JP2012102100A - Cd69アンタゴニストを含む肝炎治療用組成物 - Google Patents
Cd69アンタゴニストを含む肝炎治療用組成物 Download PDFInfo
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- JP2012102100A JP2012102100A JP2011247036A JP2011247036A JP2012102100A JP 2012102100 A JP2012102100 A JP 2012102100A JP 2011247036 A JP2011247036 A JP 2011247036A JP 2011247036 A JP2011247036 A JP 2011247036A JP 2012102100 A JP2012102100 A JP 2012102100A
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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Landscapes
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
【解決手段】CD69アンタゴニストを含む組成物であって、炎症症状又は炎症症状に対する感受性を治療する又は低減するために使用される組成物、例えばCD69を特異的に認識する抗体(抗CD69抗体)をCD69アンタゴニストとして含む、肝炎又は肝炎に対する感受性を治療する又は低減するために使用される薬剤又は医薬組成物、並びに、炎症症状又は炎症症状に対する感受性の治療又は低減におけるCD69アンタゴニストの使用、例えば、肝炎又は肝炎に対する感受性の治療又は低減におけるCD69アンタゴニストとしての抗CD69抗体の使用。
【選択図】なし
Description
1.本発明は、少なくとも1つの炎症症状及び/又は少なくとも1つの炎症症状に対する感受性を治療する又は低減する方法であって、
少なくとも1つのCD69アンタゴニストを、肝炎又は肝炎に対する感受性であると診断されている対象に、肝炎又は肝炎に対する感受性を治療する又は低減するのに効果的な量で投与することを含む、方法に関する。
2.肝炎の少なくとも1つの症状をモニタリングすることをさらに含む、任意の前述又は以下の実施形態/特徴/態様の方法。
3.症状が急性炎症、アスパラギン酸アミノトランスフェラーゼ(AST)レベルの上昇、及びアラニンアミノトランスフェラーゼ(ALT)レベルの上昇の少なくとも1つを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
4.少なくとも1つの症状が持続する、所与の範囲内にある、又は閾値より高い若しくは低いままである場合、投与を継続すること、又は
少なくとも1つの症状が持続しない、所与の範囲内にない、又は閾値より高く若しくは低くなくなった場合、投与を中止することをさらに含む、任意の前述又は以下の実施形態/特徴/態様の方法。
5.症状が急性炎症、アスパラギン酸アミノトランスフェラーゼ(AST)レベルの上昇、及び/又はアラニンアミノトランスフェラーゼ(ALT)レベルの上昇の少なくとも1つを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
6.投与されるCD69アンタゴニストが、抗体、又は該抗体の抗原結合断片を含むポリペプチドを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
7.抗体がキメラ抗体である、任意の前述又は以下の実施形態/特徴/態様の方法。
8.抗体がヒト化抗体である、任意の前述又は以下の実施形態/特徴/態様の方法。
9.抗体が完全ヒト化抗体である、任意の前述又は以下の実施形態/特徴/態様の方法。
10.抗体がモノクローナル抗体である、任意の前述又は以下の実施形態/特徴/態様の方法。
11.抗体がポリクローナル抗体である、任意の前述又は以下の実施形態/特徴/態様の方法。
12.抗体が一本鎖抗体である、任意の前述又は以下の実施形態/特徴/態様の方法。
13.抗体又はポリペプチドが機能的薬剤と複合して、免疫複合体を形成する、任意の前述又は以下の実施形態/特徴/態様の方法。
14.機能的薬剤が抗生物質、放射性同位体、核酸分解酵素、毒素、又はそれらの任意の組み合わせである細胞毒性薬である、任意の前述又は以下の実施形態/特徴/態様の方法。
15.抗体、又は抗体の抗原結合断片を含むポリペプチドが、CD69の細胞外ドメインと結合する、任意の前述又は以下の実施形態/特徴/態様の方法。
