JP2019509483A - 質量分析キット - Google Patents
質量分析キット Download PDFInfo
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- JP2019509483A JP2019509483A JP2018544901A JP2018544901A JP2019509483A JP 2019509483 A JP2019509483 A JP 2019509483A JP 2018544901 A JP2018544901 A JP 2018544901A JP 2018544901 A JP2018544901 A JP 2018544901A JP 2019509483 A JP2019509483 A JP 2019509483A
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- fragment
- immunoglobulin
- antibody
- sample
- light chain
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Abstract
Description
トリス(ジメチルアミノ)ホスフィン(CAS Number 1608-26-0)、
トリス(ジエチルアミノ)ホスフィン(CAS Number 2283-11-6)、
トリメチル亜リン酸(CAS Number 121-45-9)、
トリブチルホスフィン(CAS Number 998-40-3)が挙げられる。
ビスマレイミドは、ホモ二官能スルフヒドリル反応性架橋剤である
ビス(マレイミド)エタン(CAS Number 5132-30-9)、
1,4−ビス(マレイミド)ブタン(CAS Number 28537-70-4)が挙げられる。
参考文献:
α,α’−ジブロモ−m−キシレンは使用可能なホモ二官能性スルフヒドリル反応性架橋剤である
参考文献:
安定したチオエーテル結合を形成する別のスルフヒドリル反応性架橋化合物
ビス(マレイミド)ヘキサン、N−N’−Mエチレンビスマレイミド、ビス(N−マレイミドメチル)エーテル、N,N’−(1,3−フェニレン)−ビスマレイミド、ビス(N−マレイミド)−4,4’−ビベンジル、ナフタレン−1,5−ジマレイミド
1,3−ジブロモアセトン、N,N’−ビス(ヨードアセチル)ポリメチレンジアミン、N,N’−ジ(ブロモアセチル)フェニルヒドラジン、1,2−ジ(ブロモアセチル)アミノ−3−フェニルヒドラジン、γ−(2,4−ジニトロフェニル)−α−ブロモアセチル−L−ジアミノ酪酸=ブロモアセチル−ヒドラジド
α,α’−ジブロモ−p−キシレンスルホン酸、α,α’−ジヨード−p−キシレンスルホン酸、ジ(2−クロロエチル)スルフィド、トリ(2−クロロエチル)アミン、N,N−ビス(β−ブロモエチル)ベンジルアミン
ジクロロ−6−メトキシ−s−トリアジン、2,4,6−トリクロロ−s−トリアジン(シアヌル酸)、2,4−ジクロロ−6−(3’−メチル−4−アミノアニリノ)−s−トリアジン、2,4−ジクロロ−6−アミノ−s−トリアジン
2,4,6−トリ(エチレンイミド)−s−トリアジン、N,N’−エチレンイミノイル−1,6−ジアミノヘキサン、トリ[1−(2−メチルアジリジニル)]−ホスフィンオキシド
1,2:3,4−ジエポキシブタン、1,2:5,6−ジエポキシヘキサン、ビス(2,−エポキシプロピル)エーテル、1,4−ブタジオールジグリシドキシエーテル
(i)相当する対象の検体または断片と識別可能な1種以上の対照検体または断片を所定量、前記試料に加えること、
(ii)前記試料中の前記対象の検体または断片の相対量と前記対照検体または断片の量を測定すること、および
(iii)対象の検体または断片の相対量と対照検体または断片の相対量を比較して元の対象の試料中の検体または断片の量を定量すること、を含む。
(i)典型的には免疫グロブリンまたは断片である1種以上の検体を含む対象に由来する試料を準備すること、
(ii)所定量の1種以上の対照検体またはその断片、典型的には免疫グロブリンまたはその断片を前記試料に加えること、
(iii)上記の架橋された抗体または断片を用いて前記検体(典型的には免疫グロブリンまたは断片)の少なくとも一部を前記対象および対照検体(典型的には免疫グロブリンまたは断片)から共精製すること、および必要に応じて
(iv)前記共精製された検体(例えば、免疫グロブリンまたは断片)の一部を質量分析標的に配置させること、を含む。
抗ラムダ全F(ab’) 2 断片のビスマレイミドエタン(BMOE)架橋
BMOE架橋抗遊離ラムダおよび抗遊離カッパ抗血清
チオエーテル架橋はセファロース結合抗IgG3抗体を安定させる
BMOE架橋は抗遊離カッパ抗体および抗遊離ラムダ抗体を安定化させる
質量分析により対照検体を対象の検体と識別することができる
対照検体を用いて対象の検体についての定量情報を提供することができる
Claims (28)
- 免疫グロブリンを精製または特徴付ける方法であって、
前記免疫グロブリンを含む試料を、少なくとも1つの重鎖またはその断片と少なくとも1つの軽鎖またはその断片の間に1つ以上の非ジスルフィド架橋を含む抗体または断片と接触させること、
前記免疫グロブリンを前記抗体または断片と結合させること、
前記抗体または断片に結合させた免疫グロブリンから未結合の材料を洗い落とすこと、および
前記結合させた免疫グロブリンを前記抗体または断片から除去して、精製された免疫グロブリンまたは断片を生成することを含む、方法。 - 前記精製された免疫グロブリンを質量分析によって特徴付けることをさらに含む、請求項1に記載の方法。
