JP2016533343A - インターロイキン−4受容体結合融合タンパク質及びその使用 - Google Patents
インターロイキン−4受容体結合融合タンパク質及びその使用 Download PDFInfo
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Abstract
Description
GGGSMQIFVRTLTGRTITLEVEPSDTIENVRARIQDREGIPPDQQRLIFAGRQLEDGRTLSDYNIQRESTLHLVLRLRGGGS(配列番号19)若しくはその変異形を含むものでもよい。リンカーとしての使用に好適なユビキチン分子は、例えば、Bachran, Cら、"Anthrax toxin-mediated delivery of the Pseudomonas exotoxin A enzymatic domain to the cytosol of tumor cells via cleavable ubiquitin fusions MBio. 2013 Apr 30; 4(3): e00201-13、又はPCT公開第WO/2012/139112号に記載されている。
Claims (26)
- インターロイキン−4(IL−4)受容体結合タンパク質及び抗アポトーシス性Bcl−2ファミリーポリペプチドを含む融合タンパク質。
- 前記インターロイキン−4(IL−4)受容体結合タンパク質は、環状順列置換されている(cp)請求項1に記載の融合タンパク質。
- 前記抗アポトーシス性Bcl−2ファミリーポリペプチドは、Bcl−xL、Bcl−w又はBcl−2である請求項1又は2に記載の融合タンパク質。
- 前記融合タンパク質は、I型又はII型IL−4受容体(IL−4R)を発現している標的細胞の、細胞生存を増強すること、細胞死若しくはアポトーシスを阻害すること、細胞死に対して保護すること、細胞活性化を高めること又は細胞成熟を促進することができる請求項1から請求項3のいずれか一項記載の融合タンパク質。
- 前記IL−4受容体結合タンパク質は、IL−4Rに対する結合に対して選択的な変異体IL−4又はIL−13である請求項1から請求項4のいずれか一項記載の融合タンパク質。
- II型IL−4Rへの結合に対して選択的な前記変異体IL−4は、KFR変異形若しくはKF変異形を含み、又はI型IL−4Rへの結合に対して選択的な前記変異体IL−4は、RGA変異形を含む請求項5に記載の融合タンパク質。
- 前記変異体IL−13は、A11変異形又はDN変異形を含む請求項5に記載の融合タンパク質。
- リンカーをさらに含む請求項1から請求項7のいずれか一項記載の融合タンパク質。
- 前記リンカーが配列GSを有するか、又はユビキチン若しくはユビキチン変異形分子である請求項8に記載の融合タンパク質。
- 配列番号18及び20〜24のいずれか1つのアミノ酸配列を含む請求項1又は2に記載の融合タンパク質。
- 請求項1から請求項10のいずれか一項記載の融合タンパク質をエンコードする核酸分子。
- 配列番号30又は31のいずれか1つの核酸配列を含む核酸分子。
- 請求項11又は12に記載の核酸分子を含むベクター。
- 請求項13に記載のベクターを含む宿主細胞。
- 請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11若しくは12に記載の核酸分子、請求項13に記載のベクター、又は請求項14に記載の宿主細胞を含む医薬組成物。
- 細胞増殖を刺激する、細胞生存を増強する、細胞死若しくはアポトーシスを阻害する、細胞死に対して保護する、細胞活性化を高める又は細胞成熟を促進する方法であって、それを必要とする被験者に、請求項1から請求項10のいずれか一項記載の融合タンパク質を含む融合タンパク質、請求項11若しくは12に記載の核酸分子、請求項13に記載のベクター、又は請求項14に記載の宿主細胞を投与することを含む方法。
- 細胞増殖を刺激する、細胞生存を増強する、細胞死若しくはアポトーシスを阻害する、細胞死に対して保護する、細胞活性化を高める又は細胞成熟を促進する方法であって、IL−4Rを発現する標的細胞を、請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11又は12に記載の核酸分子、又は請求項13に記載のベクターに接触させることを含む方法。
- 免疫応答を増強する方法であって、それを必要とする被験者に、請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11若しくは12に記載の核酸分子、請求項13に記載のベクター、又は請求項14に記載の宿主細胞を投与することを含む方法。
- 免疫応答を増強する方法であって、IL−4Rを発現する標的細胞に、請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11若しくは12に記載の核酸分子、又は請求項13に記載のベクターを接触させることを含む方法。
- 神経障害若しくは病態又は自己免疫障害を処置する方法であって、それを必要とする被験者に、請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11若しくは12に記載の核酸分子、請求項13に記載のベクター、又は請求項14に記載の宿主細胞を投与することを含む方法。
- 神経障害又は病態を処置する方法であって、IL−4Rを発現する神経細胞に、請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11若しくは12に記載の核酸分子、又は請求項13に記載のベクターを接触させることを含む方法。
- 請求項1から請求項10のいずれか一項記載の融合タンパク質を含み、GM−CSF−Bcl−XL融合タンパク質をさらに含む組成物。
- GM−CSF−Bcl−XL融合タンパク質を投与することをさらに含む請求項16又は17に記載の方法。
- 細胞増殖を刺激するため、免疫応答を増強するため又は神経障害若しくは自己免疫障害を処置するための、それを必要とする被験者における、請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11又は12に記載の核酸分子、又は請求項13に記載のベクターの使用。
- 前記被験者はヒトである、請求項16、18若しくは20に記載の方法、又は請求項24に記載の使用。
- 養子細胞移入療法又はキメラ抗原受容体(CAR)療法において使用するための、設計操作されたT細胞を増殖又は拡張する方法であって、前記設計操作されたT細胞を、請求項1から請求項10のいずれか一項記載の融合タンパク質、請求項11若しくは12に記載の核酸分子、又は請求項13に記載のベクターに接触させることを含む方法。
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US11084856B2 (en) | 2021-08-10 |
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JP2020010701A (ja) | 2020-01-23 |
EP3910061A1 (en) | 2021-11-17 |
JP6661530B2 (ja) | 2020-03-11 |
US20160215035A1 (en) | 2016-07-28 |
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WO2015042705A1 (en) | 2015-04-02 |
US10106592B2 (en) | 2018-10-23 |
JP2023052641A (ja) | 2023-04-11 |
EP3049525A4 (en) | 2017-05-03 |
CN113563478A (zh) | 2021-10-29 |
US20160237135A1 (en) | 2016-08-18 |
WO2015042706A1 (en) | 2015-04-02 |
CA2925417C (en) | 2023-10-24 |
US20190100568A1 (en) | 2019-04-04 |
JP6936934B2 (ja) | 2021-09-22 |
CA3180148A1 (en) | 2015-04-02 |
JP2016533166A (ja) | 2016-10-27 |
US10093708B2 (en) | 2018-10-09 |
CA2925417A1 (en) | 2015-04-02 |
EP3049526A4 (en) | 2017-10-11 |
US20220048965A1 (en) | 2022-02-17 |
CN105722982A (zh) | 2016-06-29 |
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