JP5319549B2 - 溶液内捕捉イムノアッセイで使用する非変性細胞溶解試薬 - Google Patents
溶液内捕捉イムノアッセイで使用する非変性細胞溶解試薬 Download PDFInfo
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- JP5319549B2 JP5319549B2 JP2009544194A JP2009544194A JP5319549B2 JP 5319549 B2 JP5319549 B2 JP 5319549B2 JP 2009544194 A JP2009544194 A JP 2009544194A JP 2009544194 A JP2009544194 A JP 2009544194A JP 5319549 B2 JP5319549 B2 JP 5319549B2
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
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Description
本発明は、捕捉抗体を使用するイムノアッセイにおいて使用する試験サンプルを調製する方法を提供する。特定の実施形態においては、試験サンプルには、ヒト血液サンプルが含まれる。方法は、試験サンプルを細胞溶解試薬に接触させて細胞溶解混合物を形成させることを含む。細胞溶解試薬は、エチレングリコール、プロピレングリコールおよびそれらの類似体よりなる群から選ばれるグリコールを含む。典型的な実施形態においては、グリコールは細胞溶解試薬中に約60%から約80%の範囲の濃度で存在する。捕捉抗体の動物種と同じ動物種の免疫グロブリンが細胞溶解試薬中に含まれ、または細胞溶解混合物に加えられる。ある実施形態においては、免疫グロブリンには、マウス免疫グロブリン、例えば非特異的ポリクローナルマウスIgGが含まれる。典型的な実施形態においては、免疫グロブリンは細胞溶解試薬中に約90μg/mLから110μg/mLの範囲の濃度で存在する。
本発明は、後続の分離工程を伴うことなくアッセイされうる均一細胞溶解混合物を得るために試験サンプルと混合されうる非変性細胞溶解試薬に関する。本発明の方法および試薬は、基本的には、後続のイムノアッセイにおいて使用される抗体、例えば捕捉抗体の動物種と同じ動物種の免疫グロブリンに特異的なサンプル抗体の潜在的阻害を中和する。
特許請求の範囲および明細書において用いる用語は、特に示さない限り、以下に記載するとおりに定義される。
本発明の方法は、一般に、動物、好ましくは哺乳動物、より好ましくはヒトに由来する試験サンプルに関して行われる。
A.総論
本発明のイムノアッセイは、試験サンプル中のアナライトの定性的特定および/または定量のために用いられうる。これらの方法は、例えば、免疫抑制薬、例えばラパマイシン(シロリムス)、タクロリムス、エベロリムス、テムソロリムス、ゾタロリムス、シクロスポリンおよびこれらの化合物のいずれかの類似体のイムノアッセイに適用可能である。そのようなイムノアッセイは、前記のとおり、細胞溶解試薬を試験サンプルと混合して細胞溶解混合物を形成させることにより行われうる。細胞溶解混合物を、アナライトに特異的な少なくとも1つの抗体と、存在する場合のアナライトへの抗体の結合に適した条件下で接触させて、アッセイ混合物を形成させ、ついでアナライトへの抗体の結合を検出する。
試験サンプル中のアナライトの定性的または定量的検出のためのイムノアッセイにおいては、アナライトに結合する少なくとも1つの抗体を、アナライトを含有する疑いのある細胞溶解混合物に接触させて、抗体−アナライト免疫複合体を形成させる。免疫抑制薬を検出するために、その特定の薬物に結合する任意の適当な抗体を本発明のイムノアッセイにおいて使用することが可能である。ラパマイシン(シロリムス)、タクロリムス、ゾタロリムス、シクロスポリンおよびエベロリムスのそれぞれに対する抗体は当技術分野で公知であり、および/または商業的に入手可能であり、これらのいずれもが使用可能である。シロリムスを測定するためのAbbott Laboratoriesの商業的に入手可能なIMx(登録商標)Sirolimusアッセイ(Abbott Laboratories,Abbott Park,IL)またはAbbott Laboratoriesにより販売されている任意の他のSirolimusアッセイキット(例えば、異なる市販の自動化形態上で使用するためのもの)の成分であるモノクローナル抗体を使用することが好ましい。
ついで任意の適当な技術を用いて、抗体−アナライト免疫複合体を検出することが可能である。例えば、抗体−アナライト複合体の存在を検出するために、検出可能な標識で抗体を標識することが可能である。個々の標識の選択は決定的に重要なものではないが、選択される標識は、単独で又は1以上の追加的物質と共に、検出可能なシグナルを生成しうるものでなければならない。
本発明のイムノアッセイは、当技術分野で公知の任意の形態、例えばサンドイッチ形態、競合阻害形態(フォワード(前方向)またはリバース(逆方向)競合阻害アッセイを含む)または蛍光偏光形態(これらに限定されるものではない)を用いて行われうる。好ましい実施形態においては、形態は、前記の溶液内捕捉アプローチに適したものである。後記の典型的な形態は免疫抑制薬のアッセイに関して記載されている。しかし、当業者に理解されるとおり、記載されている形態は任意のアナライトに適用可能である。