- 少なくとも1つの重鎖またはその断片と少なくとも1つの軽鎖またはその断片の間に1つ以上の非ジスルフィド架橋を含む抗体(または断片)、および1種以上の質量分析基準物質を含む、質量分析に使用する免疫グロブリン精製およびアッセイキット。
- 対象に由来する試料中の対象の検体または検体の断片を定量する方法であって、
(i)相当する対象の検体または断片と識別可能な1種以上の対照検体またはその断片の所定量を前記試料に加えること、
(ii)前記試料中の前記対象の検体または断片の相対量および前記対照検体または断片の量を測定すること、および
(iii)前記対象の検体または断片の相対量を前記対照検体または断片の相対量と比較して、元の対象の試料中の前記検体または断片の量を定量することを含む、方法。 - 前記検体は免疫グロブリンまたはその断片である、請求項4に記載の方法。
- 免疫グロブリンまたは断片などの前記対象の検体を定量する前に少なくとも1つの精製工程で精製し、その精製工程前に所定量の免疫グロブリンまたは断片などの対照検体を前記試料に加える、請求項4または5に記載の方法。
- 免疫グロブリンまたは断片などの前記対象の検体および対照検体の量は質量分析により決定される、請求項4〜6のいずれか一項に記載の方法。
- 前記対象の免疫グロブリンまたは断片は、無傷の免疫グロブリン、重鎖、カッパ軽鎖、ラムダ軽鎖、Fc断片、またはFab断片である、請求項4〜7のいずれか一項に記載の方法。
- 前記対照免疫グロブリンは、前記対象免疫グロブリンまたはその断片に比べて1種以上の重鎖、カッパ軽鎖、またはラムダ軽鎖のN末端またはC末端に複数のアミノ酸を含むか、あるいは前記対照タンパク質はモノクローナル抗体またはその断片である、請求項4〜8のいずれか一項に記載の方法。
- 前記カッパ軽鎖および/またはラムダ軽鎖は遊離カッパ軽鎖または遊離ラムダ軽鎖である、請求項9に記載の方法。
- 前記複数のアミノ酸は、前記対象の免疫グロブリンまたはその断片に比べて、C末端にある、請求項9または10に記載の方法。
- 前記対照免疫グロブリンは、無傷の免疫グロブリン、遊離カッパ軽鎖、または遊離ラムダ軽鎖のうちの2つ以上を含む、請求項5〜11のいずれか一項に記載の方法。
- 前記対象はB細胞関連疾患を持つ、上記の請求項のいずれか一項に記載の方法。
- 質量分析用の試料を調製する方法であって、
(i)免疫グロブリンまたはその断片を含む対象に由来する試料を準備すること、
(ii)所定の分子量を持つ対照免疫グロブリンまたは断片の所定量を前記試料に加えること、
(iii)少なくとも1つの重鎖またはその断片と少なくとも1つの軽鎖またはその断片の間に1つ以上の非ジスルフィド架橋を含む抗免疫グロブリン抗体または断片を用いて、前記対照免疫グロブリンまたは断片を前記免疫グロブリンまたは断片と共に免疫精製により共精製すること、および必要に応じて
(iv)前記共精製された試料を質量分析標的に配置させることを含む、方法。 - 前記対照免疫グロブリンまたは断片は、質量分析により測定される目的の免疫グロブリンまたは断片よりも高いまたは低い分子量を持つ、請求項14に記載の方法。
- 前記共精製された試料を含む標的を質量分析にかけて前記試料を分析する工程をさらに含む、請求項14または15に記載の方法。
- 少なくとも1つの重鎖またはその断片と少なくとも1つの軽鎖またはその断片の間に1つ以上の非ジスルフィド架橋を含む抗体または断片、および免疫グロブリンまたは断片の質量分析標準物質を含む、アッセイキット。
- 質量分析標的を含む、請求項17に記載のアッセイキット。
- 前記抗体または断片はポリクロナール抗体またはその断片である、請求項1、2または14〜16のいずれか一項に記載の方法、あるいは請求項3、17、または18に記載のキット。
- 前記抗体またはその断片は、抗遊離軽鎖クラスに特異的、抗重鎖クラスに特異的、抗重鎖サブクラスに特異的、抗重鎖クラス−軽鎖タイプに特異的、または抗軽鎖タイプに特異的である、請求項1〜3または14〜19のいずれか一項に記載の方法またはキット。
- 前記抗体またはその断片が、前記抗体またはその断片の少なくとも1つの重鎖またはその断片と少なくとも1つの軽鎖またはその断片の間に1つ以上の非ジスルフィド架橋を含むことを特徴とする抗免疫グロブリン特異的抗体(またはその断片)。
- 抗遊離軽鎖に特異的、抗重鎖クラスに特異的、抗重鎖サブクラスに特異的、抗重鎖クラス−軽鎖タイプに特異的、または抗軽鎖タイプに特異的である、請求項21に記載の抗体または断片。
- 前記架橋はビスマレイミドまたはチオエーテル結合を含む、請求項21または22に記載の抗体または断片。
- 支持体に結合させた、請求項21〜23のいずれか一項に記載の抗体または断片。
- 前記抗体または断片は、モノクローナル抗体または断片、もしくはポリクロナール抗体またはその断片である、請求項21〜24のいずれか一項に記載の抗体または断片。
- 前記抗体は、抗体の断片であり、F(ab’)2断片である、請求項21〜25のいずれか一項に記載の抗体または断片。
- 1種以上の免疫グロブリンの精製に用いられる請求項21〜26のいずれか一項に記載の抗体または断片。
- B細胞関連疾患または他の免疫関連疾患を診断あるいは予後診断する方法であって、抗体を用いて免疫グロブリンを精製あるいは特徴付けを行うことを含み、上記請求項のいずれか一項に記載のアッセイキットを使用する方法。
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