JP4964781B2 - MHC−IIトランスジェニック動物の耐性の調査(study)方法 - Google Patents
MHC−IIトランスジェニック動物の耐性の調査(study)方法 Download PDFInfo
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Description
(a)前記ほ乳類抗原との接触によって、前記トランスジェニックほ乳類に前記ほ乳類抗原に対する耐性を与えるステップと;
(b)前記トランスジェニックほ乳類を前記変異型抗原と接触させるステップと;
(c)前記トランスジェニックほ乳類の前記変異型抗原の免疫原性を測定するステップと;
を具える。
Claims (32)
- 第1のほ乳類の抗原由来の変異抗原の免疫原性を、非ヒトの第2のほ乳類において試験する方法であって:
i.前記第2のほ乳類が前記第1のほ乳類由来のMHCクラスII分子に対して遺伝子導入され;
ii.前記第1のほ乳類及び前記第2のほ乳類が異なる種であり;
前記方法が:
(a)前記第2のほ乳類が前記抗原に対して耐性化するように、前記第2のほ乳類を前記第1のほ乳類の抗原と接触させるステップと;
(b)該耐性化した第2のほ乳類を前記変異抗原と接触させるステップと;
(c)前記第2のほ乳類において前記変異抗原の免疫原性を測定するステップと;
を具えることを特徴とする方法。 - 請求項1に記載の方法において、前記抗原との接触が、該ほ乳類抗原をコードする1以上の発現コンストラクトを前記第2のほ乳類に導入することによって達成できることを特徴とする方法。
- 請求項1又は請求項2に記載の方法において、前記抗原が可溶性タンパク質であることを特徴とする方法。
- 請求項3に記載の方法において、前記抗原が可溶性のヒトタンパク質であることを特徴とする方法。
- 請求項3に記載の方法において、前記抗原がモノクノーナル抗体であり、前記第2のほ乳類が、可溶性で単量体である、その形状と接触することを特徴とする方法。
- 請求項3に記載の方法において、前記抗原がほ乳類ポリクローナル抗体の配合物であり、前記第2のほ乳類が、可溶性のその形状と接触することを特徴とする方法。
- 請求項3ないし6のいずれか1項に記載の方法において、前記タンパク質が、アジュバント中にあることを特徴とする方法。
- 請求項1又は請求項2に記載の方法が、ヒトワクチンを試験するのに用いられることを特徴とする方法。
- 請求項1ないし8のいずれか1項に記載の方法において、該非ヒトほ乳類が齧歯類であることを特徴とする方法。
- 請求項9に記載の方法において、前記齧歯類がマウスであり、該ほ乳類MHCクラスII分子がヒト型であることを特徴とする方法。
- 請求項10に記載の方法において、前記マウスがヒトHLA−DRトランスジェニックマウスであることを特徴とする方法。
- 請求項11に記載の方法において、該トランスジェニックマウスが、前記抗原に対する耐性を誘発するために、最大生後6週、前記抗原と接触した新生仔マウスであることを特徴とする方法。
- 請求項12に記載の方法において、前記トランスジェニックマウスが、前記抗原に対する耐性を誘発するために、生後32時間以内に前記抗原と接触することを特徴とする方法。
- 請求項9ないし13のいずれか1項に記載の方法において、該ほ乳類抗原がヒト抗原であることを特徴とする方法。
- 請求項9ないし13のいずれか1項に記載の方法において、該ほ乳類抗原が非ヒト抗原であることを特徴とする方法。
- 請求項11ないし15のいずれか1項に記載の方法において、該トランスジェニックマウスが、前記抗原又は前記抗原の変異体を発現するマウスの遺伝子を欠失又は不活化するように修飾されることを特徴とする方法。
- 請求項16に記載の方法において、前記トランスジェニックマウスが次いで、1以上の非マウスタンパク質の変異体の免疫原性の誘発又は測定前に、非マウスタンパク質である前記抗原に対して耐性化されることを特徴とする方法。
- 請求項17に記載の方法において、前記非マウスタンパク質がヒト免疫グロブリンであり、該1以上の変異タンパク質が、試験するモノクローナル抗体又はポリクローナル抗体であることを特徴とする方法。
- 請求項11に記載の方法において、前記トランスジェニックマウスがヒト免疫グロブリンの重鎖及び軽鎖をコードすることを特徴とする方法。
- 請求項11ないし19のいずれか1項に記載の方法において、免疫原性が、試験するモノクローナル抗体又はポリクローナル抗体、又は試験するタンパク質に対する抗原の誘発について試験するために、該トランスジェニックほ乳類由来の血清を用いて測定されることを特徴とする方法。
- 請求項10ないし19のいずれか1項に記載の方法において、免疫原性が、マウスT細胞の供給源としてのマウスの血液又は組織サンプルを用いてT細胞増殖又はT細胞活性化アッセイで測定されることを特徴とする方法。
- 請求項10ないし19のいずれか1項に記載の方法において、ヒト免疫原性が、特異ペプチド−MHC複合体の結合によるタンパク質反応性T細胞の産生について試験するか、サイトカイン産生物、増殖、細胞表面マーカ発現、Ca2+フラックス、PCR又はDNAフィンガープリントの測定によってT細胞又はB細胞を試験するか、あるいは特異的免疫反応性のB細胞又はT細胞の発生について試験することによって、測定することを特徴とする方法。
- 変異抗原のライブラリの免疫原性の試験における請求項1ないし22のいずれか1項に記載の方法の使用。
- 請求項23に記載の使用において、前記変異抗原がヒト抗原であることを特徴とする使用。
- 請求項24に記載の使用において、前記ヒト抗原がタンパク質であることを特徴とする使用。
- 請求項23に記載の使用において、前記変異抗原が非ヒト抗原であることを特徴とする使用。
- 請求項26に記載の使用において、前記非ヒト抗原がタンパク質であることを特徴とする使用。
- 請求項25に記載の使用において、前記タンパク質が抗体のライブラリ、又は抗体のフラグメントであることを特徴とする使用。
- 請求項23に記載の使用において、変異したヒト抗原が、個々の変異したヒト抗原に誘発された前記抗体を決定すべく前記変異したヒト抗原の混合物に誘発された抗体を試験することによって、あるいは前記変異したヒト抗原の混合物を前記混合物に誘発された抗体で前吸収することによって直接的に選択されることを特徴とする使用。