本発明はまた、アナライトに関して試験サンプルをアッセイするための試験キットを提供する。本発明の試験キットは、本発明の1以上のイムノアッセイを実施するのに有用な1以上の試薬を含む。試験キットは、一般に、試薬を1以上の別々の組成物として又は場合によっては試薬の混和性が許容する場合には混合物として収容する1以上の容器を伴うパッケージを含む。試験キットはまた、使用者の立場から望ましい可能性がある他の物質、例えばバッファー、希釈剤、標準および/またはサンプルの加工、洗浄もしくは任意の他のアッセイ工程の実施において有用な任意の他の物質を含みうる。
以下の実施例は、特許請求されている本発明を例示するために記載されており、本発明を限定するものではない。
この実施例は、シクロスポリンに関する自動化イムノアッセイにおける細胞溶解試薬中のマウスIgGの添加の効果を例示する。
この実施例は、単一工程均一系サンプル前処理を用いる溶液内捕捉アッセイにおけるヒト抗マウス抗体(「HAMA」)阻害の予防に関する、細胞溶解試薬におけるマウスIgGの添加の効果を例示する。
この実施例は、シクロスポリンに関する自動化イムノアッセイにおける細胞溶解試薬へのバッファーの添加の効果を例示する。
Claims (38)
- アナライトの存在または濃度を決定するためのイムノアッセイ方法であって、 (a)試験サンプルを細胞溶解試薬に接触させて、細胞溶解混合物を形成させる工程と、ここで、細胞溶解試薬は、エチレングリコール、プロピレングリコールおよびそれらの類似体よりなる群から選ばれるグリコールを含み、アナライトに結合する捕捉抗体の動物種と同じ動物種の免疫グロブリンが細胞溶解試薬中に含まれるか、または細胞溶解混合物に加えられる、
(b)細胞溶解混合物を、捕捉抗体に対する固相固定結合パートナーを含む固相に、および捕捉抗体に接触させる工程と、ここで、捕捉抗体は結合パートナーに予め結合しておらず、接触は、捕捉抗体がアナライトおよび固相固定結合パートナーに結合して捕捉抗体およびアナライトが固相固定免疫複合体を形成するのに適した条件下で行われ、前記免疫グロブリンは固相固定結合パートナーとの結合について捕捉抗体と競合する、
(c)検出用物質が固相固定免疫複合体に結合するのに適した条件下、固相を検出用物質に接触させる工程と、
(d)固相固定免疫複合体への検出用物質の結合を検出する工程と
を含む、イムノアッセイ方法。 - イムノアッセイ方法が競合イムノアッセイを含み、検出用物質が標識アナライトまたは標識アナライト類似体を含み、ならびに標識からのシグナルが試験サンプル中のアナライトの濃度に反比例する、請求項1の方法。
- アナライトが免疫抑制薬を含む、請求項1または2の方法。
- 免疫抑制薬が、シロリムス、タクロリムス、エベロリムス、テムソロリムス、ゾタロリムス、シクロスポリンおよびこれらの化合物のいずれかの類似体よりなる群から選ばれる、請求項3の方法。
- 試験サンプルがヒト血液サンプルを含む、請求項3または4の方法。
- 免疫グロブリンがマウス免疫グロブリンである、請求項1の方法。
- マウス免疫グロブリンが非特異的ポリクローナルマウスIgGを含む、請求項6の方法。
- グリコールが細胞溶解試薬中に60%から80%の範囲の濃度で存在する、請求項1の方法。
- 免疫グロブリンが細胞溶解試薬中に90μg/mLから110μg/mLの範囲の濃度で存在する、請求項1の方法。
- 試験サンプルを細胞溶解試薬に1:2から1:4の範囲の比で加える、請求項1の方法。
- 方法が、細胞溶解混合物を遠心分離することを含まない、請求項1の方法。
- 細胞溶解試薬が更に、5個以下の炭素を有する少なくとも1種のアルコールを含む、請求項1の方法。
- 細胞溶解試薬が更に、7.0から8.0の範囲のpHのバッファーを含む、請求項1の方法。
- 方法が、試験サンプルまたは細胞溶解混合物を界面活性剤に接触させることを含まない、請求項1の方法。
- 方法が、試験サンプルまたは細胞溶解混合物を界面活性剤に接触させることを含む、請求項1の方法。
- アッセイが、試験サンプル中の1以上の結合タンパク質に結合したアナライトを検出し、方法が更に、試験サンプルまたは細胞溶解混合物を、前記の1以上の結合タンパク質からアナライトを遊離させる物質に接触させることを含む、請求項1から15のいずれかの方法。
- 物質が前記の1以上の結合タンパク質への結合に関してアナライトと競合する、請求項16の方法。
- アナライトが免疫抑制薬を含み、ならびに物質が、異なるが構造的に類似している免疫抑制薬を含む、請求項17の方法。
- アナライトが非タンパク質分子を含み、ならびに物質が、前記の1以上の結合タンパク質を分解するプロテアーゼを含む、請求項17の方法。
- (a)アナライトに特異的に結合することができる捕捉抗体、
(b)エチレングリコール、プロピレングリコールおよびそれらの類似体よりなる群から選ばれるグリコールを含む細胞溶解試薬、
(c)捕捉抗体の動物種と同じ動物種の免疫グロブリン、ならびに
(d)捕捉抗体に対する固相固定結合パートナーを含む固相、ここで、前記免疫グロブリンは固相固定結合パートナーとの結合について捕捉抗体と競合する、
を含んでなる、イムノアッセイにおいて使用する試験キット。 - 細胞溶解試薬および免疫グロブリンが組合され、単一の容器内に梱包される、請求項20の試験キット。
- 固相および捕捉抗体が別々の容器内に梱包される、請求項20の試験キット。
- 免疫グロブリンがマウス免疫グロブリンである、請求項20の試験キット。
- マウス免疫グロブリンが非特異的ポリクローナルマウスIgGを含む、請求項20の試験キット。
- アナライトが免疫抑制薬を含む、請求項20の試験キット。
- 免疫抑制薬が、シロリムス、タクロリムス、エベロリムス、テムソロリムス、ゾタロリムス、シクロスポリンおよびこれらの化合物のいずれかの類似体よりなる群から選ばれる、請求項25の試験キット。
