | Gigagen, Inc. | System and Methods for Genetic Analysis of Mixed Cell Populations |
CN104540964A (zh) | 2012-07-24 | 2015-04-22 | 赛昆塔公司 | 使用序列标签的单细胞分析 |
WO2014026031A1 (en) | 2012-08-10 | 2014-02-13 | Sequenta, Inc. | High sensitivity mutation detection using sequence tags |
US20140065629A1 (en) * | 2012-08-29 | 2014-03-06 | Israel Barken | Methods of treating diseases |
JP2015530096A (ja) | 2012-09-24 | 2015-10-15 | シービー バイオテクノロジーズ インコーポレイテッド | 非干渉性、ノイズキャンセル性のポリヌクレオチド識別タグを用いたマルチプレックスパイロシーケンシング |
US10150996B2 (en) | 2012-10-19 | 2018-12-11 | Adaptive Biotechnologies Corp. | Quantification of adaptive immune cell genomes in a complex mixture of cells |
CA2888514A1 (en) | 2012-10-19 | 2014-04-24 | Sequenta, Inc. | Monitoring clonotypes of plasma cell proliferative disorders in peripheral blood |
JP2015534806A (ja) | 2012-10-19 | 2015-12-07 | シーケンタ・インコーポレイテッド | 末梢血試料によるびまん性大細胞型b細胞性リンパ腫のモニタリング関連出願の相互参照本出願は、2012年10月19日出願の米国特許仮出願第61/716,270号の利益を主張するものであり、当該出願は参照により本明細書にその全体が組み込まれる。 |
EP2909348A4 (en) | 2012-10-22 | 2016-07-06 | Adaptive Biotechnologies Corp | MONITORING COAT CLINOTYPES IN PERIPHERAL BLOOD AFTER IMMUNTRANSPLANTATION |
EP2959020B1 (en) | 2013-02-22 | 2019-09-18 | Adaptive Biotechnologies Corporation | Method to select rare clonotypes |
US20140255944A1 (en) | 2013-03-08 | 2014-09-11 | Sequenta, Inc. | Monitoring treatment-resistant clones in lymphoid and myeloid neoplasms by relative levels of evolved clonotypes |
US20140255929A1 (en) | 2013-03-11 | 2014-09-11 | Sequenta, Inc. | Mosaic tags for labeling templates in large-scale amplifications |
SG11201506991VA (en) | 2013-03-15 | 2015-10-29 | Adaptive Biotechnologies Corp | Uniquely tagged rearranged adaptive immune receptor genes in a complex gene set |
US9708657B2 (en) | 2013-07-01 | 2017-07-18 | Adaptive Biotechnologies Corp. | Method for generating clonotype profiles using sequence tags |
US20160186260A1 (en) | 2013-07-26 | 2016-06-30 | Sequenta, Llc | Cancer vaccination with antigen evolution |
AU2014337063A1 (en) | 2013-10-18 | 2016-05-19 | Adaptive Biotechnologies Corp. | Predicting patient responsiveness to immune checkpoint inhibitors |
AU2015204569A1 (en) | 2014-01-10 | 2016-07-21 | Adaptive Biotechnologies Corp. | Methods for defining and predicting immune response to allograft |
US20150218656A1 (en) | 2014-02-03 | 2015-08-06 | Adaptive Biotechnologies Corp. | Methods for detection and diagnosis of a lymphoid malignancy using high throughput sequencing |
ES2741740T3 (es) | 2014-03-05 | 2020-02-12 | Adaptive Biotechnologies Corp | Métodos que usan moléculas sintéticas que contienen segmentos de nucleótidos aleatorios |
US10066265B2 (en) | 2014-04-01 | 2018-09-04 | Adaptive Biotechnologies Corp. | Determining antigen-specific t-cells |
EP3715455A1 (en) | 2014-10-29 | 2020-09-30 | Adaptive Biotechnologies Corp. | Highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune receptor heterodimers from many samples |
US10246701B2 (en) | 2014-11-14 | 2019-04-02 | Adaptive Biotechnologies Corp. | Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture |
ES2858306T3 (es) | 2015-02-24 | 2021-09-30 | Adaptive Biotechnologies Corp | Método para determinar el estado de HLA mediante secuenciación del repertorio inmunitario |
CA2979726A1 (en) | 2015-04-01 | 2016-10-06 | Adaptive Biotechnologies Corp. | Method of identifying human compatible t cell receptors specific for an antigenic target |
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