- 請求項23に記載の使用において、前記変異したヒト抗原が粒子に付着し、該粒子が個々の変異体を同定するのに用いられることを特徴とする使用。
- 請求項23に記載の使用において、前記変異したヒト抗原が生存細胞に付着し、該生存細胞が個々の変異体を同定するのに用いられることを特徴とする使用。
- 請求項23及び29ないし31に記載の使用において、1以上の変異抗原が抗体由来であることを特徴とする使用。
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GBGB0425713.5A GB0425713D0 (en) | 2004-11-23 | 2004-11-23 | Immunogencity testing and antibody selection methods |
GB0425713.5 | 2004-11-23 | ||
PCT/GB2005/004498 WO2006056769A1 (en) | 2004-11-23 | 2005-11-23 | Methods of studying tolerance in mhc-ii transgenic animals |
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JP2008520229A JP2008520229A (ja) | 2008-06-19 |
JP4964781B2 true JP4964781B2 (ja) | 2012-07-04 |
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EP (1) | EP1814386B1 (ja) |
JP (1) | JP4964781B2 (ja) |
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US8911995B2 (en) | 2007-08-22 | 2014-12-16 | Probiogen Ag | Culture system and method for immunogenicity and immunofunction testing in vitro |
AU2008347321B2 (en) * | 2007-12-31 | 2015-05-21 | Baxalta GmbH | Transgenic non-human animals expressing human blood clotting factors |
US9557323B2 (en) | 2010-09-24 | 2017-01-31 | The United States Of America As Represented By The Secretary Of The Navy | Humanized transgenic mouse model |
JP6444321B2 (ja) * | 2013-02-22 | 2018-12-26 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | ヒト化主要組織適合性遺伝子複合体を発現するマウス |
US20210051929A1 (en) * | 2018-03-24 | 2021-02-25 | Regeneron Pharmaceuticals, Inc. | Genetically modified non-human animals for generating therapeutic antibodies against peptide-mhc complexes, methods of making and uses thereof |
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US6277969B1 (en) | 1991-03-18 | 2001-08-21 | New York University | Anti-TNF antibodies and peptides of human tumor necrosis factor |
DK0590058T3 (da) | 1991-06-14 | 2004-03-29 | Genentech Inc | Humaniseret heregulin-antistof |
FR2827302B1 (fr) * | 2001-07-13 | 2003-10-10 | Genoway | Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations |
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DK1814386T3 (da) | 2011-06-06 |
CN101060776A (zh) | 2007-10-24 |
GB0425713D0 (en) | 2004-12-22 |
PL1814386T3 (pl) | 2011-07-29 |
AU2005308597B2 (en) | 2011-08-25 |
KR101385821B1 (ko) | 2014-04-24 |
US20090226893A1 (en) | 2009-09-10 |
WO2006056769A1 (en) | 2006-06-01 |
EP1814386B1 (en) | 2011-03-02 |
AU2005308597A1 (en) | 2006-06-01 |
CA2589163A1 (en) | 2006-06-01 |
ES2359640T3 (es) | 2011-05-25 |
CA2589163C (en) | 2017-01-24 |
CN101060776B (zh) | 2015-01-28 |
KR20070094612A (ko) | 2007-09-20 |
EP1814386A1 (en) | 2007-08-08 |
US9648857B2 (en) | 2017-05-16 |
DE602005026688D1 (de) | 2011-04-14 |
PT1814386E (pt) | 2011-04-14 |
ATE499833T1 (de) | 2011-03-15 |
JP2008520229A (ja) | 2008-06-19 |
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