- (a)の少なくとも1つのアナライトを含む対照組成物を更に含む、請求項20の試験キット。
- グリコールが細胞溶解試薬中に60%から80%の範囲の濃度で存在する、請求項20の試験キット。
- 免疫グロブリンが細胞溶解試薬中に90μg/mLから110μg/mLの範囲の濃度で存在する、請求項21の試験キット。
- 細胞溶解試薬が更に、5個以下の炭素を有する少なくとも1種のアルコールを含む、請求項20の試験キット。
- 細胞溶解試薬が更に、7.0から8.0の範囲のpHのバッファーを含む、請求項20の試験キット。
- 更に界面活性剤を含む、請求項20から31のいずれかの試験キット。
- 試験キットが更に、試験サンプル中の1以上の結合タンパク質からアナライトを遊離させる物質を含む、請求項20から31のいずれかの試験キット。
- 物質が前記の1以上の結合タンパク質への結合に関してアナライトと競合する、請求項33の試験キット。
- アナライトが免疫抑制薬を含み、ならびに物質が、異なるが構造的に類似している免疫抑制薬を含む、請求項34の試験キット。
- 物質が、前記の1以上の結合タンパク質を分解するプロテアーゼを含む、請求項33の試験キット。
- (a)シロリムス、タクロリムス、エベロリムス、テムソロリムス、ゾタロリムスおよびシクロスポリンよりなる群から選ばれる少なくとも1つの免疫抑制薬に特異的に結合しうる捕捉抗体、
(b)エチレングリコール、プロピレングリコールおよびそれらの類似体よりなる群から選ばれるグリコール、および
アナライトに結合する捕捉抗体の動物種と同じ動物種の免疫グロブリン
とを含む細胞溶解試薬、
(c)捕捉抗体に対する固相固定結合パートナーを含む固相、ここで、前記免疫グロブリンは固相固定結合パートナーとの結合について捕捉抗体と競合し、固相および捕捉抗体は別々の容器内で提供される、ならびに
(d)(a)の少なくとも1つの免疫抑制薬を含む対照組成物
を含んでなる試験キット。 - 少なくとも1つの免疫抑制薬がシクロスポリンを含む、請求項37の試験キット。
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US60/878,017 | 2006-12-29 | ||
PCT/US2007/088109 WO2008082984A2 (en) | 2006-12-29 | 2007-12-19 | Non-denaturing lysis reagent for use with capture-in-solution immunoassay |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7500140B2 (ja) | 2020-11-26 | 2024-06-17 | 大和製衡株式会社 | 組合せ秤 |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7883855B2 (en) | 2006-07-21 | 2011-02-08 | Abbott Laboratories | Immunosuppressant drug extraction reagent for immunoassays |
US7914999B2 (en) | 2006-12-29 | 2011-03-29 | Abbott Laboratories | Non-denaturing lysis reagent |
EP2118654B1 (en) | 2006-12-29 | 2013-03-27 | Abbott Laboratories | Diagnostic test for the detection of a molecule or drug in whole blood |
WO2008082984A2 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Non-denaturing lysis reagent for use with capture-in-solution immunoassay |
WO2008082982A1 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Improved assay for immunosuppressant drugs |
WO2008147982A1 (en) | 2007-05-24 | 2008-12-04 | Abbott Laboratories | Immunoassays exhibiting reduced cross-reactivity with hydrophobic drug analyte metabolites |
BRPI1013688A8 (pt) | 2009-03-05 | 2017-02-14 | Abbott Lab | Proteínas de ligação de il-17. |
US8389293B2 (en) * | 2009-11-17 | 2013-03-05 | Abbott Point Of Care Inc. | Reducing leukocyte interference in competitive immunoassays |
