JP5840623B2 - 気道のウイルス感染症の治療に用いるev576 - Google Patents
気道のウイルス感染症の治療に用いるev576 Download PDFInfo
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Description
a)古典的補体経路、代替補体経路及びレクチン補体経路を阻害し、
b)エイコサノイド活性を阻害する
剤の治療有効量又は予防有効量をそれを必要とする対象に投与することを含む方法を提供する。
a)古典的補体経路、代替補体経路及びレクチン補体経路を阻害し、
b)エイコサノイド活性を阻害する、
治療有効量又は予防有効量の剤も提供する。
剤の投与は他の薬物と同時に、逐次的に又は別々に行うことができる。例えば、剤の投与は他の薬物の投与前又は投与後に行うことができる。
パスツール研究所から入手したヒトH1N1ウイルスの亜致死量(104PFU)又は致死量(106PFU)をBalbCマウスに経鼻感染させるか、又はリン酸緩衝食塩水(PBS)により偽感染させた。
104プラーク形成単位(PFU)の場合、EV576で処理したマウスでは、媒体処理マウスと比べて、タンパク質のレベル(図5)及び総細胞数(図4)が有意に低下し、好中球数(図3及び15)が非常に有意に低下した。106PFUの場合も、EV576で処理したマウスでは好中球数が媒体処理と比べて有意に低下した。
実施例1で上述したようにBalbCマウスの感染及び処理を行った。
高接種レベル及び低接種レベルの両方において、感染後最大10日間、BAL液中のC5aが有意に増加する(図19及び20)。EV576で処理したマウスでは、C5aレベルの上昇が有意に抑制された。媒体及びEV131ではC5aレベルの上昇は抑制されなかった(図21及び22)。
実験プロトコルは参考文献24に記載のものと同様である。
・体重(毎日)
・群特異的生存率%
・各々の肺、背腹の写真(各時点)
・肺重量(各時点)
・肺ウイルス価(各時点)
・肺ミエロペルオキシダーゼ活性(各時点)
・オプション1:病理組織学的試験(各時点)
・オプション2:肺好中球ケモカイン(KC及びMIP−2)
・オプション3:肺単球/NK/T細胞ケモカイン(MCP1、MIP1α)
・オプション4:肺サイトカイン(IL−6、TNFα、IFNα、IFNγ、IL−1β)
・オプション5:IFによる肺全体のウイルス分布
・オプション6:フローサイトメトリーによるBALF中の細胞数カウント
[1] Mastellos, D., et al., Clin Immunol, 2005. 1 15(3): p. 225-35
[2] Peiris JSM, Cheung CY, Leung CYH, Nicholls JM. Innate immune responses to influenza A H5N1 :friend or foe? Trends in Immunology 2009; 30,12: 574-584.
[3] Lee SMY, Gardy JL, Cheung CY et al. Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages. PLoS One, December 2009; 4, 12: 1-1 1.
[4] Guo, R.F. and P.A. Ward, Annu Rev Immunol, 2005, 23: p. 821-52
[5] Neumann, E., et al., Arthritis Rheum, 2002. 46(4): p. 934-45
[6] Williams, A.S., et al., Arthritis Rheum, 2004, 50(9): p. 3035-44
[7] Quigg, R.J., Curr Dir Autoimmun, 2004. 7: p. 165-80
[8] Papagianni, A.A., et al., Nephrol Dial Transplant, 2002, 17(1): p. 57-63
[9] He, C, et al., J Immunol, 2005. 174(9): p. 5750-7
[10] Mead, R.J., et al., J Immunol, 2002. 168(1): p. 458-65
[11] Nakashima, S., et al., J Immunol, 2002. 169(8): p. 4620-7
[12] Mizuno, M. and D.S. Cole, Expert Opin Investig Drugs, 2005. 14(7): p. 807-21
[13] Allegrerti, M., et al.,. Curr Med Chem, 2005. 12(2): p. 217-36
[14] WO2004/106369
[15] WO/2007/028968
[16] WO/2008/029169
[17] WO/2008/029167
[18] WO2009/098454
[19] Terpe K, Appl Microbiol Biotechnol, 60: 523-33, 2003
[20] Sambrook et al (2000)
[21] Fernandez & Hoeffler (1998)
[22] Ausubel et al. (1991)