16.CD69アンタゴニストがCD69に結合するアプタマーを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
17.アプタマーが核酸を含む、任意の前述又は以下の実施形態/特徴/態様の方法。
18.アプタマーがRNAを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
19.アプタマーがDNAを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
20.アプタマーがアミノ酸を含む、任意の前述又は以下の実施形態/特徴/態様の方法。
21.CD69アンタゴニストがmRNAアンタゴニストを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
22.mRNAアンタゴニストがRNA干渉を含む、任意の前述又は以下の実施形態/特徴/態様の方法。
23.mRNAアンタゴニストがリボザイムを含む、任意の前述又は以下の実施形態/特徴/態様の方法。
24.2つ以上のCD69アンタゴニストを投与する、任意の前述又は以下の実施形態/特徴/態様の方法。
25.2つ以上のCD69アンタゴニストが、炎症症状及び/又は少なくとも1つの炎症症状に対する感受性を治療する又は低減するように相乗的に作用する、任意の前述又は以下の実施形態/特徴/態様の方法。
26.少なくとも1つのCD69アンタゴニストを、肝炎又は肝炎に対する感受性を対象とする1つ又は複数のさらなる治療薬と組み合わせて投与する、任意の前述又は以下の実施形態/特徴/態様の方法。
27.少なくとも1つのCD69アンタゴニストと、1つ又は複数のさらなる治療薬との組み合わせが、少なくとも1つの炎症症状に対する感受性を治療する又は低減するように相乗的に作用する、任意の前述又は以下の実施形態/特徴/態様の方法。
28.CD69アンタゴニストが抗CD69抗体を含み、1つ又は複数のさらなる治療薬が、少なくとも1つのワクチン、少なくとも1つの免疫グロブリン、又はそれらの任意の組み合わせである、1つ又は複数の抗A型肝炎治療薬を含む、任意の前述又は以下の実施形態/特徴/態様の方法。
29.CD69アンタゴニストが抗CD69抗体を含み、1つ又は複数のさらなる治療薬が、少なくとも1つのワクチン、少なくとも1つのインターフェロン、少なくとも1つのヌクレオシド系逆転写酵素阻害薬、又はそれらの任意の組み合わせである、1つ又は複数の抗B型肝炎治療薬を含む、任意の前述又は以下の実施形態/特徴/態様の方法。
30.CD69アンタゴニストが抗CD69抗体を含み、1つ又は複数のさらなる治療薬が、少なくとも1つのワクチン、少なくとも1つのペグインターフェロン、少なくとも1つのリバビリン、又はそれらの任意の組み合わせである、1つ又は複数の抗C型肝炎治療薬を含む、任意の前述又は以下の実施形態/特徴/態様の方法。
ConA誘導性肝炎におけるCD69の生理学的役割を、CD69欠損マウスを用いて検査した。CD69欠損(CD69−KO)マウス(非特許文献20)は、BALB/c又はC57BL/6と15回戻し交配することによって得た。全ての動物の世話は、千葉大学及び山口大学のガイドラインに従って行った。ConA(Sigma)をパイロジェンフリーのリン酸緩衝生理食塩水(PBS)中に溶解させ、10mg/kgの用量でC57BL/6マウスに尾静脈を通して静脈内注射した。個々のマウスからの血清を、ConA注射の12時間後に得た。血清アミノトランスフェラーゼ[アラニンアミノトランスフェラーゼ(ALT)及びアスパラギン酸アミノトランスフェラーゼ(AST)]活性を、自動分析器(富士フイルムメディカル株式会社、東京、日本)を用いて、標準的な測光法によって測定した。
抗CD69 mAbの投与を検討して、かかる投与がConAの静脈内注射によって誘導される肝傷害を阻害するか確認を行った。抗CD69抗体処理については、マウスに抗CD69 mAb(H1.2F3、400μg/マウス)をConA注射の30分前に腹腔内注射した。組織学的分析については、個々のマウスから得た肝臓を10%ホルマリン中で固定し、パラフィン包埋し、薄片にし、組織学的検査のためにH&E染色した。標本を光学顕微鏡下で検査した。
Claims (4)
- CD69アンタゴニストを含む肝炎の治療用組成物。
- CD69アンタゴニストがCD69を特異的に認識する抗体である請求項1に記載の肝炎の治療用組成物。
- 肝炎の治療におけるCD69アンタゴニストの使用。
- CD69アンタゴニストがCD69を特異的に認識する抗体である請求項3に記載のCD69アンタゴニストの使用。
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