US20110229921A1 (en) | 2010-03-18 | 2011-09-22 | Abbott Laboratories | METHODS OF ASSAYING URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (uNGAL) IN THE PROGNOSIS OF CADAVERIC KIDNEY TRANSPLANT FUNCTION IN A PATIENT, INCLUDING A PATIENT DIAGNOSED WITH DELAYED GRAFT FUNCTION (DGF), A METHOD OF ASSAYING uNGAL IN THE ASSESSMENT OF RISK OF DGF IN A PATIENT DIAGNOSED WITH EARLY GRAFT FUNCTION (EGF), AND RELATED KITS |
MY161302A (en) | 2010-05-14 | 2017-04-14 | Abbvie Inc | IL-1 binding proteins |
US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
US8409807B2 (en) | 2010-10-22 | 2013-04-02 | T2 Biosystems, Inc. | NMR systems and methods for the rapid detection of analytes |
US8563298B2 (en) | 2010-10-22 | 2013-10-22 | T2 Biosystems, Inc. | NMR systems and methods for the rapid detection of analytes |
CA3155334A1 (en) | 2010-10-22 | 2012-04-26 | T2 Biosystems, Inc. | NMR SYSTEMS AND METHODS FOR RAPID ANALYTE DETECTION |
US20120115244A1 (en) | 2010-11-09 | 2012-05-10 | Abbott Laboratories | Materials and methods for immunoassay of pterins |
WO2012162133A1 (en) | 2011-05-20 | 2012-11-29 | Advandx, Inc. | Selective ultrasonic lysis of blood and other biological fluids and tissues |
WO2013063095A1 (en) | 2011-10-24 | 2013-05-02 | Abbvie Inc. | Immunobinders directed against sclerostin |
US9562271B2 (en) | 2012-04-20 | 2017-02-07 | T2 Biosystems, Inc. | Compositions and methods for detection of Candida species |
UY34905A (es) | 2012-07-12 | 2014-01-31 | Abbvie Inc | Proteínas de unión a il-1 |
CN104749009B (zh) * | 2015-03-30 | 2018-05-04 | 上海云泽生物科技有限公司 | 用于免疫分析的免疫抑制剂药物提取试剂 |
US11229910B2 (en) | 2015-08-13 | 2022-01-25 | President And Fellows Of Harvard College | Microfluidic devices and systems for cell culture and/or assay |
JP7523776B2 (ja) | 2016-01-21 | 2024-07-29 | ティー2 バイオシステムズ,インコーポレーテッド | 細菌を迅速に検出するnmr法及びシステム |
Family Cites Families (76)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3225027A1 (de) * | 1982-07-05 | 1984-01-05 | Boehringer Mannheim Gmbh, 6800 Mannheim | Immunchemisches messverfahren |
US4652517A (en) * | 1984-06-11 | 1987-03-24 | Diagnostic Research Limited Partnership | Methods for the in vitro detection and identification of unknown pathogens or genetic entities |
US5169773A (en) * | 1984-10-04 | 1992-12-08 | Sandoz Ltd. | Monoclonal antibodies to cyclosporins |
ATE98700T1 (de) | 1987-06-05 | 1994-01-15 | Fujisawa Pharmaceutical Co | Anti-fr-900506-stoffe-antikoerper und hoechstempfindliches enzym-immunoassay-verfahren. |
AT390739B (de) | 1988-11-03 | 1990-06-25 | Ewald Dipl Ing Dr Benes | Verfahren und einrichtung zur separation von teilchen, welche in einem dispersionsmittel dispergiert sind |