[23] Remington's Pharmaceutical Sciences; Mack Pub. Co., N.J. 1991
[24] Garigliany et al., (2010) Emerg Infect Dis 16:595-603
Claims (14)
- 気道のウイルス感染を有する対象において気道のウイルス感染による炎症を治療又は予防するための組成物であって、
a)古典的補体経路、代替補体経路及びレクチン補体経路を阻害し、及び/又は
b)エイコサノイド活性を阻害する、
治療有効量又は予防有効量の剤を含み、
該剤が、
(i)配列番号2に示されるアミノ酸配列のアミノ酸19〜168又はアミノ酸1〜168からなるタンパク質、
(ii)配列番号2に示されるアミノ酸配列に対して少なくとも90%の同一性を有するアミノ酸配列からなるタンパク質、
(iii)上記a)及び/又はb)の活性を保持する、(i)又は(ii)のタンパク質の断片
であり、ここで前記気道のウイルス感染による炎症が急性呼吸促迫症候群ではない、前記組成物。 - 剤は補体C5と結合する、請求項1に記載の組成物。
- 剤は、C5転換酵素によって補体C5が補体C5aと補体C5b−9(MAC)へ切断されることを阻害する、請求項2に記載の組成物。
- 剤はLTB4と結合する、請求項1〜3のいずれか1項に記載の組成物。
- 剤は吸血性節足動物に由来する、請求項1〜4のいずれか1項に記載の組成物。
- 気道のウイルス感染を有する対象において気道のウイルス感染による炎症を治療又は予防するための組成物であって、
a)古典的補体経路、代替補体経路及びレクチン補体経路を阻害し、及び/又は
b)エイコサノイド活性を阻害する、
治療有効量又は予防有効量の剤を含み、
該剤は、請求項1に記載のタンパク質をコードする核酸分子であり、ここで前記気道のウイルス感染による炎症が急性呼吸促迫症候群ではない、前記組成物。 - 核酸分子は、配列番号1に示されるヌクレオチド配列の塩基53〜507を含むか又は該塩基で構成される、請求項6に記載の組成物。
- 核酸分子は、配列番号1に示されるヌクレオチド配列の塩基1〜507を含むか又は該塩基で構成される、請求項7に記載の組成物。
- 対象は哺乳動物である、請求項1〜8のいずれか1項に記載の組成物。
- 哺乳動物がヒトである、請求項9に記載の組成物。
- 剤は、対象内で可能な限り多量の有効C5及び/又はLTB4と結合するのに十分な用量で投与する、請求項4〜10のいずれか1項に記載の組成物。
- 剤は、有効C5全量と結合するのに十分な用量で投与する、請求項11に記載の組成物。
- 気道のウイルス感染による炎症は、急性肺傷害を含む呼吸不全、又は多臓器不全を含む呼吸不全の続発症である、請求項1〜12のいずれか1項に記載の組成物。
- ウイルス感染は、インフルエンザAH5N1(トリインフルエンザ)やインフルエンザAH1N1(ブタインフルエンザ)を含む汎発流行性インフルエンザウイルスやSARSコロナウイルスを含む上気道又は下気道の感染である、請求項1〜13のいずれか1項に記載の組成物。
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GBGB1005071.4A GB201005071D0 (en) | 2010-03-25 | 2010-03-25 | Method of treatment |
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IL309975A (en) | 2016-06-14 | 2024-03-01 | Regeneron Pharma | Antibodies against C5 and their uses |
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CN111630065A (zh) | 2017-12-13 | 2020-09-04 | 瑞泽恩制药公司 | 抗c5抗体组合及其用途 |
JP2022500389A (ja) | 2018-09-10 | 2022-01-04 | ヴォリューション イミュノ ファーマシューティカルズ エスエイ | リウマチ性疾患の治療に使用するためのコバーシン |
GB201905810D0 (en) | 2019-04-25 | 2019-06-05 | Volution Immuno Pharmaceuticals Sa | Method of treatment |
US11607428B2 (en) | 2019-06-06 | 2023-03-21 | Spiritus Therapeutics, Inc. | Mesenchymal stem cell-derived extracellular vesicles and uses thereof for treating and diagnosing fibrotic diseases |
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US11912784B2 (en) | 2019-10-10 | 2024-02-27 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
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