US5063081A (en) | 1988-11-14 | 1991-11-05 | I-Stat Corporation | Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor |
US5698448A (en) * | 1988-12-02 | 1997-12-16 | Soldin; Steven J. | Immunosuppressive drug binding proteins and use |
AU4958590A (en) * | 1988-12-05 | 1990-07-10 | Trustees Of Columbia University In The City Of New York, The | Novel derivatives of cyclosporine a, antibodies directed thereto and uses thereof |
US5217971A (en) * | 1989-01-05 | 1993-06-08 | Fujisawa Pharmaceutical Co., Ltd. | Thiazole compounds and pharmaceutical composition comprising the same |
EP0440044A1 (en) | 1990-01-31 | 1991-08-07 | Abbott Laboratories | Avoidance of human anti-mouse antibody interference in in vitro diagnostic testing |
US5135875A (en) * | 1990-08-15 | 1992-08-04 | Abbott Laboratories | Protein precipitation reagent |
EP0473961B1 (en) * | 1990-08-15 | 1996-01-03 | Abbott Laboratories | Immunoassay reagents and method for determining cyclosporine |
US5134875A (en) * | 1990-09-28 | 1992-08-04 | Jensen Richard E | Breath alcohol simulator solution containers and method of using same |
DE69133095T2 (de) * | 1990-11-20 | 2003-03-27 | Dade Behring Marburg Gmbh | Cyclosporin-Immunoassay |
NL9002661A (nl) * | 1990-12-04 | 1992-07-01 | Pacques Bv | Werkwijze voor de verwijdering van h2s uit gas. |
US5322772A (en) * | 1991-04-09 | 1994-06-21 | Children's Research Institute | Rapamycin assay |
AU2007192A (en) | 1991-05-08 | 1992-12-21 | Vertex Pharmaceuticals Incorporated | Rfkbp: a novel prolyl isomerase and rapamycin/fk506 binding protein |
US5498597A (en) * | 1992-01-17 | 1996-03-12 | Dana-Farber Cancer Institute, Inc. | FKBP-13, an FK506-binding immunophilin |
AU4400593A (en) | 1992-06-05 | 1994-01-04 | Abbott Laboratories | Methods and reagents for the determination of immunosuppressive agents |
GB9307491D0 (en) * | 1993-04-08 | 1993-06-02 | Sandoz Ltd | Organic compounds |
US5354845A (en) | 1993-04-21 | 1994-10-11 | Children's Research Institute | FK-506 and rapamycin specific binding immunophilin |
WO1994025072A1 (en) | 1993-04-23 | 1994-11-10 | American Home Products Corporation | Rapamycin conjugates and antibodies |
DE69435044T2 (de) * | 1993-04-23 | 2008-09-18 | Wyeth | Rapamycin - Konjugate und Antikörper |
US7279561B1 (en) * | 1993-04-23 | 2007-10-09 | Wyeth | Anti-rapamycin monoclonal antibodies |
US6187547B1 (en) * | 1993-09-08 | 2001-02-13 | Novartis Ag | Assay kit |
JP3745772B2 (ja) | 1993-12-17 | 2006-02-15 | ノバルティス アクチエンゲゼルシャフト | 免疫抑制剤として有用なラパマイシン誘導体 |
GB9405350D0 (en) * | 1994-03-18 | 1994-05-04 | Sandoz Ltd | Organic compounds |
JP3720395B2 (ja) * | 1994-09-20 | 2005-11-24 | 京都薬品工業株式会社 | 新規ヘテロ環誘導体、その製造方法およびその医薬用途 |
WO1996012018A2 (en) | 1994-10-14 | 1996-04-25 | The Salk Institute For Biological Studies | Novel immunophilins and corresponding nucleic acids |
IL115742A (en) | 1994-10-26 | 2000-06-01 | Novartis Ag | Pharmaceutical compositions comprising a difficultly soluble active agent a hydrophilic phase a lipophilic phase and a surfactant |
US5955108A (en) * | 1994-12-16 | 1999-09-21 | Quadrant Healthcare (Uk) Limited | Cross-linked microparticles and their use as therapeutic vehicles |
JPH08228795A (ja) * | 1994-12-27 | 1996-09-10 | Nakano Vinegar Co Ltd | 糖鎖分析用試料の調製方法及び該試料を用いた診断方法 |
BE1009856A5 (fr) | 1995-07-14 | 1997-10-07 | Sandoz Sa | Composition pharmaceutique sous la forme d'une dispersion solide comprenant un macrolide et un vehicule. |
US5650288A (en) * | 1995-07-14 | 1997-07-22 | Macfarlane; Gordon D. | Immunophilin-bound immunosuppressant assay |
GB9517674D0 (en) * | 1995-08-30 | 1995-11-01 | Lynxvale Ltd | Plastid inner envelope membrane targeting polypeptides;manufacture and use thereof |
US5650228A (en) * | 1995-10-31 | 1997-07-22 | May; Michael W. | Replacement surface for bathtub and shower floor |
GB9601120D0 (en) * | 1996-01-19 | 1996-03-20 | Sandoz Ltd | Organic compounds |
JP2001514737A (ja) | 1996-07-03 | 2001-09-11 | サイバ、カンパニー | 前処理試薬およびそれを使用する方法 |
US6087134A (en) * | 1997-01-14 | 2000-07-11 | Applied Imaging Corporation | Method for analyzing DNA from a rare cell in a cell population |
WO1998045333A1 (en) | 1997-04-09 | 1998-10-15 | Isotechnika, Inc. | Method for production of antibodies to specific sites of rapamycin |
US6146836A (en) * | 1997-05-19 | 2000-11-14 | Bayer Corporation | Immunoassays using anti-allotypic monoclonal antibodies |
US6682648B1 (en) | 1997-08-12 | 2004-01-27 | University Of Southern California | Electrochemical reporter system for detecting analytical immunoassay and molecular biology procedures |
WO1999058664A1 (en) * | 1998-05-14 | 1999-11-18 | Whitehead Institute For Biomedical Research | Solid phase technique for selectively isolating nucleic acids |
WO1999063346A1 (en) | 1998-06-01 | 1999-12-09 | Roche Diagnostics Corporation | Method and device for electrochemical immunoassay of multiple analytes |
US20020055124A1 (en) | 1998-09-23 | 2002-05-09 | The Scripps Research Institute | Soluble support for organic synthesis |
US6858439B1 (en) * | 1999-03-15 | 2005-02-22 | Aviva Biosciences | Compositions and methods for separation of moieties on chips |
ES2283344T3 (es) | 1999-10-29 | 2007-11-01 | Kosan Biosciences, Inc. | Analogos de la rapamicina. |
WO2001038873A2 (en) | 1999-11-24 | 2001-05-31 | Biotronic Technologies, Inc. | Devices and methods for detecting analytes using electrosensor having capture reagent |
DE10009503A1 (de) * | 2000-02-29 | 2001-08-30 | Roche Diagnostics Gmbh | Verfahren zur Immobilisierung von Konjugaten in diagnostischen Tests |
FR2810739B1 (fr) | 2000-06-26 | 2007-01-26 | Centre Nat Rech Scient | Immunodosage electrochimiques a l'aide de marqueurs metalliques colloidaux |
US6410340B1 (en) * | 2000-08-23 | 2002-06-25 | Children's Research Institute | Use of an 8.4 kDa protein as an immunophilin reagent in protein binding assays for immunosuppressive drugs |
US6887714B2 (en) | 2000-10-16 | 2005-05-03 | Board Of Trustees Of The University Of Arkansas, N.A. | Microvolume immunoabsorbant assays with amplified electrochemical detection |
WO2002036335A1 (fr) * | 2000-11-06 | 2002-05-10 | Sumitomo Special Metals Co., Ltd. | Procede et dispositif pour mouler de la poudre par pression, et procede de fabrication d'aimant a base de terres rares |
US6913580B2 (en) * | 2001-01-23 | 2005-07-05 | Benjamin Curtis Stone | Method of body fluid specimen collection |
EP1399475A2 (en) * | 2001-06-07 | 2004-03-24 | F. Hoffmann-La Roche Ag | Mutants of igf binding proteins and methods of production of antagonists thereof |
CA2475224C (en) * | 2002-02-07 | 2011-11-01 | The Trustees Of Columbia University In The City Of New York | Zinc salt compositions for the prevention of mucosal irritation from spermicides and microbicides |
US20030157556A1 (en) * | 2002-02-13 | 2003-08-21 | Maggiore Jack A. | Biological fluid stabilizing composition and method of use thereof |
US7419821B2 (en) | 2002-03-05 | 2008-09-02 | I-Stat Corporation | Apparatus and methods for analyte measurement and immunoassay |
US20040062793A1 (en) * | 2002-07-05 | 2004-04-01 | Dyke Mark Van | Tissue defect dressings comprising proteinaceous networks |
US20040018577A1 (en) | 2002-07-29 | 2004-01-29 | Emerson Campbell John Lewis | Multiple hybrid immunoassay |
US7682833B2 (en) | 2003-09-10 | 2010-03-23 | Abbott Point Of Care Inc. | Immunoassay device with improved sample closure |
US7723099B2 (en) | 2003-09-10 | 2010-05-25 | Abbott Point Of Care Inc. | Immunoassay device with immuno-reference electrode |
CN1595319A (zh) * | 2003-09-10 | 2005-03-16 | 发那科株式会社 | 数值控制装置 |
US7186518B2 (en) * | 2003-11-21 | 2007-03-06 | Dade Behring Inc. | Method and composition useful for determining FK 506 |
EP1702214A4 (en) * | 2003-12-24 | 2007-12-19 | Wyeth Corp | METHOD FOR THE TREATMENT OF ASTHMA |
EP1610818A4 (en) * | 2004-03-03 | 2007-09-19 | Millennium Pharm Inc | MODIFIED ANTIBODIES AGAINST A PROSTATE-SPECIFIC MEMBRANE-ANTIGEN AND USE THEREOF |
US20060020401A1 (en) * | 2004-07-20 | 2006-01-26 | Charles Stark Draper Laboratory, Inc. | Alignment and autoregressive modeling of analytical sensor data from complex chemical mixtures |
JP2006180738A (ja) * | 2004-12-27 | 2006-07-13 | Tokyo Univ Of Pharmacy & Life Science | 新規plc様タンパク質およびその利用 |
MX2007012447A (es) * | 2005-04-06 | 2007-10-19 | Abbott Lab | Metodos para medir complejos inmunosupresores tacrolimus, sirolimus y ciclosporina a en una muestra de sangre. |
US7189582B2 (en) * | 2005-04-27 | 2007-03-13 | Dade Behring Inc. | Compositions and methods for detection of sirolimus |
US8022188B2 (en) * | 2006-04-24 | 2011-09-20 | Abbott Laboratories | Immunosuppressant binding antibodies and methods of obtaining and using same |
US7883855B2 (en) * | 2006-07-21 | 2011-02-08 | Abbott Laboratories | Immunosuppressant drug extraction reagent for immunoassays |
EP2118654B1 (en) * | 2006-12-29 | 2013-03-27 | Abbott Laboratories | Diagnostic test for the detection of a molecule or drug in whole blood |
US7914999B2 (en) * | 2006-12-29 | 2011-03-29 | Abbott Laboratories | Non-denaturing lysis reagent |
WO2008082984A2 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Non-denaturing lysis reagent for use with capture-in-solution immunoassay |
WO2008082982A1 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Improved assay for immunosuppressant drugs |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP7500140B2 (ja) | 2020-11-26 | 2024-06-17 | 大和製衡株式会社 | 組合せ秤 |
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US7993851B2 (en) | 2011-08-09 |
EP2118657A2 (en) | 2009-11-18 |
US20090325198A1 (en) | 2009-12-31 |
JP2010515065A (ja) | 2010-05-06 |
CA2673314A1 (en) | 2008-07-10 |
CA2673314C (en) | 2014-03-11 |
EP2118657B1 (en) | 2014-05-21 |
WO2008082984A2 (en) | 2008-07-10 |
US8329415B2 (en) | 2012-12-11 |
EP2118657A4 (en) | 2010-05-12 |
US20110294140A1 (en) | 2011-12-01 |
WO2008082984A3 (en) | 2008-11-20 |
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